LYRICA is indicated for:

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LYRICA is given orally with or without food.

When discontinuing LYRICA, taper gradually over a minimum of 1 week [see Warnings and Precautions (5.6)].

Because LYRICA is eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function [see Dosage and Administration (2.7)].

The maximum recommended dose of LYRICA is 100 mg three times a day (300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

Although LYRICA was also studied at 600 mg/day, there is no evidence that this dose confers additional significant benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 300 mg/day is not recommended [see Adverse Reactions (6.1)].

The recommended dose of LYRICA is 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 75 mg two times a day, or 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with 300 mg/day, and who are able to tolerate LYRICA, may be treated with up to 300 mg two times a day, or 200 mg three times a day (600 mg/day). In view of the dose-dependent adverse reactions and the higher rate of treatment discontinuation due to adverse reactions, reserve dosing above 300 mg/day for those patients who have on-going pain and are tolerating 300 mg daily [see Adverse Reactions (6.1)].

The recommended dosages for adults and pediatric patients 1 month of age and older are included in Table 1. Administer the total daily dosage orally in two or three divided doses as indicated in Table 1. In pediatric patients, the recommended dosing regimen is dependent upon body weight. Based on clinical response and tolerability, dosage may be increased, approximately weekly.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 1. Recommended Dosage for Adults and Pediatric Patients 1 Month and Older</span> </caption> <col width="20%"/> <col width="22%"/> <col width="22%"/> <col width="22%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Age and Body Weight</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Recommended Initial Dosage</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Recommended Maximum Dosage</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Frequency of Administration</span></th> </tr> </thead> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Adults (17 years and older)</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">150 mg/day</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">600 mg/day</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">2 or 3 divided doses</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pediatric patients weighing 30 kg or more</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.5 mg/kg/day</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10 mg/kg/day<br/>(not to exceed 600 mg/day)</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2 or 3 divided doses</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pediatric patients weighing less than 30 kg</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3.5 mg/kg/day</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">14 mg/kg/day</p> </td><td class="Botrule Rrule" valign="top"> <p class="First"> <span class="Italics">1 month to less than 4 years of age:</span> <br/>3 divided doses <br/> <span class="Italics">4 years of age and older:</span> <br/>2 or 3 divided doses</p> </td> </tr> </tbody> </table></div>

Both the efficacy and adverse event profiles of LYRICA have been shown to be dose-related.

The effect of dose escalation rate on the tolerability of LYRICA has not been formally studied.

The efficacy of adjunctive LYRICA in patients taking gabapentin has not been evaluated in controlled trials. Consequently, dosing recommendations for the use of LYRICA with gabapentin cannot be offered.

The recommended dose of LYRICA for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). Although LYRICA was also studied at 600 mg/day, there is no evidence that this dose confers additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended [see Adverse Reactions (6.1)].

The recommended dose range of LYRICA for the treatment of neuropathic pain associated with spinal cord injury is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient pain relief after 2 to 3 weeks of treatment with 150 mg two times a day and who tolerate LYRICA may be treated with up to 300 mg two times a day [see Clinical Studies (14.5)].

In view of dose-dependent adverse reactions and since LYRICA is eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function. The use of LYRICA in pediatric patients with compromised renal function has not been studied.

Base the dose adjustment in patients with renal impairment on creatinine clearance (CLcr), as indicated in Table 2. To use this dosing table, an estimate of the patient's CLcr in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation:

Next, refer to the Dosage and Administration section to determine the recommended total daily dose based on indication, for a patient with normal renal function (CLcr greater than or equal to 60 mL/min). Then refer to Table 2 to determine the corresponding renal adjusted dose.

(For example: A patient initiating LYRICA therapy for postherpetic neuralgia with normal renal function (CLcr greater than or equal to 60 mL/min), receives a total daily dose of 150 mg/day pregabalin. Therefore, a renal impaired patient with a CLcr of 50 mL/min would receive a total daily dose of 75 mg/day pregabalin administered in two or three divided doses.)

For patients undergoing hemodialysis, adjust the pregabalin daily dose based on renal function. In addition to the daily dose adjustment, administer a supplemental dose immediately following every 4-hour hemodialysis treatment (see Table 2).

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 2. Pregabalin Dosage Adjustment Based on Renal Function</span> </caption> <col width="26%"/> <col width="9%"/> <col width="7%"/> <col width="10%"/> <col width="10%"/> <col width="25%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Toprule" valign="top"><span class="Bold">Creatinine Clearance (CLcr)</span> <br/> <span class="Bold">(mL/min)</span></th><th align="left" class="Botrule Lrule Toprule" colspan="4" valign="top"><span class="Bold">Total Pregabalin Daily Dose</span> <br/> <span class="Bold">(mg/day)</span><a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th><th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Dose Regimen</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top">TID= Three divided doses; BID = Two divided doses; QD = Single daily dose.</td> </tr> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose.</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>Supplementary dose is a single additional dose.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Greater than or equal to 60</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">150</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">300</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">450</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">600</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">BID or TID</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">30–60</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">75</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">150</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">225</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">300</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">BID or TID</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">15–30</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">25–50</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">75</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">100–150</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">150</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">QD or BID</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Less than 15</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">25</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">25–50</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">50–75</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">75</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">QD</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="6" valign="top"> <p class="First">Supplementary dosage following hemodialysis (mg)<a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a> </p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="6" valign="top"> <p class="First">Patients on the 25 mg QD regimen: take one supplemental dose of 25 mg or 50 mg</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="6" valign="top"> <p class="First">Patients on the 25–50 mg QD regimen: take one supplemental dose of 50 mg or 75 mg</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="6" valign="top"> <p class="First">Patients on the 50–75 mg QD regimen: take one supplemental dose of 75 mg or 100 mg</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="6" valign="top"> <p class="First">Patients on the 75 mg QD regimen: take one supplemental dose of 100 mg or 150 mg</p> </td> </tr> </tbody> </table></div>

Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg

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Oral Solution: 20 mg/mL

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[see Description (11) and How Supplied/Storage and Handling (16)]

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LYRICA is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see Warnings and Precautions (5.2)].

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There have been postmarketing reports of angioedema in patients during initial and chronic treatment with LYRICA. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue LYRICA immediately in patients with these symptoms.

Exercise caution when prescribing LYRICA to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema.

There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with LYRICA. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue LYRICA immediately in patients with these symptoms.

Antiepileptic drugs (AEDs), including LYRICA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5–100 years) in the clinical trials analyzed.

Table 3 shows absolute and relative risk by indication for all evaluated AEDs.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 3. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis</span> </caption> <col width="16%"/> <col width="16%"/> <col width="16%"/> <col width="21%"/> <col width="17%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Indication</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo Patients with Events Per 1000 Patients</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Drug Patients with Events Per 1000 Patients</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Risk Difference: Additional Drug Patients with Events Per 1000 Patients</span></th> </tr> </thead> <tbody> <tr class="First"> <td class="Lrule Rrule Toprule" valign="top"> <p class="First">Epilepsy</p> </td><td class="Rrule Toprule" valign="top"> <p class="First">1.0</p> </td><td class="Rrule Toprule" valign="top"> <p class="First">3.4</p> </td><td class="Rrule Toprule" valign="top"> <p class="First">3.5</p> </td><td class="Rrule Toprule" valign="top"> <p class="First">2.4</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Psychiatric</p> </td><td class="Rrule" valign="top"> <p class="First">5.7</p> </td><td class="Rrule" valign="top"> <p class="First">8.5</p> </td><td class="Rrule" valign="top"> <p class="First">1.5</p> </td><td class="Rrule" valign="top"> <p class="First">2.9</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Other</p> </td><td class="Rrule" valign="top"> <p class="First">1.0</p> </td><td class="Rrule" valign="top"> <p class="First">1.8</p> </td><td class="Rrule" valign="top"> <p class="First">1.9</p> </td><td class="Rrule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Total</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4.3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.9</p> </td> </tr> </tbody> </table></div>

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing LYRICA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

There is evidence from case reports, human studies, and animal studies associating LYRICA with serious, life-threatening, or fatal respiratory depression when co-administered with central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment. When the decision is made to co-prescribe LYRICA with another CNS depressant, particularly an opioid, or to prescribe LYRICA to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating LYRICA at a low dose. The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including LYRICA).

There is more limited evidence from case reports, animal studies, and human studies associating LYRICA with serious respiratory depression, without co-administered CNS depressants or without underlying respiratory impairment.

LYRICA may cause dizziness and somnolence. Inform patients that LYRICA-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery [see Patient Counseling Information (17)].

In the LYRICA controlled trials in adult patients, dizziness was experienced by 30% of LYRICA-treated patients compared to 8% of placebo-treated patients; somnolence was experienced by 23% of LYRICA-treated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of LYRICA therapy and occurred more frequently at higher doses. Dizziness and somnolence were the adverse reactions most frequently leading to withdrawal (4% each) from controlled studies. In LYRICA-treated patients reporting these adverse reactions in short-term, controlled studies, dizziness persisted until the last dose in 30% and somnolence persisted until the last dose in 42% of patients [see Drug Interactions (7)].

In the LYRICA controlled trials in pediatric patients 4 to less than 17 years of age and 1 month to less than 4 years of age for the treatment of partial-onset seizures, somnolence was reported in 21% and 15% of LYRICA-treated patients compared to 14% and 9% of placebo-treated patients, respectively, and occurred more frequently at higher doses. For patients 1 month to less than 4 years of age, somnolence includes related terms lethargy, sluggishness, and hypersomnia.

As with all antiepileptic drugs (AEDs), withdraw LYRICA gradually to minimize the potential of increased seizure frequency in patients with seizure disorders.

Following abrupt or rapid discontinuation of LYRICA, some patients reported symptoms including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea.

If LYRICA is discontinued, taper the drug gradually over a minimum of 1 week rather than discontinue the drug abruptly.

LYRICA treatment may cause peripheral edema. In short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications such as hypertension or congestive heart failure. Peripheral edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function.

In controlled clinical trials in adult patients, the incidence of peripheral edema was 6% in the LYRICA group compared with 2% in the placebo group. In controlled clinical trials, 0.5% of LYRICA patients and 0.2% placebo patients withdrew due to peripheral edema.

Higher frequencies of weight gain and peripheral edema were observed in patients taking both LYRICA and a thiazolidinedione antidiabetic agent compared to patients taking either drug alone. The majority of patients using thiazolidinedione antidiabetic agents in the overall safety database were participants in studies of pain associated with diabetic peripheral neuropathy. In this population, peripheral edema was reported in 3% (2/60) of patients who were using thiazolidinedione antidiabetic agents only, 8% (69/859) of patients who were treated with LYRICA only, and 19% (23/120) of patients who were on both LYRICA and thiazolidinedione antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on thiazolidinediones only; 4% (35/859) of patients on LYRICA only; and 7.5% (9/120) of patients on both drugs.

As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, exercise caution when co-administering LYRICA and these agents.

Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, exercise caution when using LYRICA in these patients.

LYRICA treatment may cause weight gain. In LYRICA controlled clinical trials in adult patients of up to 14 weeks, a gain of 7% or more over baseline weight was observed in 9% of LYRICA-treated patients and 2% of placebo-treated patients. Few patients treated with LYRICA (0.3%) withdrew from controlled trials due to weight gain. LYRICA associated weight gain was related to dose and duration of exposure, but did not appear to be associated with baseline BMI, gender, or age. Weight gain was not limited to patients with edema [see Warnings and Precautions (5.7)].

Although weight gain was not associated with clinically important changes in blood pressure in short-term controlled studies, the long-term cardiovascular effects of LYRICA-associated weight gain are unknown.

Among diabetic patients, LYRICA-treated patients gained an average of 1.6 kg (range: -16 to 16 kg), compared to an average 0.3 kg (range: -10 to 9 kg) weight gain in placebo patients. In a cohort of 333 diabetic patients who received LYRICA for at least 2 years, the average weight gain was 5.2 kg.

While the effects of LYRICA-associated weight gain on glycemic control have not been systematically assessed, in controlled and longer-term open label clinical trials with diabetic patients, LYRICA treatment did not appear to be associated with loss of glycemic control (as measured by HbA1C).

In standard preclinical in vivo lifetime carcinogenicity studies of LYRICA, an unexpectedly high incidence of hemangiosarcoma was identified in two different strains of mice [see Nonclinical Toxicology (13.1)]. The clinical significance of this finding is unknown. Clinical experience during LYRICA's premarketing development provides no direct means to assess its potential for inducing tumors in humans.

In clinical studies across various patient populations, comprising 6396 patient-years of exposure in patients greater than 12 years of age, new or worsening-preexisting tumors were reported in 57 patients. Without knowledge of the background incidence and recurrence in similar populations not treated with LYRICA, it is impossible to know whether the incidence seen in these cohorts is or is not affected by treatment.

In controlled studies in adult patients, a higher proportion of patients treated with LYRICA reported blurred vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases with continued dosing. Less than 1% of patients discontinued LYRICA treatment due to vision-related events (primarily blurred vision).

Prospectively planned ophthalmologic testing, including visual acuity testing, formal visual field testing and dilated funduscopic examination, was performed in over 3600 patients. In these patients, visual acuity was reduced in 7% of patients treated with LYRICA, and 5% of placebo-treated patients. Visual field changes were detected in 13% of LYRICA-treated, and 12% of placebo-treated patients. Funduscopic changes were observed in 2% of LYRICA-treated and 2% of placebo-treated patients.

Although the clinical significance of the ophthalmologic findings is unknown, inform patients to notify their physician if changes in vision occur. If visual disturbance persists, consider further assessment. Consider more frequent assessment for patients who are already routinely monitored for ocular conditions [see Patient Counseling Information (17)].

LYRICA treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for LYRICA-treated patients and 28 U/L for the placebo patients. In all controlled trials in adult patients across multiple patient populations, 1.5% of patients on LYRICA and 0.7% of placebo patients had a value of creatine kinase at least three times the upper limit of normal. Three LYRICA-treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and LYRICA is not completely understood because the cases had documented factors that may have caused or contributed to these events. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Discontinue treatment with LYRICA if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.

LYRICA treatment was associated with a decrease in platelet count. LYRICA-treated subjects experienced a mean maximal decrease in platelet count of 20 × 103/µL, compared to 11 × 103/µL in placebo patients. In the overall database of controlled trials in adult patients, 2% of placebo patients and 3% of LYRICA patients experienced a potentially clinically significant decrease in platelets, defined as 20% below baseline value and less than 150 × 103/µL. A single LYRICA-treated subject developed severe thrombocytopenia with a platelet count less than 20 × 103/ µL. In randomized controlled trials, LYRICA was not associated with an increase in bleeding-related adverse reactions.

LYRICA treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data in adult patients, the mean PR interval increase was 3–6 msec at LYRICA doses greater than or equal to 300 mg/day. This mean change difference was not associated with an increased risk of PR increase greater than or equal to 25% from baseline, an increased percentage of subjects with on-treatment PR greater than 200 msec, or an increased risk of adverse reactions of second or third degree AV block.

Subgroup analyses did not identify an increased risk of PR prolongation in patients with baseline PR prolongation or in patients taking other PR prolonging medications. However, these analyses cannot be considered definitive because of the limited number of patients in these categories.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In all controlled and uncontrolled trials across various patient populations during the premarketing development of LYRICA, more than 10,000 patients have received LYRICA. Approximately 5000 patients were treated for 6 months or more, over 3100 patients were treated for 1 year or longer, and over 1400 patients were treated for at least 2 years.

Adverse Reactions Most Commonly Leading to Discontinuation in All Premarketing Controlled Clinical Studies

In premarketing controlled trials of all adult populations combined, 14% of patients treated with LYRICA and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (4%) and somnolence (4%). In the placebo group, 1% of patients withdrew due to dizziness and less than 1% withdrew due to somnolence. Other adverse reactions that led to discontinuation from controlled trials more frequently in the LYRICA group compared to the placebo group were ataxia, confusion, asthenia, thinking abnormal, blurred vision, incoordination, and peripheral edema (1% each).

Most Common Adverse Reactions in All Controlled Clinical Studies in Adults

In premarketing controlled trials of all adult patient populations combined (including DPN, PHN, and adult patients with partial-onset seizures), dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and "thinking abnormal" (primarily difficulty with concentration/attention) were more commonly reported by subjects treated with LYRICA than by subjects treated with placebo (greater than or equal to 5% and twice the rate of that seen in placebo).

Controlled Studies with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy

Adverse Reactions Leading to Discontinuation

In clinical trials in adults with neuropathic pain associated with diabetic peripheral neuropathy, 9% of patients treated with LYRICA and 4% of patients treated with placebo discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (3%) and somnolence (2%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the LYRICA group than in the placebo group, were asthenia, confusion, and peripheral edema. Each of these events led to withdrawal in approximately 1% of patients.

Most Common Adverse Reactions

Table 4 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with diabetic neuropathy in the combined LYRICA group for which the incidence was greater in this combined LYRICA group than in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 4. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Diabetic Peripheral Neuropathy</span> </caption> <col width="16%"/> <col width="11%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Body system</span> <br/> <span class="Bold">Preferred term</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">75 mg/day</span> <br/> <span class="Bold">[N=77]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">150 mg/day</span> <br/> <span class="Bold">[N=212]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">300 mg/day</span> <br/> <span class="Bold">[N=321]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">600 mg/day</span> <br/> <span class="Bold">[N=369]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">All PGB</span><a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a> <br/> <span class="Bold">[N=979] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo </span> <br/> <span class="Bold">[N=459] </span> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>PGB: pregabalin</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">‡</a> </dt> <dd>Investigator term; summary level term is amblyopia</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Body as a whole</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Asthenia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Accidental injury</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Back pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Chest pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Face edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Digestive system</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dry mouth</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Constipation</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Flatulence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Metabolic and nutritional disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Peripheral edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Weight gain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Hypoglycemia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Nervous system</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dizziness</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">23</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">29</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">21</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Somnolence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">13</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">16</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Neuropathy</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Ataxia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vertigo</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Confusion</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Euphoria</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Incoordination</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Thinking abnormal<a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Tremor</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abnormal gait</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Amnesia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nervousness</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Respiratory system</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dyspnea</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Special senses</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Blurry vision<a class="Sup" href="#footnote-5" name="footnote-reference-5">‡</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abnormal vision</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

Controlled Studies in Postherpetic Neuralgia

Adverse Reactions Leading to Discontinuation

In clinical trials in adults with postherpetic neuralgia, 14% of patients treated with LYRICA and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (4%) and somnolence (3%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring in greater frequency in the LYRICA group than in the placebo group, were confusion (2%), as well as peripheral edema, asthenia, ataxia, and abnormal gait (1% each).

Most Common Adverse Reactions

Table 5 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with postherpetic neuralgia in the combined LYRICA group for which the incidence was greater in this combined LYRICA group than in the placebo group. In addition, an event is included, even if the incidence in the all LYRICA group is not greater than in the placebo group, if the incidence of the event in the 600 mg/day group is more than twice that in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate". Overall, 12.4% of all pregabalin-treated patients and 9.0% of all placebo-treated patients had at least one severe event while 8% of pregabalin-treated patients and 4.3% of placebo-treated patients had at least one severe treatment-related adverse event.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 5. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Postherpetic Neuralgia</span> </caption> <col width="16%"/> <col width="11%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <col width="12%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Body system</span> <br/> <span class="Bold">Preferred term</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">75 mg/d</span> <br/> <span class="Bold">[N=84]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">150 mg/d</span> <br/> <span class="Bold">[N=302]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">300 mg/d</span> <br/> <span class="Bold">[N=312]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">600 mg/d</span> <br/> <span class="Bold">[N=154]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">All PGB</span><a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a> <br/> <span class="Bold">[N=852]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo</span> <br/> <span class="Bold">[N=398]</span> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>PGB: pregabalin</dd> <dt> <a href="#footnote-reference-7" name="footnote-7">†</a> </dt> <dd>Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking. </dd> <dt> <a href="#footnote-reference-8" name="footnote-8">‡</a> </dt> <dd>Investigator term; summary level term is amblyopia</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Body as a whole</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Infection</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">14</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Headache</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Accidental injury</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Flu syndrome</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Face edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Digestive system</span> </p> </td><td class="Botrule Rrule" valign="top"></td><td class="Botrule Rrule" valign="top"></td><td class="Botrule Rrule" valign="top"></td><td class="Botrule Rrule" valign="top"></td><td class="Botrule Rrule" valign="top"></td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dry mouth</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">15</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Constipation</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Flatulence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vomiting</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Metabolic and nutritional disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Peripheral edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">16</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">16</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Weight gain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Musculoskeletal system</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Myasthenia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Nervous system</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dizziness</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">18</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">31</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">37</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">26</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Somnolence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">18</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">25</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">16</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Ataxia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abnormal gait</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Confusion</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Thinking abnormal<a class="Sup" href="#footnote-7" name="footnote-reference-7">†</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Incoordination</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Amnesia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Speech disorder</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Respiratory system</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Bronchitis</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Special senses</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Blurry vision<a class="Sup" href="#footnote-8" name="footnote-reference-8">‡</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diplopia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abnormal vision</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Eye Disorder</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Urogenital System</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Urinary Incontinence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

Controlled Studies of Adjunctive Therapy for Partial-Onset Seizures in Adult Patients

Adverse Reactions Leading to Discontinuation

Approximately 15% of patients receiving LYRICA and 6% of patients receiving placebo in trials of adjunctive therapy for partial-onset seizures discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (6%), ataxia (4%), and somnolence (3%). In comparison, less than 1% of patients in the placebo group withdrew due to each of these events. Other adverse reactions that led to discontinuation of at least 1% of patients in the LYRICA group and at least twice as frequently compared to the placebo group were asthenia, diplopia, blurred vision, thinking abnormal, nausea, tremor, vertigo, headache, and confusion (which each led to withdrawal in 2% or less of patients).

Most Common Adverse Reactions

Table 6 lists all dose-related adverse reactions occurring in at least 2% of all LYRICA-treated patients. Dose-relatedness was defined as the incidence of the adverse event in the 600 mg/day group was at least 2% greater than the rate in both the placebo and 150 mg/day groups. In these studies, 758 patients received LYRICA and 294 patients received placebo for up to 12 weeks. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 6. Dose-related Adverse Reaction Incidence in Controlled Trials of Adjunctive Therapy for Partial-Onset Seizures in Adult Patients </span> </caption> <col width="17%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">Body System</span> <br/> <span class="Bold">Preferred Term</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">150 mg/d </span> <br/> <span class="Bold">[N=185] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">300 mg/d </span> <br/> <span class="Bold">[N=90] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">600 mg/d </span> <br/> <span class="Bold">[N=395] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">All PGB</span><a class="Sup" href="#footnote-9" name="footnote-reference-9">*</a> <br/> <span class="Bold">[N=670]</span><a class="Sup" href="#footnote-10" name="footnote-reference-10">†</a> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo </span> <br/> <span class="Bold">[N=294] </span> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-9" name="footnote-9">*</a> </dt> <dd>PGB: pregabalin</dd> <dt> <a href="#footnote-reference-10" name="footnote-10">†</a> </dt> <dd>Excludes patients who received the 50 mg dose in Study E1.</dd> <dt> <a href="#footnote-reference-11" name="footnote-11">‡</a> </dt> <dd>Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking.</dd> <dt> <a href="#footnote-reference-12" name="footnote-12">§</a> </dt> <dd>Investigator term; summary level term is amblyopia. </dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="6" valign="top"> <p class="First"> <span class="Bold">Body as a Whole</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Accidental Injury</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="6" valign="top"> <p class="First"> <span class="Bold">Digestive System</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Increased Appetite</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dry Mouth</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Constipation</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="6" valign="top"> <p class="First"> <span class="Bold">Metabolic and Nutritional Disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Weight Gain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">16</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Peripheral Edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="6" valign="top"> <p class="First"> <span class="Bold">Nervous System</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dizziness</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">18</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">31</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">38</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">32</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Somnolence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">18</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">28</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">22</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Ataxia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">20</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">15</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Tremor</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Thinking Abnormal<a class="Sup" href="#footnote-11" name="footnote-reference-11">‡</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Amnesia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Speech Disorder</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Incoordination</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abnormal Gait</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Twitching</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Confusion</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Myoclonus</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="6" valign="top"> <p class="First"> <span class="Bold">Special Senses</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Blurred Vision<a class="Sup" href="#footnote-12" name="footnote-reference-12">§</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diplopia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abnormal Vision</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> </tbody> </table></div>

Controlled Study of Adjunctive Therapy for Partial-Onset Seizures in Patients 4 to Less Than 17 Years of Age

Adverse Reactions Leading to Discontinuation

Approximately 2.5% of patients receiving LYRICA and no patients receiving placebo in trials of adjunctive therapy for partial-onset seizures discontinued prematurely due to adverse reactions. In the LYRICA treatment group, the adverse reactions leading to discontinuation were somnolence (3 patients), worsening of epilepsy (1 patient), and hallucination (1 patient).

Most Common Adverse Reactions

Table 7 lists all dose-related adverse reactions occurring in at least 2% of all LYRICA-treated patients. Dose-relatedness was defined as an incidence of the adverse event in the 10 mg/kg/day group that was at least 2% greater than the rate in both the placebo and 2.5 mg/kg/day groups. In this study, 201 patients received LYRICA and 94 patients received placebo for up to 12 weeks. A majority of pregabalin-treated patients in the clinical study had adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 7. Dose-related Adverse Reaction Incidence in a Controlled Trial in Adjunctive Therapy for Partial-Onset Seizures in Patients 4 to Less Than 17 Years of Age</span> </caption> <col width="26%"/> <col width="18%"/> <col width="18%"/> <col width="13%"/> <col width="13%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Body System</span> <br/> <span class="Bold">Preferred Term</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">2.5 mg/kg/day</span><a class="Sup" href="#footnote-13" name="footnote-reference-13">*</a> <br/> <span class="Bold">[N=104]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">10 mg/kg/day</span><a class="Sup" href="#footnote-14" name="footnote-reference-14">†</a> <br/> <span class="Bold">[N=97]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">All PGB</span> <br/> <span class="Bold">[N=201]</span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo</span> <br/> <span class="Bold">[N=94]</span> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="5" valign="top">Abbreviations: N=number of patients; PGB = pregabalin.</td> </tr> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-13" name="footnote-13">*</a> </dt> <dd>2.5 mg/kg/day: Maximum dose 150 mg/day. Includes patients less than 30 kg for whom dose was adjusted to 3.5 mg/kg/day.</dd> <dt> <a href="#footnote-reference-14" name="footnote-14">†</a> </dt> <dd>10 mg/kg/day: Maximum dose 600 mg/day. Includes patients less than 30 kg for whom dose was adjusted to 14 mg/kg/day.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Gastrointestinal disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Salivary hypersecretion</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Investigations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Weight increased</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">13</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Metabolism and nutrition disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Increased appetite</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Nervous system disorders</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Somnolence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">17</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">26</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">21</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">14</p> </td> </tr> </tbody> </table></div>

Controlled Study of Adjunctive Therapy for Partial-Onset Seizures in Patients 1 Month to Less Than 4 Years of Age

Most Common Adverse Reactions

Table 8 lists all dose-related adverse reactions occurring in at least 2% of all LYRICA-treated patients. Dose-relatedness was defined as an incidence of the adverse event in the 14 mg/kg/day group that was at least 2% greater than the rate in both the placebo and 7 mg/kg/day groups. In this study, 105 patients received LYRICA and 70 patients received placebo for up to 14 days.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 8. Dose-related Adverse Reaction Incidence in a Controlled Trial in Adjunctive Therapy for Partial-Onset Seizures in Patients 1 Month to Less Than 4 Years of Age</span> </caption> <col width="21%"/> <col width="17%"/> <col width="17%"/> <col width="16%"/> <col width="16%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Body System </span> <br/> <span class="Bold">Preferred Term</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">7 mg/kg/day </span> <br/> <span class="Bold">[N=71] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">14 mg/kg/day </span> <br/> <span class="Bold">[N=34] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">All PGB </span> <br/> <span class="Bold">[N=105] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo </span> <br/> <span class="Bold">[N=70] </span> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="5" valign="top">Abbreviations: N=number of patients; PGB=pregabalin.</td> </tr> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-15" name="footnote-15">*</a> </dt> <dd>includes related terms including lethargy, sluggishness, and hypersomnia.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Nervous system disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Somnolence<a class="Sup" href="#footnote-15" name="footnote-reference-15">*</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">13</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">21</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">15</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Infections and infestations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pneumonia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Viral infection</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> </tbody> </table></div>

Controlled Studies with Fibromyalgia

Adverse Reactions Leading to Discontinuation

In clinical trials of patients with fibromyalgia, 19% of patients treated with pregabalin (150–600 mg/day) and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (6%) and somnolence (3%). In comparison, less than 1% of placebo-treated patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue, headache, balance disorder, and weight increased. Each of these adverse reactions led to withdrawal in approximately 1% of patients.

Most Common Adverse Reactions

Table 9 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients with fibromyalgia in the 'all pregabalin' treatment group for which the incidence was greater than in the placebo treatment group. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 9. Adverse Reaction Incidence in Controlled Trials in Fibromyalgia</span> </caption> <col width="20%"/> <col width="11%"/> <col width="11%"/> <col width="11%"/> <col width="11%"/> <col width="12%"/> <col width="11%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">System Organ Class</span> <br/> <span class="Bold">Preferred term</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">150 mg/d </span> <br/> <span class="Bold">[N=132] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">300 mg/d </span> <br/> <span class="Bold">[N=502] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">450 mg/d </span> <br/> <span class="Bold">[N=505] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="middle"><span class="Bold">600 mg/d </span> <br/> <span class="Bold">[N=378] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">All PGB</span><a class="Sup" href="#footnote-16" name="footnote-reference-16">*</a> <br/> <span class="Bold">[N=1517] </span> <br/> <span class="Bold">%</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo </span> <br/> <span class="Bold">[N=505] </span> <br/> <span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="7"> <dl class="Footnote"> <dt> <a href="#footnote-reference-16" name="footnote-16">*</a> </dt> <dd>PGB: pregabalin</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Ear and Labyrinth Disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vertigo</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Eye Disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vision blurred</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Gastrointestinal Disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dry mouth</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Constipation</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vomiting</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Flatulence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Abdominal distension</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">General Disorders and Administrative Site Conditions</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fatigue</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Edema peripheral</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Chest pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Feeling abnormal</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Feeling drunk</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Infections and Infestations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Sinusitis</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Investigations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Weight increased</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">14</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Metabolism and Nutrition Disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Increased appetite</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fluid retention</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Musculoskeletal and Connective Tissue Disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Arthralgia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Muscle spasms</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Back pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Nervous System Disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dizziness</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">23</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">31</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">43</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">45</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">38</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Somnolence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">13</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">18</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">22</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">22</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">20</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Headache</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">14</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Disturbance in attention</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Balance disorder</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Memory impairment</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Coordination abnormal</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Hypoesthesia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Lethargy</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Tremor</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Psychiatric Disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Euphoric Mood</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Confusional state</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Anxiety</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Disorientation</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Depression</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="7" valign="top"> <p class="First"> <span class="Bold">Respiratory, Thoracic and Mediastinal Disorders</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pharyngolaryngeal pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2</p> </td> </tr> </tbody> </table></div>

Controlled Studies in Neuropathic Pain Associated with Spinal Cord Injury

Adverse Reactions Leading to Discontinuation

In clinical trials of adults with neuropathic pain associated with spinal cord injury, 13% of patients treated with pregabalin and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were somnolence (3%) and edema (2%). In comparison, none of the placebo-treated patients withdrew due to somnolence and edema. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue and balance disorder. Each of these adverse reactions led to withdrawal in less than 2% of patients.

Most Common Adverse Reactions

Table 10 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients for which the incidence was greater than in the placebo treatment group with neuropathic pain associated with spinal cord injury in the controlled trials. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 10. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Spinal Cord Injury</span> </caption> <col width="31%"/> <col width="28%"/> <col width="28%"/> <thead> <tr class="First"> <th align="left" class="Lrule Rrule Toprule" rowspan="2" valign="top"><span class="Bold">System Organ Class </span> <br/> <span class="Bold">Preferred term</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">PGB</span><a class="Sup" href="#footnote-17" name="footnote-reference-17">*</a><span class="Bold"> (N=182)</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo (N=174)</span></th> </tr> <tr class="Last"> <th align="center" class="Botrule Rrule" valign="top"><span class="Bold">%</span></th><th align="left" class="Botrule Rrule" valign="top"><span class="Bold">%</span></th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-17" name="footnote-17">*</a> </dt> <dd>PGB: Pregabalin</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Ear and labyrinth disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vertigo</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Eye disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vision blurred</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6.6</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Gastrointestinal disorders</span> </p> </td><td class="Botrule Rrule" valign="top"></td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dry mouth</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11.0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Constipation</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nausea</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4.9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Vomiting</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">General disorders and administration site conditions</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Fatigue</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11.0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Edema peripheral</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10.4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Edema</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3.3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Infections and infestations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nasopharyngitis</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">8.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Investigations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Weight increased</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3.3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Blood creatine phosphokinase increased</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Musculoskeletal and connective tissue disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Muscular weakness</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4.9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Pain in extremity</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3.3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Neck pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Back pain</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.7</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Joint swelling</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Nervous system disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Somnolence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">35.7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">11.5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Dizziness</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">20.9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">6.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Disturbance in attention</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3.8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Memory impairment</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3.3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Paresthesia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Psychiatric disorders</span> </p> </td><td class="Botrule Rrule" valign="top"></td><td class="Botrule Rrule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Insomnia</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">3.8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Euphoric mood</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Renal and urinary disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Urinary incontinence</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Skin and subcutaneous tissue disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Decubitus ulcer</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Vascular disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Hypertension</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">1.1</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Hypotension</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">2.2</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

Other Adverse Reactions Observed During the Clinical Studies of LYRICA

Following is a list of treatment-emergent adverse reactions reported by patients treated with LYRICA during all clinical trials. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening.

Events are categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse reactions are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients. Events of major clinical importance are described in the Warnings and Precautions section (5).

Body as a Whole – Frequent: Abdominal pain, Allergic reaction, Fever, Infrequent: Abscess, Cellulitis, Chills, Malaise, Neck rigidity, Overdose, Pelvic pain, Photosensitivity reaction, Rare: Anaphylactoid reaction, Ascites, Granuloma, Hangover effect, Intentional Injury, Retroperitoneal Fibrosis, Shock

Cardiovascular System – Infrequent: Deep thrombophlebitis, Heart failure, Hypotension, Postural hypotension, Retinal vascular disorder, Syncope; Rare: ST Depressed, Ventricular Fibrillation

Digestive System – Frequent: Gastroenteritis, Increased appetite; Infrequent: Cholecystitis, Cholelithiasis, Colitis, Dysphagia, Esophagitis, Gastritis, Gastrointestinal hemorrhage, Melena, Mouth ulceration, Pancreatitis, Rectal hemorrhage, Tongue edema; Rare: Aphthous stomatitis, Esophageal Ulcer, Periodontal abscess

Hemic and Lymphatic System – Frequent: Ecchymosis; Infrequent: Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare: Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia, Alanine aminotransferase increased, Aspartate aminotransferase increased

Metabolic and Nutritional Disorders – Rare: Glucose Tolerance Decreased, Urate Crystalluria

Musculoskeletal System – Frequent: Arthralgia, Leg cramps, Myalgia, Myasthenia; Infrequent: Arthrosis; Rare: Chondrodystrophy, Generalized Spasm

Nervous System – Frequent: Anxiety, Depersonalization, Hypertonia, Hypoesthesia, Libido decreased, Nystagmus, Paresthesia, Sedation, Stupor, Twitching; Infrequent: Abnormal dreams, Agitation, Apathy, Aphasia, Circumoral paresthesia, Dysarthria, Hallucinations, Hostility, Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased, Myoclonus, Neuralgia; Rare: Addiction, Cerebellar syndrome, Cogwheel rigidity, Coma, Delirium, Delusions, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal syndrome, Guillain-Barré syndrome, Hypalgesia, Intracranial hypertension, Manic reaction, Paranoid reaction, Peripheral neuritis, Personality disorder, Psychotic depression, Schizophrenic reaction, Sleep disorder, Torticollis, Trismus

Respiratory System – Rare: Apnea, Atelectasis, Bronchiolitis, Hiccup, Laryngismus, Lung edema, Lung fibrosis, Yawn

Skin and Appendages – Frequent: Pruritus, Infrequent: Alopecia, Dry skin, Eczema, Hirsutism, Skin ulcer, Urticaria, Vesiculobullous rash; Rare: Angioedema, Exfoliative dermatitis, Lichenoid dermatitis, Melanosis, Nail Disorder, Petechial rash, Purpuric rash, Pustular rash, Skin atrophy, Skin necrosis, Skin nodule, Stevens-Johnson syndrome, Subcutaneous nodule

Special senses – Frequent: Conjunctivitis, Diplopia, Otitis media, Tinnitus; Infrequent: Abnormality of accommodation, Blepharitis, Dry eyes, Eye hemorrhage, Hyperacusis, Photophobia, Retinal edema, Taste loss, Taste perversion; Rare: Anisocoria, Blindness, Corneal ulcer, Exophthalmos, Extraocular palsy, Iritis, Keratitis, Keratoconjunctivitis, Miosis, Mydriasis, Night blindness, Ophthalmoplegia, Optic atrophy, Papilledema, Parosmia, Ptosis, Uveitis

Urogenital System – Frequent: Anorgasmia, Impotence, Urinary frequency, Urinary incontinence; Infrequent: Abnormal ejaculation, Albuminuria, Amenorrhea, Dysmenorrhea, Dysuria, Hematuria, Kidney calculus, Leukorrhea, Menorrhagia, Metrorrhagia, Nephritis, Oliguria, Urinary retention, Urine abnormality; Rare: Acute kidney failure, Balanitis, Bladder Neoplasm, Cervicitis, Dyspareunia, Epididymitis, Female lactation, Glomerulitis, Ovarian disorder, Pyelonephritis

Comparison of Gender and Race

The overall adverse event profile of pregabalin was similar between women and men. There are insufficient data to support a statement regarding the distribution of adverse experience reports by race.

The following adverse reactions have been identified during postapproval use of LYRICA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous System Disorders – Headache

Gastrointestinal Disorders – Nausea, Diarrhea

Reproductive System and Breast Disorders – Gynecomastia, Breast Enlargement

Skin and subcutaneous tissue disorders – Bullous pemphigoid

There are postmarketing reports of life-threatening or fatal respiratory depression in patients taking LYRICA with opioids or other CNS depressants, or in the setting of underlying respiratory impairment.

In addition, there are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when LYRICA was co-administered with medications that have the potential to produce constipation, such as opioid analgesics.

Pharmacodynamics

Multiple oral doses of LYRICA were co-administered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when LYRICA was co-administered with these drugs. No clinically important effects on respiration were seen.

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LYRICA during pregnancy. To provide information regarding the effects of in utero exposure to LYRICA, physicians are advised to recommend that pregnant patients taking LYRICA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

Risk Summary

There are no adequate and well-controlled studies with LYRICA in pregnant women.

However, in animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (AUC) greater than or equal to 16 times human exposure at the maximum recommended dose (MRD) of 600 mg/day [see Data]. In an animal development study, lethality, growth retardation, and nervous and reproductive system functional impairment were observed in the offspring of rats given pregabalin during gestation and lactation. The no-effect dose for developmental toxicity was approximately twice the human exposure at MRD. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2–4% and of miscarriage is 15–20% of clinically recognized pregnancies. Advise pregnant women of the potential risk to a fetus.

Data

Animal Data

When pregnant rats were given pregabalin (500, 1250, or 2500 mg/kg) orally throughout the period of organogenesis, incidences of specific skull alterations attributed to abnormally advanced ossification (premature fusion of the jugal and nasal sutures) were increased at greater than or equal to 1250 mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses. Fetal body weights were decreased at the highest dose. The low dose in this study was associated with a plasma exposure (AUC) approximately 17 times human exposure at the MRD of 600 mg/day. A no-effect dose for rat embryo-fetal developmental toxicity was not established.

When pregnant rabbits were given LYRICA (250, 500, or 1250 mg/kg) orally throughout the period of organogenesis, decreased fetal body weight and increased incidences of skeletal malformations, visceral variations, and retarded ossification were observed at the highest dose. The no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a plasma exposure approximately 16 times human exposure at the MRD.

In a study in which female rats were dosed with LYRICA (50, 100, 250, 1250, or 2500 mg/kg) throughout gestation and lactation, offspring growth was reduced at greater than or equal to 100 mg/kg and offspring survival was decreased at greater than or equal to 250 mg/kg. The effect on offspring survival was pronounced at doses greater than or equal to 1250 mg/kg, with 100% mortality in high-dose litters. When offspring were tested as adults, neurobehavioral abnormalities (decreased auditory startle responding) were observed at greater than or equal to 250 mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1250 mg/kg. The no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a plasma exposure approximately 2 times human exposure at the MRD.

In the prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures greater than or equal to 50 times the mean human exposure (AUC (0–24) of 123 µg∙hr/mL) at the MRD.

Risk Summary

Small amounts of pregabalin have been detected in the milk of lactating women. A pharmacokinetic study in lactating women detected pregabalin in breast milk at average steady state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose [see Data]. The study did not evaluate the effects of LYRICA on milk production or the effects of LYRICA on the breastfed infant.

Based on animal studies, there is a potential risk of tumorigenicity with pregabalin exposure via breast milk to the breastfed infant [see Nonclinical Toxicology (13.1)]. Available clinical study data in patients greater than 12 years of age do not provide a clear conclusion about the potential risk of tumorigenicity with pregabalin [see Warnings and Precautions (5.9)]. Because of the potential risk of tumorigenicity, breastfeeding is not recommended during treatment with LYRICA.

Data

A pharmacokinetic study in ten lactating women, who were at least 12 weeks postpartum, evaluated the concentrations of pregabalin in plasma and breast milk. LYRICA 150 mg oral capsule was given every 12 hours (300 mg daily dose) for a total of four doses. Pregabalin was detected in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose. The study did not evaluate the effects of LYRICA on milk production. Infants did not receive breast milk obtained during the dosing period, therefore, the effects of LYRICA on the breast fed infant were not evaluated.

Infertility

Male

Effects on Spermatogenesis

In a randomized, double-blind, placebo-controlled non-inferiority study to assess the effect of pregabalin on sperm characteristics, healthy male subjects received pregabalin at a daily dose up to 600 mg (n=111) or placebo (n=109) for 13 weeks (one complete sperm cycle) followed by a 13-week washout period (off-drug). A total of 65 subjects in the pregabalin group (59%) and 62 subjects in the placebo group (57%) were included in the per protocol (PP) population. These subjects took study drug for at least 8 weeks, had appropriate timing of semen collections and did not have any significant protocol violations. Among these subjects, approximately 9% of the pregabalin group (6/65) vs. 3% in the placebo group (2/62) had greater than or equal to 50% reduction in mean sperm concentrations from baseline at Week 26 (the primary endpoint). The difference between pregabalin and placebo was within the pre-specified non-inferiority margin of 20%. There were no adverse effects of pregabalin on sperm morphology, sperm motility, serum FSH or serum testosterone levels as compared to placebo. In subjects in the PP population with greater than or equal to 50% reduction in sperm concentration from baseline, sperm concentrations were no longer reduced by greater than or equal to 50% in any affected subject after an additional 3 months off-drug. In one subject, however, subsequent semen analyses demonstrated reductions from baseline of greater than or equal to 50% at 9 and 12 months off-drug. The clinical relevance of these data is unknown.

In the animal fertility study with pregabalin in male rats, adverse reproductive and developmental effects were observed [see Nonclinical Toxicology (13.1)].

Neuropathic Pain Associated with Diabetic Peripheral Neuropathy, Postherpetic Neuralgia, and Neuropathic Pain Associated with Spinal Cord Injury

Safety and effectiveness in pediatric patients have not been established.

Fibromyalgia

Safety and effectiveness in pediatric patients have not been established.

A 15-week, placebo-controlled trial was conducted with 107 pediatric patients with fibromyalgia, ages 12 through 17 years, at LYRICA total daily doses of 75–450 mg per day. The primary efficacy endpoint of change from baseline to Week 15 in mean pain intensity (derived from an 11-point numeric rating scale) showed numerically greater improvement for the pregabalin-treated patients compared to placebo-treated patients, but did not reach statistical significance. The most frequently observed adverse reactions in the clinical trial included dizziness, nausea, headache, weight increased, and fatigue. The overall safety profile in adolescents was similar to that observed in adults with fibromyalgia.

