Limitations of use: The safety and effectiveness of GLOPERBA for acute treatment of gout flares during prophylaxis has not been studied.

GLOPERBA is not an analgesic medication and should not be used to treat pain from other causes.

For prophylaxis of gout flares, the recommended dosage of GLOPERBA is 0.6 mg (5 mL) once or twice daily. The maximum dose is 1.2 mg/day.

GLOPERBA is administered orally, without regard to meals.

Ready to use solution for oral administration containing 0.6 mg/5 mL of colchicine. The oral solution is a slightly hazy, red liquid with a cherry odor.

{ "type": "p", "children": [], "text": "Ready to use solution for oral administration containing 0.6 mg/5 mL of colchicine. The oral solution is a slightly hazy, red liquid with a cherry odor." }

Patients with renal or hepatic impairment should not be given GLOPERBA in conjunction with drugs that inhibit both CYP3A4 and P-gp [see Drug Interactions (7)]. Combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life threatening or fatal colchicine toxicity.

{ "type": "p", "children": [], "text": "Patients with renal or hepatic impairment should not be given GLOPERBA in conjunction with drugs that inhibit both CYP3A4 and P-gp\n \n [see\n \n Drug Interactions (7)].\n \n Combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life threatening or fatal colchicine toxicity.\n\n " }

Patients with both renal and hepatic impairment should not be given GLOPERBA.

{ "type": "p", "children": [], "text": "Patients with both renal and hepatic impairment should not be given GLOPERBA." }

Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Overdosage (10)]. GLOPERBA should be kept out of the reach of children.

Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported with colchicine used in therapeutic doses.

Because colchicine is a substrate for both the CYP3A4 metabolizing enzyme and the P-gp efflux transporter, inhibition of either of these pathways may lead to colchicine related toxicity. Inhibition of both CYP3A4 and P-gp by dual inhibitors (i.e., clarithromycin) has been reported to produce life threatening or fatal colchicine toxicity due to significant increases in systemic colchicine levels. Therefore, concomitant use of GLOPERBA with inhibitors of both CYP3A4 and P-gp should be avoided. If treatment with colchicine is necessary, a reduced daily dose should be considered and the patient should be closely monitored for colchicine toxicity [see Drug Interactions (7)].

Use of GLOPERBA in conjunction with drugs that inhibit both CYP3A4 and P-gp is contraindicated in patients with renal or hepatic impairment [see Contraindications (4)].

Colchicine induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses, especially in combination with other drugs known to cause this effect. Patients with impaired renal function and elderly patients, even those with normal renal and hepatic function, are at increased risk. Once colchicine treatment is stopped, the symptoms generally resolve within one week to several months.

Gastrointestinal disorders are the most common adverse reactions with colchicine. These disorders are often the first signs of toxicity and may indicate that the colchicine dose needs to be reduced or therapy stopped. These disorders include diarrhea, nausea, vomiting, and abdominal pain.

{ "type": "p", "children": [], "text": "Gastrointestinal disorders are the most common adverse reactions with colchicine. These disorders are often the first signs of toxicity and may indicate that the colchicine dose needs to be reduced or therapy stopped. These disorders include diarrhea, nausea, vomiting, and abdominal pain." }

Colchicine has been reported to cause neuromuscular toxicity, which may present as muscle pain or weakness [see Warnings and Precautions (5.4)] .

{ "type": "p", "children": [], "text": "Colchicine has been reported to cause neuromuscular toxicity, which may present as muscle pain or weakness\n \n [see\n \n Warnings and Precautions (5.4)]\n \n .\n\n " }

Toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation and injury to cells in the renal, hepatic, circulatory and central nervous systems. These toxicities most often occur with excessive accumulation or overdosage [see Overdosage (10)] .

{ "type": "p", "children": [], "text": "Toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation and injury to cells in the renal, hepatic, circulatory and central nervous systems. These toxicities most often occur with excessive accumulation or overdosage\n \n [see\n \n Overdosage (10)]\n \n .\n\n " }

The following adverse reactions have been reported with colchicine. These adverse reactions have been generally reversible upon interrupting treatment or lowering the dose of colchicine.