Adjunctive Therapy for Partial-Onset Seizures

Safety and effectiveness in pediatric patients below the age of 1 month have not been established.

4 to Less Than 17 Years of Age with Partial-Onset Seizures

The safety and effectiveness of LYRICA as adjunctive treatment for partial-onset seizures in pediatric patients 4 to less than 17 years of age have been established in a 12-week, double-blind, placebo-controlled study (n=295) [see Clinical Studies (14.3)]. Patients treated with LYRICA 10 mg/kg/day had, on average, a 21.0% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0185). Patients treated with LYRICA 2.5 mg/kg/day had, on average, a 10.5% greater reduction in partial-onset seizures than patients treated with placebo, but the difference was not statistically significant (p=0.2577).

Responder rates (50% or greater reduction in partial-onset seizure frequency) were a key secondary efficacy parameter and showed numerical improvement with LYRICA compared with placebo: the responder rates were 40.6%, 29.1%, and 22.6%, for LYRICA 10 mg/kg/day, LYRICA 2.5 mg/kg/day, and placebo, respectively.

The most common adverse reactions (≥5%) with LYRICA in this study were somnolence, weight increased, and increased appetite [see Adverse Reactions (6.1)].

The use of LYRICA 2.5 mg/kg/day in pediatric patients is further supported by evidence from adequate and well-controlled studies in adults with partial-onset seizures and pharmacokinetic data from adult and pediatric patients [see Clinical Pharmacology (12.3)].

1 Month to Less than 4 Years of Age with Partial-Onset Seizures

The safety and effectiveness of LYRICA as adjunctive treatment for partial-onset seizures in pediatric patients 1 month to less than 4 years of age have been established in a 14-day double-blind, placebo-controlled study (N=175) [see Clinical Studies (14.3)]. The youngest subject evaluated was 3 months of age; use in patients 1 month to less than 3 months of age is supported by additional pharmacokinetic analyses. Patients treated with LYRICA 14 mg/kg/day had, on average, 43.9% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0223). In addition, pediatric patients treated with LYRICA 14 mg/kg/day showed numerical improvement in responder rates (≥50% reduction in partial-onset seizure frequency) compared with placebo (53.6% versus 41.5%). Patients treated with LYRICA 7 mg/kg/day did not show improvement relative to placebo for either endpoint.

The most common dose-related adverse reactions (≥5%) with LYRICA in this study were somnolence, pneumonia, and viral infection [see Adverse Reactions (6.1)].

Juvenile Animal Data

In studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from early in the postnatal period (Postnatal Day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory startle responding and habituation) and reproductive impairment (delayed sexual maturation and decreased fertility in males and females) were observed at doses greater than or equal to 50 mg/kg. The neurobehavioral changes of acoustic startle persisted at greater than or equal to 250 mg/kg and locomotor activity and water maze performance at greater than or equal to 500 mg/kg in animals tested after cessation of dosing and, thus, were considered to represent long-term effects. The low effect dose for developmental neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately equal to human exposure at the maximum recommended dose of 600 mg/day. A no-effect dose was not established.

In controlled clinical studies of LYRICA in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older.

In controlled clinical studies of LYRICA in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older.

In controlled clinical studies of LYRICA in epilepsy, there were only 10 patients 65 to 74 years of age, and 2 patients who were 75 years of age or older.

No overall differences in safety and efficacy were observed between these patients and younger patients.

In controlled clinical studies of LYRICA in fibromyalgia, 106 patients were 65 years of age or older. Although the adverse reaction profile was similar between the two age groups, the following neurological adverse reactions were more frequent in patients 65 years of age or older: dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and lethargy.

LYRICA is known to be substantially excreted by the kidney, and the risk of toxic reactions to LYRICA may be greater in patients with impaired renal function. Because LYRICA is eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment [see Dosage and Administration (2.7)].

LYRICA is eliminated primarily by renal excretion and dose adjustment is recommended for adult patients with renal impairment [see Dosage and Administration (2.7) and Clinical Pharmacology (12.3)]. The use of LYRICA in pediatric patients with compromised renal function has not been studied.

LYRICA is a Schedule V controlled substance.

LYRICA is not known to be active at receptor sites associated with drugs of abuse. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of LYRICA misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).

In a study of recreational users (N=15) of sedative/hypnotic drugs, including alcohol, LYRICA (450 mg, single dose) received subjective ratings of "good drug effect," "high" and "liking" to a degree that was similar to diazepam (30 mg, single dose). In controlled clinical studies in over 5500 patients, 4 % of LYRICA-treated patients and 1 % of placebo-treated patients overall reported euphoria as an adverse reaction, though in some patient populations studied, this reporting rate was higher and ranged from 1 to 12%.

In clinical studies, following abrupt or rapid discontinuation of LYRICA, some patients reported symptoms including insomnia, nausea, headache or diarrhea [see Warnings and Precautions (5.6)], consistent with physical dependence. In the postmarketing experience, in addition to these reported symptoms there have also been reported cases of anxiety and hyperhidrosis.

Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans

In the postmarketing experience, the most commonly reported adverse events observed with pregabalin when taken in overdose include reduced consciousness, depression/anxiety, confusional state, agitation, and restlessness. Seizures and heart block have also been reported. Deaths have been reported in the setting of lone LYRICA overdose and in combination with other CNS depressants.

Treatment or Management of Overdose

There is no specific antidote for overdose with LYRICA. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with LYRICA.

LYRICA can be removed by hemodialysis. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4 hours).

Pregabalin is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C8H17NO2 and the molecular weight is 159.23. The chemical structure of pregabalin is:

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Pregabalin is a white to off-white, crystalline solid with a pKa1 of 4.2 and a pKa2 of 10.6. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is – 1.35.

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LYRICA (pregabalin) Capsules are administered orally and are supplied as imprinted hard-shell capsules containing 25, 50, 75, 100, 150, 200, 225, and 300 mg of pregabalin, along with lactose monohydrate, cornstarch, and talc as inactive ingredients. The capsule shells contain gelatin and titanium dioxide. In addition, the orange capsule shells contain red iron oxide and the white capsule shells contain sodium lauryl sulfate and colloidal silicon dioxide. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells. The imprinting ink contains shellac, black iron oxide, propylene glycol, and potassium hydroxide.

{ "type": "p", "children": [], "text": "LYRICA (pregabalin) Capsules are administered orally and are supplied as imprinted hard-shell capsules containing 25, 50, 75, 100, 150, 200, 225, and 300 mg of pregabalin, along with lactose monohydrate, cornstarch, and talc as inactive ingredients. The capsule shells contain gelatin and titanium dioxide. In addition, the orange capsule shells contain red iron oxide and the white capsule shells contain sodium lauryl sulfate and colloidal silicon dioxide. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells. The imprinting ink contains shellac, black iron oxide, propylene glycol, and potassium hydroxide." }

LYRICA (pregabalin) oral solution, 20 mg/mL, is administered orally and is supplied as a clear, colorless solution contained in a 16 fluid ounce white HDPE bottle with a polyethylene-lined closure. The oral solution contains 20 mg/mL of pregabalin, along with methylparaben, propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and purified water as inactive ingredients.

{ "type": "p", "children": [], "text": "LYRICA (pregabalin) oral solution, 20 mg/mL, is administered orally and is supplied as a clear, colorless solution contained in a 16 fluid ounce white HDPE bottle with a polyethylene-lined closure. The oral solution contains 20 mg/mL of pregabalin, along with methylparaben, propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and purified water as inactive ingredients." }

LYRICA (pregabalin) binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin's anti-nociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha2-delta containing-calcium channel trafficking and/or reducing calcium currents. Evidence from other animal models of nerve damage and persistent pain suggest the anti-nociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord.

While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.

Pregabalin is well absorbed after oral administration, is eliminated largely by renal excretion, and has an elimination half-life of about 6 hours.

Absorption and Distribution

Following oral administration of LYRICA capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin oral bioavailability is greater than or equal to 90% and is independent of dose. Following single- (25 to 300 mg) and multiple-dose (75 to 900 mg/day) administration, maximum plasma concentrations (Cmax) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.

The rate of pregabalin absorption is decreased when given with food, resulting in a decrease in Cmax of approximately 25% to 30% and an increase in Tmax to approximately 3 hours. However, administration of pregabalin with food has no clinically relevant effect on the total absorption of pregabalin. Therefore, pregabalin can be taken with or without food.

Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. Although there are no data in humans, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys. In addition, pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats.

Metabolism and Elimination

Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled pregabalin, approximately 90% of the administered dose was recovered in the urine as unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbits, or monkeys.

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67.0 to 80.9 mL/min in young healthy subjects. Because pregabalin is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to creatinine clearance (CLcr) [see Dosage and Administration (2.7)].

Pharmacokinetics in Specific Populations

Race

In population pharmacokinetic analyses of the clinical studies in various populations, the pharmacokinetics of LYRICA were not significantly affected by race (Caucasians, Blacks, and Hispanics).

Gender

Population pharmacokinetic analyses of the clinical studies showed that the relationship between daily dose and LYRICA drug exposure is similar between genders.

Renal Impairment and Hemodialysis

Pregabalin clearance is nearly proportional to creatinine clearance (CLcr). Dosage reduction in patients with renal dysfunction is necessary. Pregabalin is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, plasma pregabalin concentrations are reduced by approximately 50%. For patients on hemodialysis, dosing must be modified [see Dosage and Administration (2.7)].

Elderly

Pregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with age-related decreases in CLcr. Reduction of pregabalin dose may be required in patients who have age-related compromised renal function [see Dosage and Administration (2.7)].

Pediatric Pharmacokinetics

Pediatric Patients (3 months to less than 17 years of age)

Pregabalin pharmacokinetics were evaluated in 358 pediatric patients 3 months to less than 17 years of age with partial-onset seizures at dose levels of 2.5, 5, 10, and 15 mg/kg/day after single and multiple oral administration of pregabalin. Following oral administration, pregabalin reaches peak plasma concentration at 0.5 hours to 2 hours in the fasted state. Both apparent clearance (CL/F) and apparent volume of distribution increase as body weight increases. A weight-based dosing regimen is necessary to achieve pregabalin exposures in pediatric patients 1 month to less than 17 years of age similar to those observed in adults treated for partial-onset seizures at effective doses [see Dosage and Administration (2.4)]. The mean t½ is 3 to 4 hours in pediatric subjects up to 6 years of age, and 4 to 6 hours in those 7 years of age and older. Pregabalin CL/F is nearly proportional to CLcr (mL/min). The relationship is similar in pediatric and adult subjects. When normalized per body weight, CL/F (mL/min/kg) in pediatric subjects weighing less than 30 kg is approximately 40% higher in comparison to subjects weighing greater than or equal to 30 kg [see Dosage and Administration (2.4)].

Drug Interactions

In Vitro Studies

Pregabalin, at concentrations that were, in general, 10-times those attained in clinical trials, does not inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzyme systems. In vitro drug interaction studies demonstrate that pregabalin does not induce CYP1A2 or CYP3A4 activity. Therefore, an increase in the metabolism of coadministered CYP1A2 substrates (e.g. theophylline, caffeine) or CYP 3A4 substrates (e.g., midazolam, testosterone) is not anticipated.

In Vivo Studies

The drug interaction studies described in this section were conducted in healthy adults, and across various patient populations.

Gabapentin

The pharmacokinetic interactions of pregabalin and gabapentin were investigated in 12 healthy subjects following concomitant single-dose administration of 100-mg pregabalin and 300-mg gabapentin and in 18 healthy subjects following concomitant multiple-dose administration of 200-mg pregabalin every 8 hours and 400-mg gabapentin every 8 hours. Gabapentin pharmacokinetics following single- and multiple-dose administration were unaltered by pregabalin coadministration. The extent of pregabalin absorption was unaffected by gabapentin coadministration, although there was a small reduction in rate of absorption.

Oral Contraceptive

Pregabalin coadministration (200 mg three times a day) had no effect on the steady-state pharmacokinetics of norethindrone and ethinyl estradiol (1 mg/35 µg, respectively) in healthy subjects.

Lorazepam

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of lorazepam single-dose pharmacokinetics and single-dose administration of lorazepam (1 mg) had no effect on the steady-state pharmacokinetics of pregabalin.

Oxycodone

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of oxycodone single-dose pharmacokinetics. Single-dose administration of oxycodone (10 mg) had no effect on the steady-state pharmacokinetics of pregabalin.

Ethanol

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of ethanol single-dose pharmacokinetics and single-dose administration of ethanol (0.7 g/kg) had no effect on the steady-state pharmacokinetics of pregabalin.

Phenytoin, carbamazepine, valproic acid, and lamotrigine

Steady-state trough plasma concentrations of phenytoin, carbamazepine and carbamazepine 10,11 epoxide, valproic acid, and lamotrigine were not affected by concomitant pregabalin (200 mg three times a day) administration.

Population pharmacokinetic analyses in patients treated with pregabalin and various concomitant medications suggest the following:

<div class="scrollingtable"><table width="50%"> <col width="22%"/> <col width="36%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Toprule" valign="top"><span class="Bold">Therapeutic class</span></th><th align="left" class="Botrule Toprule" valign="top"><span class="Bold">Specific concomitant drug studied</span></th> </tr> </thead> <tbody> <tr class="First"> <td class="Botrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold"><span class="Italics">Concomitant drug has no effect on the pharmacokinetics of pregabalin</span></span> </p> </td> </tr> <tr> <td valign="top"> <p class="First">Hypoglycemics</p> </td><td valign="top"> <p class="First">Glyburide, insulin, metformin</p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">Diuretics</p> </td><td class="Botrule" valign="top"> <p class="First">Furosemide</p> </td> </tr> <tr> <td class="Botrule" valign="top"> <p class="First">Antiepileptic Drugs</p> </td><td class="Botrule" valign="top"> <p class="First">Tiagabine</p> </td> </tr> <tr> <td class="Botrule" colspan="2" valign="top"> <p class="First"> <span class="Bold"><span class="Italics">Concomitant drug has no effect on the pharmacokinetics of pregabalin and pregabalin has no effect on the pharmacokinetics of concomitant drug</span></span> </p> </td> </tr> <tr class="Last"> <td class="Botrule" valign="top"> <p class="First">Antiepileptic Drugs</p> </td><td class="Botrule" valign="top"> <p class="First">Carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, valproic acid</p> </td> </tr> </tbody> </table></div>

Carcinogenesis

A dose-dependent increase in the incidence of malignant vascular tumors (hemangiosarcomas) was observed in two strains of mice (B6C3F1 and CD-1) given pregabalin (200, 1000, or 5000 mg/kg) in the diet for two years. Plasma pregabalin exposure (AUC) in mice receiving the lowest dose that increased hemangiosarcomas was approximately equal to the human exposure at the maximum recommended dose (MRD) of 600 mg/day. A no-effect dose for induction of hemangiosarcomas in mice was not established. No evidence of carcinogenicity was seen in two studies in Wistar rats following dietary administration of pregabalin for two years at doses (50, 150, or 450 mg/kg in males and 100, 300, or 900 mg/kg in females) that were associated with plasma exposures in males and females up to approximately 14 and 24 times, respectively, human exposure at the MRD.

Mutagenesis

Pregabalin was not mutagenic in bacteria or in mammalian cells in vitro, was not clastogenic in mammalian systems in vitro and in vivo, and did not induce unscheduled DNA synthesis in mouse or rat hepatocytes.

Impairment of Fertility

In fertility studies in which male rats were orally administered pregabalin (50 to 2500 mg/kg) prior to and during mating with untreated females, a number of adverse reproductive and developmental effects were observed. These included decreased sperm counts and sperm motility, increased sperm abnormalities, reduced fertility, increased preimplantation embryo loss, decreased litter size, decreased fetal body weights, and an increased incidence of fetal abnormalities. Effects on sperm and fertility parameters were reversible in studies of this duration (3–4 months). The no-effect dose for male reproductive toxicity in these studies (100 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately 3 times human exposure at the maximum recommended dose (MRD) of 600 mg/day.

In addition, adverse reactions on reproductive organ (testes, epididymides) histopathology were observed in male rats exposed to pregabalin (500 to 1250 mg/kg) in general toxicology studies of four weeks or greater duration. The no-effect dose for male reproductive organ histopathology in rats (250 mg/kg) was associated with a plasma exposure approximately 8 times human exposure at the MRD.

In a fertility study in which female rats were given pregabalin (500, 1250, or 2500 mg/kg) orally prior to and during mating and early gestation, disrupted estrous cyclicity and an increased number of days to mating were seen at all doses, and embryolethality occurred at the highest dose. The low dose in this study produced a plasma exposure approximately 9 times that in humans receiving the MRD. A no-effect dose for female reproductive toxicity in rats was not established.

Dermatopathy

Skin lesions ranging from erythema to necrosis were seen in repeated-dose toxicology studies in both rats and monkeys. The etiology of these skin lesions is unknown. At the maximum recommended human dose (MRD) of 600 mg/day, there is a 2-fold safety margin for the dermatological lesions. The more severe dermatopathies involving necrosis were associated with pregabalin exposures (as expressed by plasma AUCs) of approximately 3 to 8 times those achieved in humans given the MRD. No increase in incidence of skin lesions was observed in clinical studies.

Ocular Lesions

Ocular lesions (characterized by retinal atrophy [including loss of photoreceptor cells] and/or corneal inflammation/mineralization) were observed in two lifetime carcinogenicity studies in Wistar rats. These findings were observed at plasma pregabalin exposures (AUC) greater than or equal to 2 times those achieved in humans given the maximum recommended dose of 600 mg/day. A no-effect dose for ocular lesions was not established. Similar lesions were not observed in lifetime carcinogenicity studies in two strains of mice or in monkeys treated for 1 year.

The efficacy of the maximum recommended dose of LYRICA for the management of neuropathic pain associated with diabetic peripheral neuropathy was established in three double-blind, placebo-controlled, multicenter studies with three times a day dosing, two of which studied the maximum recommended dose. Patients were enrolled with either Type 1 or Type 2 diabetes mellitus and a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for 1 to 5 years. A total of 89% of patients completed Studies DPN 1 and DPN 2. The patients had a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). The baseline mean pain scores across the two studies ranged from 6.1 to 6.7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.

Study DPN 1: This 5-week study compared LYRICA 25, 100, or 200 mg three times a day with placebo. Treatment with LYRICA 100 and 200 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. There was no evidence of a greater effect on pain scores of the 200 mg three times a day dose than the 100 mg three times a day dose, but there was evidence of dose dependent adverse reactions [see Adverse Reactions (6.1)]. For a range of levels of improvement in pain intensity from baseline to study endpoint, Figure 1 shows the fraction of patients achieving that level of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 1: Patients Achieving Various Levels of Improvement in Pain Intensity – Study DPN 1

Study DPN 2: This 8-week study compared LYRICA 100 mg three times a day with placebo. Treatment with LYRICA 100 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 2 shows the fraction of patients achieving that level of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 2: Patients Achieving Various Levels of Improvement in Pain Intensity– Study DPN 2

The efficacy of LYRICA for the management of postherpetic neuralgia was established in three double-blind, placebo-controlled, multicenter studies. These studies enrolled patients with neuralgia persisting for at least 3 months following healing of herpes zoster rash and a minimum baseline score of greater than or equal to 4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). Seventy-three percent of patients completed the studies. The baseline mean pain scores across the 3 studies ranged from 6 to 7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.

Study PHN 1: This 13-week study compared LYRICA 75, 150, and 300 mg twice daily with placebo. Patients with creatinine clearance (CLcr) between 30 to 60 mL/min were randomized to 75 mg, 150 mg, or placebo twice daily. Patients with creatinine clearance greater than 60 mL/min were randomized to 75 mg, 150 mg, 300 mg or placebo twice daily. In patients with creatinine clearance greater than 60 mL/min treatment with all doses of LYRICA statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. Despite differences in dosing based on renal function, patients with creatinine clearance between 30 to 60 mL/min tolerated LYRICA less well than patients with creatinine clearance greater than 60 mL/min as evidenced by higher rates of discontinuation due to adverse reactions. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 3 shows the fraction of patients achieving that level of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 3: Patients Achieving Various Levels of Improvement in Pain Intensity– Study PHN 1

Study PHN 2: This 8-week study compared LYRICA 100 or 200 mg three times a day with placebo, with doses assigned based on creatinine clearance. Patients with creatinine clearance between 30 to 60 mL/min were treated with 100 mg three times a day, and patients with creatinine clearance greater than 60 mL/min were treated with 200 mg three times daily. Treatment with LYRICA statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 4 shows the fraction of patients achieving those levels of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 4: Patients Achieving Various Levels of Improvement in Pain Intensity – Study PHN 2

Study PHN 3: This 8-week study compared LYRICA 50 or 100 mg three times a day with placebo with doses assigned regardless of creatinine clearance. Treatment with LYRICA 50 and 100 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. Patients with creatinine clearance between 30 to 60 mL/min tolerated LYRICA less well than patients with creatinine clearance greater than 60 mL/min as evidenced by markedly higher rates of discontinuation due to adverse reactions. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 5 shows the fraction of patients achieving that level of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 5: Patients Achieving Various Levels of Improvement in Pain Intensity– Study PHN 3

Adjunctive Therapy for Partial-Onset Seizures in Adult Patients

The efficacy of LYRICA as adjunctive therapy for partial-onset seizures in adult patients was established in three 12-week, randomized, double-blind, placebo-controlled, multicenter studies. Patients were enrolled who had partial-onset seizures with or without secondary generalization and were not adequately controlled with 1 to 3 concomitant antiepileptic drugs (AEDs). Patients taking gabapentin were required to discontinue gabapentin treatment 1 week prior to entering baseline. During an 8-week baseline period, patients had to experience at least 6 partial-onset seizures with no seizure-free period exceeding 4 weeks. The mean duration of epilepsy was 25 years in these 3 studies and the mean and median baseline seizure frequencies were 22.5 and 10 seizures per month, respectively. Approximately half of the patients were taking 2 concurrent AEDs at baseline. Among the LYRICA-treated patients, 80% completed the double-blind phase of the studies.

Table 11 shows median baseline seizure rates and median percent reduction in seizure frequency by dose.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 11. Seizure Response in Controlled, Adjunctive Epilepsy Studies in Adults</span> </caption> <col width="15%"/> <col width="15%"/> <col width="12%"/> <col width="16%"/> <col width="14%"/> <col width="14%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Daily Dose of Pregabalin</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Dosing Regimen</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">N</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Baseline Seizure Frequency/mo</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Median % Change from Baseline</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">p-value, vs. placebo</span></th> </tr> </thead> <tbody> <tr class="First"> <td class="Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Study E1</span> </p> </td><td class="Rrule Toprule" valign="top"></td><td class="Rrule Toprule" valign="top"></td><td class="Rrule Toprule" valign="top"></td><td class="Rrule Toprule" valign="top"></td><td class="Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Placebo</p> </td><td class="Rrule" valign="top"> <p class="First">BID</p> </td><td class="Rrule" valign="top"> <p class="First">100</p> </td><td class="Rrule" valign="top"> <p class="First">9.5</p> </td><td class="Rrule" valign="top"> <p class="First">0</p> </td><td class="Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">50 mg/day</p> </td><td class="Rrule" valign="top"> <p class="First">BID</p> </td><td class="Rrule" valign="top"> <p class="First">88</p> </td><td class="Rrule" valign="top"> <p class="First">10.3</p> </td><td class="Rrule" valign="top"> <p class="First">-9</p> </td><td class="Rrule" valign="top"> <p class="First">0.4230</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">150 mg/day</p> </td><td class="Rrule" valign="top"> <p class="First">BID</p> </td><td class="Rrule" valign="top"> <p class="First">86</p> </td><td class="Rrule" valign="top"> <p class="First">8.8</p> </td><td class="Rrule" valign="top"> <p class="First">-35</p> </td><td class="Rrule" valign="top"> <p class="First">0.0001</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">300 mg/day</p> </td><td class="Rrule" valign="top"> <p class="First">BID</p> </td><td class="Rrule" valign="top"> <p class="First">90</p> </td><td class="Rrule" valign="top"> <p class="First">9.8</p> </td><td class="Rrule" valign="top"> <p class="First">-37</p> </td><td class="Rrule" valign="top"> <p class="First">0.0001</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">600 mg/day</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">BID</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">89</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">9.0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">-51</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.0001</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Study E2</span> </p> </td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Placebo</p> </td><td class="Rrule" valign="top"> <p class="First">TID</p> </td><td class="Rrule" valign="top"> <p class="First">96</p> </td><td class="Rrule" valign="top"> <p class="First">9.3</p> </td><td class="Rrule" valign="top"> <p class="First">1</p> </td><td class="Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">150 mg/day</p> </td><td class="Rrule" valign="top"> <p class="First">TID</p> </td><td class="Rrule" valign="top"> <p class="First">99</p> </td><td class="Rrule" valign="top"> <p class="First">11.5</p> </td><td class="Rrule" valign="top"> <p class="First">-17</p> </td><td class="Rrule" valign="top"> <p class="First">0.0007</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">600 mg/day</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">TID</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">92</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">12.3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">-43</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.0001</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Study E3</span> </p> </td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Placebo</p> </td><td class="Rrule" valign="top"> <p class="First">BID/TID</p> </td><td class="Rrule" valign="top"> <p class="First">98</p> </td><td class="Rrule" valign="top"> <p class="First">11</p> </td><td class="Rrule" valign="top"> <p class="First">-1</p> </td><td class="Rrule" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">600 mg/day</p> </td><td class="Rrule" valign="top"> <p class="First">BID</p> </td><td class="Rrule" valign="top"> <p class="First">103</p> </td><td class="Rrule" valign="top"> <p class="First">9.5</p> </td><td class="Rrule" valign="top"> <p class="First">-36</p> </td><td class="Rrule" valign="top"> <p class="First">0.0001</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">600 mg/day</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">TID</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">111</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">10</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">-48</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.0001</p> </td> </tr> </tbody> </table></div>

In the first study (E1), there was evidence of a dose-response relationship for total daily doses of LYRICA between 150 and 600 mg/day; a dose of 50 mg/day was not effective. In the first study (E1), each daily dose was divided into two equal doses (twice a day dosing). In the second study (E2), each daily dose was divided into three equal doses (three times a day dosing). In the third study (E3), the same total daily dose was divided into two equal doses for one group (twice a day dosing) and three equal doses for another group (three times a day dosing). While the three times a day dosing group in Study E3 performed numerically better than the twice a day dosing group, this difference was small and not statistically significant.

A secondary outcome measure included the responder rate (proportion of patients with greater than or equal to 50% reduction from baseline in partial seizure frequency). The following figure displays responder rate by dose for two of the studies.

Figure 6: Responder Rate by Adjunctive Epilepsy Study

Figure 7: Seizure Reduction by Dose (All Partial-Onset Seizures) for Studies E1, E2, and E3

Subset evaluations of the antiseizure efficacy of LYRICA showed no clinically important differences as a function of age, gender, or race.

Adjunctive Therapy for Partial-Onset Seizures in Pediatric Patients 4 to Less Than 17 Years of Age

The efficacy of LYRICA as adjunctive therapy in partial-onset seizures was established in a 12-week, randomized, double-blind, placebo-controlled, multicenter study in pediatric patients 4 years to less than 17 years of age with partial-onset seizures with or without secondary generalization. During an 8-week baseline period, patients had to experience at least 6 partial-onset seizures with no seizure-free period exceeding 4 weeks. The mean duration of epilepsy was 6 years and the mean and median baseline seizure frequencies were 57 and 18 seizures per month, respectively. Approximately 74% of the patients were taking 2 to 3 concurrent AEDs at baseline. Among the LYRICA-treated patients, 87% completed the double-blind phase of the study.

In this study, LYRICA 2.5 mg/kg/day (maximum 150 mg/day) and 10 mg/kg/day (maximum 600 mg/day) were compared to placebo. Administration of each daily dose was divided into two equal doses (twice a day dosing). Because of higher weight-normalized clearance in patients with body weight less than 30 kg [see Clinical Pharmacology (12.3)], the LYRICA dose was increased by 40% to 3.5 mg/kg/day for patients weighing less than 30 kg randomized to the 2.5 mg/kg/day group or to 14 mg/kg/day for patients randomized to the 10 mg/kg/day group.

Table 12 shows median baseline seizure rates, median percent change from baseline in seizure rates, and percent difference relative to placebo (derived from the primary analysis model) by dose.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 12. Seizure Response in Controlled Adjunctive Partial-Onset Seizure Study in Pediatric Patients 4 to Less Than 17 Years of Age</span> </caption> <col width="19%"/> <col width="7%"/> <col width="18%"/> <col width="14%"/> <col width="16%"/> <col width="12%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="bottom"><span class="Bold">Daily Dose of LYRICA</span></th><th align="left" class="Botrule Rrule Toprule" valign="bottom"><span class="Bold">N</span></th><th align="left" class="Botrule Rrule Toprule" valign="bottom"><span class="Bold">Median Baseline Seizure Frequency/28 days</span></th><th align="left" class="Botrule Rrule Toprule" valign="bottom"><span class="Bold">Median % Change from Baseline</span></th><th align="left" class="Botrule Rrule Toprule" valign="bottom"><span class="Bold">% Difference Relative to Placebo</span></th><th align="left" class="Botrule Rrule Toprule" valign="bottom"><span class="Bold">p-value, versus placebo</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top">Abbreviations: BID=twice daily; N=number.</td> </tr> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-18" name="footnote-18">*</a> </dt> <dd>2.5 mg/kg/day: Maximum dose 150 mg/day. Includes patients less than 30 kg for whom dose was adjusted to 3.5 mg/kg/day.</dd> <dt> <a href="#footnote-reference-19" name="footnote-19">†</a> </dt> <dd>10 mg/kg/day: Maximum dose 600 mg/day. Includes patients less than 30 kg for whom dose was adjusted to 14 mg/kg/day.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Placebo</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">93</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">16.5</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">-16.9</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">Not applicable</p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">2.5 mg/kg/day (BID)<a class="Sup" href="#footnote-18" name="footnote-reference-18">*</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">104</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">23.8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">-27.3</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">-10.5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.2577</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">10 mg/kg/day (BID)<a class="Sup" href="#footnote-19" name="footnote-reference-19">†</a> </p> </td><td class="Botrule Rrule" valign="top"> <p class="First">97</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">17.5</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">-37.1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">-21.0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.0185</p> </td> </tr> </tbody> </table></div>

There was evidence of a dose-response relationship for total daily doses of LYRICA between 2.5 mg/kg/day and 10 mg/kg/day. A significant improvement in seizure rate was observed for LYRICA 10 mg/kg/day group compared with placebo. While the 2.5 mg/kg/day group performed numerically better than placebo, this difference was not statistically significant.

A key secondary efficacy measure, the responder rate (proportion of patients with greater than or equal to 50% reduction from baseline in partial seizure frequency) showed improvements for LYRICA groups compared with placebo. The following figure displays responder rate by dose:

Figure 8: Responder Rate (Greater than or Equal to 50% Reduction)

Adjunctive Therapy for Partial-Onset Seizures in Pediatric Patients 1 Month to Less Than 4 Years of Age

The efficacy of LYRICA as adjunctive therapy in partial-onset seizures was established in a 14-day, randomized, double-blind, placebo-controlled, multicenter study in children 1 month to less than 4 years of age with partial-onset seizures with or without secondary generalization. The youngest patient evaluated was 3 months of age. During a 48- to 72-hour baseline video electroencephalogram (EEG), patients had to experience at least 2 partial-onset seizures. The mean duration of epilepsy at baseline was 1.6 years and the mean and median baseline seizure frequencies were 12.2 and 4.4 seizures per day, respectively. Approximately 33%, 50%, and 17% of patients were taking 1, 2, or 3 concurrent AEDs at baseline, respectively. Among the LYRICA-treated patients, 97% completed the double-blind phase of the study.

In this study, LYRICA 7 mg/kg/day and 14 mg/kg/day were compared to placebo. Administration of each daily dose was divided into three equal doses (three times a day dosing). The primary endpoint was the 24-hour partial-onset seizure rate based on the comparison of the baseline video EEG to a repeat 48–72 hour video EEG performed at the end of 14 days of double-blind treatment.

Table 13 shows median baseline seizure rates, median percent change from baseline in seizure rates, and percent difference relative to placebo (derived from the primary analysis model) by dose.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 13. Seizure Response in Controlled Adjunctive Partial-Onset Seizure Study in Pediatric Patients 1 Month to Less Than 4 Years of Age</span> </caption> <col width="20%"/> <col width="8%"/> <col width="18%"/> <col width="13%"/> <col width="14%"/> <col width="13%"/> <thead> <tr class="First Last"> <th align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Daily Dose of LYRICA</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">N</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Median Baseline Seizure Frequency/24 hours</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Median % Change from Baseline</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">% Difference Relative to Placebo</span></th><th align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold">p-value, versus placebo</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="6" valign="top">Abbreviations: N=number of patients</td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Placebo</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">53</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">2.9</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">22.2</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">Not applicable</p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">7 mg/kg/day</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">59</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">4.7</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">16.8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">15.1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.4606</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">14 mg/kg/day</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">28</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">5.4</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">70.0</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">-43.9</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">0.0223</p> </td> </tr> </tbody> </table></div>

A significant improvement in partial-onset seizure rate was observed for LYRICA 14 mg/kg/day group compared with placebo. Patients treated with LYRICA 7 mg/kg/day did not show improvement relative to placebo.

Responder rates (≥50% or greater reduction in partial-onset seizure frequency) were a secondary efficacy parameter; patients treated with LYRICA 14 mg/kg/day showed numerical improvement compared with placebo, while patients treated with LYRICA 7 mg/kg/day did not show improvement relative to placebo: the responder rates were 53.6%, 30.5%, and 41.5% for LYRICA 14 mg/kg/day, LYRICA 7 mg/kg/day, and placebo, respectively.

The efficacy of LYRICA for management of fibromyalgia was established in one 14-week, double-blind, placebo-controlled, multicenter study (F1) and one six-month, randomized withdrawal study (F2). Studies F1 and F2 enrolled patients with a diagnosis of fibromyalgia using the American College of Rheumatology (ACR) criteria (history of widespread pain for 3 months, and pain present at 11 or more of the 18 specific tender point sites). The studies showed a reduction in pain by visual analog scale. In addition, improvement was demonstrated based on a patient global assessment (PGIC), and on the Fibromyalgia Impact Questionnaire (FIQ).

Study F1: This 14-week study compared LYRICA total daily doses of 300 mg, 450 mg and 600 mg with placebo. Patients were enrolled with a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numeric pain rating scale and a score of greater than or equal to 40 mm on the 100 mm pain visual analog scale (VAS). The baseline mean pain score in this trial was 6.7. Responders to placebo in an initial one-week run-in phase were not randomized into subsequent phases of the study. A total of 64% of patients randomized to LYRICA completed the study. There was no evidence of a greater effect on pain scores of the 600 mg daily dose than the 450 mg daily dose, but there was evidence of dose-dependent adverse reactions [see Adverse Reactions (6.1)]. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study. The results are summarized in Figure 9 and Table 14.

For various levels of improvement in pain intensity from baseline to study endpoint, Figure 9 shows the fraction of patients achieving that level of improvement. The figure is cumulative. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 9: Patients Achieving Various Levels of Improvement in Pain Intensity – Fibromyalgia Study F1

<div class="scrollingtable"><table width="50%"> <caption> <span>Table 14. Patient Global Response in Fibromyalgia Study F1</span> </caption> <col width="16%"/> <col width="23%"/> <col width="19%"/> <thead> <tr class="First"> <th align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Patient Global Impression of Change</span></th> </tr> <tr class="Last"> <th align="center" class="Botrule Lrule Rrule" valign="top"><span class="Bold">Treatment Group</span> <br/> <span class="Bold">(mg/day)</span></th><th align="left" class="Botrule Rrule" valign="middle"><span class="Bold">% Any Improvement</span></th><th align="left" class="Botrule Rrule" valign="middle"><span class="Bold">95% CI</span></th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top">PGB = Pregabalin</td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Placebo</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">47.6</p> </td><td class="Botrule Rrule Toprule" valign="top"> <p class="First">(40.0,55.2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">PGB 300</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">68.1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">(60.9, 75.3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">PGB 450</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">77.8</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">(71.5, 84.0)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">PGB 600</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">66.1</p> </td><td class="Botrule Rrule" valign="top"> <p class="First">(59.1, 73.1)</p> </td> </tr> </tbody> </table></div>

Study F2: This randomized withdrawal study compared LYRICA with placebo. Patients were titrated during a 6-week open-label dose optimization phase to a total daily dose of 300 mg, 450 mg, or 600 mg. Patients were considered to be responders if they had both: 1) at least a 50% reduction in pain (VAS) and, 2) rated their overall improvement on the PGIC as "much improved" or "very much improved." Those who responded to treatment were then randomized in the double-blind treatment phase to either the dose achieved in the open-label phase or to placebo. Patients were treated for up to 6 months following randomization. Efficacy was assessed by time to loss of therapeutic response, defined as 1) less than 30% reduction in pain (VAS) from open-label baseline during two consecutive visits of the double-blind phase, or 2) worsening of FM symptoms necessitating an alternative treatment. Fifty-four percent of patients were able to titrate to an effective and tolerable dose of LYRICA during the 6-week open-label phase. Of the patients entering the randomized treatment phase assigned to remain on LYRICA, 38% of patients completed 26 weeks of treatment versus 19% of placebo-treated patients.

When considering return of pain or withdrawal due to adverse events as loss of response (LTR), treatment with LYRICA resulted in a longer time to loss of therapeutic response than treatment with placebo. Fifty-three percent of the pregabalin-treated subjects compared to 33% of placebo patients remained on study drug and maintained a therapeutic response to Week 26 of the study. Treatment with LYRICA also resulted in a longer time to loss of response based on the FIQ1, and longer time to loss of overall assessment of patient status, as measured by the PGIC2.

Figure 10: Time to Loss of Therapeutic Response, Fibromyalgia Study F2 (Kaplan-Meier Analysis)

The efficacy of LYRICA for the management of neuropathic pain associated with spinal cord injury was established in two double-blind, placebo-controlled, multicenter studies. Patients were enrolled with neuropathic pain associated with spinal cord injury that persisted continuously for at least three months or with relapses and remissions for at least six months. A total of 63% of patients completed study 1 and 84% completed study 2. The patients had a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). The baseline mean pain scores across the two studies ranged from 6.5 to 6.7.

Patients were allowed to take opioids, non-opioid analgesics, antiepileptic drugs, muscle relaxants, and antidepressant drugs if the dose was stable for 30 days prior to screening. Patients were allowed to take acetaminophen and nonsteroidal anti-inflammatory drugs during the studies.

Study SCI 1: This 12-week, randomized, double-blind, parallel-group, multicenter, flexible dose (150–600 mg/day) study compared pregabalin with placebo. The 12-week study consisted of a 3-week dose adjustment phase and a 9-week dose maintenance phase. Treatment with LYRICA 150–600 mg/day statistically significantly improved the endpoint weekly mean pain score, and increased the proportion of patients with at least a 30% and 50% reduction in pain score from baseline. The fraction of patients achieving various levels of improvement in pain intensity from baseline to Week 12 is presented in Figure 11. Some patients experienced a decrease in pain as early as week 1, which persisted throughout the study.

Figure 11: Patients Achieving Various Levels of Improvement in Pain Intensity – Study SCI 1

Study SCI 2: This 16-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, flexible dose (150–600 mg/day, in increments of 150 mg) study compared the efficacy, safety and tolerability of pregabalin with placebo. The 16-week study consisted of a 4-week dose adjustment phase and a 12-week dose maintenance phase. Treatment with LYRICA statistically significantly improved the endpoint weekly mean pain score, and increased the proportion of patients with at least a 30% and 50% reduction in pain score from baseline. The fraction of patients achieving various levels of improvement in pain intensity from baseline to Week 16 is presented in Figure 12. Some patients experienced a decrease in pain as early as week 1, which persisted throughout the study.

Figure 12: Patients Achieving Various Levels of Improvement in Pain Intensity – Study SCI 2

25 mg capsules:

White, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 25" on the body; available in:

<div class="scrollingtable"><table width="75%"> <col width="43%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First Last"> <td class="Botrule Toprule" valign="top"> <p class="First">Bottles of 90:</p> </td><td class="Botrule Toprule" valign="top"> <p class="First">NDC 0071-1012-68</p> </td> </tr> </tbody> </table></div>

50 mg capsules:

White, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 50" and an ink band on the body, available in:

<div class="scrollingtable"><table width="75%"> <col width="44%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First"> <td class="Toprule" valign="top"> <p class="First">Bottles of 90:</p> </td><td class="Toprule" valign="top"> <p class="First">NDC 0071-1013-68</p> </td> </tr> <tr class="Last"> <td class="Botrule" valign="top"> <p class="First">Unit-Dose Blister Packages of 100:</p> </td><td class="Botrule" valign="top"> <p class="First">NDC 0071-1013-41</p> </td> </tr> </tbody> </table></div>

75 mg capsules:

White/orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 75" on the body; available in:

<div class="scrollingtable"><table width="75%"> <col width="44%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First"> <td class="Toprule" valign="top"> <p class="First">Bottles of 90:</p> </td><td class="Toprule" valign="top"> <p class="First">NDC 0071-1014-68</p> </td> </tr> <tr class="Last"> <td class="Botrule" valign="top"> <p class="First">Unit-Dose Blister Packages of 100:</p> </td><td class="Botrule" valign="top"> <p class="First">NDC 0071-1014-41</p> </td> </tr> </tbody> </table></div>

100 mg capsules:

Orange, hard-gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 100" on the body, available in:

<div class="scrollingtable"><table width="75%"> <col width="44%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First"> <td class="Toprule" valign="top"> <p class="First">Bottles of 90:</p> </td><td class="Toprule" valign="top"> <p class="First">NDC 0071-1015-68</p> </td> </tr> <tr class="Last"> <td class="Botrule" valign="top"> <p class="First">Unit-Dose Blister Packages of 100:</p> </td><td class="Botrule" valign="top"> <p class="First">NDC 0071-1015-41</p> </td> </tr> </tbody> </table></div>

150 mg capsules:

White hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 150" on the body, available in:

<div class="scrollingtable"><table width="75%"> <col width="44%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First"> <td class="Toprule" valign="top"> <p class="First">Bottles of 90:</p> </td><td class="Toprule" valign="top"> <p class="First">NDC 0071-1016-68</p> </td> </tr> <tr class="Last"> <td class="Botrule" valign="top"> <p class="First">Unit-Dose Blister Packages of 100:</p> </td><td class="Botrule" valign="top"> <p class="First">NDC 0071-1016-41</p> </td> </tr> </tbody> </table></div>

200 mg capsules:

Light orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 200" on the body, available in:

<div class="scrollingtable"><table width="75%"> <col width="43%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First Last"> <td class="Botrule Toprule" valign="top"> <p class="First">Bottles of 90:</p> </td><td class="Botrule Toprule" valign="top"> <p class="First">NDC 0071-1017-68</p> </td> </tr> </tbody> </table></div>

225 mg capsules:

White/light orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 225" on the body; available in:

<div class="scrollingtable"><table width="75%"> <col width="43%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First Last"> <td class="Botrule Toprule" valign="top"> <p class="First">Bottles of 90:</p> </td><td class="Botrule Toprule" valign="top"> <p class="First">NDC 0071-1019-68</p> </td> </tr> </tbody> </table></div>

300 mg capsules:

White/orange hard gelatin capsule printed with black ink "Pfizer" on the cap, "PGN 300" on the body, available in:

<div class="scrollingtable"><table width="75%"> <col width="43%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First Last"> <td class="Botrule Toprule" valign="top"> <p class="First">Bottles of 90:</p> </td><td class="Botrule Toprule" valign="top"> <p class="First">NDC 0071-1018-68</p> </td> </tr> </tbody> </table></div>

20 mg/mL oral solution:

16 fluid ounce white high density polyethylene (HDPE) bottle with a polyethylene-lined closure:

<div class="scrollingtable"><table width="75%"> <col width="43%"/> <col width="43%"/> <tbody class="Headless"> <tr class="First Last"> <td class="Botrule Toprule" valign="top"> <p class="First">16 fluid ounce bottle</p> </td><td class="Botrule Toprule" valign="top"> <p class="First">NDC 0071-1020-01</p> </td> </tr> </tbody> </table></div>

Storage and Handling

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) (see USP Controlled Room Temperature).

Angioedema

Advise patients that LYRICA may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue LYRICA and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.1)].

Hypersensitivity

Advise patients that LYRICA has been associated with hypersensitivity reactions such as wheezing, dyspnea, rash, hives, and blisters. Instruct patients to discontinue LYRICA and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.2)].

Suicidal Thinking and Behavior

Patients, their caregivers, and families should be counseled that AEDs, including LYRICA, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.3)].

Respiratory Depression

Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs [see Warnings and Precautions (5.4)].

Dizziness and Somnolence

Counsel patients that LYRICA may cause dizziness, somnolence, blurred vision and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on LYRICA to gauge whether or not it affects their mental, visual, and/or motor performance adversely [see Warnings and Precautions (5.5)].

CNS Depressants

Inform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as respiratory depression, somnolence, and dizziness [see Warnings and Precautions (5.4, 5.5) and Drug Interactions (7)]. Advise patients to avoid consuming alcohol while taking LYRICA, as LYRICA may potentiate the impairment of motor skills and sedating effects of alcohol.

Adverse Reactions with Abrupt or Rapid Discontinuation

Advise patients to take LYRICA as prescribed. Abrupt or rapid discontinuation may result in increased seizure frequency in patients with seizure disorders, and insomnia, nausea, headache, anxiety, hyperhidrosis, or diarrhea [see Warnings and Precautions (5.6)].

Missed Dose

Counsel patients if they miss a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should skip the missed dose and take the next dose at their regularly scheduled time. Instruct patients not to take two doses at the same time.

Weight Gain and Edema

Counsel patients that LYRICA may cause edema and weight gain. Advise patients that concomitant treatment with LYRICA and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. For patients with preexisting cardiac conditions, this may increase the risk of heart failure [see Warnings and Precautions (5.7, 5.8)].

Ophthalmological Effects

Counsel patients that LYRICA may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician [see Warnings and Precautions (5.10)].

Creatine Kinase Elevations

Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever [see Warnings and Precautions (5.11)].

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LYRICA during pregnancy [see Use in Specific Populations (8.1)].

Lactation

Advise nursing mothers that breastfeeding is not recommended during treatment with LYRICA [see Use in Specific Populations (8.2)].

Male Fertility

Inform men being treated with LYRICA who plan to father a child of the potential risk of male-mediated teratogenicity. In preclinical studies in rats, pregabalin was associated with an increased risk of male-mediated teratogenicity. The clinical significance of this finding is uncertain [see Nonclinical Toxicology (13.1) and Use in Specific populations (8.3)].

Dermatopathy

Instruct diabetic patients to pay particular attention to skin integrity while being treated with LYRICA and to inform their healthcare provider about any sores or skin problems. Some animals treated with pregabalin developed skin ulcerations, although no increased incidence of skin lesions associated with LYRICA was observed in clinical trials [see Nonclinical Toxicology (13.2)].

This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.

{ "type": "p", "children": [], "text": "This product's labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com." }

LAB-0294-30.0

{ "type": "p", "children": [], "text": "LAB-0294-30.0" }

<div class="scrollingtable"><table width="100%"> <col width="2%"/> <col width="38%"/> <col width="38%"/> <col width="21%"/> <thead> <tr class="First"> <th align="center" class="Lrule Rrule Toprule" colspan="4" valign="top"><span class="Bold">MEDICATION GUIDE</span></th> </tr> <tr class="Last"> <th align="left" class="Botrule Lrule" valign="top"></th><th align="center" class="Botrule" valign="top"><span class="Bold">LYRICA (LEER-i-kah)</span> <br/> <span class="Bold">(pregabalin)</span> <br/> <span class="Bold">Capsules, CV</span></th><th align="center" class="Botrule" valign="top"><span class="Bold">LYRICA (LEER-i-kah)</span> <br/> <span class="Bold">(pregabalin)</span> <br/> <span class="Bold">Oral Solution, CV</span></th><th align="left" class="Botrule Rrule" valign="top"></th> </tr> </thead> <tfoot> <tr class="First"> <td align="left" colspan="4" valign="top">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td> </tr> <tr class="Last"> <td align="left" colspan="4" valign="top">Revised: 4/2020</td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="4" valign="top"> <p class="First">Read this Medication Guide before you start taking LYRICA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about LYRICA, ask your healthcare provider or pharmacist.</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about LYRICA?</span> </p> <p> <span class="Bold">LYRICA may cause serious side effects including:</span> </p> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">serious, even life-threatening, allergic reactions</span> </dd> <dt>•</dt> <dd> <span class="Bold">suicidal thoughts or actions</span> </dd> <dt>•</dt> <dd> <span class="Bold">serious breathing problems</span> </dd> </dl> </td><td class="Rrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">swelling of your hands, legs and feet</span> </dd> <dt>•</dt> <dd> <span class="Bold">dizziness and sleepiness</span> </dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">These serious side effects are described below:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Serious, even life-threatening, allergic reactions.</span> <br/>Stop taking LYRICA and call your healthcare provider right away if you have any of these signs of a serious allergic reaction:<dl> <dt>•</dt> <dd>swelling of your face, mouth, lips, gums, tongue, throat or neck</dd> <dt>•</dt> <dd>trouble breathing</dd> <dt>•</dt> <dd>rash, hives (raised bumps) or blisters</dd> </dl> </dd> <dt>•</dt> <dd> <span class="Bold">Like other antiepileptic drugs, LYRICA may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.</span> Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:</dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"> <dl> <dt>•</dt> <dd>thoughts about suicide or dying</dd> <dt>•</dt> <dd>attempts to commit suicide</dd> <dt>•</dt> <dd>new or worse depression</dd> <dt>•</dt> <dd>new or worse anxiety</dd> <dt>•</dt> <dd>feeling agitated or restless</dd> <dt>•</dt> <dd>panic attacks</dd> </dl> </td><td class="Rrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd>trouble sleeping (insomnia)</dd> <dt>•</dt> <dd>new or worse irritability</dd> <dt>•</dt> <dd>acting aggressive, being angry, or violent</dd> <dt>•</dt> <dd>acting on dangerous impulses</dd> <dt>•</dt> <dd>an extreme increase in activity and talking (mania)</dd> <dt>•</dt> <dd>other unusual changes in behavior or mood</dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td class="Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">If you have suicidal thoughts or actions, do not stop LYRICA without first talking to a healthcare provider.</span> </p> <dl> <dt>•</dt> <dd>Stopping LYRICA suddenly can cause serious problems.</dd> <dt>•</dt> <dd>Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.</dd> </dl> <p> <span class="Bold">How can I watch for early symptoms of suicidal thoughts and actions?</span> </p> <dl> <dt>•</dt> <dd>Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.</dd> <dt>•</dt> <dd>Keep all follow-up visits with your healthcare provider as scheduled.</dd> <dt>•</dt> <dd>Call your healthcare provider between visits as needed, especially if you are worried about symptoms.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Serious breathing problems</span> can occur when LYRICA is taken with other medicines that can cause severe sleepiness or decreased awareness, or when it is taken by someone who already has breathing problems. Watch for increased sleepiness or decreased breathing when starting LYRICA or when the dose is increased. Get help right away if breathing problems occur.</dd> <dt>•</dt> <dd> <span class="Bold">Swelling of your hands, legs and feet</span>. This swelling can be a serious problem for people with heart problems.</dd> <dt>•</dt> <dd> <span class="Bold">Dizziness and sleepiness.</span> Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA affects you. Ask your healthcare provider about when it will be okay to do these activities.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What is LYRICA?</span> </p> <p>LYRICA is a prescription medicine used in adults, 18 years of age and older to treat:</p> <dl> <dt>•</dt> <dd>pain from damaged nerves (neuropathic pain) that happens with diabetes</dd> <dt>•</dt> <dd>pain from damaged nerves (neuropathic pain) that follows healing of shingles</dd> <dt>•</dt> <dd>fibromyalgia (pain all over your body)</dd> <dt>•</dt> <dd>pain from damaged nerves (neuropathic pain) that follows spinal cord injury</dd> </dl> <p>It is not known if LYRICA is safe and effective in people under 18 years of age for the treatment of fibromyalgia and neuropathic pain with diabetes, shingles, or spinal cord injury.</p> <p>LYRICA is a prescription medicine used in people 1 month of age and older to treat:</p> <dl> <dt>•</dt> <dd>partial-onset seizures when taken together with other seizure medicines.</dd> </dl> <p>For the treatment of partial-onset seizures when taken together with other seizure medicines, it is not known if LYRICA is safe and effective in children under 1 month of age.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">Who should not take LYRICA?</span> </p> <p> <span class="Bold">Do not take LYRICA if you are allergic to pregabalin or any of the ingredients in LYRICA.</span> </p> <p>See <span class="Bold">"<a href="#_Refimportantinfo">What is the most important information I should know about LYRICA?</a>"</span> for the signs of an allergic reaction.</p> <p>See the end of this Medication Guide for a complete list of ingredients in LYRICA.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What should I tell my healthcare provider before taking LYRICA?</span> </p> <p>Before taking LYRICA, tell your healthcare provider about all your medical conditions, including if you:</p> <dl> <dt>•</dt> <dd>have or have had depression, mood problems or suicidal thoughts or behavior.</dd> <dt>•</dt> <dd>have breathing problems.</dd> <dt>•</dt> <dd>have kidney problems or get kidney dialysis.</dd> <dt>•</dt> <dd>have heart problems including heart failure.</dd> <dt>•</dt> <dd>have a bleeding problem or a low blood platelet count.</dd> <dt>•</dt> <dd>have abused prescription medicines, street drugs, or alcohol in the past.</dd> <dt>•</dt> <dd>have ever had swelling of your face, mouth, tongue, lips, gums, neck, or throat (angioedema).</dd> <dt>•</dt> <dd>plan to father a child. Animal studies have shown that pregabalin, the active ingredient in LYRICA, made male animals less fertile and caused sperm to change. Also, in animal studies, birth defects were seen in the offspring (babies) of male animals treated with pregabalin. It is not known if these problems can happen in people who take LYRICA.</dd> <dt>•</dt> <dd> <span class="Bold">are pregnant or plan to become pregnant. LYRICA may harm your unborn baby.</span> You and your healthcare provider will decide if you should take LYRICA while you are pregnant.<dl> <dt>•</dt> <dd>If you become pregnant while taking LYRICA, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. Information about the registry can also be found at the website, http://www.aedpregnancyregistry.org/.</dd> </dl> </dd> <dt>•</dt> <dd> <span class="Bold">are breastfeeding or plan to breastfeed. LYRICA passes into your breast milk. It is not known if LYRICA can harm your baby.</span> Talk to your healthcare provider about the best way to feed your baby if you take LYRICA. <span class="Bold">Breastfeeding is not recommended while taking LYRICA.</span> </dd> </dl> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins or herbal supplements. LYRICA and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take:</p> <dl> <dt>•</dt> <dd>angiotensin converting enzyme (ACE) inhibitors, which are used to treat many conditions, including high blood pressure. You may have a higher chance for swelling and hives if these medicines are taken with LYRICA.</dd> <dt>•</dt> <dd>Avandia (rosiglitazone) or Actos (pioglitazone) for diabetes. You may have a higher chance of weight gain or swelling of your hands or feet if these medicines are taken with LYRICA.</dd> <dt>•</dt> <dd>any opioid pain medicine (such as oxycodone), or medicines for anxiety (such as lorazepam) or insomnia (such as zolpidem). You may have a higher chance for dizziness, sleepiness or serious breathing problems if these medicines are taken with LYRICA.</dd> <dt>•</dt> <dd>any medicines that make you sleepy.</dd> </dl> <p>Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">How should I take LYRICA?</span> </p> <dl> <dt>•</dt> <dd>Take LYRICA exactly as prescribed. Your healthcare provider will tell you how much LYRICA to take and when to take it.</dd> <dt>•</dt> <dd>LYRICA may be taken with or without food.</dd> <dt>•</dt> <dd>Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.</dd> <dt>•</dt> <dd>Do not stop taking LYRICA without talking to your healthcare provider. If you stop taking LYRICA suddenly you may have headaches, nausea, diarrhea, trouble sleeping, increased sweating, or you may feel anxious. If you have epilepsy and you stop taking LYRICA suddenly, you may have seizures more often. Talk with your healthcare provider about how to stop LYRICA slowly.</dd> <dt>•</dt> <dd>If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.</dd> <dt>•</dt> <dd>If you take too much LYRICA, call your healthcare provider or poison control center, or go to the nearest emergency room right away.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What should I avoid while taking LYRICA?</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA affects you.</span> </dd> <dt>•</dt> <dd> <span class="Bold">Do not drink alcohol while taking LYRICA.</span> LYRICA and alcohol can affect each other and increase side effects such as sleepiness and dizziness.</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of LYRICA?</span> </p> <p>LYRICA may cause serious side effects, including:</p> <dl> <dt>•</dt> <dd>See "<a href="#_Refimportantinfo">What is the most important information I should know about LYRICA?</a>"</dd> <dt>•</dt> <dd> <span class="Bold">Muscle problems, muscle pain, soreness, or weakness</span>. If you have these symptoms, especially if you feel sick and have a fever, tell your healthcare provider right away.</dd> <dt>•</dt> <dd> <span class="Bold">Problems with your eyesight, including blurry vision.</span> Call your healthcare provider if you have any changes in your eyesight.</dd> <dt>•</dt> <dd> <span class="Bold">Weight gain.</span> If you have diabetes, weight gain may affect the management of your diabetes. Weight gain can also be a serious problem for people with heart problems.</dd> <dt>•</dt> <dd> <span class="Bold">Feeling "high"</span>.</dd> </dl> <p> <span class="Bold">The most common side effects of LYRICA in adults are:</span> </p> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd>dizziness</dd> <dt>•</dt> <dd>blurry vision</dd> <dt>•</dt> <dd>dry mouth</dd> </dl> </td><td valign="top"> <dl> <dt>•</dt> <dd>weight gain</dd> <dt>•</dt> <dd>sleepiness</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>•</dt> <dd>trouble concentrating</dd> <dt>•</dt> <dd>swelling of hands and feet</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">The most common side effects of LYRICA in children</span> are weight gain, increase in appetite, and sleepiness.</p> <p>LYRICA caused skin sores in animal studies. Skin sores did not happen in studies in people. If you have diabetes, you should pay attention to your skin while taking LYRICA and tell your healthcare provider about any sores or skin problems.</p> <p>Tell your healthcare provider about any side effect that bothers you or that does not go away.</p> <p>These are not all the possible side effects of LYRICA. For more information, ask your healthcare provider or pharmacist.</p> <p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">How should I store LYRICA?</span> </p> <dl> <dt>•</dt> <dd>Store LYRICA capsules and oral solution at room temperature between 68°F to 77°F (20°C to 25°C) in its original package.</dd> <dt>•</dt> <dd>Safely throw away any LYRICA that is out of date or no longer needed.</dd> </dl> <p> <span class="Bold">Keep LYRICA and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of LYRICA</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use LYRICA for a condition for which it was not prescribed. Do not give LYRICA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about LYRICA that is written for health professionals.</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="4" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in LYRICA?</span> </p> <p>Active ingredient: pregabalin</p> <p>Inactive ingredients:</p> <p> <span class="Bold">LYRICA capsules:</span> lactose monohydrate, cornstarch, talc</p> <p>Capsule shell: gelatin and titanium dioxide; Orange capsule shell: red iron oxide; White capsule shell: sodium lauryl sulfate, colloidal silicon dioxide. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells.</p> <p>Imprinting ink: shellac, black iron oxide, propylene glycol, potassium hydroxide.</p> <p> <span class="Bold">LYRICA oral solution:</span> methylparaben, propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and purified water.</p> <a name="id6511"></a><img alt="Logo" src="/dailymed/image.cfm?name=lyrica-14b.jpg&amp;setid=60185c88-ecfd-46f9-adb9-b97c6b00a553"/><p>LAB-0299-17.0</p> <p>You can also visit the LYRICA website at www.LYRICA.com or call 1-866-459-7422 (1-866-4LYRICA).</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"2%\"/>\n<col width=\"38%\"/>\n<col width=\"38%\"/>\n<col width=\"21%\"/>\n<thead>\n<tr class=\"First\">\n<th align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"4\" valign=\"top\"><span class=\"Bold\">MEDICATION GUIDE</span></th>\n</tr>\n<tr class=\"Last\">\n<th align=\"left\" class=\"Botrule Lrule\" valign=\"top\"></th><th align=\"center\" class=\"Botrule\" valign=\"top\"><span class=\"Bold\">LYRICA (LEER-i-kah)</span>\n<br/>\n<span class=\"Bold\">(pregabalin)</span>\n<br/>\n<span class=\"Bold\">Capsules, CV</span></th><th align=\"center\" class=\"Botrule\" valign=\"top\"><span class=\"Bold\">LYRICA (LEER-i-kah)</span>\n<br/>\n<span class=\"Bold\">(pregabalin)</span>\n<br/>\n<span class=\"Bold\">Oral Solution, CV</span></th><th align=\"left\" class=\"Botrule Rrule\" valign=\"top\"></th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First\">\n<td align=\"left\" colspan=\"4\" valign=\"top\">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" colspan=\"4\" valign=\"top\">Revised: 4/2020</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">Read this Medication Guide before you start taking LYRICA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about LYRICA, ask your healthcare provider or pharmacist.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about LYRICA?</span>\n</p>\n<p>\n<span class=\"Bold\">LYRICA may cause serious side effects including:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">serious, even life-threatening, allergic reactions</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">suicidal thoughts or actions</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">serious breathing problems</span>\n</dd>\n</dl>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">swelling of your hands, legs and feet</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">dizziness and sleepiness</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">These serious side effects are described below:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Serious, even life-threatening, allergic reactions.</span>\n<br/>Stop taking LYRICA and call your healthcare provider right away if you have any of these signs of a serious allergic reaction:<dl>\n<dt>•</dt>\n<dd>swelling of your face, mouth, lips, gums, tongue, throat or neck</dd>\n<dt>•</dt>\n<dd>trouble breathing</dd>\n<dt>•</dt>\n<dd>rash, hives (raised bumps) or blisters</dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Like other antiepileptic drugs, LYRICA may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.</span> Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>thoughts about suicide or dying</dd>\n<dt>•</dt>\n<dd>attempts to commit suicide</dd>\n<dt>•</dt>\n<dd>new or worse depression</dd>\n<dt>•</dt>\n<dd>new or worse anxiety</dd>\n<dt>•</dt>\n<dd>feeling agitated or restless</dd>\n<dt>•</dt>\n<dd>panic attacks</dd>\n</dl>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>trouble sleeping (insomnia)</dd>\n<dt>•</dt>\n<dd>new or worse irritability</dd>\n<dt>•</dt>\n<dd>acting aggressive, being angry, or violent</dd>\n<dt>•</dt>\n<dd>acting on dangerous impulses</dd>\n<dt>•</dt>\n<dd>an extreme increase in activity and talking (mania)</dd>\n<dt>•</dt>\n<dd>other unusual changes in behavior or mood</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td class=\"Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">If you have suicidal thoughts or actions, do not stop LYRICA without first talking to a healthcare provider.</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Stopping LYRICA suddenly can cause serious problems.</dd>\n<dt>•</dt>\n<dd>Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.</dd>\n</dl>\n<p>\n<span class=\"Bold\">How can I watch for early symptoms of suicidal thoughts and actions?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.</dd>\n<dt>•</dt>\n<dd>Keep all follow-up visits with your healthcare provider as scheduled.</dd>\n<dt>•</dt>\n<dd>Call your healthcare provider between visits as needed, especially if you are worried about symptoms.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Serious breathing problems</span> can occur when LYRICA is taken with other medicines that can cause severe sleepiness or decreased awareness, or when it is taken by someone who already has breathing problems. Watch for increased sleepiness or decreased breathing when starting LYRICA or when the dose is increased. Get help right away if breathing problems occur.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Swelling of your hands, legs and feet</span>. This swelling can be a serious problem for people with heart problems.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Dizziness and sleepiness.</span> Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA affects you. Ask your healthcare provider about when it will be okay to do these activities.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is LYRICA?</span>\n</p>\n<p>LYRICA is a prescription medicine used in adults, 18 years of age and older to treat:</p>\n<dl>\n<dt>•</dt>\n<dd>pain from damaged nerves (neuropathic pain) that happens with diabetes</dd>\n<dt>•</dt>\n<dd>pain from damaged nerves (neuropathic pain) that follows healing of shingles</dd>\n<dt>•</dt>\n<dd>fibromyalgia (pain all over your body)</dd>\n<dt>•</dt>\n<dd>pain from damaged nerves (neuropathic pain) that follows spinal cord injury</dd>\n</dl>\n<p>It is not known if LYRICA is safe and effective in people under 18 years of age for the treatment of fibromyalgia and neuropathic pain with diabetes, shingles, or spinal cord injury.</p>\n<p>LYRICA is a prescription medicine used in people 1 month of age and older to treat:</p>\n<dl>\n<dt>•</dt>\n<dd>partial-onset seizures when taken together with other seizure medicines.</dd>\n</dl>\n<p>For the treatment of partial-onset seizures when taken together with other seizure medicines, it is not known if LYRICA is safe and effective in children under 1 month of age.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not take LYRICA?</span>\n</p>\n<p>\n<span class=\"Bold\">Do not take LYRICA if you are allergic to pregabalin or any of the ingredients in LYRICA.</span>\n</p>\n<p>See <span class=\"Bold\">\"<a href=\"#_Refimportantinfo\">What is the most important information I should know about LYRICA?</a>\"</span> for the signs of an allergic reaction.</p>\n<p>See the end of this Medication Guide for a complete list of ingredients in LYRICA.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I tell my healthcare provider before taking LYRICA?</span>\n</p>\n<p>Before taking LYRICA, tell your healthcare provider about all your medical conditions, including if you:</p>\n<dl>\n<dt>•</dt>\n<dd>have or have had depression, mood problems or suicidal thoughts or behavior.</dd>\n<dt>•</dt>\n<dd>have breathing problems.</dd>\n<dt>•</dt>\n<dd>have kidney problems or get kidney dialysis.</dd>\n<dt>•</dt>\n<dd>have heart problems including heart failure.</dd>\n<dt>•</dt>\n<dd>have a bleeding problem or a low blood platelet count.</dd>\n<dt>•</dt>\n<dd>have abused prescription medicines, street drugs, or alcohol in the past.</dd>\n<dt>•</dt>\n<dd>have ever had swelling of your face, mouth, tongue, lips, gums, neck, or throat (angioedema).</dd>\n<dt>•</dt>\n<dd>plan to father a child. Animal studies have shown that pregabalin, the active ingredient in LYRICA, made male animals less fertile and caused sperm to change. Also, in animal studies, birth defects were seen in the offspring (babies) of male animals treated with pregabalin. It is not known if these problems can happen in people who take LYRICA.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">are pregnant or plan to become pregnant. LYRICA may harm your unborn baby.</span> You and your healthcare provider will decide if you should take LYRICA while you are pregnant.<dl>\n<dt>•</dt>\n<dd>If you become pregnant while taking LYRICA, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. Information about the registry can also be found at the website, http://www.aedpregnancyregistry.org/.</dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">are breastfeeding or plan to breastfeed. LYRICA passes into your breast milk. It is not known if LYRICA can harm your baby.</span> Talk to your healthcare provider about the best way to feed your baby if you take LYRICA. <span class=\"Bold\">Breastfeeding is not recommended while taking LYRICA.</span>\n</dd>\n</dl>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins or herbal supplements. LYRICA and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take:</p>\n<dl>\n<dt>•</dt>\n<dd>angiotensin converting enzyme (ACE) inhibitors, which are used to treat many conditions, including high blood pressure. You may have a higher chance for swelling and hives if these medicines are taken with LYRICA.</dd>\n<dt>•</dt>\n<dd>Avandia (rosiglitazone) or Actos (pioglitazone) for diabetes. You may have a higher chance of weight gain or swelling of your hands or feet if these medicines are taken with LYRICA.</dd>\n<dt>•</dt>\n<dd>any opioid pain medicine (such as oxycodone), or medicines for anxiety (such as lorazepam) or insomnia (such as zolpidem). You may have a higher chance for dizziness, sleepiness or serious breathing problems if these medicines are taken with LYRICA.</dd>\n<dt>•</dt>\n<dd>any medicines that make you sleepy.</dd>\n</dl>\n<p>Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I take LYRICA?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Take LYRICA exactly as prescribed. Your healthcare provider will tell you how much LYRICA to take and when to take it.</dd>\n<dt>•</dt>\n<dd>LYRICA may be taken with or without food.</dd>\n<dt>•</dt>\n<dd>Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.</dd>\n<dt>•</dt>\n<dd>Do not stop taking LYRICA without talking to your healthcare provider. If you stop taking LYRICA suddenly you may have headaches, nausea, diarrhea, trouble sleeping, increased sweating, or you may feel anxious. If you have epilepsy and you stop taking LYRICA suddenly, you may have seizures more often. Talk with your healthcare provider about how to stop LYRICA slowly.</dd>\n<dt>•</dt>\n<dd>If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.</dd>\n<dt>•</dt>\n<dd>If you take too much LYRICA, call your healthcare provider or poison control center, or go to the nearest emergency room right away.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I avoid while taking LYRICA?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA affects you.</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not drink alcohol while taking LYRICA.</span> LYRICA and alcohol can affect each other and increase side effects such as sleepiness and dizziness.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of LYRICA?</span>\n</p>\n<p>LYRICA may cause serious side effects, including:</p>\n<dl>\n<dt>•</dt>\n<dd>See \"<a href=\"#_Refimportantinfo\">What is the most important information I should know about LYRICA?</a>\"</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Muscle problems, muscle pain, soreness, or weakness</span>. If you have these symptoms, especially if you feel sick and have a fever, tell your healthcare provider right away.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Problems with your eyesight, including blurry vision.</span> Call your healthcare provider if you have any changes in your eyesight.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Weight gain.</span> If you have diabetes, weight gain may affect the management of your diabetes. Weight gain can also be a serious problem for people with heart problems.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Feeling \"high\"</span>.</dd>\n</dl>\n<p>\n<span class=\"Bold\">The most common side effects of LYRICA in adults are:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>dizziness</dd>\n<dt>•</dt>\n<dd>blurry vision</dd>\n<dt>•</dt>\n<dd>dry mouth</dd>\n</dl>\n</td><td valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>weight gain</dd>\n<dt>•</dt>\n<dd>sleepiness</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>trouble concentrating</dd>\n<dt>•</dt>\n<dd>swelling of hands and feet</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">The most common side effects of LYRICA in children</span> are weight gain, increase in appetite, and sleepiness.</p>\n<p>LYRICA caused skin sores in animal studies. Skin sores did not happen in studies in people. If you have diabetes, you should pay attention to your skin while taking LYRICA and tell your healthcare provider about any sores or skin problems.</p>\n<p>Tell your healthcare provider about any side effect that bothers you or that does not go away.</p>\n<p>These are not all the possible side effects of LYRICA. For more information, ask your healthcare provider or pharmacist.</p>\n<p>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store LYRICA?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Store LYRICA capsules and oral solution at room temperature between 68°F to 77°F (20°C to 25°C) in its original package.</dd>\n<dt>•</dt>\n<dd>Safely throw away any LYRICA that is out of date or no longer needed.</dd>\n</dl>\n<p>\n<span class=\"Bold\">Keep LYRICA and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of LYRICA</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use LYRICA for a condition for which it was not prescribed. Do not give LYRICA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about LYRICA that is written for health professionals.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in LYRICA?</span>\n</p>\n<p>Active ingredient: pregabalin</p>\n<p>Inactive ingredients:</p>\n<p>\n<span class=\"Bold\">LYRICA capsules:</span> lactose monohydrate, cornstarch, talc</p>\n<p>Capsule shell: gelatin and titanium dioxide; Orange capsule shell: red iron oxide; White capsule shell: sodium lauryl sulfate, colloidal silicon dioxide. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells.</p>\n<p>Imprinting ink: shellac, black iron oxide, propylene glycol, potassium hydroxide.</p>\n<p>\n<span class=\"Bold\">LYRICA oral solution:</span> methylparaben, propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and purified water.</p>\n<a name=\"id6511\"></a><img alt=\"Logo\" src=\"/dailymed/image.cfm?name=lyrica-14b.jpg&amp;setid=60185c88-ecfd-46f9-adb9-b97c6b00a553\"/><p>LAB-0299-17.0</p>\n<p>You can also visit the LYRICA website at www.LYRICA.com or call 1-866-459-7422 (1-866-4LYRICA).</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Pfizer NDC 0071-1012-68

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Lyrica® (pregabalin) capsules

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ALWAYS DISPENSE WITH MEDICATION GUIDE

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90 Capsules Rx only

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Lyrica® (pregabalin)Capsule

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CV

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50 mg

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DIST BY PARKE-DAVISDIV OF PFIZER INC, NY, NY 10017

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LOT 00000VX EXP XXX 00

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Pfizer NDC 0071-1013-41

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Lyrica® (pregabalin) capsules

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CV

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50 mg

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ALWAYS DISPENSE WITH MEDICATION GUIDE

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For in-institution use only

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100 Capsules Rx only

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Pfizer NDC 0071-1013-68

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Lyrica® (pregabalin) capsules

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CV

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50 mg

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ALWAYS DISPENSE WITH MEDICATION GUIDE

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90 Capsules Rx only

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Lyrica® (pregabalin)Capsule

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CV

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75 mg

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DIST BY PARKE-DAVISDIV OF PFIZER INC, NY, NY 10017

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LOT 00000VX EXP XXX 00

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Pfizer NDC 0071-1014-41

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Lyrica® (pregabalin) capsules

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CV

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75 mg

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ALWAYS DISPENSE WITH MEDICATION GUIDE

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For in-institution use only

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100 Capsules Rx only

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Pfizer NDC 0071-1014-68

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Lyrica® (pregabalin) capsules

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CV

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75 mg

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ALWAYS DISPENSE WITH MEDICATION GUIDE

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90 Capsules Rx only

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Lyrica® (pregabalin)Capsule

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CV

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100 mg

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DIST BY PARKE-DAVISDIV OF PFIZER INC, NY, NY 10017

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LOT 00000VX EXP XXX 00

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Pfizer NDC 0071-1015-41

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Lyrica® (pregabalin) capsules

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CV

{ "type": "p", "children": [], "text": "\nCV\n" }

100 mg

{ "type": "p", "children": [], "text": "\n100 mg\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

For in-institution use only

{ "type": "p", "children": [], "text": "For in-institution use only" }

100 Capsules Rx only

{ "type": "p", "children": [], "text": "100 Capsules\nRx only\n" }

Pfizer NDC 0071-1015-68

{ "type": "p", "children": [], "text": "\nPfizer\nNDC 0071-1015-68" }

Lyrica® (pregabalin) capsules

{ "type": "p", "children": [], "text": "\nLyrica®\n(pregabalin) \ncapsules\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

100 mg

{ "type": "p", "children": [], "text": "\n100 mg\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\n MEDICATION GUIDE\n" }

90 Capsules Rx only

{ "type": "p", "children": [], "text": "90 Capsules\nRx only\n" }

Lyrica® (pregabalin)Capsule

{ "type": "p", "children": [], "text": "\nLyrica®\n(pregabalin)Capsule" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

150 mg

{ "type": "p", "children": [], "text": "\n150 mg\n" }

DIST BY PARKE-DAVISDIV OF PFIZER INC, NY, NY 10017

{ "type": "p", "children": [], "text": "DIST BY PARKE-DAVISDIV OF PFIZER INC, NY, NY 10017" }

LOT 00000VX EXP XXX 00

{ "type": "p", "children": [], "text": "LOT 00000VX EXP XXX 00" }

Pfizer NDC 0071-1016-41

{ "type": "p", "children": [], "text": "\nPfizer\nNDC 0071-1016-41" }

Lyrica® (pregabalin) capsules

{ "type": "p", "children": [], "text": "\nLyrica®\n(pregabalin) capsules\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

150 mg

{ "type": "p", "children": [], "text": "\n150 mg\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

For in-institution use only

{ "type": "p", "children": [], "text": "For in-institution use only" }

100 Capsules Rx only

{ "type": "p", "children": [], "text": "100 Capsules\nRx only\n" }

Pfizer NDC 0071-1016-68

{ "type": "p", "children": [], "text": "\nPfizer\nNDC 0071-1016-68" }

Lyrica® (pregabalin) capsules

{ "type": "p", "children": [], "text": "\nLyrica®\n(pregabalin) \ncapsules\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

150 mg

{ "type": "p", "children": [], "text": "\n150 mg\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\n MEDICATION GUIDE\n" }

{ "type": "", "children": [], "text": "" }

Pfizer NDC 0071-1017-68

{ "type": "p", "children": [], "text": "\nPfizer\nNDC 0071-1017-68" }

Lyrica® (pregabalin) capsules

{ "type": "p", "children": [], "text": "\nLyrica®\n(pregabalin) \ncapsules\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

200 mg

{ "type": "p", "children": [], "text": "\n200 mg\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH \n\n MEDICATION GUIDE\n" }

90 Capsules Rx only

{ "type": "p", "children": [], "text": "90 Capsules\nRx only\n" }

Pfizer NDC 0071-1019-68

{ "type": "p", "children": [], "text": "\nPfizer\nNDC 0071-1019-68" }

Lyrica® (pregabalin) capsules

{ "type": "p", "children": [], "text": "\nLyrica®\n(pregabalin) \ncapsules\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

225 mg

{ "type": "p", "children": [], "text": "\n225 mg\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH\n\n MEDICATION GUIDE\n" }

{ "type": "", "children": [], "text": "" }

Pfizer NDC 0071-1018-68

{ "type": "p", "children": [], "text": "\nPfizer\nNDC 0071-1018-68" }

Lyrica® (pregabalin) capsules

{ "type": "p", "children": [], "text": "\nLyrica®\n(pregabalin) \ncapsules\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

300 mg

{ "type": "p", "children": [], "text": "\n300 mg\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH \n\n MEDICATION GUIDE\n" }

{ "type": "", "children": [], "text": "" }

Pfizer

{ "type": "p", "children": [], "text": "\nPfizer\n" }

NDC 0071-1020-01

{ "type": "p", "children": [], "text": "NDC 0071-1020-01" }

Lyrica® (pregabalin)

{ "type": "p", "children": [], "text": "\nLyrica®\n(pregabalin)" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

20 mg per mL

{ "type": "p", "children": [], "text": "\n20 mg per mL\n" }

oral solution

{ "type": "p", "children": [], "text": "\noral solution\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

FOR ORAL USE ONLY

{ "type": "p", "children": [], "text": "\nFOR ORAL USE ONLY\n" }

16 fl oz (473 mL) Rx only

{ "type": "p", "children": [], "text": "16 fl oz (473 mL)\nRx only\n" }

Pfizer

{ "type": "p", "children": [], "text": "Pfizer" }

NDC 0071-1020-01

{ "type": "p", "children": [], "text": "NDC 0071-1020-01" }

Lyrica® (pregabalin)

{ "type": "p", "children": [], "text": "Lyrica®\n(pregabalin)" }

CV

{ "type": "p", "children": [], "text": "CV" }

20 mg per mL

{ "type": "p", "children": [], "text": "20 mg per mL" }

oral solution

{ "type": "p", "children": [], "text": "oral solution" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "ALWAYS DISPENSE WITH MEDICATION GUIDE" }

FOR ORAL USE ONLY

{ "type": "p", "children": [], "text": "FOR ORAL USE ONLY" }

16 fl oz (473 mL) Rx only

{ "type": "p", "children": [], "text": "16 fl oz (473 mL) Rx only" }

Pregabalin capsule is indicated for:

{ "type": "p", "children": [], "text": "\nPregabalin capsule is indicated for:" }

{ "type": "ul", "children": [ "Management of neuropathic pain associated with diabetic peripheral neuropathy", "Management of postherpetic neuralgia", "Adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older", "Management of fibromyalgia", "Management of neuropathic pain associated with spinal cord injury" ], "text": "" }

Pregabalin capsules are given orally with or without food.

When discontinuing pregabalin capsules, taper gradually over a minimum of 1 week [see Warnings and Precautions (5.4)].

Because pregabalin capsules are eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function [see Dosage and Administration (2.7)].

The maximum recommended dose of pregabalin capsules are 100 mg three times a day (300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

Although pregabalin capsules were also studied at 600 mg/day, there is no evidence that this dose confers additional significant benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 300 mg/day is not recommended [see Adverse Reactions (6.1)].

The recommended dose of pregabalin capsules are 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 75 mg two times a day, or 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with 300 mg/day, and who are able to tolerate pregabalin capsules, may be treated with up to 300 mg two times a day, or 200 mg three times a day (600 mg/day). In view of the dose-dependent adverse reactions and the higher rate of treatment discontinuation due to adverse reactions, reserve dosing above 300 mg/day for those patients who have on-going pain and are tolerating 300 mg daily [see Adverse Reactions (6.1)].

The recommended dosages for adults and pediatric patients 1 month of age and older are included in Table 1. Administer the total daily dosage orally in two or three divided doses as indicated in Table 1. In pediatric patients, the recommended dosing regimen is dependent upon body weight. Based on clinical response and tolerability, dosage may be increased, approximately weekly.

<div class="scrollingtable"><table class="Noautorules" width="640"> <caption> <span>Table 1. Recommended Dosage for Adults and Pediatric Patients 1 Month and Older</span> </caption> <col width="160"/> <col width="160"/> <col width="160"/> <col width="160"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Age and Body Weight</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Recommended Initial Dosage</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Recommended Maximum Dosage</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Frequency of Administration</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top">Adults <br/> (17 years and older) <br/> </td><td align="center" class="Botrule Rrule">150 mg/day <br/> </td><td align="center" class="Botrule Rrule">600 mg/day <br/> </td><td align="center" class="Botrule Rrule">2 or 3 divided doses <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top">Pediatric patients <br/> weighing 30 kg or more <br/> </td><td align="center" class="Botrule Rrule">2.5 mg/kg/day <br/> </td><td align="center" class="Botrule Rrule">10 mg/kg/day (not to exceed 600 mg/day) <br/> </td><td align="center" class="Botrule Rrule">2 or 3 divided doses <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top">Pediatric patients weighing less than 30 kg <br/> </td><td align="center" class="Botrule Rrule">3.5 mg/kg/day <br/> </td><td align="center" class="Botrule Rrule">14 mg/kg/day <br/> </td><td align="center" class="Botrule Rrule"><span class="Italics">1 month to less than 4</span>years of age: 3 divided doses <br/> <span class="Italics">4 years of age and older</span>: 2 or 3 divided doses <br/> </td> </tr> </tbody> </table></div>

Both the efficacy and adverse event profiles of pregabalin capsules have been shown to be dose-related.

The effect of dose escalation rate on the tolerability of pregabalin capsules has not been formally studied.

The efficacy of adjunctive pregabalin capsules in patients taking gabapentin has not been evaluated in controlled trials. Consequently, dosing recommendations for the use of pregabalin capsules with gabapentin cannot be offered.

The recommended dose of pregabalin capsules for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). Although pregabalin capsules were also studied at 600 mg/day, there is no evidence that this dose confers additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended [see Adverse Reactions (6.1)].

The recommended dose range of pregabalin capsules for the treatment of neuropathic pain associated with spinal cord injury is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient pain relief after 2 to 3 weeks of treatment with 150 mg two times a day and who tolerate pregabalin capsules may be treated with up to 300 mg two times a day [see Clinical Studies (14.5)].

In view of dose-dependent adverse reactions and since pregabalin capsules are eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function. The use of pregabalin capsules in pediatric patients with compromised renal function has not been studied.

Base the dose adjustment in patients with renal impairment on creatinine clearance (CLcr), as indicated in Table 2. To use this dosing table, an estimate of the patient's CLcr in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation:

Next, refer to the Dosage and Administration section to determine the recommended total daily dose based on indication, for a patient with normal renal function (CLcr greater than or equal to 60 mL/min). Then refer to Table 2 to determine the corresponding renal adjusted dose.

(For example: A patient initiating pregabalin capsules therapy for postherpetic neuralgia with normal renal function (CLcr greater than or equal to 60 mL/min), receives a total daily dose of 150 mg/day pregabalin. Therefore, a renal impaired patient with a CLcr of 50 mL/min would receive a total daily dose of 75 mg/day pregabalin administered in two or three divided doses.)

For patients undergoing hemodialysis, adjust the pregabalin daily dose based on renal function. In addition to the daily dose adjustment, administer a supplemental dose immediately following every 4-hour hemodialysis treatment (see Table 2).

<div class="scrollingtable"><table class="Noautorules" width="41%"> <caption> <span>T able 2. Pregabalin Dosag e Adjustment Based on Renal Function</span> </caption> <col width="244"/> <col width="80"/> <col width="80"/> <col width="80"/> <col width="80"/> <col width="193"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Creatinine Clearance (CLcr) (mL/min)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="4"><span class="Bold">Total Pregabalin Daily Dose (mg/day)*</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Dose Regimen</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Greater than or equal to 60 <br/> </td><td align="center" class="Botrule Rrule">150 <br/> </td><td align="center" class="Botrule Rrule">300 <br/> </td><td align="center" class="Botrule Rrule">450 <br/> </td><td align="center" class="Botrule Rrule">600 <br/> </td><td align="center" class="Botrule Rrule">BID or TID <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">30-60 <br/> </td><td align="center" class="Botrule Rrule">75 <br/> </td><td align="center" class="Botrule Rrule">150 <br/> </td><td align="center" class="Botrule Rrule">225 <br/> </td><td align="center" class="Botrule Rrule">300 <br/> </td><td align="center" class="Botrule Rrule">BID or TID <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">15–30 <br/> </td><td align="center" class="Botrule Rrule">25–50 <br/> </td><td align="center" class="Botrule Rrule">75 <br/> </td><td align="center" class="Botrule Rrule">100–150 <br/> </td><td align="center" class="Botrule Rrule">150 <br/> </td><td align="center" class="Botrule Rrule">QD or BID <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule">Less than 15 <br/> </td><td align="center" class="Botrule Rrule">25 <br/> </td><td align="center" class="Botrule Rrule">25–50 <br/> </td><td align="center" class="Botrule Rrule">50–75 <br/> </td><td align="center" class="Botrule Rrule">75 <br/> </td><td align="center" class="Botrule Rrule">QD <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="6">Supplementary dosage following hemodialysis (mg) <span class="Sup">†</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="6" valign="top">Patients on the 25 mg QD regimen: take one supplemental dose of 25 mg or 50 mg <br/> Patients on the 25–50 mg QD regimen: take one supplemental dose of 50 mg or 75 mg <br/> Patients on the 50–75 mg QD regimen: take one supplemental dose of 75 mg or 100 mg <br/> Patients on the 75 mg QD regimen: take one supplemental dose of 100 mg or 150 mg <br/> </td> </tr> </tbody> </table></div>

TID= Three divided doses; BID = Two divided doses; QD = Single daily dose.

 * Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose.

 †Supplementary dose is a single additional dose.

Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg

{ "type": "p", "children": [], "text": "\nCapsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg" }

[see Description (11)and How Supplied/Storage and Handling (16)]

{ "type": "p", "children": [], "text": "\n[see\n \n Description (11)and\n \n How Supplied/Storage and Handling (16)]\n \n \n" }

Pregabalin capsules are contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "\nPregabalin capsules are contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy\n \n [see\n \n Warnings and Precautions (5.2)].\n \n \n" }

There have been postmarketing reports of angioedema in patients during initial and chronic treatment with pregabalin capsules. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue pregabalin capsules immediately in patients with these symptoms.

Exercise caution when prescribing pregabalin capsules to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema.

There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with pregabalin capsules. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue pregabalin capsules immediately in patients with these symptoms.

Antiepileptic drugs (AEDs), including pregabalin, the active ingredient in pregabalin capsules, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Suicidal behavior and ideation have also been reported in patients after discontinuation of pregabalin [see Warnings and Precautions (5.4)]. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug–treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5–100 years) in the clinical trials analyzed.

Table 3 shows absolute and relative risk by indication for all evaluated AEDs.

<div class="scrollingtable"><table class="Noautorules" width="51%"> <caption> <span>Table 3. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis</span> </caption> <col width="148"/> <col width="144"/> <col width="152"/> <col width="212"/> <col width="288"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Botrule Lrule Rrule Toprule"><span class="Bold">Indication</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Placebo Patients with Events Per</span> <br/> <span class="Bold">1000 Patients</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Drug</span> <br/> <span class="Bold">Patients with</span> <br/> <span class="Bold">Events Per</span> <br/> <span class="Bold">1000 Patients</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Relative Risk: Incidence of Events in Drug Patients /Incidence in Placebo Patients</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Risk Difference: Additional Drug Patients with Events Per 1000 Patients</span> <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule">Epilepsy <br/> </td><td align="center" class="Rrule">1.0 <br/> </td><td align="center" class="Rrule">3.4 <br/> </td><td align="center" class="Rrule">3.5 <br/> </td><td align="center" class="Rrule">2.4 <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule">Psychiatric <br/> </td><td align="center" class="Rrule">5.7 <br/> </td><td align="center" class="Rrule">8 .5 <br/> </td><td align="center" class="Rrule">1.5 <br/> </td><td align="center" class="Rrule">2.9 <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule">Other <br/> </td><td align="center" class="Rrule">1.0 <br/> </td><td align="center" class="Rrule">1.8 <br/> </td><td align="center" class="Rrule">1.9 <br/> </td><td align="center" class="Rrule">0.9 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Total <br/> </td><td align="center" class="Botrule Rrule">2.4 <br/> </td><td align="center" class="Botrule Rrule">4 .3 <br/> </td><td align="center" class="Botrule Rrule">1.8 <br/> </td><td align="center" class="Botrule Rrule">1.9 <br/> </td> </tr> </tbody> </table></div>

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing pregabalin capsules or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

As with all antiepileptic drugs (AEDs), withdraw pregabalin capsules gradually to minimize the potential of increased seizure frequency in patients with seizure disorders.

Following abrupt or rapid discontinuation of pregabalin capsules, some patients reported symptoms including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea [see Adverse Reactions (6.2), Drug Abuse and Dependence (9.3)] . Suicidal behavior and ideation have also been reported in patients after discontinuation of pregabalin [see Warnings and Precautions (5.3)] .

If pregabalin capsules are discontinued, taper the drug gradually over a minimum of 1 week rather than discontinue the drug abruptly.

There is evidence from case reports, human studies, and animal studies associating pregabalin capsules with serious, life-threatening, or fatal respiratory depression when co-administered with central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment. When the decision is made to co-prescribe pregabalin capsules with another CNS depressant, particularly an opioid, or to prescribe pregabalin capsules to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating pregabalin capsules at a low dose. The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including pregabalin capsules).

There is more limited evidence from case reports, animal studies, and human studies associating pregabalin capsules with serious respiratory depression, without co-administered CNS depressants or without underlying respiratory impairment.

Pregabalin capsules may cause dizziness and somnolence. Inform patients that pregabalin capsules - related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery [see Patient Counseling Information (17)].

In the pregabalin capsules controlled trials in adult patients, dizziness was experienced by 30% of pregabalin capsules - treated patients compared to 8% of placebo-treated patients; somnolence was experienced by 23% of pregabalin capsules treated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of pregabalin capsules therapy and occurred more frequently at higher doses. Dizziness and somnolence were the adverse reactions most frequently leading to withdrawal (4% each) from controlled studies. In pregabalin capsules- treated patients reporting these adverse reactions in short-term, controlled studies, dizziness persisted until the last dose in 30% and somnolence persisted until the last dose in 42% of patients [see Drug Interactions (7)].

In the pregabalin capsules controlled trials in pediatric patients 4 to less than 17 years of age and 1 month to less than 4 years of age for the treatment of partial-onset seizures, somnolence was reported in 21% and 15% of pregabalin-treated patients compared to 14% and 9% of placebo-treated patients, respectively, and occurred more frequently at higher doses. For patients 1 month to less than 4 years of age, somnolence includes related terms lethargy, sluggishness, and hypersomnia.

Pregabalin capsules treatment may cause peripheral edema. In short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications such as hypertension or congestive heart failure. Peripheral edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function.

In controlled clinical trials in adult patients, the incidence of peripheral edema was 6% in the pregabalin capsules group compared with 2% in the placebo group. In controlled clinical trials, 0.5% of pregabalin capsules patients and 0.2% placebo patients withdrew due to peripheral edema.

Higher frequencies of weight gain and peripheral edema were observed in patients taking both pregabalin capsules and a thiazolidinedione antidiabetic agent compared to patients taking either drug alone. The majority of patients using thiazolidinedione antidiabetic agents in the overall safety database were participants in studies of pain associated with diabetic peripheral neuropathy. In this population, peripheral edema was reported in 3% (2/60) of patients who were using thiazolidinedione antidiabetic agents only, 8% (69/859) of patients who were treated with pregabalin capsules only, and 19% (23/120) of patients who were on both pregabalin capsules and thiazolidinedione antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on thiazolidinediones only; 4% (35/859) of patients on pregabalin capsules only; and 7.5% (9/120) of patients on both drugs.

As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, exercise caution when co-administering pregabalin capsules and these agents.

Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, exercise caution when using pregabalin capsules in these patients.

Pregabalin capsules treatment may cause weight gain. In pregabalin capsules controlled clinical trials in adult patients of up to 14 weeks, a gain of 7% or more over baseline weight was observed in 9% of pregabalin capsules - treated patients and 2% of placebo-treated patients. Few patients treated with pregabalin capsules (0.3%) withdrew from controlled trials due to weight gain. Pregabalin capsules associated weight gain was related to dose and duration of exposure but did not appear to be associated with baseline BMI, gender, or age. Weight gain was not limited to patients with edema [see Warnings and Precautions (5.7)].

Although weight gain was not associated with clinically important changes in blood pressure in short-term controlled studies, the long-term cardiovascular effects of pregabalin capsules-associated weight gain are unknown.

Among diabetic patients, pregabalin capsules-treated patients gained an average of 1.6 kg (range: -16 to 16 kg), compared to an average 0.3 kg (range: -10 to 9 kg) weight gain in placebo patients. In a cohort of 333 diabetic patients who received pregabalin capsules for at least 2 years, the average weight gain was 5.2 kg.

While the effects of pregabalin capsules-associated weight gain on glycemic control have not been systematically assessed, in controlled and longer-term open label clinical trials with diabetic patients, pregabalin capsules treatment did not appear to be associated with loss of glycemic control (as measured by HbA 1C).

In standard preclinical in vivolifetime carcinogenicity studies of pregabalin capsules, an unexpectedly high incidence of hemangiosarcoma was identified in two different strains of mice [see Nonclinical Toxicology (13.1)]. The clinical significance of this finding is unknown. Clinical experience during pregabalin capsules premarketing development provides no direct means to assess its potential for inducing tumors in humans.

In clinical studies across various patient populations, comprising 6396 patient-years of exposure in patients greater than 12 years of age, new or worsening-preexisting tumors were reported in 57 patients. Without knowledge of the background incidence and recurrence in similar populations not treated with pregabalin capsules, it is impossible to know whether the incidence seen in these cohorts is or is not affected by treatment.

In controlled studies in adult patients, a higher proportion of patients treated with pregabalin capsules reported blurred vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases with continued dosing. Less than 1% of patients discontinued pregabalin capsules treatment due to vision-related events (primarily blurred vision).

Prospectively planned ophthalmologic testing, including visual acuity testing, formal visual field testing and dilated funduscopic examination, was performed in over 3600 patients. In these patients, visual acuity was reduced in 7% of patients treated with pregabalin capsules, and 5% of placebo-treated patients. Visual field changes were detected in 13% of pregabalin capsules-treated, and 12% of placebo-treated patients. Funduscopic changes were observed in 2% of pregabalin capsules-treated and 2% of placebo-treated patients.

Although the clinical significance of the ophthalmologic findings is unknown, inform patients to notify their physician if changes in vision occur. If visual disturbance persists, consider further assessment. Consider more frequent assessment for patients who are already routinely monitored for ocular conditions [see Patient Counseling Information (17)].

Pregabalin capsules treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for pregabalin capsules - treated patients and 28 U/L for the placebo patients. In all controlled trials in adult patients across multiple patient populations, 1.5% of patients on pregabalin capsules and 0.7% of placebo patients had a value of creatine kinase at least three times the upper limit of normal. Three pregabalin capsules-treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and pregabalin capsules are not completely understood because the cases had documented factors that may have caused or contributed to these events. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Discontinue treatment with pregabalin capsules if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.

Pregabalin capsules treatment was associated with a decrease in platelet count. Pregabalin capsules-treated subjects experienced a mean maximal decrease in platelet count of 20 × 10 3/µL, compared to 11 × 10 3/µL in placebo patients. In the overall database of controlled trials in adult patients, 2% of placebo patients and 3% of pregabalin capsules patients experienced a potentially clinically significant decrease in platelets, defined as 20% below baseline value and less than 150×10 3/µL. A single pregabalin capsule-treated subject developed severe thrombocytopenia with a platelet count less than 20 × 10 3/µL. In randomized controlled trials, pregabalin capsule was not associated with an increase in bleeding-related adverse reactions.

Pregabalin capsules treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data in adult patients, the mean PR interval increase was 3–6 msec at pregabalin capsules doses greater than or equal to 300 mg/day. This mean change difference was not associated with an increased risk of PR increase greater than or equal to 25% from baseline, an increased percentage of subjects with on-treatment PR greater than 200 msec, or an increased risk of adverse reactions of second or third degree AV block.

Subgroup analyses did not identify an increased risk of PR prolongation in patients with baseline PR prolongation or in patients taking other PR prolonging medications. However, these analyses cannot be considered definitive because of the limited number of patients in these categories.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In all controlled and uncontrolled trials across various patient populations during the premarketing development of pregabalin capsules, more than 10,000 patients have received pregabalin capsules. Approximately 5000 patients were treated for 6 months or more, over 3100 patients were treated for 1 year or longer, and over 1400 patients were treated for at least 2 years.

Adverse Reactions Most Commonly Leading to Discontinuation in All Premarketing Controlled Clinical Studies

In premarketing controlled trials of all adult populations combined, 14% of patients treated with pregabalin capsules and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (4%) and somnolence (4%). In the placebo group, 1% of patients withdrew due to dizziness and less than 1% withdrew due to somnolence. Other adverse reactions that led to discontinuation from controlled trials more frequently in the pregabalin capsules group compared to the placebo group were ataxia, confusion, asthenia, thinking abnormal, blurred vision, incoordination, and peripheral edema (1% each).

Most Common Adverse Reactions in All Controlled Clinical Studies in Adults

In premarketing controlled trials of all adult patient populations combined (including DPN, PHN, and adult patients with partial-onset seizures), dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and "thinking abnormal" (primarily difficulty with concentration/attention) were more commonly reported by subjects treated with pregabalin capsules than by subjects treated with placebo (greater than or equal to 5% and twice the rate of that seen in placebo).

Controlled Studies with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy

Adverse Reactions Leading to Discontinuation

In clinical trials in adults with neuropathic pain associated with diabetic peripheral neuropathy, 9% of patients treated with pregabalin capsules and 4% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (3%) and somnolence (2%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin capsules group than in the placebo group, were asthenia, confusion, and peripheral edema. Each of these events led to withdrawal in approximately 1% of patients.

Most Common Adverse Reactions

Table 4 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with diabetic neuropathy in the combined pregabalin capsules group for which the incidence was greater in this combined pregabalin capsules group than in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table class="Noautorules" width="44%"> <caption> <span>Table 4. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Diabetic Peripheral Neuropathy</span> </caption> <col width="168"/> <col width="111"/> <col width="111"/> <col width="111"/> <col width="111"/> <col width="109"/> <col width="95"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Body system Preferred term</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">75 mg/day [N=77]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">150 mg/day [N=212]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">300 mg/day [N=321]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">600 mg/day [N=369]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">All PGB*</span> <br/> <br/> <span class="Bold">[N=979]%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Placebo</span> <br/> <br/> <span class="Bold">[N=459]</span> <br/> <span class="Bold">%</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold"> Body as a whole</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Asthenia <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Accidental injury <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Back pain <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Chest pain <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Face edema <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold"> Digestive system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Dry mouth <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Constipation <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Flatulence <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold"> Metabolic and nutritional disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Peripheral edema <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Weight gain <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">  Edema <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Hypoglycemia <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold"> Nervous system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Dizziness <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">23 <br/> </td><td align="center" class="Botrule Rrule">29 <br/> </td><td align="center" class="Botrule Rrule">21 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Somnolence <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">13 <br/> </td><td align="center" class="Botrule Rrule">16 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Neuropathy <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Ataxia <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Vertigo <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Confusion <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Euphoria <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Incoordination <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Thinking abnormal† <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Tremor <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Abnormal gait <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Amnesia <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Nervousness <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold"> Respiratory system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Dyspnea <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold"> Special senses</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Blurry vision‡ <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Abnormal vision <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> </tbody> </table></div>

* PGB: pregabalin

†Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking.

‡Investigator term; summary level term is amblyopia

Controlled Studies in Postherpetic Neuralgia

Adverse Reactions Leading to Discontinuation

In clinical trials in adults with postherpetic neuralgia, 14% of patients treated with pregabalin capsules and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (4%) and somnolence (3%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring in greater frequency in the pregabalin capsules group than in the placebo group, were confusion (2%), as well as peripheral edema, asthenia, ataxia, and abnormal gait (1% each).

Most Common Adverse Reactions

Table 5 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with postherpetic neuralgia in the combined pregabalin capsules group for which the incidence was greater in this combined pregabalin capsules group than in the placebo group. In addition, an event is included, even if the incidence in the all pregabalin capsules group is not greater than in the placebo group, if the incidence of the event in the 600 mg/day group is more than twice that in the placebo group. A majority of pregabalin -treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate". Overall, 12.4% of all pregabalin-treated patients and 9.0% of all placebo-treated patients had at least one severe event while 8% of pregabalin-treated patients and 4.3% of placebo-treated patients had at least one severe treatment-related adverse event.

<div class="scrollingtable"><table class="Noautorules" width="652"> <caption> <span>Table 5. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Postherpetic Neuralgia</span> </caption> <col width="128"/> <col width="91"/> <col width="91"/> <col width="91"/> <col width="91"/> <col width="85"/> <col width="76"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold">Body system Preferred term</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">75 mg/d [N=84]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">150 mg/d [N=302]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">300 mg/d [N=312]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">600 mg/d [N=154]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">All PGB*</span> <br/> <span class="Bold">[N=852]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Placebo</span> <br/> <span class="Bold">[N=398]</span> <br/> <span class="Bold">%</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Body as a whole</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Infection <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Headache <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Pain <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"> Accidental injury <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Flu syndrome <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Face edema <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Digestive system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Dry mouth <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">15 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Constipation <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Flatulence <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Vomiting <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Metabolic and nutritional disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Peripheral edema <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">16 <br/> </td><td align="center" class="Botrule Rrule">16 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Weight gain <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Edema <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Musculoskeletal system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Myasthenia <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Nervous system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Dizziness <br/> </td><td align="center" class="Botrule Rrule">11 <br/> </td><td align="center" class="Botrule Rrule">18 <br/> </td><td align="center" class="Botrule Rrule">31 <br/> </td><td align="center" class="Botrule Rrule">37 <br/> </td><td align="center" class="Botrule Rrule">26 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Somnolence <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">18 <br/> </td><td align="center" class="Botrule Rrule">25 <br/> </td><td align="center" class="Botrule Rrule">16 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Ataxia <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Abnormal gait <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Confusion <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Thinking abnormal <span class="Sup">†</span> <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Incoordination <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Amnesia <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Speech disorder <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Respiratory system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Bronchitis <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Special senses</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Blurry vision <span class="Sup">‡</span> <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Diplopia <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Abnormal vision <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Eye Disorder <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Urogenital System</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Urinary Incontinence <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> </tbody> </table></div>

* PGB: pregabalin

†Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking.

‡Investigator term; summary level term is amblyopia

Controlled Studies of Adjunctive Therapy for Partial-Onset Seizures in Adult Patients

Adverse Reactions Leading to Discontinuation

Approximately 15% of patients receiving pregabalin capsules and 6% of patients receiving placebo in trials of adjunctive therapy for partial-onset seizures discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (6%), ataxia (4%), and somnolence (3%). In comparison, less than 1% of patients in the placebo group withdrew due to each of these events. Other adverse reactions that led to discontinuation of at least 1% of patients in the pregabalin capsules group and at least twice as frequently compared to the placebo group were asthenia, diplopia, blurred vision, thinking abnormal, nausea, tremor, vertigo, headache, and confusion (which each led to withdrawal in 2% or less of patients).

Most Common Adverse Reactions

Table 6 lists all dose-related adverse reactions occurring in at least 2% of all pregabalin capsules -treated patients. Dose-relatedness was defined as the incidence of the adverse event in the 600 mg /day group was at least 2% greater than the rate in both the placebo and 150 mg /day groups. In these studies, 758 patients received pregabalin capsules and 294 patients received placebo for up to 12 weeks. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table class="Noautorules" width="34%"> <caption> <span>Table 6. Dose-related Adverse Reaction Incidence in Controlled Trials of Adjunctive Therapy for Partial Onset Seizures in Adult Patients</span> </caption> <col width="142"/> <col width="98"/> <col width="107"/> <col width="97"/> <col width="102"/> <col width="91"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Body system Preferred term</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">150 mg/d</span> <br/> <span class="Bold"> [N=185]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">300 mg/d</span> <br/> <span class="Bold"> [N=90]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">600 mg/d</span> <br/> <span class="Bold"> [N=395]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">All PGB*</span> <br/> <span class="Bold"> [N=670 ] <span class="Sup">†</span></span> <br/> <span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Placebo</span> <br/> <span class="Bold"> [N=294]</span> <br/> <span class="Bold">%</span> <br/> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="6"><span class="Bold">Body as a whole</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Accidental injury <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">11 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Pain <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="6"><span class="Bold">Digestive system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Increased Appetite <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Dry mouth <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Constipation <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="6"><span class="Bold">Metabolic and Nutritional disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Weight Gain <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">16 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Peripheral Edema <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="6"><span class="Bold">Nervous system</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Dizziness <br/> </td><td align="center" class="Botrule Rrule">18 <br/> </td><td align="center" class="Botrule Rrule">31 <br/> </td><td align="center" class="Botrule Rrule">38 <br/> </td><td align="center" class="Botrule Rrule">32 <br/> </td><td align="center" class="Botrule Rrule">11 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Somnolence <br/> </td><td align="center" class="Botrule Rrule">11 <br/> </td><td align="center" class="Botrule Rrule">18 <br/> </td><td align="center" class="Botrule Rrule">28 <br/> </td><td align="center" class="Botrule Rrule">22 <br/> </td><td align="center" class="Botrule Rrule">11 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Ataxia <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">20 <br/> </td><td align="center" class="Botrule Rrule">15 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Tremor <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">11 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Thinking Abnormal <span class="Sup">‡</span> <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Amnesia <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Speech disorder <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Incoordination <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Abnormal Gait <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Twitching <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Confusion <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Myoclonus <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="6"><span class="Bold">Special senses</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Blurry Vision <span class="Sup">§</span> <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Diplopia <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Abnormal vision <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> </tbody> </table></div>

* PGB: pregabalin

†Excludes patients who received the 50 mg dose in Study E1.

‡Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking.

§Investigator term; summary level term is amblyopia.

Controlled Study of Adjunctive Therapy for Partial-Onset Seizures in Patients 4 to Less Than 17 Years of Age

Adverse Reactions Leading to Discontinuation

Approximately 2.5% of patients receiving pregabalin capsules and no patients receiving placebo in trials of adjunctive therapy for partial-onset seizures discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the adverse reactions leading to discontinuation were somnolence (3 patients), worsening of epilepsy (1 patient), and hallucination (1 patient).

Most Common Adverse Reactions

Table 7 lists all dose-related adverse reactions occurring in at least 2% of all pregabalin capsules-treated patients. Dose-relatedness was defined as an incidence of the adverse event in the 10 mg/kg/day group that was at least 2% greater than the rate in both the placebo and 2.5 mg/kg/day groups. In this study, 201 patients received pregabalin capsules and 94 patients received placebo for up to 12 weeks. A majority of pregabalin-treated patients in the clinical study had adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table class="Noautorules" width="574"> <caption> <span>Table 7. Dose-related Adverse Reaction Incidence in a Controlled Trial in Adjunctive Therapy for Partial-Onset Seizures in Patients 4 to Less Than 17 Years of Age</span> </caption> <col width="152"/> <col width="103"/> <col width="121"/> <col width="110"/> <col width="88"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Body System</span> <br/> <span class="Bold">Preferred Term</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">2.5 mg/kg/day <span class="Sup">a</span></span> <br/> <span class="Bold">[N=104]%</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">10 mg/kg/day <span class="Sup">b</span></span> <br/> <span class="Bold">[N=97]%</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">All PGB</span> <br/> <span class="Bold">[N=201]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">Placebo</span> <br/> <span class="Bold">[N=94]</span> <br/> <span class="Bold">%</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="5"><span class="Bold">Gastrointestinal disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Salivary hypersecretion <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="5"><span class="Bold">Investigations</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Weight increased <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">13 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="5"><span class="Bold">Metabolism and nutrition disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Increased appetite <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="5"><span class="Bold">Nervous system disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Somnolence <br/> </td><td align="center" class="Botrule Rrule">17 <br/> </td><td align="center" class="Botrule Rrule">26 <br/> </td><td align="center" class="Botrule Rrule">21 <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td> </tr> </tbody> </table></div>

Abbreviations: N=number of patients; PGB = pregabalin

a2.5 mg/kg/day: Maximum dose 150 mg/day. Includes patients less than 30 kg for whom dose was adjusted to 3.5 mg/kg/day.

b10 mg/kg/day: Maximum dose 600 mg/day. Includes patients less than 30 kg for whom dose was adjusted to 14 mg/kg/day

Controlled Study of Adjunctive Therapy for Partial-Onset Seizures in Patients 1 Month to Less Than 4 Years of Age

Most Common Adverse Reactions

Table 8 lists all dose-related adverse reactions occurring in at least 2% of all pregabalin capsules-treated patients. Dose-relatedness was defined as an incidence of the adverse event in the 14 mg/kg/day group that was at least 2% greater than the rate in both the placebo and 7 mg/kg/day groups. In this study, 105 patients received pregabalin capsules and 70 patients received placebo for up to 14 days.

<div class="scrollingtable"><table class="Noautorules" width="606"> <caption> <span>Table 8.  Dose-related Adverse Reaction Incidence in a Controlled Trial in Adjunctive Therapy for Partial- Onset Seizures in Patients 1 Month to Less Than 4 Years of Age</span> </caption> <col width="151"/> <col width="119"/> <col width="127"/> <col width="104"/> <col width="105"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Body System Preferred</span> <br/> <span class="Bold">Term</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">7 mg/kg/day</span> <br/> <span class="Bold">[N=71]%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">14 mg/kg/day</span> <br/> <span class="Bold">[N=34]%</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">All PGB</span> <br/> <span class="Bold">[N=105] %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Placebo</span> <br/> <span class="Bold">[N=70]%</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="5"><span class="Bold">Nervous system disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">Somnolence* <br/> </td><td align="center" class="Botrule Rrule">13 <br/> </td><td align="center" class="Botrule Rrule">21 <br/> </td><td align="center" class="Botrule Rrule">15 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="5"><span class="Bold">Infections and infestations</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Pneumonia <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Viral infection <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td> </tr> </tbody> </table></div>

Abbreviations: N= number of patients; PGB= pregabalin.

*includes related terms including lethargy, sluggishness, and hypersomnia.

Controlled Studies with Fibromyalgia

Adverse Reactions Leading to Discontinuation

In clinical trials of patients with fibromyalgia, 19% of patients treated with pregabalin (150–600 mg /day) and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (6%) and somnolence (3%). In comparison, less than 1% of placebo-treated patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue, headache, balance disorder, and weight increased. Each of these adverse reactions led to withdrawal in approximately 1% of patients.

Most Common Adverse Reactions

Table 9 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients with fibromyalgia in the 'all pregabalin' treatment group for which the incidence was greater than in the placebo treatment group. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table class="Noautorules" width="639"> <caption> <span>Table 9. Adverse Reaction Incidence in Controlled Trials in Fibromyalgia</span> </caption> <col width="144"/> <col width="86"/> <col width="85"/> <col width="80"/> <col width="81"/> <col width="85"/> <col width="78"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">System Organ</span> <br/> <span class="Bold">Class</span> <br/> <span class="Bold">Preferred term</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">150 mg/d [N=132]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">300 mg/d [N=502]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">450 mg/d [N=505]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">600 mg/d [N=378]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">All PGB*</span> <br/> <span class="Bold">[N=1517]</span> <br/> <span class="Bold">%</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">Placebo</span> <br/> <span class="Bold">[N=505]</span> <br/> <span class="Bold">%</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7" valign="top"><span class="Bold">Ear and Labyrinth Disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Vertigo <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7" valign="top"><span class="Bold">Eye Disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Vision blurred <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7" valign="top"><span class="Bold">Gastrointestinal Disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Dry mouth <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Constipation <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Vomiting <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Flatulence <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Abdominal distension <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">General Disorders and Administrative Site Conditions</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Fatigue <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Edema peripheral <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Chest pain <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Feeling abnormal <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Edema <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Feeling drunk <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Infections and Infestations</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Sinusitis <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Investigations</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Weight increased <br/> </td><td align="center" class="Botrule Rrule">8 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td><td align="center" class="Botrule Rrule">11 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Metabolism and Nutrition Disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Increased appetite <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Fluid retention <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Musculoskeletal and Connective Tissue Disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Arthralgia <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Muscle spasms <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Back pain <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7" valign="top"><span class="Bold">Nervous System Disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Dizziness <br/> </td><td align="center" class="Botrule Rrule">23 <br/> </td><td align="center" class="Botrule Rrule">31 <br/> </td><td align="center" class="Botrule Rrule">43 <br/> </td><td align="center" class="Botrule Rrule">45 <br/> </td><td align="center" class="Botrule Rrule">38 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Somnolence <br/> </td><td align="center" class="Botrule Rrule">13 <br/> </td><td align="center" class="Botrule Rrule">18 <br/> </td><td align="center" class="Botrule Rrule">22 <br/> </td><td align="center" class="Botrule Rrule">22 <br/> </td><td align="center" class="Botrule Rrule">20 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Headache <br/> </td><td align="center" class="Botrule Rrule">11 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">14 <br/> </td><td align="center" class="Botrule Rrule">10 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td><td align="center" class="Botrule Rrule">12 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Disturbance <br/> in attention <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Balance disorder <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">9 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Memory impairment <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Coordination abnormal <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Hypoesthesia <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Lethargy <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Tremor <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Psychiatric Disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Euphoric Mood <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">5 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">7 <br/> </td><td align="center" class="Botrule Rrule">6 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Confusional state <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">4 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Anxiety <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Disorientation <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Depression <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="7"><span class="Bold">Respiratory, Thoracic and Mediastinal Disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Pharyngolaryngeal pain <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">1 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">3 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td><td align="center" class="Botrule Rrule">2 <br/> </td> </tr> </tbody> </table></div>

*PGB: pregabalin

Controlled Studies in Neuropathic Pain Associated with Spinal Cord Injury

Adverse Reactions Leading to Discontinuation

In clinical trials of adults with neuropathic pain associated with spinal cord injury, 13% of patients treated with pregabalin and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were somnolence (3%) and edema (2%). In comparison, none of the placebo-treated patients withdrew due to somnolence and edema. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue and balance disorder. Each of these adverse reactions led to withdrawal in less than 2% of patients.

Most Common Adverse Reactions

Table 10 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients for which the incidence was greater than in the placebo treatment group with neuropathic pain associated with spinal cord injury in the controlled trials. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of "mild" or "moderate".

<div class="scrollingtable"><table class="Noautorules" width="29%"> <caption> <span>Table 10. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Spinal Cord Injury</span> </caption> <col width="204"/> <col width="173"/> <col width="174"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" rowspan="2"><span class="Bold">System Organ Class</span> <br/> Preferred term <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">PGB* (N=182)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold">Placebo (N=174)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Rrule"><span class="Bold">%</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">%</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Ear and labyrinth disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Vertigo <br/> </td><td align="center" class="Botrule Rrule">2.7 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Eye disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Vision blurred <br/> </td><td align="center" class="Botrule Rrule">6.6 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Gastrointestinal disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Dry mouth <br/> </td><td align="center" class="Botrule Rrule">11.0 <br/> </td><td align="center" class="Botrule Rrule">2.9 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Constipation <br/> </td><td align="center" class="Botrule Rrule">8.2 <br/> </td><td align="center" class="Botrule Rrule">5.7 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Nausea <br/> </td><td align="center" class="Botrule Rrule">4.9 <br/> </td><td align="center" class="Botrule Rrule">4.0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Vomiting <br/> </td><td align="center" class="Botrule Rrule">2.7 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">General disorders and administration site conditions</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Fatigue <br/> </td><td align="center" class="Botrule Rrule">11.0 <br/> </td><td align="center" class="Botrule Rrule">4.0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Edema peripheral <br/> </td><td align="center" class="Botrule Rrule">10.4 <br/> </td><td align="center" class="Botrule Rrule">5.2 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Edema <br/> </td><td align="center" class="Botrule Rrule">8.2 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Pain <br/> </td><td align="center" class="Botrule Rrule">3.3 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Infections and infestations</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Nasopharyngitis <br/> </td><td align="center" class="Botrule Rrule">8.2 <br/> </td><td align="center" class="Botrule Rrule">4.6 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule"><span class="Bold">Investigations</span> <br/> </td><td class="Botrule Rrule"></td><td class="Botrule Rrule"></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Weight increased <br/> </td><td align="center" class="Botrule Rrule">3.3 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Blood creatine phosphokinase increased <br/> </td><td align="center" class="Botrule Rrule">2.7 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Musculoskeletal and connective tissue disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Muscular weakness <br/> </td><td align="center" class="Botrule Rrule">4.9 <br/> </td><td align="center" class="Botrule Rrule">1.7 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Pain in extremity <br/> </td><td align="center" class="Botrule Rrule">3.3 <br/> </td><td align="center" class="Botrule Rrule">2.3 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Neck pain <br/> </td><td align="center" class="Botrule Rrule">2.7 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Back pain <br/> </td><td align="center" class="Botrule Rrule">2.2 <br/> </td><td align="center" class="Botrule Rrule">1.7 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Joint swelling <br/> </td><td align="center" class="Botrule Rrule">2.2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Nervous system disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Somnolence <br/> </td><td align="center" class="Botrule Rrule">35.7 <br/> </td><td align="center" class="Botrule Rrule">11.5 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Dizziness <br/> </td><td align="center" class="Botrule Rrule">20.9 <br/> </td><td align="center" class="Botrule Rrule">6.9 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Disturbance in attention <br/> </td><td align="center" class="Botrule Rrule">3.8 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Memory impairment <br/> </td><td align="center" class="Botrule Rrule">3.3 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Paresthesia <br/> </td><td align="center" class="Botrule Rrule">2.2 <br/> </td><td align="center" class="Botrule Rrule">0.6 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Psychiatric disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Insomnia <br/> </td><td align="center" class="Botrule Rrule">3.8 <br/> </td><td align="center" class="Botrule Rrule">2.9 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Euphoric mood <br/> </td><td align="center" class="Botrule Rrule">2.2 <br/> </td><td align="center" class="Botrule Rrule">0.6 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Renal and urinary disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Urinary incontinence <br/> </td><td align="center" class="Botrule Rrule">2.7 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Skin and subcutaneous tissue disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Decubitus ulcer <br/> </td><td align="center" class="Botrule Rrule">2.7 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">Vascular disorders</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Hypertension <br/> </td><td align="center" class="Botrule Rrule">2.2 <br/> </td><td align="center" class="Botrule Rrule">1.1 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Hypotension <br/> </td><td align="center" class="Botrule Rrule">2.2 <br/> </td><td align="center" class="Botrule Rrule">0 <br/> </td> </tr> </tbody> </table></div>

* PGB: Pregabalin

Other Adverse Reactions Observed During the Clinical Studies of pregabalin capsules

Following is a list of treatment-emergent adverse reactions reported by patients treated with pregabalin capsules during all clinical trials. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening.

Events are categorized by body system and listed in order of decreasing frequency according to the following definitions: frequentadverse reactions are those occurring on one or more occasions in at least 1/100 patients ; infrequentadverse reactions are those occurring in 1/100 to 1/1000 patients; rarereactions are those occurring in fewer than 1/1000 patients. Events of major clinical importance are described in the Warnings and Precautionssection (5).

Body as a Whole – Frequent: Abdominal pain, Allergic reaction, Fever, Infrequent: Abscess, Cellulitis, Chills, Malaise, Neck rigidity, Overdose, Pelvic pain, Photosensitivity reaction, Rare: Anaphylactoid reaction, Ascites, Granuloma, Hangover effect, Intentional Injury, Retroperitoneal Fibrosis, Shock

Cardiovascular System – Infrequent: Deep thrombophlebitis, Heart failure, Hypotension, Postural hypotension, Retinal vascular disorder, Syncope; Rare: ST Depressed, Ventricular Fibrillation

Digestive System – Frequent: Gastroenteritis, Increased appetite; Infrequent:Cholecystitis, Cholelithiasis, Colitis, Dysphagia, Esophagitis, Gastritis, Gastrointestinal hemorrhage, Melena, Mouth ulceration, Pancreatitis, Rectal hemorrhage, Tongue edema; Rare: Aphthous stomatitis, Esophageal Ulcer, Periodontal abscess.

Hemic and Lymphatic System – Frequent:Ecchymosis; Infrequent:Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare:Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia, Alanine aminotransferase increased, Aspartate aminotransferase increased

Metabolic and Nutritional Disorders – Rare:Glucose Tolerance Decreased, Urate Crystalluria

Musculoskeletal System – Frequent: Arthralgia, Leg cramps, Myalgia, Myasthenia; Infrequent:Arthrosis; Rare: Chondrodystrophy, Generalized Spasm

Nervous System – Frequent: Anxiety, Depersonalization, Hypertonia, Hypoesthesia, Libido decreased, Nystagmus, Paresthesia, Sedation, Stupor, Twitching ; Infrequent:Abnormal dreams, Agitation, Apathy, Aphasia, Circumoral paresthesia, Dysarthria, Hallucinations, Hostility, Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased, Myoclonus, Neuralgia; Rare:Addiction, Cerebellar syndrome, Cogwheel rigidity, Coma, Delirium, Delusions, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal syndrome, Guillain-Barr¡SR syndrome, Hypalgesia, Intracranial hypertension, Manic reaction, Paranoid reaction, Peripheral neuritis, Personality disorder, Psychotic depression, Schizophrenic reaction, Sleep disorder, Torticollis, Trismus

Respiratory System – Rare:Apnea, Atelectasis, Bronchiolitis, Hiccup, Laryngismus, Lung edema, Lung fibrosis, Yawn

Skin and Appendages – Frequent:Pruritus, Infrequent: Alopecia, Dry skin, Eczema, Hirsutism, Skin ulcer, Urticaria, Vesiculobullous rash; Rare: Angioedema, Exfoliative dermatitis, Lichenoid dermatitis, Melanosis, Nail Disorder, Petechial rash, Purpuric rash, Pustular rash, Skin atrophy, Skin necrosis, Skin nodule, Stevens-Johnson syndrome, Subcutaneous nodule

Special senses – Frequent: Conjunctivitis, Diplopia, Otitis media, Tinnitus; Infrequent:Abnormality of accommodation, Blepharitis, Dry eyes, Eye hemorrhage, Hyperacusis, Photophobia, Retinal edema, Taste loss, Taste perversion; Rare:Anisocoria, Blindness, Corneal ulcer, Exophthalmos, Extraocular palsy, Iritis, Keratitis, Keratoconjunctivitis, Miosis, Mydriasis, Night blindness, Ophthalmoplegia, Optic atrophy, Papilledema, Parosmia, Ptosis, Uveitis

Urogenital System – Frequent:Anorgasmia, Impotence, Urinary frequency, Urinary incontinence; Infrequent:Abnormal ejaculation, Albuminuria, Amenorrhea, Dysmenorrhea, Dysuria, Hematuria, Kidney calculus, Leukorrhea, Menorrhagia, Metrorrhagia, Nephritis, Oliguria, Urinary retention, Urine abnormality; Rare:Acute kidney failure, Balanitis, Bladder Neoplasm, Cervicitis, Dyspareunia, Epididymitis, Female lactation, Glomerulitis, Ovarian disorder, Pyelonephritis

Comparison of Gender and Race

The overall adverse event profile of pregabalin was similar between women and men. There are insufficient data to support a statement regarding the distribution of adverse experience reports by race.

The following adverse reactions have been identified during postapproval use of pregabalin capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous System Disorders – Headache

Gastrointestinal Disorders – Nausea, Diarrhea

Reproductive System and Breast Disorders – Gynecomastia, Breast Enlargement

Skin and subcutaneous tissue disorder – Bullous pemphigoid

There are postmarketing reports of life-threatening or fatal respiratory depression in patients taking pregabalin capsules with opoids or other CNS depressants, or in the setting of underlying respiratory impairment.

In addition, there are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when pregabalin capsules was co-administered with medications that have the potential to produce constipation, such as opioid analgesics.

There are postmarketing reports of withdrawal symptoms after discontinuation of pregabalin. Reported adverse reactions include, but are not limited to, seizures, depression, suicidal ideation and behavior, agitation, confusion, disorientation, psychotic symptoms, anxiety, insomnia, nausea, pain, sweating, tremor, headache, dizziness, malaise, and diarrhea.

Since pregabalin capsules are predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (less than 2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. In vitroand in vivostudies showed that pregabalin capsules are unlikely to be involved in significant pharmacokinetic drug interactions. Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate. Important pharmacokinetic interactions would also not be expected to occur between pregabalin capsules and commonly used antiepileptic drugs [see Clinical Pharmacology (12)].

{ "type": "p", "children": [], "text": "\nSince pregabalin capsules are predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (less than 2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement.\n \n In vitroand\n \n in vivostudies showed that pregabalin capsules are unlikely to be involved in significant pharmacokinetic drug interactions. Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate. Important pharmacokinetic interactions would also not be expected to occur between pregabalin capsules and commonly used antiepileptic drugs\n \n [see\n \n Clinical Pharmacology (12)].\n \n \n" }

Pharmacodynamics

{ "type": "p", "children": [], "text": "\nPharmacodynamics\n" }

Multiple oral doses of pregabalin capsules were co-administered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when pregabalin capsule was co-administered with these drugs. No clinically important effects on respiration were seen.

{ "type": "p", "children": [], "text": "Multiple oral doses of pregabalin capsules were co-administered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when pregabalin capsule was co-administered with these drugs. No clinically important effects on respiration were seen." }

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pregabalin capsules during pregnancy. To provide information regarding the effects of in uteroexposure to pregabalin capsules, physicians are advised to recommend that pregnant patients taking pregabalin capsules enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

Risk Summary

Observational studies on the use of pregabalin capsules during pregnancy suggest a possible small increase in the rate of overall major birth defects, but there was no consistent or specific pattern of major birth defects identified (see Data). Available postmarketing data on miscarriage and other maternal, fetal, and long term developmental adverse effects were insufficient to identify risk associated with pregabalin.

Postmarketing data suggest that extended gabapentinoid use with opioids close to delivery may increase the risk of neonatal withdrawal versus opioids alone  (see Clinical Considerations).

There are no comparative epidemiologic studies evaluating this association. Therefore, it is not known whether exposure to pregabalin alone late in pregnancy may cause withdrawal signs and symptoms.

In animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (AUC) greater than or equal to 16 times human exposure at the maximum recommended dose (MRD) of 600 mg/day (see Data). In an animal development study, lethality, growth retardation, and nervous and reproductive system functional impairment were observed in the offspring of rats given pregabalin during gestation and lactation. The no-effect dose for developmental toxicity was approximately twice the human exposure at MRD.

The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentinoids in utero for an extended period of time when also exposed to opioids close to delivery. Neonatal withdrawal signs and symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia, irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern, and tremor. Reported signs and symptoms that may also be related to withdrawal include tongue thrusting, wandering eye movements while awake, back arching, and continuous extremity movements.

Observe neonates exposed to pregabalin capsules and opioids for signs and symptoms of neonatal withdrawal and manage accordingly.

Data

Human Data

One database study, which included over 2,700 pregnancies exposed to Pregabalin (monotherapy) during the first trimester compared to 3,063,251 pregnancies unexposed to  antiepileptics demonstrated prevalence ratios for major malformations overall of 1.14 (CI 95%  0.96-1.35) for pregabalin, 1.29 (CI 95% 1.01-1.65) for lamotrigine, 1.39 (CI 95% 1.07-1.82) for  duloxetine, and 1.24 (CI 95% 1.00-1.54) for exposure to either lamotrigine or duloxetine.

Important study limitations include uncertainty of whether women who filled a prescription took the medication and inability to adequately control for the underlying disease and other potential confounders.

A published study included results from two separate databases. One database, which included 353 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 368,489 pregnancies unexposed to antiepileptics, showed no increase in risk of major birth defects; adjusted relative risk 0.87 (CI 95% 0.53-1.42). The second database, which included 118 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 380,347 pregnancies unexposed to antiepileptics, suggested a small increase in risk of major birth defects; adjusted relative risk 1.26 (CI 95% 0.64-2.49). The risk estimates crossed the null, and the study had limitations similar to the prior study.

Other published epidemiologic studies reported inconsistent findings. No specific pattern of birth defects was identified across studies. All of the studies had limitations due to their retrospective design.

Animal Data

When pregnant rats were given pregabalin (500, 1250, or 2500 mg/kg) orally throughout the period of organogenesis, incidences of specific skull alterations attributed to abnormally advanced ossification (premature fusion of the jugal and nasal sutures) were increased at greater than or equal to 1250 mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses. Fetal body weights were decreased at the highest dose. The low dose in this study was associated with a plasma exposure (AUC) approximately 17 times human exposure at the MRD of 600 mg/day. A no-effect dose for rat embryo-fetal developmental toxicity was not established.

When pregnant rabbits were given pregabalin capsules (250, 500, or 1250 mg/kg) orally throughout the period of organogenesis, decreased fetal body weight and increased incidences of skeletal malformations, visceral variations, and retarded ossification were observed at the highest dose. The no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a plasma exposure approximately 16 times human exposure at the MRD.

In a study in which female rats were dosed with pregabalin capsules (50, 100, 250, 1250, or 2500 mg/kg) throughout gestation and lactation, offspring growth was reduced at greater than or equal to 100 mg/kg and offspring survival was decreased at greater than or equal to 250 mg/kg. The effect on offspring survival was pronounced at doses greater than or equal to 1250 mg/kg, with 100% mortality in high-dose litters. When offspring were tested as adults, neurobehavioral abnormalities (decreased auditory startle responding) were observed at greater than or equal to 250 mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1250 mg/kg. The no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a plasma exposure approximately 2 times human exposure at the MRD.

In the prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures greater than or equal to 50 times the mean human exposure (AUC (0-24)of 123 µg·hr/mL) at the MRD.

Risk Summary

Small amounts of pregabalin have been detected in the milk of lactating women. A pharmacokinetic study in lactating women detected pregabalin in breast milk at average steady state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg /day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose (see Data).The study did not evaluate the effects of pregabalin capsules on milk production or the effects of pregabalin capsules on the breastfed infant.

Based on animal studies, there is a potential risk of tumorigenicity with pregabalin exposure via breast milk to the breastfed infant [see Nonclinical Toxicology (13.1)]. Available clinical study data in patients greater than 12 years of age do not provide a clear conclusion about the potential risk of tumorigenicity with pregabalin [see Warnings and Precautions (5.9)]. Because of the potential risk of tumorigenicity, breastfeeding is not recommended during treatment with pregabalin capsules.

Data

A pharmacokinetic study in ten lactating women, who were at least 12 weeks postpartum, evaluated the concentrations of pregabalin in plasma and breast milk. Pregabalin capsules 150 mg oral capsule was given every 12 hours (300 mg daily dose) for a total of four doses. Pregabalin was detected in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose. The study did not evaluate the effects of pregabalin capsules on milk production. Infants did not receive breast milk obtained during the dosing period, therefore, the effects of pregabalin capsules on the breast fed infant were not evaluated.

Infertility

Males

Effects on Spermatogenesis

In a randomized, double-blind, placebo-controlled non-inferiority study to assess the effect of pregabalin on sperm characteristics, healthy male subjects received pregabalin at a daily dose up to 600 mg (n=111) or placebo (n=109) for 13 weeks (one complete sperm cycle) followed by a 13-week washout period (off-drug). A total of 65 subjects in the pregabalin group (59%) and 62 subjects in the placebo group (57%) were included in the per protocol (PP) population. These subjects took study drug for at least 8 weeks, had appropriate timing of semen collections and did not have any significant protocol violations. Among these subjects, approximately 9% of the pregabalin group (6/65) vs. 3% in the placebo group (2/62) had greater than or equal to 50% reduction in mean sperm concentrations from baseline at Week 26 (the primary endpoint). The difference between pregabalin and placebo was within the pre-specified non-inferiority margin of 20%. There were no adverse effects of pregabalin on sperm morphology, sperm motility, serum FSH or serum testosterone levels as compared to placebo. In subjects in the PP population with greater than or equal to 50% reduction in sperm concentration from baseline, sperm concentrations were no longer reduced by greater than or equal to 50% in any affected subject after an additional 3 months off-drug. In one subject, however, subsequent semen analyses demonstrated reductions from baseline of greater than or equal to 50% at 9 and 12 months off-drug. The clinical relevance of these data is unknown.

In the animal fertility study with pregabalin in male rats, adverse reproductive and developmental effects were observed [see Nonclinical Toxicology (13.1)] .

Neuropathic Pain Associated with Diabetic Peripheral Neuropathy, Postherpetic Neuralgia, and Neuropathic Pain Associated with Spinal Cord Injury

Safety and effectiveness in pediatric patients have not been established.

Fibromyalgia

Safety and effectiveness in pediatric patients have not been established.

A 15-week, placebo-controlled trial was conducted with 107 pediatric patients with fibromyalgia, ages 12 through 17 years, at pregabalin capsules total daily doses of 75-450 mg per day. The primary efficacy endpoint of change from baseline to Week 15 in mean pain intensity (derived from an 11-point numeric rating scale) showed numerically greater improvement for the pregabalin-treated patients compared to placebo-treated patients, but did not reach statistical significance. The most frequently observed adverse reactions in the clinical trial included dizziness, nausea, headache, weight increased, and fatigue. The overall safety profile in adolescents was similar to that observed in adults with fibromyalgia

Adjunctive Therapy for Partial-Onset Seizures 

Safety and effectiveness in pediatric patients below the age of 1 month have not been established.

4 to Less Than 17 Years of Age with Partial-Onset Seizures

The safety and effectiveness of pregabalin capsules as adjunctive treatment for partial-onset seizures in pediatric patients 4 to less than 17 years of age have been established in a 12-week, double-blind, placebo-controlled study (n=295) [see Clinical Studies (14.3)]. Patients treated with pregabalin capsules 10 mg/kg/day had, on average, a 21.0% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0185). Patients treated with pregabalin capsules 2.5 mg/kg/day had, on average, a 10.5% greater reduction in partial-onset seizures than patients treated with placebo, but the difference was not statistically significant (p=0.2577).

Responder rates (50% or greater reduction in partial-onset seizure frequency) were a key secondary efficacy parameter and showed numerical improvement with pregabalin capsules compared with placebo: the responder rates were 40.6%, 29.1%, and 22.6%, for pregabalin capsules 10 mg/kg/day, pregabalin capsules 2.5 mg/kg/day, and placebo, respectively.

The most common adverse reactions (≥ 5%) with pregabalin capsules in this study were somnolence, weight increased, and increased appetite [see Adverse Reactions (6.1)].  

The use of pregabalin capsules 2.5 mg/kg/day in pediatric patients is further supported by evidence from adequate and well-controlled studies in adults with partial-onset seizures and pharmacokinetic data from adult and pediatric patients [see Clinical Pharmacology (12.3)].

1 Month to Less than 4 Years of Age with Partial-Onset Seizures

The safety and effectiveness of pregabalin capsules as adjunctive treatment for partial-onset seizures in pediatric patients 1 month to less than 4 years of age have been established in a 14-day double-blind, placebo-controlled study (N=175) [see Clinical Studies (14.3)]. The youngest subject evaluated was 3 months of age; use in patients 1 month to less than 3 months of age is supported by additional pharmacokinetic analyses. Patients treated with pregabalin capsules 14 mg/kg/day had, on average, 43.9% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0223). In addition, pediatric patients treated with pregabalin capsules 14 mg/kg/day showed numerical improvement in responder rates (≥ 50% reduction in partial-onset seizure frequency) compared with placebo (53.6% versus 41.5%). Patients treated with pregabalin capsules 7 mg/kg/day did not show improvement relative to placebo for either endpoint.

The most common dose-related adverse reactions (> 5%) with pregabalin capsules in this study were somnolence, pneumonia, and viral infection [see Adverse Reactions (6.1)].

Juvenile Animal Data

In studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from early in the postnatal period (Postnatal Day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory startle responding and habituation) and reproductive impairment (delayed sexual maturation and decreased fertility in males and females) were observed at doses greater than or equal to 50 mg/kg. The neurobehavioral changes of acoustic startle persisted at greater than or equal to 250 mg/kg and locomotor activity and water maze performance at greater than or equal to 500 mg/kg in animals tested after cessation of dosing and, thus, were considered to represent long-term effects. The low effect dose for developmental neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately equal to human exposure at the maximum recommended dose of 600 mg/day. A no-effect dose was not established.

In controlled clinical studies of pregabalin capsules in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older.

In controlled clinical studies of pregabalin capsules in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older.

In controlled clinical studies of pregabalin capsules in epilepsy, there were only 10 patients 65 to 74 years of age, and 2 patients who were 75 years of age or older.

No overall differences in safety and efficacy were observed between these patients and younger patients.

In controlled clinical studies of pregabalin capsules in fibromyalgia, 106 patients were 65 years of age or older. Although the adverse reaction profile was similar between the two age groups, the following neurological adverse reactions were more frequent in patients 65 years of age or older: dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and lethargy.

Pregabalin capsules are known to be substantially excreted by the kidney, and the risk of toxic reactions to pregabalin capsules may be greater in patients with impaired renal function. Because pregabalin capsules are eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment [see Dosage and Administration (2.7)].

Pregabalin capsules are eliminated primarily by renal excretion and dose adjustment is recommended for adult patients with renal impairment [see Dosage and Administration (2.7)and Clinical Pharmacology (12.3)]. The use of pregabalin capsules in pediatric patients with compromised renal function has not been studied.

Pregabalin capsules are a Schedule V controlled substance.

Pregabalin capsules are not known to be active at receptor sites associated with drugs of abuse. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin capsules misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).

In a study of recreational users (N=15) of sedative/hypnotic drugs, including alcohol, pregabalin capsules (450 mg, single dose) received subjective ratings of "good drug effect," "high" and "liking" to a degree that was similar to diazepam (30 mg, single dose). In controlled clinical studies in over 5500 patients, 4% of pregabalin capsules-treated patients and 1% of placebo-treated patients overall reported euphoria as an adverse reaction, though in some patient populations studied, this reporting rate was higher and ranged from 1 to 12%.

In clinical studies, following abrupt or rapid discontinuation of pregabalin capsules, some patients reported symptoms including insomnia, nausea, headache or diarrhea [see Warnings and Precautions (5.4)], consistent with physical dependence. In the postmarketing setting, in addition to these reported symptoms, other reported adverse reactions include, but are not limited to, seizures, depression, suicidal ideation and behavior, agitation, confusion, disorientation, psychotic symptoms, pain, sweating, tremor, dizziness, and malaise.

Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans

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In the postmarketing experience, the most commonly reported adverse events observed with pregabalin when taken in overdose include reduced consciousness, depression/anxiety, confusional state, agitation, and restlessness. Seizures and heart block have also been reported. Deaths have been reported in the setting of lone pregabalin capsules overdose and in combination with other CNS depressants.

{ "type": "p", "children": [], "text": "In the postmarketing experience, the most commonly reported adverse events observed with pregabalin when taken in overdose include reduced consciousness, depression/anxiety, confusional state, agitation, and restlessness. Seizures and heart block have also been reported. Deaths have been reported in the setting of lone pregabalin capsules overdose and in combination with other CNS depressants." }

Treatment or Management of Overdose

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There is no specific antidote for overdose with pregabalin capsules. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with pregabalin capsules.

{ "type": "p", "children": [], "text": "There is no specific antidote for overdose with pregabalin capsules. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with pregabalin capsules." }

Pregabalin capsules can be removed by hemodialysis. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50 % in 4 hours).

{ "type": "p", "children": [], "text": "Pregabalin capsules can be removed by hemodialysis. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50 % in 4 hours)." }

Pregabalin USP is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C 8H 17NO 2and the molecular weight is 159.23. The chemical structure of pregabalin is:

{ "type": "p", "children": [], "text": "\nPregabalin USP is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C\n \n 8H\n \n 17NO\n \n 2and the molecular weight is 159.23. The chemical structure of pregabalin is:\n\n " }

Pregabalin USP is a white to off-white, crystalline solid with a pK a1of 4.2 and a pK a2of 10.6. It is sparingly soluble in water and freely soluble in both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is –1.35.

{ "type": "p", "children": [], "text": "\nPregabalin USP is a white to off-white, crystalline solid with a pK\n \n a1of 4.2 and a pK\n \n a2of 10.6. It is sparingly soluble in water and freely soluble in both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is –1.35.\n\n " }

Pregabalin capsules are administered orally and are supplied as imprinted hard-shell capsules containing 25, 50, 75, 100, 150, 200, 225, and 300 mg of pregabalin, along with lactose monohydrate, pregelatinised starch, and talc as inactive ingredients.

{ "type": "p", "children": [], "text": "Pregabalin capsules are administered orally and are supplied as imprinted hard-shell capsules containing 25, 50, 75, 100, 150, 200, 225, and 300 mg of pregabalin, along with lactose monohydrate, pregelatinised starch, and talc as inactive ingredients." }

The capsule shells contain gelatin and titanium dioxide. In addition, the orange capsule shells contain red iron oxide.

{ "type": "p", "children": [], "text": "The capsule shells contain gelatin and titanium dioxide. In addition, the orange capsule shells contain red iron oxide." }

The imprinting ink contains shellac, black iron oxide, propylene glycol, ammonium solution concentrated and potassium hydroxide.

{ "type": "p", "children": [], "text": "The imprinting ink contains shellac, black iron oxide, propylene glycol, ammonium solution concentrated and potassium hydroxide." }

Pregabalin binds with high affinity to the alpha 2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha 2-delta subunit may be involved in pregabalin's anti-nociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha 2-delta containing-calcium channel trafficking and/or reducing calcium currents. Evidence from other animal models of nerve damage and persistent pain suggest the anti-nociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord.

While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-amino butyric acid (GABA), it does not bind directly to GABA A, GABA B, or benzo diazepine receptors, does not augment GABA Aresponses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.

Pregabalin is well absorbed after oral administration, is eliminated largely by renal excretion, and has an elimination half-life of about 6 hours.

Absorption and Distribution

Following oral administration of pregabalin capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin oral bioavailability is greater than or equal to 90% and is independent of dose. Following single- (25 to 300 mg) and multiple-dose (75 to 900 mg/day) administration, maximum plasma concentrations (C max) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.

The rate of pregabalin absorption is decreased when given with food, resulting in a decrease in C maxof approximately 25% to 30% and an increase in T maxto approximately 3 hours. However, administration of pregabalin with food has no clinically relevant effect on the total absorption of pregabalin. Therefore, pregabalin can be taken with or without food.

Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. Although there are no data in humans, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys. In addition, pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats.

Metabolism and Elimination

Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled pregabalin, approximately 90% of the administered dose was recovered in the urine as unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbits, or monkeys.

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67.0 to 80.9 mL/min in young healthy subjects. Because pregabalin is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to creatinine clearance (CLcr) [see Dosage and Administration (2.7)].

Pharmacokinetics in Specific Populations

Race

In population pharmacokinetic analyses of the clinical studies in various populations, the pharmacokinetics of pregabalin capsules were not significantly affected by race (Caucasians, Blacks, and Hispanics).

Gender

Population pharmacokinetic analyses of the clinical studies showed that the relationship between daily dose and pregabalin capsules drug exposure is similar between genders.

Renal Impairment and Hemodialysis

Pregabalin clearance is nearly proportional to creatinine clearance (CLcr). Dosage reduction in patients with renal dysfunction is necessary. Pregabalin is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, plasma pregabalin concentrations are reduced by approximately 50%. For patients on hemodialysis, dosing must be modified [see Dosage and Administration (2.7)].

Elderly

Pregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with age-related decreases in CLcr. Reduction of pregabalin dose may be required in patients who have age-related compromised renal function [see Dosage and Administration (2.7)].

Pediatric Pharmacokinetics

Pediatric Patients (3 months to less than 17 years of age)

Pregabalin pharmacokinetics were evaluated in 358 pediatric patients 3 months to less than 17 years of age with partial-onset seizures at dose levels of 2.5, 5, 10, and 15 mg/kg/day after single and multiple oral administration of pregabalin. Following oral administration, pregabalin reaches peak plasma concentration at 0.5 hours to 2 hours in the fasted state. Both apparent clearance (CL/F) and apparent volume of distribution increase as body weight increases. A weight-based dosing regimen is necessary to achieve pregabalin exposures in pediatric patients 1 month to less than 17 years of age similar to those observed in adults treated for partial-onset seizures at effective doses [see Dosage and Administration (2.4)]. The mean t ½is 3 to 4 hours in pediatric subjects up to 6 years of age, and 4 to 6 hours in those 7 years of age and older. Pregabalin CL/F is nearly proportional to CLcr (mL/min). The relationship is similar in pediatric and adult subjects. When normalized per body weight, CL/F (mL/min/kg) in pediatric subjects weighing less than 30 kg is approximately 40% higher in comparison to subjects weighing greater than or equal to 30 kg [see Dosage and Administration (2.4)].

Drug Interactions

In Vitro Studies

Pregabalin, at concentrations that were, in general, 10-times those attained in clinical trials, does not inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzyme systems. In vitro drug interaction studies demonstrate that pregabalin does not induce CYP1A2 or CYP3A4 activity. Therefore, an increase in the metabolism of coadministered CYP1A2 substrates (e.g. theophylline, caffeine) or CYP3A4 substrates (e.g., midazolam, testosterone) is not anticipated.

In Vivo Studies

The drug interaction studies described in this section were conducted in healthy adults, and across various patient populations.

Gabapentin

The pharmacokinetic interactions of pregabalin and gabapentin were investigated in 12 healthy subjects following concomitant single-dose administration of 100-mg pregabalin and 300-mg gabapentin and in 18 healthy subjects following concomitant multiple-dose administration of 200-mg pregabalin every 8 hours and 400-mg gabapentin every 8 hours. Gabapentin pharmacokinetics following single- and multiple-dose administration were unaltered by pregabalin coadministration. The extent of pregabalin absorption was unaffected by gabapentin coadministration, although there was a small reduction in rate of absorption.

Oral Contraceptive

Pregabalin coadministration (200 mg three times a day) had no effect on the steady-state pharmacokinetics of norethindrone and ethinyl estradiol (1 mg/35 μg, respectively) in healthy subjects.

Lorazepam

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of lorazepam single-dose pharmacokinetics and single-dose administration of lorazepam (1 mg) had no effect on the steady-state pharmacokinetics of pregabalin.

Oxycodone

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of oxycodone single-dose pharmacokinetics. Single-dose administration of oxycodone (10 mg) had no effect on the steady-state pharmacokinetics of pregabalin.

Ethanol

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of ethanol single-dose pharmacokinetics and single-dose administration of ethanol (0.7 g /kg) had no effect on the steady-state pharmacokinetics of pregabalin.

Phenytoin, carbamazepine, valproic acid, and lamotrigine

Steady-state trough plasma concentrations of phenytoin, carbamazepine and carbamazepine 10, 11 epoxide, valproic acid, and lamotrigine were not affected by concomitant pregabalin (200 mg three times a day) administration.

Population pharmacokinetic analyses in patients treated with pregabalin and various concomitant medications suggest the following:

<div class="scrollingtable"><table class="Noautorules" width="548"> <col width="227"/> <col width="321"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Toprule"><span class="Bold">Therapeutic Class</span> <br/> </td><td align="left" class="Botrule Toprule"><span class="Bold">Specific concomitant drug studied</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule" colspan="2"><span class="Bold"><span class="Italics">Concomitant drug has no effect on the pharmacokinetics of pregabalin</span></span> <br/> </td> </tr> <tr> <td align="left">Hypoglycemics <br/> </td><td align="left">Glyburide, insulin, metformin <br/> </td> </tr> <tr> <td align="left" class="Botrule">Diuretics <br/> </td><td align="left" class="Botrule">Furosemide <br/> </td> </tr> <tr> <td align="left" class="Botrule">Antiepiletic Drugs <br/> </td><td align="left" class="Botrule">Tiagabine <br/> </td> </tr> <tr> <td align="left" class="Botrule" colspan="2"><span class="Bold"><span class="Italics">Concomitant drug has no effect on the pharmacokinetics of pregabalin and pregabalin has no effect on the pharmacokinetics of concomitant drug</span></span> <br/> </td> </tr> <tr> <td align="left" class="Botrule">Antiepiletic Drugs <br/> </td><td align="left" class="Botrule">Carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, valproic acid <br/> </td> </tr> </tbody> </table></div>

Carcinogenesis

A dose-dependent increase in the incidence of malignant vascular tumors (hemangiosarcomas) was observed in two strains of mice (B6C3F1 and CD-1) given pregabalin (200, 1000, or 5000 mg/kg) in the diet for two years. Plasma pregabalin exposure (AUC) in mice receiving the lowest dose that increased hemangiosarcomas was approximately equal to the human exposure at the maximum recommended dose (MRD) of 600 mg/day. A no-effect dose for induction of hemangiosarcomas in mice was not established. No evidence of carcinogenicity was seen in two studies in Wistar rats following dietary administration of pregabalin for two years at doses (50, 150, or 450 mg/kg in males and 100, 300, or 900 mg/kg in females) that were associated with plasma exposures in males and females up to approximately 14 and 24 times, respectively, human exposure at the MRD.

Mutagenesis

Pregabalin was not mutagenic in bacteria or in mammalian cells in vitro, was not clastogenic in mammalian systems in vitroand in vivo, and did not induce unscheduled DNA synthesis in mouse or rat hepatocytes.

Impairment of Fertility

In fertility studies in which male rats were orally administered pregabalin (50 to 2500 mg/kg) prior to and during mating with untreated females, a number of adverse reproductive and developmental effects were observed. These included decreased sperm counts and sperm motility, increased sperm abnormalities, reduced fertility, increased preimplantation embryo loss, decreased litter size, decreased fetal body weights, and an increased incidence of fetal abnormalities. Effects on sperm and fertility parameters were reversible in studies of this duration (3–4 months). The no-effect dose for male reproductive toxicity in these studies (100 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately 3 times human exposure at the maximum recommended dose (MRD) of 600 mg/day.

In addition, adverse reactions on reproductive organ (testes, epididymides) histopathology were observed in male rats exposed to pregabalin (500 to 1250 mg/kg) in general toxicology studies of four weeks or greater duration. The no-effect dose for male reproductive organ histopathology in rats (250 mg/kg) was associated with a plasma exposure approximately 8 times human exposure at the MRD.

In a fertility study in which female rats were given pregabalin (500, 1250, or 2500 mg/kg) orally prior to and during mating and early gestation, disrupted estrous cyclicity and an increased number of days to mating were seen at all doses, and embryolethality occurred at the highest dose.The low dose in this study produced a plasma exposure approximately 9 times that in humans receiving the MRD. A no-effect dose for female reproductive toxicity in rats was not established.

Dermatopathy

Skin lesions ranging from erythema to necrosis were seen in repeated-dose toxicology studies in both rats and monkeys. The etiology of these skin lesions is unknown. At the maximum recommended human dose (MRD) of 600 mg/day, there is a 2-fold safety margin for the dermatological lesions. The more severe dermatopathies involving necrosis were associated with pregabalin exposures (as expressed by plasma AUCs) of approximately 3 to 8 times those achieved in humans given the MRD. No increase in incidence of skin lesions was observed in clinical studies.

Ocular Lesions

Ocular lesions (characterized by retinal atrophy [including loss of photoreceptor cells] and/or corneal inflammation/mineralization) were observed in two lifetime carcinogenicity studies in Wistar rats. These findings were observed at plasma pregabalin exposures (AUC) greater than or equal to 2 times those achieved in humans given the maximum recommended dose of 600 mg/day. A no-effect dose for ocular lesions was not established. Similar lesions were not observed in lifetime carcinogenicity studies in two strains of mice or in monkeys treated for 1 year.

The efficacy of the maximum recommended dose of pregabalin capsules for the management of neuropathic pain associated with diabetic peripheral neuropathy was established in three double-blind, placebo-controlled, multicenter studies with three times a day dosing, two of which studied the maximum recommended dose. Patients were enrolled with either Type 1 or Type 2 diabetes mellitus and a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for 1 to 5 years. A total of 89% of patients completed Studies DPN 1 and DPN 2. The patients had a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). The baseline mean pain scores across the two studies ranged from 6.1 to 6.7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.

Study DPN 1: This 5-week study compared pregabalin capsules 25, 100 or 200 mg three times a day with placebo. Treatment with pregabalin capsules 100 and 200 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. There was no evidence of a greater effect on pain scores of the 200 mg three times a day dose than the 100 mg three times a day dose, but there was evidence of dose dependent adverse reactions [see Adverse Reactions (6.1)].For a range of levels of improvement in pain intensity from baseline to study endpoint, Figure 1 shows the fraction of patients achieving that level of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 1: Patients Achieving Various Levels of Improvement in Pain Intensity – Study DPN 1

Study DPN 2: This 8-week study compared pregabalin capsules 100 mg three times a day with placebo. Treatment with pregabalin capsules 100 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 2 shows the fraction of patients achieving that level of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 2: Patients Achieving Various Levels of Improvement in Pain Intensity – Study DPN 2

The efficacy of pregabalin capsules for the management of postherpetic neuralgia was established in three double-blind, placebo-controlled, multicenter studies. These studies enrolled patients with neuralgia persisting for at least 3 months following healing of herpes zoster rash and a minimum baseline score of greater than or equal to 4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). Seventy-three percent of patients completed the studies. The baseline mean pain scores across the 3 studies ranged from 6 to 7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.

Study PHN 1:This 13-week study compared pregabalin capsules 75, 150, and 300 mg twice daily with placebo. Patients with creatinine clearance (CLcr) between 30 to 60 mL/min were randomized to 75 mg, 150 mg, or placebo twice daily. Patients with creatinine clearance greater than 60 mL/min were randomized to 75 mg, 150 mg, 300 mg or placebo twice daily. In patients with creatinine clearance greater than 60 mL/min treatment with all doses of pregabalin capsules statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. Despite differences in dosing based on renal function, patients with creatinine clearance between 30 to 60 mL/min tolerated pregabalin capsules less well than patients with creatinine clearance greater than 60 mL/min as evidenced by higher rates of discontinuation due to adverse reactions. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 3 shows the fraction of patients achieving that level of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 3: Patients Achieving Various Levels of Improvement in Pain Intensity– Study PHN 1

Study PHN 2:This 8-week study compared pregabalin capsules 100 or 200 mg three times a day with placebo, with doses assigned based on creatinine clearance. Patients with creatinine clearance between 30 to 60 mL/min were treated with 100 mg three times a day, and patients with creatinine clearance greater than 60 mL/min were treated with 200 mg three times daily. Treatment with pregabalin capsules statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 4 shows the fraction of patients achieving those levels of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 4: Patients Achieving Various Levels of Improvement in Pain Intensity – Study PHN 2

Study PHN 3:This 8-week study compared pregabalin capsules 50 or 100 mg three times a day with placebo with doses assigned regardless of creatinine clearance. Treatment with pregabalin capsules 50 and 100 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. Patients with creatinine clearance between 30 to 60 mL/min tolerated pregabalin capsules less well than patients with creatinine clearance greater than 60 mL/min as evidenced by markedly higher rates of discontinuation due to adverse reactions. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 5 shows the fraction of patients achieving that level of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 5:Patients Achieving Various Levels of Improvement in Pain Intensity– Study PHN 3

Adjunctive Therapy for Partial-Onset Seizures in Adult Patients

The efficacy of pregabalin capsules as adjunctive therapy for partial-onset seizures in adult patients was established in three 12-week, randomized, double-blind, placebo-controlled, multicenter studies. Patients were enrolled who had partial onset seizures with or without secondary generalization and were not adequately controlled with 1 to 3 concomitant antiepileptic drugs (AEDs). Patients taking gabapentin were required to discontinue gabapentin treatment 1 week prior to entering baseline. During an 8-week baseline period, patients had to experience at least 6 partial onset seizures with no seizure-free period exceeding 4 weeks. The mean duration of epilepsy was 25 years in these 3 studies and the mean and median baseline seizure frequencies were 22.5 and 10 seizures per month, respectively. Approximately half of the patients were taking 2 concurrent AEDs at baseline. Among the pregabalin capsules -treated patients, 80% completed the double-blind phase of the studies.

Table 11 shows median baseline seizure rates and median percent reduction in seizure frequency by dose.

Table 11. Seizure Response in Controlled, Adjunctive Epilepsy Studies in Adults

<div class="scrollingtable"><table class="Noautorules" width="614"> <col width="123"/> <col width="85"/> <col width="47"/> <col width="123"/> <col width="142"/> <col width="95"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Daily Dose of Pregabalin</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Dosing Regimen</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">N</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Baseline Seizure Frequency/mo</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Median % Change from Baseline</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">p-value, vs. placebo</span> <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule" valign="top"><span class="Bold">Study E1</span> <br/> </td><td align="left" class="Rrule" valign="top"> <br/> </td><td align="left" class="Rrule" valign="top"> <br/> </td><td align="left" class="Rrule" valign="top"> <br/> </td><td align="left" class="Rrule" valign="top"> <br/> </td><td align="left" class="Rrule" valign="top"> <br/> </td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">Placebo <br/> </td><td align="center" class="Rrule" valign="top">BID <br/> </td><td align="center" class="Rrule" valign="top">100 <br/> </td><td align="center" class="Rrule" valign="top">9.5 <br/> </td><td align="center" class="Rrule" valign="top">0 <br/> </td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">50 mg/day <br/> </td><td align="center" class="Rrule" valign="top">BID <br/> </td><td align="center" class="Rrule" valign="top">88 <br/> </td><td align="center" class="Rrule" valign="top">10.3 <br/> </td><td align="center" class="Rrule" valign="top">-9 <br/> </td><td align="center" class="Rrule" valign="top">0.4230 <br/> </td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">150 mg/day <br/> </td><td align="center" class="Rrule" valign="top">BID <br/> </td><td align="center" class="Rrule" valign="top">86 <br/> </td><td align="center" class="Rrule" valign="top">8.8 <br/> </td><td align="center" class="Rrule" valign="top">-35 <br/> </td><td align="center" class="Rrule" valign="top">0.0001 <br/> </td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">300 mg/day <br/> </td><td align="center" class="Rrule" valign="top">BID <br/> </td><td align="center" class="Rrule" valign="top">90 <br/> </td><td align="center" class="Rrule" valign="top">9.8 <br/> </td><td align="center" class="Rrule" valign="top">-37 <br/> </td><td align="center" class="Rrule" valign="top">0.0001 <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top">600 mg/day <br/> </td><td align="center" class="Botrule Rrule" valign="top">BID <br/> </td><td align="center" class="Botrule Rrule" valign="top">89 <br/> </td><td align="center" class="Botrule Rrule" valign="top">9.0 <br/> </td><td align="center" class="Botrule Rrule" valign="top">-51 <br/> </td><td align="center" class="Botrule Rrule" valign="top">0.0001 <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule" valign="top"><span class="Bold">Study E2</span> <br/> </td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">Placebo <br/> </td><td align="center" class="Rrule" valign="top">TID <br/> </td><td align="center" class="Rrule" valign="top">96 <br/> </td><td align="center" class="Rrule" valign="top">9.3 <br/> </td><td align="center" class="Rrule" valign="top">1 <br/> </td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">150 mg/day <br/> </td><td align="center" class="Rrule" valign="top">TID <br/> </td><td align="center" class="Rrule" valign="top">99 <br/> </td><td align="center" class="Rrule" valign="top">11.5 <br/> </td><td align="center" class="Rrule" valign="top">-17 <br/> </td><td align="center" class="Rrule" valign="top">0.0007 <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top">600 mg/day <br/> </td><td align="center" class="Botrule Rrule" valign="top">TID <br/> </td><td align="center" class="Botrule Rrule" valign="top">92 <br/> </td><td align="center" class="Botrule Rrule" valign="top">12.3 <br/> </td><td align="center" class="Botrule Rrule" valign="top">-43 <br/> </td><td align="center" class="Botrule Rrule" valign="top">0.0001 <br/> </td> </tr> <tr> <td align="left" class="Lrule Rrule" valign="top"><span class="Bold">Study E3</span> <br/> </td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">Placebo <br/> </td><td align="center" class="Rrule" valign="top">BID/TID <br/> </td><td align="center" class="Rrule" valign="top">98 <br/> </td><td align="center" class="Rrule" valign="top">11 <br/> </td><td align="center" class="Rrule" valign="top">-1 <br/> </td><td class="Rrule" valign="top"></td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="top">600 mg/day <br/> </td><td align="center" class="Rrule" valign="top">BID <br/> </td><td align="center" class="Rrule" valign="top">103 <br/> </td><td align="center" class="Rrule" valign="top">9.5 <br/> </td><td align="center" class="Rrule" valign="top">-36 <br/> </td><td align="center" class="Rrule" valign="top">0.0001 <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top">600 mg/day <br/> </td><td align="center" class="Botrule Rrule" valign="top">TID <br/> </td><td align="center" class="Botrule Rrule" valign="top">111 <br/> </td><td align="center" class="Botrule Rrule" valign="top">10 <br/> </td><td align="center" class="Botrule Rrule" valign="top">-48 <br/> </td><td align="center" class="Botrule Rrule" valign="top">0.0001 <br/> </td> </tr> </tbody> </table></div>

In the first study (E1), there was evidence of a dose-response relationship for total daily doses of pregabalin capsules between 150 and 600 mg/day; a dose of 50 mg/day was not effective. In the first study (E1), each daily dose was divided into two equal doses (twice a day dosing). In the second study (E2), each daily dose was divided into three equal doses (three times a day dosing). In the third study (E3), the same total daily dose was divided into two equal doses for one group (twice a day dosing) and three equal doses for another group (three times a day dosing). While the three times a day dosing group in Study E3 performed numerically better than the twice a day dosing group, this difference was small and not statistically significant.

A secondary outcome measure included the responder rate (proportion of patients with greater than or equal to 50% reduction from baseline in partial seizure frequency). The following figure displays responder rate by dose for two of the studies.

Figure 6:Responder rate by Adjunctive Epilepsy Study

Figure 7:Seizure Reduction by Dose (All Partial-Onset Seizures) for Studies E1, E2, and E3

Subset evaluations of the antiseizure efficacy of pregabalin capsules showed no clinically important differences as a function of age, gender, or race.

Adjunctive Therapy for Partial-Onset Seizures in Pediatric Patients 4 to Less Than 17 Years of Age

The efficacy of pregabalin capsules as adjunctive therapy in partial-onset seizures was established in a 12- week, randomized, double-blind, placebo-controlled, multicenter study in pediatric patients 4 years to less than 17 years of age with partial-onset seizures with or without secondary generalization. During an 8-week baseline period, patients had to experience at least 6 partial-onset seizures with no seizure-free period exceeding 4 weeks. The mean duration of epilepsy was 6 years and the mean and median baseline seizure frequencies were 57 and 18 seizures per month, respectively. Approximately 74% of the patients were taking 2 to 3 concurrent AEDs at baseline. Among the pregabalin capsules -treated patients, 87% completed the double-blind phase of the study.

In this study pregabalin capsules 2.5 mg/kg/day (maximum 150 mg/day) and 10 mg/kg/day (maximum 600 mg/day) were compared to placebo. Administration of each daily dose was divided into two equal doses (twice a day dosing). Because of higher weight-normalized clearance in patients with body weight less than 30 kg [see Clinical Pharmacology (12.3)] , the pregabalin capsules dose was increased by 40% to 3.5 mg/kg/day for patients weighing less than 30 kg randomized to the 2.5 mg/kg/day group or to 14 mg/kg/day for patients randomized to the 10 mg/kg/day group.

Table 12 shows median baseline seizure rates, median percent change from baseline in seizure rates, and percent difference relative to placebo (derived from the primary analysis model) by dose.

<div class="scrollingtable"><table class="Noautorules" width="925"> <caption> <span>Table 12. Seizure Response in Controlled Adjunctive Partial-Onset Seizure Study in Pediatric Patients 4 to Less Than 17 Years of Age</span> </caption> <col width="213"/> <col width="71"/> <col width="185"/> <col width="157"/> <col width="157"/> <col width="142"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"><span class="Bold">Daily Dose of pregabalin capsules</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">N</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">Median Baseline Seizure Frequency/28 days</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">Median % Change from Baseline</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">% Difference Relative to Placebo</span> <br/> </td><td align="left" class="Botrule Rrule Toprule"><span class="Bold">p-value, versus placebo</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Placebo <br/> </td><td align="center" class="Botrule Rrule">93 <br/> </td><td align="center" class="Botrule Rrule">16.5 <br/> </td><td align="center" class="Botrule Rrule">-16.9 <br/> </td><td align="center" class="Botrule Rrule">Not applicable <br/> </td><td class="Botrule Rrule"></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">2.5 mg/kg/day (BID) <span class="Sup">a</span> <br/> </td><td align="center" class="Botrule Rrule">104 <br/> </td><td align="center" class="Botrule Rrule">23.8 <br/> </td><td align="center" class="Botrule Rrule">-27.3 <br/> </td><td align="center" class="Botrule Rrule">-10.5 <br/> </td><td align="center" class="Botrule Rrule">0.2577 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">10 mg/kg/day <br/> (BID) <span class="Sup">b</span> <br/> </td><td align="center" class="Botrule Rrule">97 <br/> </td><td align="center" class="Botrule Rrule">17.5 <br/> </td><td align="center" class="Botrule Rrule">-37.1 <br/> </td><td align="center" class="Botrule Rrule">-21.0 <br/> </td><td align="center" class="Botrule Rrule">0.0185 <br/> </td> </tr> </tbody> </table></div>

Abbreviations: BID=twice daily; N=number.

a. 2.5 mg/kg/day: Maximum dose 150 mg/day. Includes patients less than 30 kg for whom dose was adjusted to 3.5 mg/kg/day.

b. 10 mg/kg/day: Maximum dose 600 mg/day. Includes patients less than 30 kg for whom dose was adjusted to 14 mg/kg/day      

There was evidence of a dose-response relationship for total daily doses of pregabalin capsules between 2.5 mg/kg/day and 10 mg/kg/day. A significant improvement in seizure rate was observed for pregabalin capsules 10 mg/kg/day group compared with placebo. While the 2.5 mg/kg/day group performed numerically better than placebo, this difference was not statistically significant.

A key secondary efficacy measure, the responder rate (proportion of patients with greater than or equal to 50% reduction from baseline in partial seizure frequency) showed improvements for pregabalin capsules groups compared with placebo. The following figure displays responder rate by dose:

Figure 8:Responder Rate (Greater than or Equal to 50% Reduction)

Adjunctive Therapy for Partial-Onset Seizures in Pediatric Patients 1 Month to Less Than 4 Years of Age

The efficacy of pregabalin capsules as adjunctive therapy in partial-onset seizures was established in a 14- day, randomized, double-blind, placebo-controlled, multicenter study in children 1 month to less than 4 years of age with partial-onset seizures with or without secondary generalization. The youngest patient evaluated was 3 months of age. During a 48- to 72-hour baseline video electroencephalogram (EEG), patients had to experience at least 2 partial-onset seizures. The mean duration of epilepsy at baseline was 1.6 years and the mean and median baseline seizure frequencies were 12.2 and 4.4 seizures per day, respectively. Approximately 33%, 50%, and 17% of patients were taking 1, 2, or 3 concurrent AEDs at baseline, respectively. Among the pregabalin capsules -treated patients, 97% completed the double-blind phase of the study.

In this study, pregabalin capsules 7 mg/kg/day and 14 mg/kg/day were compared to placebo. Administration of each daily dose was divided into three equal doses (three times a day dosing). The primary endpoint was the 24-hour partial-onset seizure rate based on the comparison of the baseline video EEG to a repeat 48-72 hour video EEG performed at the end of 14 days of double-blind treatment.

Table 13 shows median baseline seizure rates, median percent change from baseline in seizure rates, and percent difference relative to placebo (derived from the primary analysis model) by dose.

<div class="scrollingtable"><table class="Noautorules" width="996"> <caption> <span>Table 13. Seizure Response in Controlled Adjunctive Partial-Onset Seizure Study in Pediatric Patients 1 Month to Less Than 4 Years of Age</span> </caption> <col width="203"/> <col width="72"/> <col width="188"/> <col width="171"/> <col width="209"/> <col width="153"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Daily Dose</span> <br/> <span class="Bold">of pregabalin capsules</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">N</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Median Baseline</span> <br/> <span class="Bold">Seizure Frequency</span> <br/> <span class="Bold">/24 hours</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">Median % Change from</span> <br/> <span class="Bold">Baseline</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">% Difference Relative to Placebo</span> <br/> </td><td align="center" class="Botrule Rrule Toprule"><span class="Bold">p-value, versus</span> <br/> <span class="Bold">placebo</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">Placebo <br/> </td><td align="center" class="Botrule Rrule">53 <br/> </td><td align="center" class="Botrule Rrule">2.9 <br/> </td><td align="center" class="Botrule Rrule">22.2 <br/> </td><td align="center" class="Botrule Rrule">Not applicable <br/> </td><td class="Botrule Rrule"></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">7 mg/kg/day <br/> </td><td align="center" class="Botrule Rrule">59 <br/> </td><td align="center" class="Botrule Rrule">4.7 <br/> </td><td align="center" class="Botrule Rrule">16.8 <br/> </td><td align="center" class="Botrule Rrule">15.1 <br/> </td><td align="center" class="Botrule Rrule">0.4606 <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule">14 mg/kg/day <br/> </td><td align="center" class="Botrule Rrule">28 <br/> </td><td align="center" class="Botrule Rrule">5.4 <br/> </td><td align="center" class="Botrule Rrule">70 <br/> </td><td align="center" class="Botrule Rrule">-43.9 <br/> </td><td align="center" class="Botrule Rrule">0.0223 <br/> </td> </tr> </tbody> </table></div>

Abbreviations: N=number of patients

A significant improvement in partial-onset seizure rate was observed for pregabalin capsules 14 mg/kg/day group compared with placebo. Patients treated with pregabalin capsules 7 mg/kg/day did not show improvement relative to placebo.

Responder rates (≥50% or greater reduction in partial-onset seizure frequency) were a secondary efficacy parameter; patients treated with pregabalin capsules 14 mg/kg/day showed numerical improvement compared with placebo, while patients treated with pregabalin capsules 7 mg/kg/day did not show improvement relative to placebo: the responder rates were 53.6%, 30.5%, and 41.5% for pregabalin capsules 14 mg/kg/day, pregabalin capsules 7 mg/kg/day, and placebo, respectively.

The efficacy of pregabalin capsules for management of fibromyalgia was established in one 14-week, double-blind, placebo-controlled, multicenter study (F1) and one six-month, randomized withdrawal study (F2). Studies F1 and F2 enrolled patients with a diagnosis of fibromyalgia using the American College of Rheumatology (ACR) criteria (history of widespread pain for 3 months, and pain present at 11 or more of the 18 specific tender point sites). The studies showed a reduction in pain by visual analog scale. In addition, improvement was demonstrated based on a patient global assessment (PGIC), and on the Fibromyalgia Impact Questionnaire (FIQ).

Study F1:This 14-week study compared pregabalin capsules total daily doses of 300 mg, 450 mg and 600 mg with placebo. Patients were enrolled with a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numeric pain rating scale and a score of greater than or equal to 40 mm on the 100 mm pain visual analog scale (VAS). The baseline mean pain score in this trial was 6.7. Responders to placebo in an initial one-week run-in phase were not randomized into subsequent phases of the study. A total of 64% of patients randomized to pregabalin capsules completed the study. There was no evidence of a greater effect on pain scores of the 600 mg daily dose than the 450 mg daily dose, but there was evidence of dose-dependent adverse reactions [see Adverse Reactions (6.1)]. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study. The results are summarized in Figure 9 and Table 14.

For various levels of improvement in pain intensity from baseline to study endpoint, Figure 9 shows the fraction of patients achieving that level of improvement. The figure is cumulative. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.

Figure 9:Patients Achieving Various Levels of Improvement in Pain Intensity–Fibromyalgia Study F1

<div class="scrollingtable"><table class="Noautorules" width="360"> <caption> <span>Table 14. Patient Global Response in Fibromyalgia Study F1</span> </caption> <col width="120"/> <col width="120"/> <col width="120"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Patient Global Impression of Change</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><span class="Bold">Treatment Group (mg/day)</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">% Any Improvement</span> <br/> </td><td align="center" class="Botrule Rrule"><span class="Bold">95% CI</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">Placebo <br/> </td><td align="center" class="Botrule Rrule" valign="top">47.6 <br/> </td><td align="center" class="Botrule Rrule" valign="top">(40.0,55.2) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">PGB 300 <br/> </td><td align="center" class="Botrule Rrule" valign="top">68.1 <br/> </td><td align="center" class="Botrule Rrule" valign="top">(60.9, 75.3) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">PGB 450 <br/> </td><td align="center" class="Botrule Rrule" valign="top">77.8 <br/> </td><td align="center" class="Botrule Rrule" valign="top">(71.5, 84.0) <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top">PGB 600 <br/> </td><td align="center" class="Botrule Rrule" valign="top">66.1 <br/> </td><td align="center" class="Botrule Rrule" valign="top">(59.1, 73.1) <br/> </td> </tr> </tbody> </table></div>

PGB = Pregabalin

Study F2: This randomized withdrawal study compared pregabalin capsules with placebo. Patients were titrated during a 6-week open-label dose optimization phase to a total daily dose of 300 mg, 450 mg, or 600 mg. Patients were considered to be responders if they had both: 1) at least a 50% reduction in pain (VAS) and, 2) rated their overall improvement on the PGIC as "much improved" or "very much improved." Those who responded to treatment were then randomized in the double-blind treatment phase to either the dose achieved in the open-label phase or to placebo. Patients were treated for up to 6 months following randomization. Efficacy was assessed by time to loss of therapeutic response, defined as 1) less than 30% reduction in pain (VAS) from open-label baseline during two consecutive visits of the double-blind phase, or 2) worsening of FM symptoms necessitating an alternative treatment. Fifty-four percent of patients were able to titrate to an effective and tolerable dose of pregabalin capsules during the 6-week open-label phase. Of the patients entering the randomized treatment phase assigned to remain on pregabalin capsules, 38% of patients completed 26 weeks of treatment versus 19% of placebo-treated patients.

When considering return of pain or withdrawal due to adverse events as loss of response (LTR), treatment with pregabalin capsules resulted in a longer time to loss of therapeutic response than treatment with placebo. Fifty-three percent of the pregabalin-treated subjects compared to 33% of placebo patients remained on study drug and maintained a therapeutic response to Week 26 of the study. Treatment with pregabalin capsules also resulted in a longer time to loss of response based on the FIQ 1, and longer time to loss of overall assessment of patient status, as measured by the PGIC 2.

1Time to worsening of the FIQ was defined as the time to a 1-point increase from double-blind baseline in each of the subscales, and a 5-point increase from double-blind baseline evaluation for the FIQ total score.

2Time to PGIC lack of improvement was defined as time to PGIC assessments indicating less improvement than "much improvement."

Figure 10:Time to Loss of Therapeutic Response, Fibromyalgia Study F2 (Kaplan-Meier Analysis)

The efficacy of pregabalin capsules for the management of neuropathic pain associated with spinal cord injury was established in two double-blind, placebo-controlled, multicenter studies. Patients were enrolled with neuropathic pain associated with spinal cord injury that persisted continuously for at least three months or with relapses and remissions for at least six months. A total of 63% of patients completed study 1 and 84% completed study 2. The patients had a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). The baseline mean pain scores across the two studies ranged from 6.5 to 6.7.

Patients were allowed to take opioids, non-opioid analgesics, antiepileptic drugs, muscle relaxants, and antidepressant drugs if the dose was stable for 30 days prior to screening. Patients were allowed to take acetaminophen and nonsteroidal anti-inflammatory drugs during the studies.

Study SCI 1:This 12-week, randomized, double-blind, parallel-group, multicenter, flexible dose (150-600 mg/day) study compared pregabalin with placebo. The 12-week study consisted of a 3-week dose adjustment phase and a 9-week dose maintenance phase. Treatment with pregabalin capsules 150–600 mg/day statistically significantly improved the endpoint weekly mean pain score, and increased the proportion of patients with at least a 30% and 50% reduction in pain score from baseline. The fraction of patients achieving various levels of improvement in pain intensity from baseline to Week 12 is presented in Figure 11. Some patients experienced a decrease in pain as early as week 1, which persisted throughout the study.

Figure 11: Patients Achieving Various Levels of Improvement in Pain Intensity – Study SCI 1

Study SCI 2:This 16-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, flexible dose (150–600 mg/day, in increments of 150 mg) study compared the efficacy, safety and tolerability of pregabalin with placebo. The 16-week study consisted of a 4-week dose adjustment phase and a 12-week dose maintenance phase. Treatment with pregabalin capsules statistically significantly improved the endpoint weekly mean pain score, and increased the proportion of patients with at least a 30% and 50% reduction in pain score from baseline. The fraction of patients achieving various levels of improvement in pain intensity from baseline to Week 16 is presented in Figure 12. Some patients experienced a decrease in pain as early as week 1, which persisted throughout the study.

Figure 12: Patients Achieving Various Levels of Improvement in Pain Intensity – Study SCI 2

25 mg capsules:

{ "type": "p", "children": [], "text": "\n25 mg capsules:\n" }

Size "4", white, hard gelatin capsule printed with black ink "CW" on cap and "25" on body, containing white to off–white crystalline powder; available in:

{ "type": "p", "children": [], "text": "Size \"4\", white, hard gelatin capsule printed with black ink \"CW\" on cap and \"25\" on body, containing white to off–white crystalline powder; available in:" }

Bottles of 90:    NDC 82619-122-01

{ "type": "p", "children": [], "text": "Bottles of 90:    NDC 82619-122-01" }

50 mg capsules:

{ "type": "p", "children": [], "text": "\n50 mg capsules:\n" }

Size "3", white, hard gelatin capsule printed with black ink "CW" on cap and "50" on body, containing white to off–white crystalline powder; available in:

{ "type": "p", "children": [], "text": "Size \"3\", white, hard gelatin capsule printed with black ink \"CW\" on cap and \"50\" on body, containing white to off–white crystalline powder; available in:" }

Bottles of 90:    NDC 82619-123-01

{ "type": "p", "children": [], "text": "Bottles of 90:    NDC 82619-123-01" }

75 mg capsules:

{ "type": "p", "children": [], "text": "\n75 mg capsules:\n" }

Size "4", white body and orange cap, hard gelatin capsule printed with black ink "CW" on cap and "75" on body, containing white to off–white crystalline powder; available in:

{ "type": "p", "children": [], "text": "Size \"4\", white body and orange cap, hard gelatin capsule printed with black ink \"CW\" on cap and \"75\" on body, containing white to off–white crystalline powder; available in:" }

Bottles of 90:    NDC 82619-124-01

{ "type": "p", "children": [], "text": "Bottles of 90:    NDC 82619-124-01" }

100 mg capsules:

{ "type": "p", "children": [], "text": "\n100 mg capsules:\n" }

Size "3", orange, hard gelatin capsule printed with black ink "CW" on cap and "100" on body, containing white to off–white crystalline powder; available in:

{ "type": "p", "children": [], "text": "Size \"3\", orange, hard gelatin capsule printed with black ink \"CW\" on cap and \"100\" on body, containing white to off–white crystalline powder; available in:" }

Bottles of 90:   NDC 82619-125-01

{ "type": "p", "children": [], "text": "Bottles of 90:   NDC 82619-125-01" }

150 mg capsules:

{ "type": "p", "children": [], "text": "\n150 mg capsules:\n" }

Size "2", white, hard gelatin capsule printed with black ink "CW" on cap and "150" on body, containing white to off–white crystalline powder; available in:

{ "type": "p", "children": [], "text": "Size \"2\", white, hard gelatin capsule printed with black ink \"CW\" on cap and \"150\" on body, containing white to off–white crystalline powder; available in:" }

Bottles of 90:    NDC 82619-126-01

{ "type": "p", "children": [], "text": "Bottles of 90:    NDC 82619-126-01" }

200 mg capsules:

{ "type": "p", "children": [], "text": "\n200 mg capsules:\n" }

Size "1", light orange, hard gelatin capsule printed with black ink "CW" on cap and "200" on body, containing white to off–white crystalline powder; available in:

{ "type": "p", "children": [], "text": "Size \"1\", light orange, hard gelatin capsule printed with black ink \"CW\" on cap and \"200\" on body, containing white to off–white crystalline powder; available in:" }

Bottles of 90:    NDC 82619-127-01

{ "type": "p", "children": [], "text": "Bottles of 90:    NDC 82619-127-01" }

225 mg capsules:

{ "type": "p", "children": [], "text": "\n225 mg capsules:\n" }

Size "1", white body and light orange cap, hard gelatin capsule printed with black ink "CW"  on cap and "225" on body, containing white to off–white crystalline powder; available in:

{ "type": "p", "children": [], "text": "Size \"1\", white body and light orange cap, hard gelatin capsule printed with black ink \"CW\"  on cap and \"225\" on body, containing white to off–white crystalline powder; available in:" }

Bottles of 90:    NDC 82619-128-01

{ "type": "p", "children": [], "text": "Bottles of 90:    NDC 82619-128-01" }

300 mg capsules:

{ "type": "p", "children": [], "text": "\n300 mg capsules:\n" }

Size "0", white body and orange cap, hard gelatin capsule printed with black ink "CW" on cap and "300" on body, containing white to off–white crystalline powder; available in:

{ "type": "p", "children": [], "text": "Size \"0\", white body and orange cap, hard gelatin capsule printed with black ink \"CW\" on cap and \"300\" on body, containing white to off–white crystalline powder; available in:" }

Bottles of 90:    NDC 82619-129-01

{ "type": "p", "children": [], "text": "Bottles of 90:    NDC 82619-129-01" }

Storage and Handling

{ "type": "p", "children": [], "text": "Storage and Handling" }

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]." }

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

{ "type": "p", "children": [], "text": "\nAdvise the patient to read the FDA-approved patient labeling (Medication Guide)." }

Angioedema

{ "type": "p", "children": [], "text": "\nAngioedema\n" }

Advise patients that pregabalin capsules may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue pregabalin capsules and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients that pregabalin capsules may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue pregabalin capsules and immediately seek medical care if they experience these symptoms\n \n [see\n \n Warnings and Precautions (5.1)].\n \n \n" }

Hypersensitivity

{ "type": "p", "children": [], "text": "\nHypersensitivity\n" }

Advise patients that pregabalin capsules has been associated with hypersensitivity reactions such as wheezing, dyspnea, rash, hives, and blisters. Instruct patients to discontinue pregabalin capsules and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients that pregabalin capsules has been associated with hypersensitivity reactions such as wheezing, dyspnea, rash, hives, and blisters. Instruct patients to discontinue pregabalin capsules and immediately seek medical care if they experience these symptoms\n \n [see\n \n Warnings and Precautions (5.2)].\n \n \n" }

Suicidal Thinking and Behavior

{ "type": "p", "children": [], "text": "\nSuicidal Thinking and Behavior\n" }

Counsel patients, their caregivers, and families that AEDs, including pregabalin capsules, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to healthcare providers Also inform patients who plan to or have discontinued pregabalin capsules that suicidal thoughts and behavior can appear even after the drug is stopped [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Counsel patients, their caregivers, and families that AEDs, including pregabalin capsules, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to healthcare providers Also inform patients who plan to or have discontinued pregabalin capsules that suicidal thoughts and behavior can appear even after the drug is stopped\n \n [see\n \n Warnings and Precautions (5.3)].\n \n \n" }

Respiratory Depression

{ "type": "p", "children": [], "text": "\nRespiratory Depression\n" }

Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs\n \n [see\n \n Warnings and Precautions (5.5)].\n \n \n" }

Dizziness and Somnolence

{ "type": "p", "children": [], "text": "\nDizziness and Somnolence\n" }

Counsel patients that pregabalin capsules may cause dizziness, somnolence, blurred vision and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on pregabalin capsules to gauge whether or not it affects their mental, visual, and/or motor performance adversely [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Counsel patients that pregabalin capsules may cause dizziness, somnolence, blurred vision and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on pregabalin capsules to gauge whether or not it affects their mental, visual, and/or motor performance adversely\n \n [see\n \n Warnings and Precautions (5.6)].\n \n \n" }

CNS Depressants

{ "type": "p", "children": [], "text": "\nCNS Depressants\n" }

Inform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as respiratory depression, somnolence, and dizziness [see Warnings and Precautions ( 5.5, 5.6) and Drug Interactions (7)]. Advise patients to avoid consuming alcohol while taking pregabalin capsules, as pregabalin capsules may potentiate the impairments of motor skills and sedating effects of alcohol.

{ "type": "p", "children": [], "text": "Inform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as respiratory depression, somnolence, and dizziness\n \n [see Warnings and Precautions (\n \n 5.5,\n \n 5.6) and\n \n Drug Interactions (7)].\n \n Advise patients to avoid consuming alcohol while taking pregabalin capsules, as pregabalin capsules may potentiate the impairments of motor skills and sedating effects of alcohol.\n\n " }

Adverse Reactions with Abrupt or Rapid Discontinuation

{ "type": "p", "children": [], "text": "\nAdverse Reactions with Abrupt or Rapid Discontinuation\n" }

Advise patients to take pregabalin capsules as prescribed. Abrupt or rapid discontinuation may result in increased seizure frequency in patients with seizure disorders, and insomnia, nausea, headache, anxiety, hyperhidrosis, or diarrhea [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Advise patients to take pregabalin capsules as prescribed. Abrupt or rapid discontinuation may result in increased seizure frequency in patients with seizure disorders, and insomnia, nausea, headache, anxiety, hyperhidrosis, or diarrhea\n \n [see\n \n Warnings and Precautions (5.4)].\n \n \n" }

Missed Dose

{ "type": "p", "children": [], "text": "\nMissed Dose\n" }

Counsel patients if they miss a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should skip the missed dose and take the next dose at their regularly scheduled time. Instruct patients not to take two doses at the same time.

{ "type": "p", "children": [], "text": "Counsel patients if they miss a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should skip the missed dose and take the next dose at their regularly scheduled time. Instruct patients not to take two doses at the same time." }

Weight Gain and Edema

{ "type": "p", "children": [], "text": "\nWeight Gain and Edema\n" }

Counsel patients that pregabalin capsules may cause edema and weight gain. Advise patients that concomitant treatment with pregabalin capsules and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. For patients with preexisting cardiac conditions, this may increase the risk of heart failure [see Warnings and Precautions ( 5.7, 5.8)].

{ "type": "p", "children": [], "text": "Counsel patients that pregabalin capsules may cause edema and weight gain. Advise patients that concomitant treatment with pregabalin capsules and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. For patients with preexisting cardiac conditions, this may increase the risk of heart failure\n \n [see Warnings and Precautions (\n \n 5.7,\n \n 5.8)].\n \n \n" }

Ophthalmological Effects

{ "type": "p", "children": [], "text": "\nOphthalmological Effects\n" }

Counsel patients that pregabalin capsules may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician [see Warnings and Precautions (5.10)].

{ "type": "p", "children": [], "text": "Counsel patients that pregabalin capsules may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician\n \n [see\n \n Warnings and Precautions (5.10)].\n \n \n" }

Creatine Kinase Elevations

{ "type": "p", "children": [], "text": "\nCreatine Kinase Elevations\n" }

Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever [see Warnings and Precautions (5.11)].

{ "type": "p", "children": [], "text": "Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever\n \n [see\n \n Warnings and Precautions (5.11)].\n \n \n" }

Use in Pregnancy

{ "type": "p", "children": [], "text": "\nUse in Pregnancy\n" }

Instruct patients to inform their healthcare provider if they are pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy [see Use in Specific Populations (8.1)and (8.2)] .

{ "type": "p", "children": [], "text": "Instruct patients to inform their healthcare provider if they are pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy\n \n [see\n \n Use in Specific Populations (8.1)and\n \n (8.2)]\n \n .\n\n " }

Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233- 2334 [see Use in Specific Populations (8.1)].  

{ "type": "p", "children": [], "text": "Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233- 2334\n \n [see\n \n Use in Specific Populations (8.1)].\n \n  \n\n " }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Advise nursing mothers that breastfeeding is not recommended during treatment with pregabalin capsules [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise nursing mothers that breastfeeding is not recommended during treatment with pregabalin capsules\n \n [see\n \n Use in Specific Populations (8.2)].\n \n \n" }

Male Fertility

{ "type": "p", "children": [], "text": "\nMale Fertility\n" }

Inform men being treated with pregabalin capsules who plan to father a child of the potential risk of male-mediated teratogenicity. In preclinical studies in rats, pregabalin was associated with an increased risk of male-mediated teratogenicity. The clinical significance of this finding is uncertain [see Nonclinical Toxicology (13.1)and Use in Specific populations (8.3)] .

{ "type": "p", "children": [], "text": "Inform men being treated with pregabalin capsules who plan to father a child of the potential risk of male-mediated teratogenicity. In preclinical studies in rats, pregabalin was associated with an increased risk of male-mediated teratogenicity. The clinical significance of this finding is uncertain\n \n [see\n \n Nonclinical Toxicology (13.1)and\n \n Use in Specific populations (8.3)]\n \n .\n\n " }

Dermatopathy

{ "type": "p", "children": [], "text": "\nDermatopathy\n" }

Instruct diabetic patients to pay particular attention to skin integrity while being treated with pregabalin capsules and to inform their healthcare provider about any sores or skin problems. Some animals treated with pregabalin capsules developed skin ulcerations, although no increased incidence of skin lesions associated with pregabalin capsules was observed in clinical trials [see Nonclinical Toxicology (13.2)].  

{ "type": "p", "children": [], "text": "Instruct diabetic patients to pay particular attention to skin integrity while being treated with pregabalin capsules and to inform their healthcare provider about any sores or skin problems. Some animals treated with pregabalin capsules developed skin ulcerations, although no increased incidence of skin lesions associated with pregabalin capsules was observed in clinical trials\n \n [see\n \n Nonclinical Toxicology (13.2)].\n \n  \n\n " }

Revised: 06/2025

{ "type": "p", "children": [], "text": "Revised: 06/2025" }

Manufactured by:

{ "type": "p", "children": [], "text": "Manufactured by:" }

V-Ensure Pharma Technologies Pvt. Ltd

{ "type": "p", "children": [], "text": "\nV-Ensure Pharma Technologies Pvt. Ltd\n" }

Raigad, Maharashtra-410206, India.

{ "type": "p", "children": [], "text": "Raigad, Maharashtra-410206, India." }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Creekwood Pharmaceuticals LLC.

{ "type": "p", "children": [], "text": "\nCreekwood Pharmaceuticals LLC.\n" }

Parsippany, NJ 07054.

{ "type": "p", "children": [], "text": "Parsippany, NJ 07054." }

PA1220106

{ "type": "p", "children": [], "text": "PA1220106" }

Pregabalin (pree gab' a lin) Capsules, CV

{ "type": "p", "children": [], "text": "\nPregabalin (pree gab' a lin) Capsules, CV\n" }

Read this Medication Guide before you start taking pregabalin capsules and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about pregabalin capsules, ask your healthcare provider or pharmacist.

{ "type": "p", "children": [], "text": "Read this Medication Guide before you start taking pregabalin capsules and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about pregabalin capsules, ask your healthcare provider or pharmacist." }

What is the most important information I should know about pregabalin capsules?

{ "type": "p", "children": [], "text": "\nWhat is the most important information I should know about pregabalin capsules?\n" }

Pregabalin capsules may cause serious side effects including:

{ "type": "p", "children": [], "text": "\nPregabalin capsules may cause serious side effects including:\n" }

<div class="scrollingtable"><table class="Noautorules" width="591"> <col width="321"/> <col width="270"/> <tbody class="Headless"> <tr> <td valign="top"> <ul class="Disc"> <li> <span class="Bold">serious, even life-threatening, allergic reactions</span> </li> </ul> </td><td valign="top"> <ul class="Disc"> <li> <span class="Bold">swelling of your hands, legs and feet</span> </li> </ul> </td> </tr> <tr> <td valign="top"> <ul class="Disc"> <li> <span class="Bold">suicidal thoughts or actions</span> </li> </ul> </td><td valign="top"> <ul class="Disc"> <li> <span class="Bold">dizziness and sleepiness</span> </li> </ul> </td> </tr> <tr> <td valign="top"> <ul class="Disc"> <li> <span class="Bold">serious breathing problem</span> </li> </ul> </td><td align="left" valign="top"> <br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"591\">\n<col width=\"321\"/>\n<col width=\"270\"/>\n<tbody class=\"Headless\">\n<tr>\n<td valign=\"top\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">serious, even life-threatening, allergic reactions</span>\n</li>\n</ul>\n</td><td valign=\"top\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">swelling of your hands, legs and feet</span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td valign=\"top\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">suicidal thoughts or actions</span>\n</li>\n</ul>\n</td><td valign=\"top\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">dizziness and sleepiness</span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td valign=\"top\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">serious breathing problem</span>\n</li>\n</ul>\n</td><td align=\"left\" valign=\"top\">\n<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

These serious side effects are described below:

{ "type": "p", "children": [], "text": "\nThese serious side effects are described below:\n" }

●    Serious, even life-threatening, allergic reactions.

{ "type": "p", "children": [], "text": "\n●    Serious, even life-threatening, allergic reactions.\n" }

  Stop taking pregabalin capsules and call your healthcare provider right away if you have any of these signs of a serious allergic reaction:

{ "type": "p", "children": [], "text": "  Stop taking pregabalin capsules and call your healthcare provider right away if you have any of these signs of a serious allergic reaction:" }

○  swelling of your face, mouth, lips, gums, tongue, throat or neck

{ "type": "p", "children": [], "text": "○  swelling of your face, mouth, lips, gums, tongue, throat or neck" }

○  trouble breathing

{ "type": "p", "children": [], "text": "○  trouble breathing" }

○  rash, hives (raised bumps) or blisters

{ "type": "p", "children": [], "text": "○  rash, hives (raised bumps) or blisters" }

●    Like other antiepileptic drugs, pregabalin capsules may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.This can happen while you take pregabalin capsules or after stopping. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

{ "type": "p", "children": [], "text": "\n●    Like other antiepileptic drugs, pregabalin capsules may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.This can happen while you take pregabalin capsules or after stopping. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:\n\n " }

<div class="scrollingtable"><table class="Noautorules" width="628"> <col width="295"/> <col width="333"/> <tbody class="Headless"> <tr> <td align="left" valign="top">o  thoughts about suicide or dying <br/> o  attempts to commit suicide <br/> o  new or worse depression <br/> o  new or worse anxiety <br/> o  feeling agitated or restless <br/> o  panic attacks <br/> </td><td align="left" valign="top">o  trouble sleeping (insomnia) <br/> o  new or worse irritability <br/> o  acting aggressive, being angry, or violent <br/> o  acting on dangerous impulses <br/> o  an extreme increase in activity and talking (mania) <br/> o  other unusual changes in behavior or mood <br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"628\">\n<col width=\"295\"/>\n<col width=\"333\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" valign=\"top\">o  thoughts about suicide or dying \n <br/> o  attempts to commit suicide \n <br/> o  new or worse depression \n <br/> o  new or worse anxiety \n <br/> o  feeling agitated or restless \n <br/> o  panic attacks \n <br/>\n</td><td align=\"left\" valign=\"top\">o  trouble sleeping (insomnia) \n <br/> o  new or worse irritability \n <br/> o  acting aggressive, being angry, or violent \n <br/> o  acting on dangerous impulses \n <br/> o  an extreme increase in activity and talking (mania) \n <br/> o  other unusual changes in behavior or mood \n <br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

If you have suicidal thoughts or actions, do not stop pregabalin capsules without first talking to a healthcare provider.

{ "type": "p", "children": [], "text": "\nIf you have suicidal thoughts or actions, do not stop pregabalin capsules without first talking to a healthcare provider.\n" }

○   Stopping pregabalin capsules suddenly can cause serious problems.

{ "type": "p", "children": [], "text": "○   Stopping pregabalin capsules suddenly can cause serious problems." }

○   Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

{ "type": "p", "children": [], "text": "○   Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes." }

How can I watch for early symptoms of suicidal thoughts and actions?

{ "type": "p", "children": [], "text": "\nHow can I watch for early symptoms of suicidal thoughts and actions?\n" }

▪    Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

{ "type": "p", "children": [], "text": "▪    Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings." }

▪    Keep all follow-up visits with your healthcare provider as scheduled.

{ "type": "p", "children": [], "text": "▪    Keep all follow-up visits with your healthcare provider as scheduled." }

▪    Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

{ "type": "p", "children": [], "text": "▪    Call your healthcare provider between visits as needed, especially if you are worried about symptoms." }

●   Serious breathing problemscan occur when pregabalin capsules are taken with other medicines that can cause severe sleepiness or decreased awareness, or when it is taken by someone who already   has breathing problem. Watch for increased sleepiness or decreased breathing when starting pregabalin capsules or when the dose is increased. Get help right away if breathing problems occur.

{ "type": "p", "children": [], "text": "\n●   Serious breathing problemscan occur when pregabalin capsules are taken with other medicines that can cause severe sleepiness or decreased awareness, or when it is taken by someone who already   has breathing problem. Watch for increased sleepiness or decreased breathing when starting pregabalin capsules or when the dose is increased. Get help right away if breathing problems occur.\n\n " }

●   Swelling of your hands, legs and feet.This swelling can be a serious problem for people with heart problems.

{ "type": "p", "children": [], "text": "\n●   Swelling of your hands, legs and feet.This swelling can be a serious problem for people with heart problems.\n\n " }

●   Dizziness and sleepiness. Do not drive a car, work with machines, or do other dangerous activities until you know how pregabalin capsules affect you. Ask your healthcare provider about when it will be okay to do these activities.

{ "type": "p", "children": [], "text": "●  \n \n Dizziness and sleepiness. Do not drive a car, work with machines, or do other dangerous activities until you know how pregabalin capsules affect you. Ask your healthcare provider about when it will be okay to do these activities.\n\n " }

What are pregabalin capsules?

{ "type": "p", "children": [], "text": "\nWhat are pregabalin capsules?\n" }

Pregabalin capsules are a prescription medicine used in adults, 18 years of age and older to treat:

{ "type": "p", "children": [], "text": "Pregabalin capsules are a prescription medicine used in adults, 18 years of age and older to treat:" }

●   pain from damaged nerves (neuropathic pain) that happens with diabetes

{ "type": "p", "children": [], "text": "●   pain from damaged nerves (neuropathic pain) that happens with diabetes" }

●   pain from damaged nerves (neuropathic pain) that follows healing of shingles

{ "type": "p", "children": [], "text": "●   pain from damaged nerves (neuropathic pain) that follows healing of shingles" }

●   fibromyalgia (pain all over your body)

{ "type": "p", "children": [], "text": "●   fibromyalgia (pain all over your body)" }

●   pain from damaged nerves (neuropathic pain) that follows spinal cord injury

{ "type": "p", "children": [], "text": "●   pain from damaged nerves (neuropathic pain) that follows spinal cord injury" }

It is not known if pregabalin capsules are safe and effective in people under 18 years of age for the treatment of fibromyalgia and neuropathic pain with diabetes, shingles, or spinal cord injury.

{ "type": "p", "children": [], "text": "It is not known if pregabalin capsules are safe and effective in people under 18 years of age for the treatment of fibromyalgia and neuropathic pain with diabetes, shingles, or spinal cord injury." }

Pregabalin capsules are a prescription medicine used in people 1 month of age and older to treat:

{ "type": "p", "children": [], "text": "Pregabalin capsules are a prescription medicine used in people 1 month of age and older to treat:" }

●   partial-onset seizures when taken together with other seizure medicines.

{ "type": "p", "children": [], "text": "●   partial-onset seizures when taken together with other seizure medicines." }

For the treatment of partial-onset seizures when taken together with other seizure medicines, it is not known if pregabalin capsules are safe and effective in children under 1 month of age.

{ "type": "p", "children": [], "text": "For the treatment of partial-onset seizures when taken together with other seizure medicines, it is not known if pregabalin capsules are safe and effective in children under 1 month of age." }

Who should not take pregabalin capsules?

{ "type": "p", "children": [], "text": "\nWho should not take pregabalin capsules?\n" }

Do not take pregabalin capsules if you are allergic to pregabalin or any of the ingredients in pregabalin capsules.

{ "type": "p", "children": [], "text": "\nDo not take pregabalin capsules if you are allergic to pregabalin or any of the ingredients in pregabalin capsules.\n" }

See "What is the most important information I should know about pregabalin capsules?"for the signs of an allergic reaction.

{ "type": "p", "children": [], "text": "See\n \n \"What is the most important information I should know about pregabalin capsules?\"for the signs of an allergic reaction.\n\n " }

See the end of this Medication Guide for a complete list of ingredients in Pregabalin capsules.

{ "type": "p", "children": [], "text": "See the end of this Medication Guide for a complete list of ingredients in Pregabalin capsules." }

What should I tell my healthcare provider before taking pregabalin capsules?

{ "type": "p", "children": [], "text": "\nWhat should I tell my healthcare provider before taking pregabalin capsules?\n" }

Before taking pregabalin capsules, tell your healthcare provider about all your medical conditions, including if you:

{ "type": "p", "children": [], "text": "Before taking pregabalin capsules, tell your healthcare provider about all your medical conditions, including if you:" }

●   have or have had depression, mood problems or suicidal thoughts or behavior.

{ "type": "p", "children": [], "text": "●   have or have had depression, mood problems or suicidal thoughts or behavior." }

●   have breathing problems.

{ "type": "p", "children": [], "text": "●   have breathing problems." }

●   have kidney problems or get kidney dialysis.

{ "type": "p", "children": [], "text": "●   have kidney problems or get kidney dialysis." }

●   have heart problems including heart failure.

{ "type": "p", "children": [], "text": "●   have heart problems including heart failure." }

●   have a bleeding problem or a low blood platelet count.

{ "type": "p", "children": [], "text": "●   have a bleeding problem or a low blood platelet count." }

●   have abused prescription medicines, street drugs, or alcohol in the past.

{ "type": "p", "children": [], "text": "●   have abused prescription medicines, street drugs, or alcohol in the past." }

●   have ever had swelling of your face, mouth, tongue, lips, gums, neck, or throat (angioedema).

{ "type": "p", "children": [], "text": "●   have ever had swelling of your face, mouth, tongue, lips, gums, neck, or throat (angioedema)." }

●   plan to father a child. Animal studies have shown that pregabalin, the active ingredient in pregabalin capsules, made male animals less fertile and caused sperm to change. Also, in animal studies, birth defects were seen in the offspring (babies) of male animals treated with pregabalin. It is not known if these problems can happen in people who take pregabalin capsules.

{ "type": "p", "children": [], "text": "●   plan to father a child. Animal studies have shown that pregabalin, the active ingredient in pregabalin capsules, made male animals less fertile and caused sperm to change. Also, in animal studies, birth defects were seen in the offspring (babies) of male animals treated with pregabalin. It is not known if these problems can happen in people who take pregabalin capsules." }

●   are pregnant or plan to become pregnant.  Pregabalin capsules may harm your unborn baby.You and your healthcare provider will decide if you should take pregabalin capsules while you are pregnant.

{ "type": "p", "children": [], "text": "\n●   are pregnant or plan to become pregnant. \n \n Pregabalin capsules may harm your unborn baby.You and your healthcare provider will decide if you should take pregabalin capsules while you are pregnant.\n\n " }

○   If you become pregnant while taking pregabalin capsules, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. Information about the registry can also be found at the website, http://www.aedpregnancyregistry.org/.

{ "type": "p", "children": [], "text": "○   If you become pregnant while taking pregabalin capsules, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. Information about the registry can also be found at the website, http://www.aedpregnancyregistry.org/." }

●   are breastfeeding or plan to breastfeed. Pregabalin capsules passes into your breast milk. It is not known if pregabalin capsules can harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take pregabalin capsules. Breastfeeding is not recommended while taking pregabalin capsules.

{ "type": "p", "children": [], "text": "●  \n \n are breastfeeding or plan to breastfeed. Pregabalin capsules passes into your breast milk. It is not known if pregabalin capsules can harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take pregabalin capsules.\n \n Breastfeeding is not recommended while taking pregabalin capsules.\n" }

Tell your healthcare provider about all the medicines you take,including prescription and over-the-counter medicines, vitamins or herbal supplements. Pregabalin capsules and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take:

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take,including prescription and over-the-counter medicines, vitamins or herbal supplements. Pregabalin capsules and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take:\n\n " }

●   angiotensin converting enzyme (ACE) inhibitors, which are used to treat many conditions, including high blood pressure. You may have a higher chance for swelling and hives if these medicines are taken with pregabalin capsules.

{ "type": "p", "children": [], "text": "●   angiotensin converting enzyme (ACE) inhibitors, which are used to treat many conditions, including high blood pressure. You may have a higher chance for swelling and hives if these medicines are taken with pregabalin capsules." }

●   Avandia (rosiglitazone) or Actos (pioglitazone) for diabetes. You may have a higher chance of weight gain or swelling of your hands or feet if these medicines are taken with pregabalin capsules.

{ "type": "p", "children": [], "text": "●   Avandia (rosiglitazone) or Actos (pioglitazone) for diabetes. You may have a higher chance of weight gain or swelling of your hands or feet if these medicines are taken with pregabalin capsules." }

●   any opoid pain medicine (such as oxycodone), or medicines for anxiety (such as lorazepam) or insomnia (such as zolpidem). You may have a higher chance for dizziness, sleepiness or serious breathing problem if these medicines are taken with pregabalin capsules.

{ "type": "p", "children": [], "text": "●   any opoid pain medicine (such as oxycodone), or medicines for anxiety (such as lorazepam) or insomnia (such as zolpidem). You may have a higher chance for dizziness, sleepiness or serious breathing problem if these medicines are taken with pregabalin capsules." }

●   any medicines that make you sleepy.

{ "type": "p", "children": [], "text": "●   any medicines that make you sleepy." }

Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider.

{ "type": "p", "children": [], "text": "Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider." }

How should I take Pregabalin capsules?

{ "type": "p", "children": [], "text": "\nHow should I take Pregabalin capsules?\n" }

●   Take pregabalin capsules exactly as prescribed. Your healthcare provider will tell you how much pregabalin capsules to take and when to take it.

{ "type": "p", "children": [], "text": "●   Take pregabalin capsules exactly as prescribed. Your healthcare provider will tell you how much pregabalin capsules to take and when to take it." }

●   Pregabalin capsules may be taken with or without food.

{ "type": "p", "children": [], "text": "●   Pregabalin capsules may be taken with or without food." }

●   Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.

{ "type": "p", "children": [], "text": "●   Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider." }

●   Do not stop taking pregabalin capsules without talking to your healthcare provider. If you stop taking pregabalin capsules suddenly you may have headaches, nausea, diarrhea, trouble sleeping, increased sweating, or you may feel anxious. If you have epilepsy and you stop taking pregabalin capsules suddenly, you may have seizures more often. Talk with your healthcare provider about how to stop pregabalin capsules slowly.

{ "type": "p", "children": [], "text": "●  \n \n Do not stop taking pregabalin capsules without talking to your healthcare provider. If you stop taking pregabalin capsules suddenly you may have headaches, nausea, diarrhea, trouble sleeping, increased sweating, or you may feel anxious. If you have epilepsy and you stop taking pregabalin capsules suddenly, you may have seizures more often. Talk with your healthcare provider about how to stop pregabalin capsules slowly.\n\n " }

●   If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.

{ "type": "p", "children": [], "text": "●   If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time.\n \n Do not take 2 doses at the same time.\n" }

●   If you take too much pregabalin capsules, call your healthcare provider or poison control center, or go to the nearest emergency room right away.

{ "type": "p", "children": [], "text": "●   If you take too much pregabalin capsules, call your healthcare provider or poison control center, or go to the nearest emergency room right away." }

What should I avoid while taking pregabalin capsules?

{ "type": "p", "children": [], "text": "\nWhat should I avoid while taking pregabalin capsules?\n" }

●   Do not drive a car, work with machines, or do other dangerous activities until you know how pregabalin capsules affects you.

{ "type": "p", "children": [], "text": "\n●   Do not drive a car, work with machines, or do other dangerous activities until you know how pregabalin capsules affects you.\n" }

●    Do not drink alcohol while taking pregabalin capsules.Pregabalin capsules and alcohol can affect each other and increase side effects such as sleepiness and dizziness.

{ "type": "p", "children": [], "text": "●   \n \n Do not drink alcohol while taking pregabalin capsules.Pregabalin capsules and alcohol can affect each other and increase side effects such as sleepiness and dizziness.\n\n " }

What are the possible side effects of pregabalin capsules?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of pregabalin capsules?\n" }

Pregabalin capsules may cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nPregabalin capsules may cause serious side effects, including:\n\n " }

●   See "What is the most important information I should know about pregabalin capsules?"

{ "type": "p", "children": [], "text": "●   See \"What is the most important information I should know about pregabalin capsules?\"" }

●   Muscle problems, muscle pain, soreness, or weakness. If you have these symptoms, especially if you feel sick and have a fever, tell your healthcare provider right away.

{ "type": "p", "children": [], "text": "\n●   Muscle problems, muscle pain, soreness, or weakness. If you have these symptoms, especially if you feel sick and have a fever, tell your healthcare provider right away.\n\n " }

●   Problems with your eyesight, including blurry vision. Call your healthcare provider if you have any changes in your eyesight.

{ "type": "p", "children": [], "text": "\n●   Problems with your eyesight, including blurry vision. Call your healthcare provider if you have any changes in your eyesight.\n\n " }

●   Weight gain. If you have diabetes, weight gain may affect the management of your diabetes. Weight gain can also be a serious problem for people with heart problems.

{ "type": "p", "children": [], "text": "\n●   Weight gain. If you have diabetes, weight gain may affect the management of your diabetes. Weight gain can also be a serious problem for people with heart problems.\n\n " }

●   Feeling "high".

{ "type": "p", "children": [], "text": "\n●   Feeling \"high\".\n\n " }

The most common side effects of pregabalin capsules in adults are:

{ "type": "p", "children": [], "text": "\nThe most common side effects of pregabalin capsules in adults are:\n" }

<div class="scrollingtable"><table class="Noautorules" width="699"> <col width="233"/> <col width="233"/> <col width="233"/> <tbody class="Headless"> <tr> <td valign="top"> <ul class="Disc"> <li>dizziness</li> <li>blurry vision</li> <li>dry mouth</li> </ul> </td><td valign="top"> <ul class="Disc"> <li>weight gain</li> <li>sleepiness</li> </ul> </td><td valign="top"> <ul class="Disc"> <li>trouble concentrating</li> <li>swelling of hands and feet</li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"699\">\n<col width=\"233\"/>\n<col width=\"233\"/>\n<col width=\"233\"/>\n<tbody class=\"Headless\">\n<tr>\n<td valign=\"top\">\n<ul class=\"Disc\">\n<li>dizziness</li>\n<li>blurry vision</li>\n<li>dry mouth</li>\n</ul>\n</td><td valign=\"top\">\n<ul class=\"Disc\">\n<li>weight gain</li>\n<li>sleepiness</li>\n</ul>\n</td><td valign=\"top\">\n<ul class=\"Disc\">\n<li>trouble concentrating</li>\n<li>swelling of hands and feet</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

The most common side effects of pregabalin capsules in childrenare weight gain, increase in appetite, and sleepiness.

{ "type": "p", "children": [], "text": "\nThe most common side effects of pregabalin capsules in childrenare weight gain, increase in appetite, and sleepiness.\n\n " }

Pregabalin capsules caused skin sores in animal studies. Skin sores did not happen in studies in people. If you have diabetes, you should pay attention to your skin while taking pregabalin capsules and tell your healthcare provider about any sores or skin problems.

{ "type": "p", "children": [], "text": "Pregabalin capsules caused skin sores in animal studies. Skin sores did not happen in studies in people. If you have diabetes, you should pay attention to your skin while taking pregabalin capsules and tell your healthcare provider about any sores or skin problems." }

Tell your healthcare provider about any side effect that bothers you or that does not go away.

{ "type": "p", "children": [], "text": "Tell your healthcare provider about any side effect that bothers you or that does not go away." }

These are not all the possible side effects of pregabalin capsules. For more information, ask your healthcare provider or pharmacist.

{ "type": "p", "children": [], "text": "These are not all the possible side effects of pregabalin capsules. For more information, ask your healthcare provider or pharmacist." }

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

{ "type": "p", "children": [], "text": "\nCall your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.\n" }

How should I store pregabalin capsules?

{ "type": "p", "children": [], "text": "\nHow should I store pregabalin capsules?\n" }

●    Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "●    Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]." }

●    Safely throw away any pregabalin capsule that is out of date or no longer needed.

{ "type": "p", "children": [], "text": "●    Safely throw away any pregabalin capsule that is out of date or no longer needed." }

Keep pregabalin capsules and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep pregabalin capsules and all medicines out of the reach of children.\n" }

General information about the safe and effective use of pregabalin capsules

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of pregabalin capsules\n" }

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use pregabalin capsules for a condition for which it was not prescribed. Do not give pregabalin capsules to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about pregabalin capsules that is written for health professionals.

{ "type": "p", "children": [], "text": "Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use pregabalin capsules for a condition for which it was not prescribed. Do not give pregabalin capsules to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about pregabalin capsules that is written for health professionals." }

For more information contact Creekwood Pharmaceuticals LLC at 1-732-344-0220.

{ "type": "p", "children": [], "text": "\nFor more information contact Creekwood Pharmaceuticals LLC at 1-732-344-0220.\n" }

What are the ingredients in pregabalin capsules?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in pregabalin capsules?\n" }

Active ingredient: pregabalin USP

{ "type": "p", "children": [], "text": "Active ingredient: pregabalin USP" }

Inactive ingredients: lactose monohydrate, pregelatinized starch, talc

{ "type": "p", "children": [], "text": "Inactive ingredients: lactose monohydrate, pregelatinized starch, talc" }

Capsule shell: gelatin and titanium dioxide; orange capsule shell: red iron oxide

{ "type": "p", "children": [], "text": "Capsule shell: gelatin and titanium dioxide; orange capsule shell: red iron oxide" }

Imprinting ink: shellac, black iron oxide, propylene glycol, ammonium solution concentrated, potassium hydroxide.

{ "type": "p", "children": [], "text": "Imprinting ink: shellac, black iron oxide, propylene glycol, ammonium solution concentrated, potassium hydroxide." }

Manufactured by:

{ "type": "p", "children": [], "text": "Manufactured by:" }

V-Ensure Pharma Technologies Pvt. Ltd

{ "type": "p", "children": [], "text": "\nV-Ensure Pharma Technologies Pvt. Ltd\n" }

Raigad, Maharashtra-410206, India.

{ "type": "p", "children": [], "text": "Raigad, Maharashtra-410206, India." }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

Creekwood Pharmaceuticals LLC.

{ "type": "p", "children": [], "text": "\nCreekwood Pharmaceuticals LLC.\n" }

Parsippany, NJ 07054.

{ "type": "p", "children": [], "text": "Parsippany, NJ 07054." }

PA1220106

{ "type": "p", "children": [], "text": "PA1220106" }

This Medication Guide has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration." }

Revised: 06/2025

{ "type": "p", "children": [], "text": "Revised: 06/2025" }

NDC 82619-122-01

{ "type": "p", "children": [], "text": "\nNDC 82619-122-01\n" }

Pregabalin Capsules 25 mg

{ "type": "p", "children": [], "text": "\nPregabalin Capsules 25 mg\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

90 Capsules

{ "type": "p", "children": [], "text": "\n90 Capsules\n" }

NDC 82619-123-01

{ "type": "p", "children": [], "text": "\nNDC 82619-123-01\n" }

Pregabalin Capsules 50 mg

{ "type": "p", "children": [], "text": "\nPregabalin Capsules 50 mg\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

90 Capsules

{ "type": "p", "children": [], "text": "\n90 Capsules\n" }

NDC 82619-124-01

{ "type": "p", "children": [], "text": "\nNDC 82619-124-01\n" }

Pregabalin Capsules 75 mg

{ "type": "p", "children": [], "text": "\nPregabalin Capsules 75 mg\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

90 Capsules

{ "type": "p", "children": [], "text": "\n90 Capsules\n" }

NDC 82619-125-01

{ "type": "p", "children": [], "text": "\nNDC 82619-125-01\n" }

Pregabalin Capsules 100 mg

{ "type": "p", "children": [], "text": "\nPregabalin Capsules 100 mg\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

90 Capsules

{ "type": "p", "children": [], "text": "\n90 Capsules\n" }

NDC 82619-126-01

{ "type": "p", "children": [], "text": "\nNDC 82619-126-01\n" }

Pregabalin Capsules 150 mg

{ "type": "p", "children": [], "text": "\nPregabalin Capsules 150 mg\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

90 Capsules

{ "type": "p", "children": [], "text": "\n90 Capsules\n" }

NDC 82619-127-01

{ "type": "p", "children": [], "text": "\nNDC 82619-127-01\n" }

Pregabalin Capsules 200 mg

{ "type": "p", "children": [], "text": "\nPregabalin Capsules 200 mg\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

90 Capsules

{ "type": "p", "children": [], "text": "\n90 Capsules\n" }

NDC 82619-128-01

{ "type": "p", "children": [], "text": "\nNDC 82619-128-01\n" }

Pregabalin Capsules 225 mg

{ "type": "p", "children": [], "text": "\nPregabalin Capsules 225 mg\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

90 Capsules

{ "type": "p", "children": [], "text": "\n90 Capsules\n" }

NDC 82619-129-01

{ "type": "p", "children": [], "text": "\nNDC 82619-129-01\n" }

Pregabalin Capsules 300 mg

{ "type": "p", "children": [], "text": "\nPregabalin Capsules 300 mg\n" }

CV

{ "type": "p", "children": [], "text": "\nCV\n" }

ALWAYS DISPENSE WITH MEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITH MEDICATION GUIDE\n" }

Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

90 Capsules

{ "type": "p", "children": [], "text": "\n90 Capsules\n" }

LYRICA CR is indicated for the management of:

{ "type": "p", "children": [], "text": "LYRICA CR is indicated for the management of:" }

{ "type": "", "children": [], "text": "" }

Efficacy of LYRICA CR has not been established for the management of fibromyalgia or as adjunctive therapy for adult patients with partial onset seizures.

{ "type": "p", "children": [], "text": "Efficacy of LYRICA CR has not been established for the management of fibromyalgia or as adjunctive therapy for adult patients with partial onset seizures." }

LYRICA CR should be administered once daily after an evening meal.

LYRICA CR should be swallowed whole and should not be split, crushed, or chewed.

When discontinuing LYRICA CR, taper gradually over a minimum of 1 week.

Instruct patients that if they miss taking their dose of LYRICA CR after an evening meal, then they should take their usual dose of LYRICA CR prior to bedtime following a snack. If they miss taking the dose of LYRICA CR prior to bedtime, then they should take their usual dose of LYRICA CR following a morning meal. If they miss taking the dose of LYRICA CR following the morning meal, then they should take their usual dose of LYRICA CR at the usual time that evening following an evening meal [see Patient Counseling Information (17)].

Begin dosing at 165 mg once daily and increase to 330 mg once daily within 1 week based on individual patient response and tolerability. The maximum recommended dose of LYRICA CR is 330 mg once daily.

Although LYRICA was studied at 600 mg/day, there was no evidence that this dose conferred additional significant benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions with LYRICA, treatment with doses above 330 mg/day is not recommended for LYRICA CR.

Begin dosing at 165 mg once daily and increase to 330 mg once daily within 1 week based on individual patient response and tolerability.

Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with 330 mg once daily and who are able to tolerate LYRICA CR, may be treated with up to 660 mg once daily. In view of the dose-dependent adverse reactions and the higher rate of treatment discontinuation due to adverse reactions, dosing above 330 mg/day should be reserved only for those patients who have on-going pain and are tolerating 330 mg daily. The maximum recommended dose of LYRICA CR is 660 mg once daily.

When switching from LYRICA to LYRICA CR on the day of the switch, instruct patients to take their morning dose of LYRICA as prescribed and initiate LYRICA CR therapy after an evening meal.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 1. Conversion from LYRICA Capsules or Oral Solution to LYRICA CR</span> </caption> <col width="50%"/> <col width="50%"/> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>247.5 mg = 3 × 82.5 mg tablets taken once a day.</dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>495 mg = 3 × 165 mg tablets taken once a day.</dd> <dt> <a href="#footnote-reference-3" name="footnote-3">‡</a> </dt> <dd>660 mg = 2 × 330 mg tablets taken once a day.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">LYRICA<br/>Total Daily Dose<br/>(dosed 2 or 3 times daily)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">LYRICA CR<br/>Dose<br/>(dosed once a day)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">75 mg/daily</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">82.5 mg/day</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">150 mg/daily</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">165 mg/day</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">225 mg/daily</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">247.5 mg/day<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">300 mg/daily</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">330 mg/day</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">450 mg/daily</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">495 mg/day<a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">600 mg/daily</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">660 mg/day<a class="Sup" href="#footnote-3" name="footnote-reference-3">‡</a> </p> </td> </tr> </tbody> </table></div>

Use of LYRICA CR is not recommended for patients with creatinine clearance (CLcr) less than 30 mL/min or who are undergoing hemodialysis. Those patients should receive LYRICA.

In view of dose-dependent adverse reactions and because pregabalin is eliminated primarily by renal excretion, adjust the dose in patients with reduced renal function. Base the dose adjustment in patients with renal impairment on CLcr, as indicated in Table 2. To use the dosing tables, an estimate of the patient’s CLcr in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation:

Next, refer to the Dosage and Administration section to determine the recommended total daily dose based on indication, for a patient with normal renal function (CLcr greater than or equal to 60 mL/min). Then refer to Table 2 to determine the corresponding renal adjusted dose.

(For example: A patient initiating LYRICA CR therapy for postherpetic neuralgia with normal renal function [CLcr greater than or equal to 60 mL/min], receives a single daily dose of 165 mg/day pregabalin. Therefore, a renal impaired patient with a CLcr of 50 mL/min would receive a single daily dose of 82.5 mg.)

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 2. LYRICA CR Dosage Adjustment Based on Renal Function</span> </caption> <col width="26%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <col width="14%"/> <col width="17%"/> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>495 mg = 3 × 165 mg tablets taken once a day.</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">†</a> </dt> <dd>660 mg = 2 × 330 mg tablets taken once a day.</dd> <dt> <a href="#footnote-reference-6" name="footnote-6">‡</a> </dt> <dd>247.5 mg = 3 × 82.5 mg tablets taken once a day.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Creatinine Clearance (CLcr)<br/>(mL/min)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Total LYRICA CR Daily Dose<br/>(mg/day)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Dose Regimen</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">greater than or equal to 60</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">165</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">330</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">495<a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">660<a class="Sup" href="#footnote-5" name="footnote-reference-5">†</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Once a day</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">30-60</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">82.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">165</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">247.5<a class="Sup" href="#footnote-6" name="footnote-reference-6">‡</a> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">330</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Once a day</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">less than 30/hemodialysis</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="5" valign="middle"> <p class="First">Dose with LYRICA</p> </td> </tr> </tbody> </table></div>

Extended-release tablets: 82.5 mg, 165 mg, and 330 mg [see Description (11) and How Supplied/Storage and Handling (16)].

{ "type": "p", "children": [], "text": "Extended-release tablets: 82.5 mg, 165 mg, and 330 mg [see Description (11) and How Supplied/Storage and Handling (16)]." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>LYRICA CR Tablets</span> </caption> <col width="21%"/> <col width="79%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Tablet Strength (mg)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Tablet Description</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">82.5 mg</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Light blue, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 82.5” on the other side</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">165 mg</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Beige, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 165” on the other side</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">330 mg</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Rose, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 330” on the other side</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<caption>\n<span>LYRICA CR Tablets</span>\n</caption>\n<col width=\"21%\"/>\n<col width=\"79%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Tablet Strength (mg)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Tablet Description</span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">82.5 mg</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Light blue, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 82.5” on the other side</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">165 mg</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Beige, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 165” on the other side</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">330 mg</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Rose, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 330” on the other side</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

LYRICA CR is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see Warnings and Precautions (5.1, 5.2), Adverse Reactions (6)].

{ "type": "p", "children": [], "text": "LYRICA CR is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see Warnings and Precautions (5.1, 5.2), Adverse Reactions (6)]." }

There have been postmarketing reports of angioedema in patients during initial and chronic treatment with LYRICA. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue LYRICA CR immediately in patients with these symptoms.

Exercise caution when prescribing LYRICA CR to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema.

There have been postmarketing reports of hypersensitivity reactions in patients shortly after initiation of treatment with LYRICA. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue LYRICA CR immediately in patients with these symptoms.

Antiepileptic drugs (AEDs), including pregabalin, the active ingredient in LYRICA CR, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Suicidal behavior and ideation have also been reported in patients after discontinuation of pregabalin [see Warnings and Precautions (5.4)]. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.

Table 3 shows absolute and relative risk by indication for all evaluated AEDs.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 3. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis</span> </caption> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Indication</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo Patients With Events per 1000 Patients</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Drug Patients With Events per 1000 Patients</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Risk Difference: Additional Drug Patients With Events per 1000 Patients</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Epilepsy</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Psychiatric</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.7</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.5</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Other</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.9</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.9</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Total</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.3</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.8</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1.9</p> </td> </tr> </tbody> </table></div>

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing LYRICA CR must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Inform patients, their caregivers, and families that LYRICA CR can increase the risk of suicidal thoughts and behavior and advise them of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report behaviors of concern immediately to healthcare providers.

Following abrupt or rapid discontinuation of LYRICA CR, some patients reported symptoms including, insomnia, nausea, headache, anxiety, and diarrhea [see Adverse Reactions (6.2), Drug Abuse and Dependence (9.3)]. Suicidal behavior and ideation have also been reported in patients after discontinuation of pregabalin [see Warnings and Precautions (5.3)]. Increased seizure frequency may occur in patients with seizure disorders taking LYRICA CR for pain if LYRICA CR is rapidly discontinued. Taper LYRICA CR gradually over a minimum of 1 week rather than discontinuing the drug abruptly. The efficacy of LYRICA CR as adjunctive therapy for adult patients with partial onset seizures has not been established.

There is evidence from case reports, human studies, and animal studies associating pregabalin with serious, life-threatening, or fatal respiratory depression when co-administered with central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment. When the decision is made to co-prescribe LYRICA CR with another CNS depressant, particularly an opioid, or to prescribe LYRICA CR to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating LYRICA CR at a low dose. The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including LYRICA CR).

There is more limited evidence from case reports, animal studies, and human studies associating pregabalin with serious respiratory depression, without co-administered CNS depressants or without underlying respiratory impairment.

LYRICA CR may cause dizziness and somnolence. Inform patients that LYRICA CR-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery. Concomitant use of LYRICA CR with other central nervous system (CNS) depressants may exacerbate these effects [see Drug Interactions (7)].

In the LYRICA CR controlled trials for pain indications, dizziness was experienced by 24% of LYRICA CR‑treated patients during the single‑blind phase; somnolence was experienced by 15.8% of LYRICA CR-treated patients. Dizziness and somnolence generally began shortly after the initiation of LYRICA CR therapy and occurred more frequently at higher doses. Dizziness and somnolence were the adverse reactions most frequently leading to withdrawal (2.4%, 1.2% each) during the single‑blind phase of the controlled studies. In LYRICA-treated patients reporting these adverse reactions in short‑term, controlled studies, dizziness persisted until the last dose in 30% and somnolence persisted until the last dose in 42% of patients.

LYRICA CR treatment may cause peripheral edema. In short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications such as hypertension or congestive heart failure. Peripheral edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function.

In controlled clinical trials for pain indications, the incidence of peripheral edema for patients receiving LYRICA CR in the single-blind phase was 5.3% of patients. In controlled clinical trials for pain indications, 0.8% of LYRICA CR patients withdrew due to peripheral edema during the single-blind phase.

Higher frequencies of weight gain and peripheral edema were observed in patients taking both LYRICA and a thiazolidinedione antidiabetic agent compared to patients taking either drug alone. The majority of patients using thiazolidinedione antidiabetic agents in the overall safety database were participants in studies of pain associated with diabetic peripheral neuropathy. In this population, peripheral edema was reported in 3% (2/60) of patients who were using thiazolidinedione antidiabetic agents only, 8% (69/859) of patients who were treated with LYRICA only, and 19% (23/120) of patients who were on both LYRICA and thiazolidinedione antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on thiazolidinediones only; 4% (35/859) of patients on LYRICA only; and 7.5% (9/120) of patients on both drugs.

As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, monitor patients for the development of edema when co-administering LYRICA CR and these agents.

Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, monitor these patients for possible exacerbation of congestive heart failure symptoms when using LYRICA CR.

LYRICA CR treatment may cause weight gain. In LYRICA CR controlled trials for pain indications, weight gain was experienced by 4% of LYRICA CR-treated patients during the single-blind phase. Adverse events of weight gain were observed in 3.7% of LYRICA CR-treated patients and 1% of placebo-treated patients during the double-blind phase.

In LYRICA controlled clinical trials of up to 14 weeks a gain of 7% or more over baseline weight was observed in 9% of LYRICA-treated patients and 2% of placebo-treated patients. Few patients treated with LYRICA (0.3%) withdrew from controlled trials due to weight gain. In studies with LYRICA, associated weight gain was related to pregabalin dose and duration of exposure but did not appear to be associated with baseline BMI, gender, or age. Weight gain was not limited to patients with edema [see Warnings and Precautions (5.7)].

Although weight gain was not associated with clinically important changes in blood pressure in short-term controlled studies with LYRICA, the long-term cardiovascular effects of pregabalin-associated weight gain are unknown.

Among diabetic patients, LYRICA-treated patients gained an average of 1.6 kg (range: -16 to 16 kg), compared to an average 0.3 kg (range: -10 to 9 kg) weight gain in placebo patients. In a cohort of 333 diabetic patients who received LYRICA for at least 2 years, the average weight gain was 5.2 kg.

While the effects of pregabalin-associated weight gain on glycemic control have not been systematically assessed, in controlled and longer-term open-label clinical trials with diabetic patients, LYRICA treatment did not appear to be associated with loss of glycemic control (as measured by HbA1C).

In standard preclinical in vivo lifetime carcinogenicity studies of pregabalin, an unexpectedly high incidence of hemangiosarcoma was identified in 2 different strains of mice [see Nonclinical Toxicology (13.1)]. The clinical significance of this finding is unknown. Clinical experience during premarketing development of LYRICA provides no direct means to assess its potential for inducing tumors in humans.

In clinical studies across various patient populations, comprising 6396 patient-years of exposure in patients greater than 12 years of age, new or worsening preexisting tumors were reported in 57 patients. Without knowledge of the background incidence and recurrence in similar populations not treated with pregabalin, it is impossible to know whether the incidence seen in these cohorts is or is not affected by treatment.

In controlled studies for pain indications, 4.8% of patients treated with LYRICA CR in the single-blind phase reported blurred vision, which resolved in a majority of cases with continued dosing. Less than 1% of patients discontinued LYRICA CR treatment due to vision-related events (primarily blurred vision). Additionally, 0.7% of LYRICA CR-treated patients as compared to no placebo-treated patients experienced blurred vision in the double-blind phase.

Prospectively planned ophthalmologic testing during the premarketing development of pregabalin, including visual acuity testing, formal visual field testing and dilated funduscopic examination, was performed in over 3600 patients. In these patients, visual acuity was reduced in 7% of LYRICA-treated patients and 5% of placebo-treated patients. Visual field changes were detected in 13% of LYRICA-treated and 12% of placebo-treated patients. Funduscopic changes were observed in 2% of LYRICA-treated and 2% of placebo-treated patients.

Although the clinical significance of the ophthalmologic findings is unknown, inform patients to notify their physician if changes in vision occur. If visual disturbance persists, consider further assessment. Consider more frequent assessment for patients who are already routinely monitored for ocular conditions.

LYRICA treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for LYRICA‑treated patients and 28 U/L for the placebo patients. In all controlled trials across multiple patient populations, 1.5% of patients on LYRICA and 0.7% of placebo patients had a value of creatine kinase at least 3 times the upper limit of normal. Three LYRICA‑treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and LYRICA is not completely understood because the cases had documented factors that may have caused or contributed to these events. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Discontinue treatment with LYRICA CR if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.

Both LYRICA CR and LYRICA treatment were associated with a decrease in platelet count. In the double‑blind phase of controlled studies for pain indication, LYRICA CR‑treated patients experienced a median change from baseline in platelet count of 11 × 103/mm3 (for the PHN population) and 14 × 103/mm3 (for the FM population) as compared to 1 × 103/mm3 in placebo‑treated patients (for both populations). LYRICA‑treated patients experienced a mean maximal decrease in platelet count of 20 × 103/µL, compared to 11 × 103/µL in placebo patients. In the overall database of controlled trials, 2% of placebo patients and 3% of LYRICA patients experienced a potentially clinically significant decrease in platelets, defined as 20% below baseline value and less than 150 × 103/µL. A single LYRICA‑treated subject developed severe thrombocytopenia with a platelet count less than 20 × 103/µL. In randomized controlled trials, LYRICA or LYRICA CR were not associated with an increase in bleeding‑related adverse reactions.

LYRICA treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data, the mean PR interval increase was 3-6 msec at pregabalin doses greater than or equal to 300 mg/day. This mean change difference was not associated with an increased risk of PR increase greater than or equal to 25% from baseline, an increased percentage of subjects with on‑treatment PR greater than 200 msec, or an increased risk of adverse reactions of second or third degree AV block.

Subgroup analyses did not identify an increased risk of PR prolongation in patients with baseline PR prolongation or in patients taking other PR prolonging medications. However, these analyses cannot be considered definitive because of the limited number of patients in these categories.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Two randomized placebo-controlled clinical trials were conducted in patients with postherpetic neuralgia and fibromyalgia in which a total of 1242 patients received LYRICA CR. Both studies were randomized withdrawal design where a 6-week single-blind, dose optimization phase was followed by a 13-week double-blind phase. The most common adverse events leading to discontinuation from the single-blind phase of the study occurring in greater than or equal to 0.3% of patients were dizziness, somnolence, peripheral edema, fatigue, blurred vision, and increased weight. Sixty-four percent of patients experienced adverse events during the single-blind phase, with the most common adverse events occurring in greater than or equal to 4% of patients being dizziness, somnolence, headache, fatigue, peripheral edema, nausea, blurred vision, dry mouth, and weight gain.

In a clinical trial in patients with postherpetic neuralgia, 8.9% of patients treated with LYRICA CR discontinued prematurely during the single-blind phase due to adverse reactions. The most common reasons for discontinuation due to adverse reactions were dizziness (2.1%), somnolence (0.87%), and peripheral edema (0.50%).

Table 4 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with postherpetic neuralgia who received LYRICA CR, regardless of the phase of the study.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4. Incidence of Adverse Reactions Reported in Greater Than or Equal to 1% of Subjects in Any Phase of the LYRICA CR Study in Patients with Postherpetic Neuralgia* </span> </caption> <col width="41%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4" valign="top">* Table is limited to adverse reactions that occurred with higher incidence in LYRICA CR-treated patients than in placebo-treated patients for the DB Phase of the study.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">System Organ Class</span> <br/>Preferred Term</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Single-Blind Phase</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Double-Blind Phase</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">LYRICA CR<br/>[N=801]</span> <br/>n (%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">LYRICA CR<br/>[N=208]</span> <br/>n (%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo<br/>[N=205]</span> <br/>n (%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Ear and labyrinth disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Vertigo</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">31 (3.9)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Eye disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Vision blurred</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">30 (3.7)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Diplopia</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Gastrointestinal disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Dry mouth</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">30 (3.7)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Nausea</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">24 (3.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7 (3.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> Constipation</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">22 (2.7)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Diarrhea</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Vomiting</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">9 (1.1)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">General disorders and administration site conditions</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Edema peripheral</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">39 (4.9)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8 (3.8)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Fatigue</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">31 (3.9)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Edema</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (0.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Infections and infestations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Nasopharyngitis</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">12 (1.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Urinary tract infection</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">11 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Bronchitis</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (0.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Respiratory tract infection viral</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (0.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Sinusitis</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (0.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Gastroenteritis viral</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (0.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Investigations</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Weight increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">20 (2.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8 (3.8)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Alanine aminotransferase increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (0.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Aspartate aminotransferase increased</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (0.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Musculoskeletal and connective tissue disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Arthralgia</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6 (0.7)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Joint swelling</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (1.9)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Nervous system disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Dizziness</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">137 (17.1)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7 (3.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Somnolence</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">91 (11.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Headache</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">31 (3.9)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (1.9)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Balance disorder</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">21 (2.6)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Reproductive system and breast disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Erectile dysfunction</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (0.6)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Respiratory, thoracic, and mediastinal disorders</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">  Cough</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (0.2)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="4" valign="middle"> <p class="First"> <span class="Bold">Skin and subcutaneous tissue disorders</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">  Dermatitis contact</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

In addition to the adverse reactions reported during the controlled studies with LYRICA CR in postherpetic neuralgia, the following adverse reactions have been reported in patients treated with LYRICA and LYRICA CR during all clinical studies. This listing does not include those adverse reactions already listed above. The adverse reactions are categorized by system organ class and listed in order of decreasing frequency according to the following definitions: frequent adverse reactions are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients. Adverse reactions of major clinical importance are described in the Warnings and Precautions section (5).

Cardiac Disorders – Infrequent: Palpitations, Deep thrombophlebitis, Heart failure, Hypotension, Postural hypotension, Retinal vascular disorder, Syncope; Rare: Cardiac failure, Tachycardia

Eye Disorders – Infrequent: Periorbital edema

Gastrointestinal Disorders – Frequent: Increased appetite; Infrequent: Abdominal distension, Abdominal pain, Dysphagia, Pancreatitis, Tongue edema

General Disorders – Frequent: Fever; Infrequent: Chest pain, Face edema; Rare: Facial pain, Mucosal dryness

Hemic and Lymphatic System Disorders – Frequent: Ecchymosis; Infrequent: Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare: Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia

Infections and Infestations – Infrequent: Otitis media, Pneumonia

Investigations – Rare: Glucose urine present, Lipase increased, Neutrophil count increased, Proteinuria

Metabolic and Nutritional Disorders – Rare: Glucose Tolerance Decreased, Urate Crystalluria

Musculoskeletal and Connective Tissue Disorders – Frequent: Leg cramps, Myalgia, Myasthenia; Infrequent: Joint stiffness; Rare: Coccydynia, Myokymia

Nervous System Disorders – Frequent: Anxiety, Depersonalization, Hypertonia, Hypoesthesia, Libido decreased, Nystagmus, Paresthesia, Sedation, Stupor, Twitching; Infrequent: Coordination abnormal, Abnormal dreams, Agitation, Amnesia, Apathy, Aphasia, Circumoral paresthesia, Cognitive disorder, Dysarthria, Dysgeusia, Hallucinations, Hostility, Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased, Myoclonus, Neuralgia, Sciatica, Sleep phase rhythm disturbance; Rare: Addiction, Altered state of consciousness, Bradykinesia, Cerebellar syndrome, Cogwheel rigidity, Coma, Delirium, Delusions, Depressed level of consciousness, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal syndrome, Psychomotor hyperactivity, Psychomotor skills impaired

Psychiatric Disorders – Infrequent: Irritability

Respiratory System Disorders – Rare: Lung edema

Skin Disorders – Frequent: Pruritus; Rare: Stevens-Johnson syndrome

Special Senses – Frequent: Conjunctivitis, Tinnitus

Urogenital System Disorders – Frequent: Anorgasmia, Impotence, Urinary frequency, Urinary incontinence; Infrequent: Abnormal ejaculation, Albuminuria, Dysuria, Hematuria, Kidney calculus, Leukorrhea, Nephritis, Oliguria, Urinary retention

The following adverse reactions have been identified during post-approval use of LYRICA. These adverse reactions have not been listed above and data are insufficient to support an estimate of their incidence or to establish causation. The listing is alphabetized: breast enlargement, bullous pemphigoid, gynecomastia.

There are postmarketing reports of life-threatening or fatal respiratory depression in patients taking pregabalin with opioids or other CNS depressants, or in the setting of underlying respiratory impairment.

In addition, there are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when LYRICA was co-administered with medications that have the potential to produce constipation, such as opioid analgesics.

There are postmarketing reports of withdrawal symptoms after discontinuation of pregabalin. Reported adverse reactions include, but are not limited to, seizures, depression, suicidal ideation and behavior, agitation, confusion, disorientation, psychotic symptoms, anxiety, insomnia, nausea, pain, sweating, tremor, headache, dizziness, malaise, and diarrhea.

Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (less than 2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. In vitro studies showed that pregabalin is unlikely to be involved in significant pharmacokinetic drug interactions [see Clinical Pharmacology (12)].

{ "type": "p", "children": [], "text": "Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (less than 2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. In vitro studies showed that pregabalin is unlikely to be involved in significant pharmacokinetic drug interactions [see Clinical Pharmacology (12)]." }

The interactions of LYRICA CR with co-administration of other drugs have not been systematically evaluated. Co-administration of the prokinetic drug erythromycin with LYRICA CR did not result in any clinically important changes in the pharmacokinetics of LYRICA CR [see Clinical Pharmacology (12)].

{ "type": "p", "children": [], "text": "The interactions of LYRICA CR with co-administration of other drugs have not been systematically evaluated. Co-administration of the prokinetic drug erythromycin with LYRICA CR did not result in any clinically important changes in the pharmacokinetics of LYRICA CR [see Clinical Pharmacology (12)]." }

Additional studies have been performed with LYRICA. No pharmacokinetic interactions were observed between LYRICA and carbamazepine, gabapentin, lamotrigine, oral contraceptive, phenobarbital, phenytoin, topiramate, and valproic acid. A similar lack of pharmacokinetic interactions would be expected to occur with LYRICA CR.

{ "type": "p", "children": [], "text": "Additional studies have been performed with LYRICA. No pharmacokinetic interactions were observed between LYRICA and carbamazepine, gabapentin, lamotrigine, oral contraceptive, phenobarbital, phenytoin, topiramate, and valproic acid. A similar lack of pharmacokinetic interactions would be expected to occur with LYRICA CR." }

Pharmacodynamics

{ "type": "p", "children": [], "text": "\nPharmacodynamics\n" }

Although no pharmacokinetic interactions were seen with LYRICA and ethanol, lorazepam, or oxycodone, additive effects on cognitive and gross motor functioning were seen when LYRICA was co-administered with these drugs. No clinically important effects on respiration were seen in studies of LYRICA.

{ "type": "p", "children": [], "text": "Although no pharmacokinetic interactions were seen with LYRICA and ethanol, lorazepam, or oxycodone, additive effects on cognitive and gross motor functioning were seen when LYRICA was co-administered with these drugs. No clinically important effects on respiration were seen in studies of LYRICA." }

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pregabalin during pregnancy. To provide information regarding the effects of in utero exposure to LYRICA CR, physicians are advised to recommend that pregnant patients taking LYRICA CR enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

Observational studies on the use of Lyrica CR during pregnancy suggest a possible small increase in the rate of overall major birth defects, but there was no consistent or specific pattern of major birth defects identified (see Data). Available postmarketing data on miscarriage and other maternal, fetal, and long term developmental adverse effects were insufficient to identify risk associated with pregabalin.

Postmarketing data suggest that extended gabapentinoid use with opioids close to delivery may increase the risk of neonatal withdrawal versus opioids alone (see Clinical Considerations). There are no comparative epidemiologic studies evaluating this association. Therefore, it is not known whether exposure to pregabalin alone late in pregnancy may cause withdrawal signs and symptoms.

In animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (AUC) greater than or equal to 18 times human exposure at the maximum recommended dose (MRD) of 660 mg/day (see Data). In an animal development study, lethality, growth retardation, and nervous and reproductive system functional impairment were observed in the offspring of rats given pregabalin during gestation and lactation. The no-effect dose for developmental toxicity was approximately twice the human exposure at MRD.

The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentinoids in utero for an extended period of time when also exposed to opioids close to delivery. Neonatal withdrawal signs and symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia, irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern, and tremor. Reported signs and symptoms that may also be related to withdrawal include tongue thrusting, wandering eye movements while awake, back arching, and continuous extremity movements. Observe neonates exposed to LYRICA CR and opioids for signs and symptoms of neonatal withdrawal and manage accordingly.

One database study, which included over 2,700 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 3,063,251 pregnancies unexposed to antiepileptics demonstrated prevalence ratios for major malformations overall of 1.14 (CI 95% 0.96-1.35) for pregabalin, 1.29 (CI 95% 1.01-1.65) for lamotrigine, 1.39 (CI 95% 1.07-1.82) for duloxetine, and 1.24 (CI 95% 1.00-1.54) for exposure to either lamotrigine or duloxetine. Important study limitations include uncertainty of whether women who filled a prescription took the medication and inability to adequately control for the underlying disease and other potential confounders.

A published study included results from two separate databases. One database, which included 353 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 368,489 pregnancies unexposed to antiepileptics, showed no increase in risk of major birth defects; adjusted relative risk 0.87 (CI 95% 0.53-1.42). The second database, which included 118 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 380,347 pregnancies unexposed to antiepileptics, suggested a small increase in risk of major birth defects; adjusted relative risk 1.26 (CI 95% 0.64-2.49). The risk estimates crossed the null, and the study had limitations similar to the prior study.

Other published epidemiologic studies reported inconsistent findings. No specific pattern of birth defects was identified across studies. All of the studies had limitations due to their retrospective design.

When pregnant rats were given pregabalin (500, 1250, or 2500 mg/kg) orally throughout the period of organogenesis, incidences of specific skull alterations attributed to abnormally advanced ossification (premature fusion of the jugal and nasal sutures) were increased at greater than or equal to 1250 mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses. Fetal body weights were decreased at the highest dose. The low dose in this study was associated with a plasma exposure (AUC) approximately 18 times human exposure at the MRD of 660 mg/day. A no-effect dose for rat embryo-fetal developmental toxicity was not established.

When pregnant rabbits were given pregabalin (250, 500, or 1250 mg/kg) orally throughout the period of organogenesis, decreased fetal body weight and increased incidences of skeletal malformations, visceral variations, and retarded ossification were observed at the highest dose. The no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a plasma exposure approximately 17 times human exposure at the MRD.

In a study in which female rats were dosed with pregabalin (50, 100, 250, 1250, or 2500 mg/kg) throughout gestation and lactation, offspring growth was reduced at greater than or equal to 100 mg/kg and offspring survival was decreased at greater than or equal to 250 mg/kg. The effect on offspring survival was pronounced at doses greater than or equal to 1250 mg/kg, with 100% mortality in high-dose litters. When offspring were tested as adults, neurobehavioral abnormalities (decreased auditory startle responding) were observed at greater than or equal to 250 mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1250 mg/kg. The no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a plasma exposure approximately 2 times human exposure at the MRD.

In the prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures greater than or equal to 50 times the mean human exposure (AUC(0-24) of 123 µg∙hr/mL) at the MRD.

Small amounts of pregabalin have been detected in the milk of lactating women. A pharmacokinetic study in lactating women detected pregabalin in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose (see Data). The study did not evaluate the effects of pregabalin on milk production or the effects of pregabalin on the breastfed infant.

Based on animal studies, there is a potential risk of tumorigenicity with pregabalin exposure via breast milk to the breastfed infant [see Nonclinical Toxicology (13.1)]. Available clinical study data in patients greater than 12 years of age do not provide a clear conclusion about the potential risk of tumorigenicity with pregabalin [see Warnings and Precautions (5.9)]. Because of the potential risk of tumorigenicity, breastfeeding is not recommended during treatment with LYRICA CR.

A pharmacokinetic study in ten lactating women, who were at least 12 weeks postpartum, evaluated the concentrations of pregabalin in plasma and breast milk. LYRICA 150 mg oral capsule was given every 12 hours (300 mg daily dose) for a total of 4 doses. Pregabalin was detected in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose. The study did not evaluate the effects of pregabalin on milk production. Infants did not receive breast milk obtained during the dosing period, therefore, the effects of pregabalin on the breastfed infant were not evaluated.

Effects on Spermatogenesis

In a randomized, double‑blind, placebo‑controlled non‑inferiority study to assess the effect of pregabalin on sperm characteristics, healthy male subjects received pregabalin at a daily dose up to 600 mg (n=111) or placebo (n=109) for 13 weeks (1 complete sperm cycle) followed by a 13‑week washout period (off‑drug). A total of 65 subjects in the pregabalin group (59%) and 62 subjects in the placebo group (57%) were included in the per protocol (PP) population. These subjects took study drug for at least 8 weeks, had appropriate timing of semen collections and did not have any significant protocol violations. Among these subjects, approximately 9% of the pregabalin group (6/65) vs. 3% in the placebo group (2/62) had greater than or equal to 50% reduction in mean sperm concentrations from baseline at Week 26 (the primary endpoint). The difference between pregabalin and placebo was within the pre‑specified non‑inferiority margin of 20%. There were no adverse effects of pregabalin on sperm morphology, sperm motility, serum FSH or serum testosterone levels as compared to placebo. In subjects in the PP population with greater than or equal to 50% reduction in sperm concentration from baseline, sperm concentrations were no longer reduced by greater than or equal to 50% in any affected subject after an additional 3 months off‑drug. In 1 subject, however, subsequent semen analyses demonstrated reductions from baseline of greater than or equal to 50% at 9 and 12 months off‑drug. The clinical relevance of these data is unknown.

In the animal fertility study with pregabalin in male rats, adverse reproductive and developmental effects were observed [see Nonclinical Toxicology (13.1)].

The safety and effectiveness of LYRICA CR in pediatric patients have not been established.

In studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from early in the postnatal period (Postnatal Day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory startle responding and habituation) and reproductive impairment (delayed sexual maturation and decreased fertility in males and females) were observed at doses greater than or equal to 50 mg/kg. The neurobehavioral changes of acoustic startle persisted at greater than or equal to 250 mg/kg and locomotor activity and water maze performance at greater than or equal to 500 mg/kg in animals tested after cessation of dosing and, thus, were considered to represent long‑term effects. The low effect dose for developmental neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately equal to human exposure at the maximum recommended dose of 660 mg/day. A no‑effect dose was not established.

In controlled clinical studies of LYRICA in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older.

In controlled clinical studies of LYRICA in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older.

In the LYRICA CR neuropathic pain associated with postherpetic neuralgia study, 422 patients 65 years of age and older received pregabalin.

No overall differences in safety and effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Pregabalin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. See Dosage and Administration (2.5) for recommendations for dosing in patients with renal impairment.

LYRICA CR contains pregabalin, a Schedule V controlled substance.

In a study of recreational users (N=15) of sedative/hypnotic drugs, including alcohol, LYRICA (450 mg, single dose) received subjective ratings of “good drug effect,” “high” and “liking” to a degree that was similar to diazepam (30 mg, single dose). In controlled clinical studies in over 5500 patients, 4% of LYRICA-treated patients and 1% of placebo-treated patients overall reported euphoria as an adverse reaction, though in some patient populations studied, this reporting rate was higher and ranged from 1 to 12%.

Carefully evaluate all patients treated with LYRICA CR for history of drug abuse and observe them for signs of LYRICA CR misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).

In clinical studies, following abrupt or rapid discontinuation of LYRICA CR, some patients reported symptoms including insomnia, nausea, headache, diarrhea, or anxiety [see Warnings and Precautions (5.4)], consistent with physical dependence. In the postmarketing setting, in addition to these reported symptoms, other reported adverse reactions include, but are not limited to, seizures, depression, suicidal ideation and behavior, agitation, confusion, disorientation, psychotic symptoms, pain, sweating, tremor, dizziness, and malaise.

Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans

{ "type": "p", "children": [], "text": "\nSigns, Symptoms and Laboratory Findings of Acute Overdosage in Humans\n" }

In the postmarketing experience, the most commonly reported adverse events observed with pregabalin when taken in overdose include reduced consciousness, depression/anxiety, confusional state, agitation, and restlessness. Seizures and heart block have also been reported. Deaths have been reported in the setting of lone LYRICA overdose and in combination with other CNS depressants.

{ "type": "p", "children": [], "text": "In the postmarketing experience, the most commonly reported adverse events observed with pregabalin when taken in overdose include reduced consciousness, depression/anxiety, confusional state, agitation, and restlessness. Seizures and heart block have also been reported. Deaths have been reported in the setting of lone LYRICA overdose and in combination with other CNS depressants." }

Treatment or Management of Overdose

{ "type": "p", "children": [], "text": "\nTreatment or Management of Overdose\n" }

There is no specific antidote for overdose with pregabalin. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with pregabalin.

{ "type": "p", "children": [], "text": "There is no specific antidote for overdose with pregabalin. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with pregabalin." }

Pregabalin can be removed by hemodialysis. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4 hours).

{ "type": "p", "children": [], "text": "Pregabalin can be removed by hemodialysis. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4 hours)." }

LYRICA CR (pregabalin extended-release) tablets are for oral use and contain pregabalin. Pregabalin is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C8H17NO2 and the molecular weight is 159.23. The chemical structure of pregabalin is:

{ "type": "p", "children": [], "text": "LYRICA CR (pregabalin extended-release) tablets are for oral use and contain pregabalin. Pregabalin is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C8H17NO2 and the molecular weight is 159.23. The chemical structure of pregabalin is:" }

Pregabalin is a white to off-white, crystalline solid with a pKa1 of 4.2 and a pKa2 of 10.6. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is - 1.35.

{ "type": "p", "children": [], "text": "Pregabalin is a white to off-white, crystalline solid with a pKa1 of 4.2 and a pKa2 of 10.6. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is - 1.35." }

LYRICA CR extended-release tablets are administered orally and contain 82.5, 165, or 330 mg of pregabalin, along with carbomer, colorants, crospovidone, Kollidon SR (polyvinyl acetate, povidone, sodium lauryl sulphate, and silica), magnesium stearate, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, talc, and titanium dioxide as inactive ingredients.

{ "type": "p", "children": [], "text": "LYRICA CR extended-release tablets are administered orally and contain 82.5, 165, or 330 mg of pregabalin, along with carbomer, colorants, crospovidone, Kollidon SR (polyvinyl acetate, povidone, sodium lauryl sulphate, and silica), magnesium stearate, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, talc, and titanium dioxide as inactive ingredients." }

Pregabalin binds with high affinity to the alpha2‑delta site (an auxiliary subunit of voltage‑gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2‑delta subunit may be involved in pregabalin’s anti‑nociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium‑dependent release of pro‑nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha2‑delta-containing calcium channel trafficking and/or reducing calcium currents. Evidence from other animal models of nerve damage and persistent pain suggest the anti‑nociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord.

While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.

LYRICA CR has linear pharmacokinetics with dose‑proportional increases in maximum plasma concentration (Cmax) and area under the plasma concentration‑time curve (AUC) from 82.5‑660 mg/day. Following repeated administration, steady state is achieved within approximately 48‑72 hours.

LYRICA CR administered once daily following an evening meal has equivalent AUC and lower Cmax relative to a comparative dose of LYRICA administered without food twice daily (Table 5). Variability in Cmax and AUC for LYRICA CR is less than or equal to 25%.

<div class="scrollingtable"><table class="Noautorules" width="100%"> <caption> <span>Table 5. Steady-State Pharmacokinetics for LYRICA CR 165 mg Once Daily and LYRICA 75 mg Twice Daily</span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tfoot> <tr> <td align="left" colspan="3" valign="top">Note: Geometric mean (%CV) for AUC<span class="Sub">24</span>, C<span class="Sub">max</span>, C<span class="Sub">min</span>; median (range) for T<span class="Sub">max</span>.</td> </tr> <tr> <td align="left" colspan="3" valign="top">Abbreviations: AUC<span class="Sub">24</span>=area under the curve over 24 hours; BID=every 12 hours; C<span class="Sub">max</span>=peak concentrations; C<span class="Sub">min</span>=minimum concentrations; N=Number of subjects ; T<span class="Sub">max</span>=time to peak concentrations.</td> </tr> </tfoot> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">LYRICA CR<br/>Once Daily</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">LYRICA<br/>BID</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">N</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">24</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">24</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">C<span class="Sub">max</span> (µg/mL)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.0 (17)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2 (21)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">T<span class="Sub">max</span> (h)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8.0 (5.0 - 12.0)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.7 (0.7 - 1.5)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">AUC<span class="Sub">24</span> (µg•h/mL)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">29.4 (17)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">31.5 (18)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">C<span class="Sub">min</span> (µg/mL)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.44 (24)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.59 (25)</p> </td> </tr> </tbody> </table></div>

Pregabalin is absorbed from the small intestine and proximal colon. LYRICA CR absorption is linear and dose proportional.

The bioavailability of LYRICA CR is reduced if taken on an empty stomach. The AUC is approximately 30% lower when LYRICA CR is administered fasted relative to following an evening meal.

When LYRICA CR is administered following a 600 to 750 calorie (50% carbohydrates, 20% protein, 30% fat) evening meal, peak plasma concentrations occur within approximately 8 to 10 hours and AUC is approximately 93% to 97% relative to a comparative dose of LYRICA. The rate and extent of LYRICA CR absorption is similar when administered following a 400 to 500 calorie, 30% fat or an 800 to 1000 calorie, 15%, 30%, or 50% fat evening meal.

When LYRICA CR is administered following an 800 to 1000 calorie (50% carbohydrates, 20% protein, 30% fat) morning meal, peak plasma concentrations occur within approximately 12 hours and AUC is 99% relative to a comparative dose of LYRICA. AUC decreases approximately 13% to 25% when LYRICA CR is administered following a 400 to 500 calorie or 600 to 750 calorie (50% carbohydrates, 20% protein, 30% fat) morning meal relative to the 800 to 1000 calorie meal, while Cmax remains the same.

Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. Although there are no data in humans, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys. In addition, pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats.

Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled pregabalin, approximately 90% of the administered dose was recovered in the urine as unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbits, or monkeys.

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67.0 to 80.9 mL/min in young healthy subjects. Because pregabalin is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to CLcr [see Dosage and Administration (2.5)].

Pregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with age-related decreases in CLcr. Reduction of pregabalin dose may be required in patients who have age-related compromised renal function [see Dosage and Administration (2.5)].

Population pharmacokinetic analyses of the clinical studies showed that the relationship between daily dose and LYRICA CR drug exposure is similar between genders.

In population pharmacokinetic analyses of the clinical studies of LYRICA and LYRICA CR, the pharmacokinetics of pregabalin were not significantly affected by race (Caucasians, Blacks, and Hispanics).

Pregabalin clearance is nearly proportional to CLcr. Dosage reduction in patients with reduced renal function is necessary. Pregabalin is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, plasma pregabalin concentrations are reduced by approximately 50%. For patients on hemodialysis, treatment with LYRICA CR is not recommended [see Dosage and Administration (2.5)].

In vitro studies showed that pregabalin is unlikely to be involved in significant pharmacokinetic drug interactions. Pregabalin, at concentrations that were, in general, 10-times those attained in clinical trials, does not inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzyme systems. In vitro drug interaction studies demonstrate that pregabalin does not induce CYP1A2 or CYP3A4 activity. Therefore, an increase in the metabolism of co-administered CYP1A2 substrates (e.g., theophylline, caffeine) or CYP3A4 substrates (e.g., midazolam, testosterone) is not anticipated.

With the exception of erythromycin, the interactions of LYRICA CR with co-administration of other drugs have not been systematically evaluated.

Additional studies have been performed with LYRICA [see Drug Interactions (7)]. No pharmacokinetic interactions were observed between LYRICA and carbamazepine, ethanol, gabapentin, lamotrigine, lorazepam, oral contraceptive, oxycodone, phenobarbital, phenytoin, topiramate, and valproic acid. A similar lack of pharmacokinetic interactions would be expected to occur with LYRICA CR.

The drug interaction studies described in this section were conducted in healthy adults, and across various patient populations.

Multiple-dose administration of erythromycin (500 mg every 6 hours for 18 hours) in healthy subjects resulted in a 17% decrease in AUC of LYRICA CR (330 mg single dose).

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of ethanol single-dose pharmacokinetics and single-dose administration of ethanol (0.7 g/kg) had no effect on the steady-state pharmacokinetics of pregabalin. Additive effects on cognitive and gross motor functioning were seen when LYRICA was co-administered with ethanol. No clinically important effects on respiration were seen [see Drug Interactions (7)].

The pharmacokinetic interactions of pregabalin and gabapentin were investigated in 12 healthy subjects following concomitant single‑dose administration of 100‑mg pregabalin and 300‑mg gabapentin and in 18 healthy subjects following concomitant multiple‑dose administration of 200‑mg pregabalin every 8 hours and 400‑mg gabapentin every 8 hours. Gabapentin pharmacokinetics following single‑ and multiple‑dose administration were unaltered by pregabalin co-administration. The extent of pregabalin absorption was unaffected by gabapentin co-administration, although there was a small reduction in rate of absorption.

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of lorazepam single‑dose pharmacokinetics and single‑dose administration of lorazepam (1 mg) had no effect on the steady‑state pharmacokinetics of pregabalin. Additive effects on cognitive and gross motor functioning were seen when LYRICA was co‑administered with lorazepam. No clinically important effects on respiration were seen [see Drug Interactions (7)].

Pregabalin co-administration (200 mg 3 times a day) had no effect on the steady‑state pharmacokinetics of norethindrone and ethinyl estradiol (1 mg/35 μg, respectively) in healthy subjects.

Multiple-dose administration of pregabalin (300 mg twice a day) in healthy subjects had no effect on the rate and extent of oxycodone single‑dose pharmacokinetics. Single‑dose administration of oxycodone (10 mg) had no effect on the steady‑state pharmacokinetics of pregabalin. Additive effects on cognitive and gross motor functioning were seen when LYRICA was co‑administered with oxycodone. No clinically important effects on respiration were seen [see Drug Interactions (7)].

Steady-state trough plasma concentrations of phenytoin, carbamazepine, and carbamazepine 10,11 epoxide, valproic acid, and lamotrigine were not affected by concomitant pregabalin (200 mg 3 times a day) administration.

Population pharmacokinetic analyses in patients treated with pregabalin and various concomitant medications suggest the following:

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="32%"/> <col width="68%"/> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Therapeutic class</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Specific concomitant drug studied</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold"><span class="Italics">Concomitant drug has no effect on the pharmacokinetics of pregabalin</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Hypoglycemics</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Glyburide, insulin, metformin</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diuretics</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Furosemide</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Antiepileptic Drugs</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Tiagabine</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold"><span class="Italics">Concomitant drug has no effect on the pharmacokinetics of pregabalin and pregabalin has no effect on the pharmacokinetics of concomitant drug</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Antiepileptic Drugs</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, valproic acid</p> </td> </tr> </tbody> </table></div>

A dose‑dependent increase in the incidence of malignant vascular tumors (hemangiosarcomas) was observed in 2 strains of mice (B6C3F1 and CD‑1) given pregabalin (200, 1000, or 5000 mg/kg) in the diet for 2 years. Plasma pregabalin exposure (AUC) in mice receiving the lowest dose that increased hemangiosarcomas was approximately equal to the human exposure at the maximum recommended human dose (MRD) of 660 mg/day. A no‑effect dose for induction of hemangiosarcomas in mice was not established. No evidence of carcinogenicity was seen in 2 studies in Wistar rats following dietary administration of pregabalin for 2 years at doses (50, 150, or 450 mg/kg in males and 100, 300, or 900 mg/kg in females) that were associated with plasma exposures in males and females up to approximately 15 and 26 times, respectively, human exposure at the MRD.

Pregabalin was not mutagenic in bacteria or in mammalian cells in vitro, was not clastogenic in mammalian systems in vitro and in vivo, and did not induce unscheduled DNA synthesis in mouse or rat hepatocytes.

In fertility studies in which male rats were orally administered pregabalin (50 to 2500 mg/kg) prior to and during mating with untreated females, a number of adverse reproductive and developmental effects were observed. These included decreased sperm counts and sperm motility, increased sperm abnormalities, reduced fertility, increased preimplantation embryo loss, decreased litter size, decreased fetal body weights, and an increased incidence of fetal abnormalities. Effects on sperm and fertility parameters were reversible in studies of this duration (3-4 months). The no‑effect dose for male reproductive toxicity in these studies (100 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately 4 times human exposure at the MRD of 660 mg/day.

In addition, adverse reactions on reproductive organ (testes, epididymides) histopathology were observed in male rats exposed to pregabalin (500 to 1250 mg/kg) in general toxicology studies of 4 weeks or greater duration. The no‑effect dose for male reproductive organ histopathology in rats (250 mg/kg) was associated with a plasma exposure approximately 10 times human exposure at the MRD.

In a fertility study in which female rats were given pregabalin (500, 1250, or 2500 mg/kg) orally prior to and during mating and early gestation, disrupted estrous cyclicity and an increased number of days to mating were seen at all doses, and embryolethality occurred at the highest dose. The low dose in this study produced a plasma exposure approximately 10 times that in humans receiving the MRD. A no‑effect dose for female reproductive toxicity in rats was not established.

Skin lesions ranging from erythema to necrosis were seen in repeated‑dose toxicology studies in both rats and monkeys. The etiology of these skin lesions is unknown. At the MRD of 660 mg/day, there is a 2‑fold safety margin for the dermatological lesions. The more severe dermatopathies involving necrosis were associated with pregabalin exposures (as expressed by plasma AUCs) of approximately 3 to 8 times those achieved in humans given the MRD. No increase in incidence of skin lesions was observed in clinical studies.

Ocular lesions (characterized by retinal atrophy [including loss of photoreceptor cells] and/or corneal inflammation/mineralization) were observed in 2 lifetime carcinogenicity studies in Wistar rats. These findings were observed at plasma pregabalin exposures (AUC) greater than or equal to 2 times those achieved in humans given the maximum recommended dose of 660 mg/day. A no‑effect dose for ocular lesions was not established. Similar lesions were not observed in lifetime carcinogenicity studies in 2 strains of mice or in monkeys treated for 1 year.

Support for efficacy of LYRICA CR for the management of PHN and diabetic peripheral neuropathy (DPN) was based on the efficacy of LYRICA for these indications along with an adequate and well‑controlled study in adults with PHN. This 19‑week randomized withdrawal study compared daily doses of LYRICA CR 82.5 mg, 165 mg, 247.5 mg, 330 mg, 495 mg, or 660 mg with placebo. Those enrolled were required to have pain present for more than 3 months after healing of the herpes zoster skin rash and a baseline pain score of greater than or equal to 4 on the numeric rating scale (NRS)‑Pain (assessed over a 1 week recall period). The baseline mean pain scores were 6.83 for LYRICA CR‑treated patients vs. 6.85 for placebo‑treated patients. A total of 82.4% of patients completed the single‑blind phase of the study. Patients were considered responders if they had at least a 50% reduction in pain in the single‑blind phase. Those who responded to treatment were then randomized in the double‑blind phase to treatment with either the LYRICA CR dose achieved in the single‑blind phase or placebo. Patients were treated for up to 3 months following randomization. A total of 87.5% of LYRICA CR‑treated patients and 78% of placebo‑treated patients completed the double-blind phase of the study.

LYRICA CR treatment demonstrated statistically significant improvement in the endpoint change in mean pain score from baseline compared to placebo. For a range of levels of improvement in pain intensity from baseline to study endpoint, Figure 1 shows the fraction of patients achieving that degree of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. In the LYRICA CR group, 79.8% of subjects achieved at least a 30% improvement and 73.6% at least 50% improvement in pain intensity. In the placebo group, 64.9% of subjects achieved at least a 30% improvement and 54.6% at least a 50% improvement in pain intensity.

A double-blind, placebo-controlled, randomized withdrawal trial of LYRICA CR in adults with fibromyalgia failed to demonstrate efficacy.

A double-blind, placebo-controlled, randomized trial of LYRICA CR as adjunctive therapy in adults with partial onset seizures failed to demonstrate efficacy.

LYRICA CR is supplied in the following strengths and package configurations:

{ "type": "p", "children": [], "text": "LYRICA CR is supplied in the following strengths and package configurations:" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col width="25%"/> <col width="14%"/> <col width="21%"/> <col width="40%"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="4" valign="top"> <p class="First"> <span class="Bold">LYRICA CR Tablets</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Package Configuration</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Tablet<br/>Strength <br/>(mg)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">NDC</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Tablet Description</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Bottles of 30 tablets</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">82.5 mg</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 58151-245-93</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Light blue, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 82.5” on the other side</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Bottles of 30 tablets</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">165 mg</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 58151-246-93</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Beige, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 165” on the other side</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Bottles of 30 tablets</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">330 mg</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">NDC 58151-247-93</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Rose, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 330” on the other side</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col width=\"25%\"/>\n<col width=\"14%\"/>\n<col width=\"21%\"/>\n<col width=\"40%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"4\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">LYRICA CR Tablets</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Package Configuration</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Tablet<br/>Strength <br/>(mg)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">NDC</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Tablet Description</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Bottles of 30 tablets</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">82.5 mg</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">NDC 58151-245-93</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Light blue, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 82.5” on the other side</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">Bottles of 30 tablets</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">165 mg</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">NDC 58151-246-93</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Beige, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 165” on the other side</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Bottles of 30 tablets</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">330 mg</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">NDC 58151-247-93</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">Rose, film-coated, almond-shaped tablet debossed with “VLE” on one side and “PGN 330” on the other side</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F) in the original package. (See USP Controlled Room Temperature)

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F) in the original package. (See USP Controlled Room Temperature)" }

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Medication Guide)." }

Angioedema

{ "type": "p", "children": [], "text": "\nAngioedema\n" }

Advise patients that LYRICA CR may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue LYRICA CR and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients that LYRICA CR may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue LYRICA CR and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.1)]." }

Hypersensitivity

{ "type": "p", "children": [], "text": "\nHypersensitivity\n" }

Advise patients that LYRICA CR has been associated with hypersensitivity reactions such as skin redness, blisters, hives, rash, dyspnea, and wheezing. Instruct patients to discontinue LYRICA CR and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients that LYRICA CR has been associated with hypersensitivity reactions such as skin redness, blisters, hives, rash, dyspnea, and wheezing. Instruct patients to discontinue LYRICA CR and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.2)]." }

Suicidal Thinking and Behavior

{ "type": "p", "children": [], "text": "\nSuicidal Thinking and Behavior\n" }

Counsel patients, their caregivers, and families that AEDs, including pregabalin, the active ingredient in LYRICA CR, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to a healthcare provider. Also inform patients who plan to or have discontinued LYRICA CR that suicidal thoughts and behavior can appear even after the drug is stopped [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Counsel patients, their caregivers, and families that AEDs, including pregabalin, the active ingredient in LYRICA CR, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to a healthcare provider. Also inform patients who plan to or have discontinued LYRICA CR that suicidal thoughts and behavior can appear even after the drug is stopped [see Warnings and Precautions (5.3)]." }

Respiratory Depression

{ "type": "p", "children": [], "text": "\nRespiratory Depression\n" }

Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs [see Warnings and Precautions (5.5)]." }

Dizziness and Somnolence

{ "type": "p", "children": [], "text": "\nDizziness and Somnolence\n" }

Inform patients that LYRICA CR may cause dizziness, somnolence, blurred vision, and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on LYRICA CR to gauge whether or not it affects their mental, visual, and/or motor performance adversely [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "Inform patients that LYRICA CR may cause dizziness, somnolence, blurred vision, and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on LYRICA CR to gauge whether or not it affects their mental, visual, and/or motor performance adversely [see Warnings and Precautions (5.6)]." }

CNS Depressants

{ "type": "p", "children": [], "text": "\nCNS Depressants\n" }

Inform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as respiratory depression, somnolence, and dizziness [see Warnings and Precautions (5.5, 5.6) and Drug Interactions (7)]. Advise patients to avoid consuming alcohol while taking LYRICA CR, as LYRICA CR may potentiate the impairment of motor skills and sedating effects of alcohol [see Drug Interactions (7)].

{ "type": "p", "children": [], "text": "Inform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as respiratory depression, somnolence, and dizziness [see Warnings and Precautions (5.5, 5.6) and Drug Interactions (7)]. Advise patients to avoid consuming alcohol while taking LYRICA CR, as LYRICA CR may potentiate the impairment of motor skills and sedating effects of alcohol [see Drug Interactions (7)]." }

Abrupt or Rapid Discontinuation

{ "type": "p", "children": [], "text": "\nAbrupt or Rapid Discontinuation\n" }

Advise patients to take LYRICA CR as prescribed. Abrupt or rapid discontinuation may result in insomnia, nausea, headache, anxiety, or diarrhea. Advise patients with seizure disorders that abrupt or rapid discontinuation may increase seizure frequency [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Advise patients to take LYRICA CR as prescribed. Abrupt or rapid discontinuation may result in insomnia, nausea, headache, anxiety, or diarrhea. Advise patients with seizure disorders that abrupt or rapid discontinuation may increase seizure frequency [see Warnings and Precautions (5.4)]." }

Missed Dose

{ "type": "p", "children": [], "text": "\nMissed Dose\n" }

Instruct patients that if they miss taking their dose of LYRICA CR after an evening meal, then they should take their usual dose of LYRICA CR prior to bedtime following a snack. If they miss taking the dose of LYRICA CR prior to bedtime, then they should take their usual dose of LYRICA CR following a morning meal. If they miss taking the dose of LYRICA CR following the morning meal, then they should take their usual dose of LYRICA CR at the usual time that evening following an evening meal.

{ "type": "p", "children": [], "text": "Instruct patients that if they miss taking their dose of LYRICA CR after an evening meal, then they should take their usual dose of LYRICA CR prior to bedtime following a snack. If they miss taking the dose of LYRICA CR prior to bedtime, then they should take their usual dose of LYRICA CR following a morning meal. If they miss taking the dose of LYRICA CR following the morning meal, then they should take their usual dose of LYRICA CR at the usual time that evening following an evening meal." }

Weight Gain and Edema

{ "type": "p", "children": [], "text": "\nWeight Gain and Edema\n" }

Inform patients that LYRICA CR may cause edema and weight gain. Advise patients that concomitant treatment with LYRICA CR and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. Advise patients with preexisting cardiac conditions that this may increase the risk of heart failure [see Warnings and Precautions (5.7, 5.8)].

{ "type": "p", "children": [], "text": "Inform patients that LYRICA CR may cause edema and weight gain. Advise patients that concomitant treatment with LYRICA CR and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. Advise patients with preexisting cardiac conditions that this may increase the risk of heart failure [see Warnings and Precautions (5.7, 5.8)]." }

Ophthalmological Effects

{ "type": "p", "children": [], "text": "\nOphthalmological Effects\n" }

Counsel patients that LYRICA CR may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician [see Warnings and Precautions (5.10)].

{ "type": "p", "children": [], "text": "Counsel patients that LYRICA CR may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician [see Warnings and Precautions (5.10)]." }

Creatine Kinase Elevations

{ "type": "p", "children": [], "text": "\nCreatine Kinase Elevations\n" }

Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever [see Warnings and Precautions (5.11)].

{ "type": "p", "children": [], "text": "Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever [see Warnings and Precautions (5.11)]." }

Use in Pregnancy

{ "type": "p", "children": [], "text": "\nUse in Pregnancy\n" }

Instruct patients to inform their healthcare provider if they are pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy [see Use in Specific Populations (8.1) and (8.2)].

{ "type": "p", "children": [], "text": "Instruct patients to inform their healthcare provider if they are pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy [see Use in Specific Populations (8.1) and (8.2)]." }

Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334 [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334 [see Use in Specific Populations (8.1)]." }

Lactation

{ "type": "p", "children": [], "text": "\nLactation\n" }

Advise nursing mothers that breastfeeding is not recommended during treatment with LYRICA CR [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise nursing mothers that breastfeeding is not recommended during treatment with LYRICA CR [see Use in Specific Populations (8.2)]." }

Male Fertility

{ "type": "p", "children": [], "text": "\nMale Fertility\n" }

Inform men being treated with LYRICA CR who plan to father a child of the potential risk of male-mediated teratogenicity [see Nonclinical Toxicology (13.1) and Use in Specific Populations (8.3)].

{ "type": "p", "children": [], "text": "Inform men being treated with LYRICA CR who plan to father a child of the potential risk of male-mediated teratogenicity [see Nonclinical Toxicology (13.1) and Use in Specific Populations (8.3)]." }

Dermatopathy

{ "type": "p", "children": [], "text": "\nDermatopathy\n" }

Instruct diabetic patients to pay particular attention to skin integrity while being treated with LYRICA CR [see Nonclinical Toxicology (13.2)].

{ "type": "p", "children": [], "text": "Instruct diabetic patients to pay particular attention to skin integrity while being treated with LYRICA CR [see Nonclinical Toxicology (13.2)]." }

Distributed by: Viatris Specialty LLC Morgantown, WV 26505 U.S.A.

{ "type": "p", "children": [], "text": "Distributed by:\nViatris Specialty LLC\nMorgantown, WV 26505 U.S.A. " }

© 2025 Viatris Inc.

{ "type": "p", "children": [], "text": "© 2025 Viatris Inc." }

LYRICA is a registered trademark of Viatris Specialty LLC, a Viatris Company.

{ "type": "p", "children": [], "text": "LYRICA is a registered trademark of Viatris Specialty LLC, a Viatris Company." }

The brands listed are trademarks of their respective owners.

{ "type": "p", "children": [], "text": "The brands listed are trademarks of their respective owners." }

UPJ:LYRCCR:RX3

{ "type": "p", "children": [], "text": "UPJ:LYRCCR:RX3" }

LYRICA (LEER-i-kah) CR(pregabalin)extended-release tablets, CV

{ "type": "p", "children": [], "text": "\nLYRICA (LEER-i-kah) CR(pregabalin)extended-release tablets, CV\n" }

<div class="scrollingtable"><table width="100%"> <col width="48%"/> <col width="2%"/> <col width="50%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First">Read this Medication Guide before you start taking LYRICA CR and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about LYRICA CR, ask your healthcare provider or pharmacist.</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What is the most important information I should know about LYRICA CR?<br/> </span> </p> <p> <span class="Bold">LYRICA CR may cause serious side effects including:</span> </p> </td> </tr> <tr> <td class="Lrule" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Serious, even life-threatening, allergic reactions</span> </dd> <dt>•</dt> <dd> <span class="Bold">Suicidal thoughts or actions</span> </dd> <dt>•</dt> <dd> <span class="Bold">Serious breathing problems</span> </dd> </dl> </td><td class="Rrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd> <span class="Bold">Swelling of your hands, legs and feet</span> </dd> <dt>•</dt> <dd> <span class="Bold">Dizziness and sleepiness</span> </dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"></td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">These serious side effects are described below:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Serious, even life-threatening, allergic reactions.<br/> </span>Stop taking LYRICA CR and call your healthcare provider right away if you have any of these signs of a serious allergic reaction:<dl> <dt>o</dt> <dd>swelling of your face, mouth, lips, gums, tongue, throat, or neck</dd> <dt>o</dt> <dd>trouble breathing</dd> <dt>o</dt> <dd>rash, hives (raised bumps), or blisters</dd> <dt>o</dt> <dd>skin redness</dd> </dl> </dd> </dl> <p> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Like other antiepileptic drugs, LYRICA CR may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.</span> This can happen while you take LYRICA CR or after stopping. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:</dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"> <dl> <dt>o</dt> <dd>thoughts about suicide or dying</dd> <dt>o</dt> <dd>attempts to commit suicide</dd> <dt>o</dt> <dd>new or worse depression</dd> <dt>o</dt> <dd>new or worse anxiety</dd> <dt>o</dt> <dd>feeling agitated or restless</dd> <dt>o</dt> <dd>panic attacks</dd> </dl> </td><td class="Rrule" colspan="2" valign="top"> <dl> <dt>o</dt> <dd>trouble sleeping (insomnia)</dd> <dt>o</dt> <dd>new or worse irritability</dd> <dt>o</dt> <dd>acting aggressive, being angry, or violent</dd> <dt>o</dt> <dd>acting on dangerous impulses</dd> <dt>o</dt> <dd>an extreme increase in activity and talking (mania)</dd> <dt>o</dt> <dd>other unusual changes in behavior or mood</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">If you have suicidal thoughts or actions, do not stop LYRICA CR without first talking to a healthcare provider.</span> </p> <dl> <dt> </dt> <dd> <dl> <dt>o</dt> <dd>Stopping LYRICA CR suddenly can cause serious problems.</dd> <dt>o</dt> <dd>Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes. </dd> </dl> </dd> </dl> <p> <span class="Bold">How can I watch for early symptoms of suicidal thoughts and actions?</span> </p> <dl> <dt>o</dt> <dd>Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.</dd> <dt>o</dt> <dd>Keep all follow-up visits with your healthcare provider as scheduled.</dd> <dt>o</dt> <dd>Call your healthcare provider between visits as needed, especially if you are worried about symptoms.</dd> </dl> <p> <span class="Bold"> </span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Serious breathing problems</span> can occur when LYRICA is taken with other medicines that can cause severe sleepiness or decreased awareness, or when it is taken by someone who already has breathing problems. Watch for increased sleepiness or decreased breathing when starting LYRICA or when the dose is increased. Get help right away if breathing problems occur.</dd> <dt>•</dt> <dd> <span class="Bold">Swelling of your hands, legs and feet.</span> This swelling can be a serious problem for people with heart problems.</dd> <dt>•</dt> <dd> <span class="Bold">Dizziness and sleepiness.</span> Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA CR affects you. Ask your healthcare provider about when it will be okay to do these activities.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What is LYRICA CR?</span> </p> <p> </p> <p>LYRICA CR is a prescription medicine used to treat:</p> <dl> <dt>•</dt> <dd>pain from damaged nerves (neuropathic pain) that happens with diabetes </dd> <dt>•</dt> <dd>pain from damaged nerves (neuropathic pain) that follows healing of shingles </dd> </dl> <p>It is not known if LYRICA CR is safe and effective in children.</p> <p> </p> <p>It is not known if LYRICA CR is effective when used for the treatment of fibromyalgia, or when taken with other seizure medicines for adults with partial onset seizures.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Who should not take LYRICA CR?</span> </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">Do not take LYRICA CR if you are allergic to pregabalin or any of the ingredients in LYRICA CR. </span> </p> <p> <span class="Bold"> </span> </p> <p>See “What is the most important information I should know about LYRICA CR?” for the signs of an allergic reaction. </p> <p> </p> <p>See the end of this leaflet for a complete list of ingredients in LYRICA CR.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What should I tell my healthcare provider before taking LYRICA CR?</span> </p> <p> <span class="Bold"> </span> </p> <p>Before taking LYRICA CR, tell your healthcare provider about all your medical conditions, including if you:</p> <dl> <dt>•</dt> <dd>have or have had depression, mood problems or suicidal thoughts or behavior </dd> <dt>•</dt> <dd>have breathing problems</dd> <dt>•</dt> <dd>have kidney problems or get kidney dialysis </dd> <dt>•</dt> <dd>have heart problems including heart failure </dd> <dt>•</dt> <dd>have a bleeding problem or a low blood platelet count </dd> <dt>•</dt> <dd>have abused prescription medicines, street drugs, or alcohol in the past</dd> <dt>•</dt> <dd>have ever had swelling of your face, mouth, tongue, lips, gums, neck, or throat (angioedema)</dd> <dt>•</dt> <dd>plan to father a child. Animal studies have shown that pregabalin, the active ingredient in LYRICA CR, made male animals less fertile and caused sperm to change. Also, in animal studies, birth defects were seen in the offspring (babies) of male animals treated with pregabalin. It is not known if these problems can happen in people who take LYRICA CR. </dd> <dt>•</dt> <dd> <span class="Bold">are pregnant or plan to become pregnant. It is not known if LYRICA CR will harm your unborn baby.</span> You and your healthcare provider will have to decide if you should take LYRICA CR while you are pregnant. <dl> <dt>o</dt> <dd>If you become pregnant while taking LYRICA CR, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs, including pregabalin, the active ingredient in LYRICA CR. Information about the registry can be found at the website, http://www.aedpregnancyregistry.org/. </dd> </dl> </dd> <dt>•</dt> <dd> <span class="Bold">are breastfeeding or plan to breastfeed. LYRICA CR passes into your breast milk. It is not known if LYRICA CR can harm your baby.</span> Talk to your healthcare provider about the best way to feed your baby if you take LYRICA CR. <span class="Bold">Breastfeeding is not recommended while taking LYRICA CR.</span> </dd> </dl> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins or herbal supplements. LYRICA CR and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take:</p> <dl> <dt>•</dt> <dd>angiotensin converting enzyme (ACE) inhibitors, which are used to treat many conditions, including high blood pressure. You may have a higher chance for swelling and hives if these medicines are taken with LYRICA CR. See “What is the most important information I should know about LYRICA CR?”</dd> <dt>•</dt> <dd>Avandia<span class="Sup">®</span> (rosiglitazone), Avandamet<span class="Sup">®</span> (contains rosiglitazone and metformin), or Actos<span class="Sup">®</span> (pioglitazone) for diabetes. You may have a higher chance of weight gain or swelling of your hands or feet if these medicines are taken with LYRICA CR. See “What are the possible side effects of LYRICA CR.”</dd> <dt>•</dt> <dd>any opioid pain medicine (such as oxycodone), or medicines for anxiety (such as lorazepam) or insomnia (such as zolpidem). You may have a higher chance for dizziness, sleepiness or serious breathing problems if these medicines are taken with LYRICA CR.</dd> <dt>•</dt> <dd>any medicines that make you sleepy </dd> </dl> <p>Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">How should I take LYRICA CR? </span> </p> <dl> <dt>•</dt> <dd>Take LYRICA CR exactly as prescribed. Your healthcare provider will tell you how much LYRICA CR to take and when to take it. </dd> <dt>•</dt> <dd>Take LYRICA CR at the same time each day. </dd> <dt>•</dt> <dd>LYRICA CR must be taken <span class="Bold">after</span> your evening meal. Swallow the tablet whole and do not split, crush or chew the tablet.</dd> <dt>•</dt> <dd>Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.</dd> <dt>•</dt> <dd> <span class="Bold">Do not stop taking LYRICA CR without talking to your healthcare provider.</span> If you stop taking LYRICA CR suddenly, you may have headaches, nausea, diarrhea, trouble sleeping, or you may feel anxious. If you have epilepsy, are taking LYRICA CR for pain, and stop taking LYRICA CR suddenly you may have seizures more often. Talk with your healthcare provider about how to stop LYRICA CR slowly. </dd> <dt>•</dt> <dd>If you miss a dose after your evening meal, take it prior to bedtime following a snack. If you miss the dose prior to bedtime, then take it following your morning meal. If you do not take the dose the following morning, then take the next dose at your regular time after your evening meal. <span class="Bold">Do not take 2 doses at the same time.</span> </dd> <dt>•</dt> <dd>If you take too much LYRICA CR, call your healthcare provider or poison control center, or go to the nearest emergency room right away.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What should I avoid while taking LYRICA CR?</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA CR affects you. </span> </dd> <dt>•</dt> <dd> <span class="Bold">Do not drink alcohol while taking LYRICA CR.</span> LYRICA CR and alcohol can affect each other and increase side effects such as sleepiness and dizziness.</dd> </dl> <p> </p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of LYRICA CR?</span> </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">LYRICA CR may cause serious side effects, including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">muscle problems, muscle pain, soreness, or weakness.</span> If you have these symptoms, especially if you feel sick and have a fever, tell your healthcare provider right away. </dd> <dt>•</dt> <dd> <span class="Bold">problems with your eyesight, including blurry vision.</span> Call your healthcare provider if you have any changes in your eyesight.</dd> <dt>•</dt> <dd> <span class="Bold">weight gain.</span> If you have diabetes, weight gain may affect the management of your diabetes. Weight gain can also be a serious problem for people with heart problems. </dd> <dt>•</dt> <dd> <span class="Bold">Feeling “high”</span> </dd> </dl> <p> <span class="Bold">The most common side effects of LYRICA CR are:</span> </p> </td> </tr> <tr> <td class="Lrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd>dizziness</dd> <dt>•</dt> <dd>blurry vision</dd> <dt>•</dt> <dd>weight gain</dd> <dt>•</dt> <dd>sleepiness </dd> <dt>•</dt> <dd>fatigue (tiredness)</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>•</dt> <dd>swelling of hands and feet</dd> <dt>•</dt> <dd>dry mouth</dd> <dt>•</dt> <dd>nausea</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> </p> <p>LYRICA CR caused skin sores in animal studies. Skin sores did not happen in studies in people. If you have diabetes, you should pay attention to your skin while taking LYRICA CR and tell your healthcare provider about any sores or skin problems.</p> <p> </p> <p>Tell your healthcare provider about any side effect that bothers you or that does not go away.</p> <p> </p> <p>These are not all the possible side effects of LYRICA CR. For more information, ask your healthcare provider or pharmacist.</p> <p> </p> <p> <span class="Bold">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">How should I store LYRICA CR?</span> </p> <dl> <dt>•</dt> <dd>Store LYRICA CR at room temperature between 68°F to 77°F (20°C to 25°C) in its original package.</dd> <dt>•</dt> <dd>Safely throw away any LYRICA CR that is out of date or no longer needed.</dd> </dl> <p> <span class="Bold">Keep LYRICA CR and all medicines out of the reach of children.</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of LYRICA CR.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use LYRICA CR for a condition for which it was not prescribed. Do not give LYRICA CR to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about LYRICA CR that is written for health professionals.</p> <p> </p> <p>You can also call Viatris at 1-877-446-3679 (1-877-4-INFO-RX).</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in LYRICA CR?</span> </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">Active ingredient:</span> pregabalin</p> <p> <span class="Bold">Inactive ingredients:</span> carbomer, colorants, crospovidone, Kollidon SR (polyvinyl acetate, povidone, sodium lauryl sulphate, and silica), magnesium stearate, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, talc, and titanium dioxide.</p> <p> </p> <p>Distributed by:<br/> <span class="Bold">Viatris Specialty LLC<br/> </span>Morgantown, WV 26505 U.S.A. </p> <p> </p> <p>© 2025 Viatris Inc.</p> <p> </p> <p>LYRICA is a registered trademark of Viatris Specialty LLC, a Viatris Company.</p> <p> </p> <p>The brands listed are trademarks of their respective owners.</p> <p> </p> <p>UPJ:MG:LYRCCR:RX3</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"48%\"/>\n<col width=\"2%\"/>\n<col width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">Read this Medication Guide before you start taking LYRICA CR and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about LYRICA CR, ask your healthcare provider or pharmacist.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about LYRICA CR?<br/> </span>\n</p>\n<p>\n<span class=\"Bold\">LYRICA CR may cause serious side effects including:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Serious, even life-threatening, allergic reactions</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Suicidal thoughts or actions</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Serious breathing problems</span>\n</dd>\n</dl>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Swelling of your hands, legs and feet</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Dizziness and sleepiness</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">These serious side effects are described below:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Serious, even life-threatening, allergic reactions.<br/>\n</span>Stop taking LYRICA CR and call your healthcare provider right away if you have any of these signs of a serious allergic reaction:<dl>\n<dt>o</dt>\n<dd>swelling of your face, mouth, lips, gums, tongue, throat, or neck</dd>\n<dt>o</dt>\n<dd>trouble breathing</dd>\n<dt>o</dt>\n<dd>rash, hives (raised bumps), or blisters</dd>\n<dt>o</dt>\n<dd>skin redness</dd>\n</dl>\n</dd>\n</dl>\n<p> </p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Like other antiepileptic drugs, LYRICA CR may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.</span> This can happen while you take LYRICA CR or after stopping. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>thoughts about suicide or dying</dd>\n<dt>o</dt>\n<dd>attempts to commit suicide</dd>\n<dt>o</dt>\n<dd>new or worse depression</dd>\n<dt>o</dt>\n<dd>new or worse anxiety</dd>\n<dt>o</dt>\n<dd>feeling agitated or restless</dd>\n<dt>o</dt>\n<dd>panic attacks</dd>\n</dl>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>o</dt>\n<dd>trouble sleeping (insomnia)</dd>\n<dt>o</dt>\n<dd>new or worse irritability</dd>\n<dt>o</dt>\n<dd>acting aggressive, being angry, or violent</dd>\n<dt>o</dt>\n<dd>acting on dangerous impulses</dd>\n<dt>o</dt>\n<dd>an extreme increase in activity and talking (mania)</dd>\n<dt>o</dt>\n<dd>other unusual changes in behavior or mood</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">If you have suicidal thoughts or actions, do not stop LYRICA CR without first talking to a healthcare provider.</span>\n</p>\n<dl>\n<dt> </dt>\n<dd>\n<dl>\n<dt>o</dt>\n<dd>Stopping LYRICA CR suddenly can cause serious problems.</dd>\n<dt>o</dt>\n<dd>Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes. </dd>\n</dl>\n</dd>\n</dl>\n<p>\n<span class=\"Bold\">How can I watch for early symptoms of suicidal thoughts and actions?</span>\n</p>\n<dl>\n<dt>o</dt>\n<dd>Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.</dd>\n<dt>o</dt>\n<dd>Keep all follow-up visits with your healthcare provider as scheduled.</dd>\n<dt>o</dt>\n<dd>Call your healthcare provider between visits as needed, especially if you are worried about symptoms.</dd>\n</dl>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Serious breathing problems</span> can occur when LYRICA is taken with other medicines that can cause severe sleepiness or decreased awareness, or when it is taken by someone who already has breathing problems. Watch for increased sleepiness or decreased breathing when starting LYRICA or when the dose is increased. Get help right away if breathing problems occur.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Swelling of your hands, legs and feet.</span> This swelling can be a serious problem for people with heart problems.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Dizziness and sleepiness.</span> Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA CR affects you. Ask your healthcare provider about when it will be okay to do these activities.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is LYRICA CR?</span>\n</p>\n<p> </p>\n<p>LYRICA CR is a prescription medicine used to treat:</p>\n<dl>\n<dt>•</dt>\n<dd>pain from damaged nerves (neuropathic pain) that happens with diabetes </dd>\n<dt>•</dt>\n<dd>pain from damaged nerves (neuropathic pain) that follows healing of shingles </dd>\n</dl>\n<p>It is not known if LYRICA CR is safe and effective in children.</p>\n<p> </p>\n<p>It is not known if LYRICA CR is effective when used for the treatment of fibromyalgia, or when taken with other seizure medicines for adults with partial onset seizures.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not take LYRICA CR?</span>\n</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Do not take LYRICA CR if you are allergic to pregabalin or any of the ingredients in LYRICA CR. </span>\n</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>See “What is the most important information I should know about LYRICA CR?” for the signs of an allergic reaction. </p>\n<p> </p>\n<p>See the end of this leaflet for a complete list of ingredients in LYRICA CR.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I tell my healthcare provider before taking LYRICA CR?</span>\n</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>Before taking LYRICA CR, tell your healthcare provider about all your medical conditions, including if you:</p>\n<dl>\n<dt>•</dt>\n<dd>have or have had depression, mood problems or suicidal thoughts or behavior </dd>\n<dt>•</dt>\n<dd>have breathing problems</dd>\n<dt>•</dt>\n<dd>have kidney problems or get kidney dialysis </dd>\n<dt>•</dt>\n<dd>have heart problems including heart failure </dd>\n<dt>•</dt>\n<dd>have a bleeding problem or a low blood platelet count </dd>\n<dt>•</dt>\n<dd>have abused prescription medicines, street drugs, or alcohol in the past</dd>\n<dt>•</dt>\n<dd>have ever had swelling of your face, mouth, tongue, lips, gums, neck, or throat (angioedema)</dd>\n<dt>•</dt>\n<dd>plan to father a child. Animal studies have shown that pregabalin, the active ingredient in LYRICA CR, made male animals less fertile and caused sperm to change. Also, in animal studies, birth defects were seen in the offspring (babies) of male animals treated with pregabalin. It is not known if these problems can happen in people who take LYRICA CR. </dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">are pregnant or plan to become pregnant. It is not known if LYRICA CR will harm your unborn baby.</span> You and your healthcare provider will have to decide if you should take LYRICA CR while you are pregnant. <dl>\n<dt>o</dt>\n<dd>If you become pregnant while taking LYRICA CR, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs, including pregabalin, the active ingredient in LYRICA CR. Information about the registry can be found at the website, http://www.aedpregnancyregistry.org/. </dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">are breastfeeding or plan to breastfeed. LYRICA CR passes into your breast milk. It is not known if LYRICA CR can harm your baby.</span> Talk to your healthcare provider about the best way to feed your baby if you take LYRICA CR. <span class=\"Bold\">Breastfeeding is not recommended while taking LYRICA CR.</span>\n</dd>\n</dl>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins or herbal supplements. LYRICA CR and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take:</p>\n<dl>\n<dt>•</dt>\n<dd>angiotensin converting enzyme (ACE) inhibitors, which are used to treat many conditions, including high blood pressure. You may have a higher chance for swelling and hives if these medicines are taken with LYRICA CR. See “What is the most important information I should know about LYRICA CR?”</dd>\n<dt>•</dt>\n<dd>Avandia<span class=\"Sup\">®</span> (rosiglitazone), Avandamet<span class=\"Sup\">®</span> (contains rosiglitazone and metformin), or Actos<span class=\"Sup\">®</span> (pioglitazone) for diabetes. You may have a higher chance of weight gain or swelling of your hands or feet if these medicines are taken with LYRICA CR. See “What are the possible side effects of LYRICA CR.”</dd>\n<dt>•</dt>\n<dd>any opioid pain medicine (such as oxycodone), or medicines for anxiety (such as lorazepam) or insomnia (such as zolpidem). You may have a higher chance for dizziness, sleepiness or serious breathing problems if these medicines are taken with LYRICA CR.</dd>\n<dt>•</dt>\n<dd>any medicines that make you sleepy </dd>\n</dl>\n<p>Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I take LYRICA CR? </span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Take LYRICA CR exactly as prescribed. Your healthcare provider will tell you how much LYRICA CR to take and when to take it. </dd>\n<dt>•</dt>\n<dd>Take LYRICA CR at the same time each day. </dd>\n<dt>•</dt>\n<dd>LYRICA CR must be taken <span class=\"Bold\">after</span> your evening meal. Swallow the tablet whole and do not split, crush or chew the tablet.</dd>\n<dt>•</dt>\n<dd>Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not stop taking LYRICA CR without talking to your healthcare provider.</span> If you stop taking LYRICA CR suddenly, you may have headaches, nausea, diarrhea, trouble sleeping, or you may feel anxious. If you have epilepsy, are taking LYRICA CR for pain, and stop taking LYRICA CR suddenly you may have seizures more often. Talk with your healthcare provider about how to stop LYRICA CR slowly. </dd>\n<dt>•</dt>\n<dd>If you miss a dose after your evening meal, take it prior to bedtime following a snack. If you miss the dose prior to bedtime, then take it following your morning meal. If you do not take the dose the following morning, then take the next dose at your regular time after your evening meal. <span class=\"Bold\">Do not take 2 doses at the same time.</span>\n</dd>\n<dt>•</dt>\n<dd>If you take too much LYRICA CR, call your healthcare provider or poison control center, or go to the nearest emergency room right away.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I avoid while taking LYRICA CR?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA CR affects you. </span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not drink alcohol while taking LYRICA CR.</span> LYRICA CR and alcohol can affect each other and increase side effects such as sleepiness and dizziness.</dd>\n</dl>\n<p> </p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of LYRICA CR?</span>\n</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">LYRICA CR may cause serious side effects, including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">muscle problems, muscle pain, soreness, or weakness.</span> If you have these symptoms, especially if you feel sick and have a fever, tell your healthcare provider right away. </dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">problems with your eyesight, including blurry vision.</span> Call your healthcare provider if you have any changes in your eyesight.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">weight gain.</span> If you have diabetes, weight gain may affect the management of your diabetes. Weight gain can also be a serious problem for people with heart problems. </dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Feeling “high”</span>\n</dd>\n</dl>\n<p>\n<span class=\"Bold\">The most common side effects of LYRICA CR are:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>dizziness</dd>\n<dt>•</dt>\n<dd>blurry vision</dd>\n<dt>•</dt>\n<dd>weight gain</dd>\n<dt>•</dt>\n<dd>sleepiness </dd>\n<dt>•</dt>\n<dd>fatigue (tiredness)</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>swelling of hands and feet</dd>\n<dt>•</dt>\n<dd>dry mouth</dd>\n<dt>•</dt>\n<dd>nausea</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\"> </p>\n<p>LYRICA CR caused skin sores in animal studies. Skin sores did not happen in studies in people. If you have diabetes, you should pay attention to your skin while taking LYRICA CR and tell your healthcare provider about any sores or skin problems.</p>\n<p> </p>\n<p>Tell your healthcare provider about any side effect that bothers you or that does not go away.</p>\n<p> </p>\n<p>These are not all the possible side effects of LYRICA CR. For more information, ask your healthcare provider or pharmacist.</p>\n<p> </p>\n<p>\n<span class=\"Bold\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store LYRICA CR?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Store LYRICA CR at room temperature between 68°F to 77°F (20°C to 25°C) in its original package.</dd>\n<dt>•</dt>\n<dd>Safely throw away any LYRICA CR that is out of date or no longer needed.</dd>\n</dl>\n<p>\n<span class=\"Bold\">Keep LYRICA CR and all medicines out of the reach of children.</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of LYRICA CR.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use LYRICA CR for a condition for which it was not prescribed. Do not give LYRICA CR to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about LYRICA CR that is written for health professionals.</p>\n<p> </p>\n<p>You can also call Viatris at 1-877-446-3679 (1-877-4-INFO-RX).</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in LYRICA CR?</span>\n</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient:</span> pregabalin</p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span> carbomer, colorants, crospovidone, Kollidon SR (polyvinyl acetate, povidone, sodium lauryl sulphate, and silica), magnesium stearate, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, talc, and titanium dioxide.</p>\n<p> </p>\n<p>Distributed by:<br/>\n<span class=\"Bold\">Viatris Specialty LLC<br/>\n</span>Morgantown, WV 26505 U.S.A. </p>\n<p> </p>\n<p>© 2025 Viatris Inc.</p>\n<p> </p>\n<p>LYRICA is a registered trademark of Viatris Specialty LLC, a Viatris Company.</p>\n<p> </p>\n<p>The brands listed are trademarks of their respective owners.</p>\n<p> </p>\n<p>UPJ:MG:LYRCCR:RX3</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Medication Guide has been approved by the U.S. Food and Drug Administration.          Revised: 04/2025

{ "type": "p", "children": [], "text": "This Medication Guide has been approved by the U.S. Food and Drug Administration.          Revised: 04/2025" }

NDC 58151-245-93

{ "type": "p", "children": [], "text": "\nNDC 58151-245-93\n" }

Lyrica® CR   CV(pregabalin)extended release tablets82.5 mg

{ "type": "p", "children": [], "text": "\nLyrica® CR   CV(pregabalin)extended release tablets82.5 mg\n" }

ALWAYS DISPENSE WITHMEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITHMEDICATION GUIDE\n" }

30 Tablets    Rx only

{ "type": "p", "children": [], "text": "\n30 Tablets    Rx only\n" }

Store at 20°C to 25°C (68°F to 77°F);excursions permitted between 15°Cand 30°C (between 59°F and 86°F)in the original package.[See USP Controlled Room Temperature]

{ "type": "p", "children": [], "text": "\nStore at 20°C to 25°C (68°F to 77°F);excursions permitted between 15°Cand 30°C (between 59°F and 86°F)in the original package.[See USP Controlled Room Temperature]\n" }

Dispense in tight (USP), child-resistantcontainers.

{ "type": "p", "children": [], "text": "Dispense in tight (USP), child-resistantcontainers." }

DOSAGE AND USE See accompanying prescribing information.

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\nSee accompanying prescribing information." }

Each tablet contains 82.5 mg pregabalin.

{ "type": "p", "children": [], "text": "Each tablet contains 82.5 mg pregabalin." }

Distributed by: Viatris Specialty LLC Morgantown, WV 26505 U.S.A.© 2024 Viatris Inc.

{ "type": "p", "children": [], "text": "Distributed by:\nViatris Specialty LLC\nMorgantown, WV 26505 U.S.A.© 2024 Viatris Inc." }

Made in Germany

{ "type": "p", "children": [], "text": "Made in Germany" }

RUPJ245H

{ "type": "p", "children": [], "text": "RUPJ245H" }

NDC 58151-246-93

{ "type": "p", "children": [], "text": "\nNDC 58151-246-93\n" }

Lyrica® CR   CV(pregabalin)extended release tablets165 mg

{ "type": "p", "children": [], "text": "\nLyrica® CR   CV(pregabalin)extended release tablets165 mg\n" }

ALWAYS DISPENSE WITHMEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITHMEDICATION GUIDE\n" }

30 Tablets    Rx only

{ "type": "p", "children": [], "text": "\n30 Tablets    Rx only\n" }

Store at 20°C to 25°C (68°F to 77°F);excursions permitted between 15°Cand 30°C (between 59°F and 86°F)in the original package.[See USP Controlled Room Temperature]

{ "type": "p", "children": [], "text": "\nStore at 20°C to 25°C (68°F to 77°F);excursions permitted between 15°Cand 30°C (between 59°F and 86°F)in the original package.[See USP Controlled Room Temperature]\n" }

Dispense in tight (USP), child-resistantcontainers.

{ "type": "p", "children": [], "text": "Dispense in tight (USP), child-resistantcontainers." }

DOSAGE AND USE See accompanying prescribing information.

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\nSee accompanying prescribing information." }

Each tablet contains 165 mg pregabalin.

{ "type": "p", "children": [], "text": "Each tablet contains 165 mg pregabalin." }

Distributed by: Viatris Specialty LLC Morgantown, WV 26505 U.S.A.© 2024 Viatris Inc.

{ "type": "p", "children": [], "text": "Distributed by:\nViatris Specialty LLC\nMorgantown, WV 26505 U.S.A.© 2024 Viatris Inc." }

Made in Germany

{ "type": "p", "children": [], "text": "Made in Germany" }

RUPJ246H

{ "type": "p", "children": [], "text": "RUPJ246H" }

NDC 58151-247-93

{ "type": "p", "children": [], "text": "\nNDC 58151-247-93\n" }

Lyrica® CR   CV(pregabalin)extended release tablets330 mg

{ "type": "p", "children": [], "text": "\nLyrica® CR   CV(pregabalin)extended release tablets330 mg\n" }

ALWAYS DISPENSE WITHMEDICATION GUIDE

{ "type": "p", "children": [], "text": "\nALWAYS DISPENSE WITHMEDICATION GUIDE\n" }

30 Tablets    Rx only

{ "type": "p", "children": [], "text": "\n30 Tablets    Rx only\n" }

Store at 20°C to 25°C (68°F to 77°F);excursions permitted between 15°Cand 30°C (between 59°F and 86°F)in the original package.[See USP Controlled Room Temperature]

{ "type": "p", "children": [], "text": "\nStore at 20°C to 25°C (68°F to 77°F);excursions permitted between 15°Cand 30°C (between 59°F and 86°F)in the original package.[See USP Controlled Room Temperature]\n" }

Dispense in tight (USP), child-resistantcontainers.

{ "type": "p", "children": [], "text": "Dispense in tight (USP), child-resistantcontainers." }

DOSAGE AND USE See accompanying prescribing information.

{ "type": "p", "children": [], "text": "\nDOSAGE AND USE\nSee accompanying prescribing information." }

Each tablet contains 330 mg pregabalin.

{ "type": "p", "children": [], "text": "Each tablet contains 330 mg pregabalin." }

Distributed by: Viatris Specialty LLC Morgantown, WV 26505 U.S.A.© 2024 Viatris Inc.

{ "type": "p", "children": [], "text": "Distributed by:\nViatris Specialty LLC\nMorgantown, WV 26505 U.S.A.© 2024 Viatris Inc." }

Made in Germany

{ "type": "p", "children": [], "text": "Made in Germany" }

RUPJ247H

{ "type": "p", "children": [], "text": "RUPJ247H" }