{ "type": "p", "children": [], "text": "The following adverse reactions have been reported with colchicine. These adverse reactions have been generally reversible upon interrupting treatment or lowering the dose of colchicine." }

Neurological:sensory motor neuropathy

{ "type": "p", "children": [], "text": "\nNeurological:sensory motor neuropathy\n\n " }

Dermatological:alopecia, maculopapular rash, purpura, rash

{ "type": "p", "children": [], "text": "\nDermatological:alopecia, maculopapular rash, purpura, rash\n\n " }

Digestive:abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting

{ "type": "p", "children": [], "text": "\nDigestive:abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting\n\n " }

Hematological:leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia

{ "type": "p", "children": [], "text": "\nHematological:leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia\n\n " }

Hepatobiliary:elevated AST, elevated ALT

{ "type": "p", "children": [], "text": "\nHepatobiliary:elevated AST, elevated ALT\n\n " }

Musculoskeletal:myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis

{ "type": "p", "children": [], "text": "\nMusculoskeletal:myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis\n\n " }

Reproductive:azoospermia, oligospermia

{ "type": "p", "children": [], "text": "\nReproductive:azoospermia, oligospermia\n\n " }

The concomitant use of GLOPERBA and CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, grapefruit juice, erythromycin, verapamil, etc.) should be avoided due to the potential for serious and life threatening toxicity [see Warnings and Precautions (5.3)and Clinical Pharmacology (12.3)] .

If co-administration of GLOPERBA and a CYP3A4 inhibitor is necessary, the dose of GLOPERBA should be adjusted by either reducing the daily dose or reducing the dose frequency, and the patient should be monitored carefully for colchicine toxicity [see Clinical Pharmacology (12.3)].

The concomitant use of GLOPERBA and inhibitors of P-glycoprotein (e.g. clarithromycin, ketoconazole, cyclosporine, etc.) should be avoided due to the potential for serious and life threatening toxicity [see Warnings and Precautions (5.3)and Clinical Pharmacology (12.3)] .

If co-administration of GLOPERBA and a P-gp inhibitor is necessary, the dose of GLOPERBA should be adjusted by either reducing the daily dose or reducing the dose frequency, and the patient should be monitored carefully for colchicine toxicity [see Clinical Pharmacology (12.3)] .

Some drugs such as HMG-CoA reductase inhibitors and fibrates may increase the risk of myopathy when combined with GLOPERBA. Complaints of muscle pain or weakness could be an indication to check serum creatinine kinase levels for signs of myopathy.

Two pharmacokinetic studies evaluated the effects of co-administration of posaconazole (300 mg QD), ciprofloxacin (500 mg BID), amlodipine (5 to 10 mg QD), and carvedilol (20 to 40 mg QD) on the systemic levels of colchicine.

GLOPERBA can be administered with amlodipine, carvedilol, and ciprofloxacin at the tested doses without a need for dose adjustment. However, the results should not be extrapolated to other co-administered drugs. Colchicine plasma levels were markedly elevated when GLOPERBA was co-administered with posaconazole. The recommended dose of GLOPERBA when co-administered with posaconazole is 0.24 mg (2 mL).

Risk Summary

Available human data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Although animal reproduction and development studies were not conducted with GLOPERBA, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity and altered postnatal development at exposures within or above the clinical therapeutic range.

The estimated background risk of major birth defects and miscarriage for the indicated population is 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.

Data

Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, Behçet's disease, or familial Mediterranean fever (FMF)) treated with colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.

Risk Summary

Colchicine is present in human milk (see Data) . Adverse events in breastfed infants have not been reported in the published literature after administration of colchicine to lactating women. There are no data on the effects of colchicine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for GLOPERBA and any potential adverse effects on the breastfed infant from GLOPERBA or from the underlying maternal condition.

Data

Limited published data from case reports and a small lactation study demonstrate that colchicine is present in breastmilk. A systematic review of literature reported no adverse effects in 149 breastfed children and advised to reconsider breastfeeding if the infant has diarrhea. In a prospective observational cohort study, no gastrointestinal or other symptoms were reported in 38 colchicine exposed breastfed infants.

Infertility

Case reports and epidemiology studies in human male subjects on colchicine therapy indicate that infertility from colchicine is rare and may be reversible.

Gout is rare in pediatric patients; safety and effectiveness of GLOPERBA in pediatric patients has not been established.

Because of the increased incidence of decreased renal function in the elderly population, and the higher incidence of other co-morbid conditions in the elderly population requiring the use of other medications, reducing the dosage of colchicine when elderly patients are treated with colchicine should be carefully considered [see Clinical Pharmacology (12.3)] .

No dedicated pharmacokinetic study has been conducted using GLOPERBA in patients with varying degrees of renal impairment. Colchicine is known to be excreted in urine in humans and the presence of severe renal impairment has been associated with colchicine toxicity. Urinary clearance of colchicine and its metabolites may be decreased in patients with impaired renal function. Dose reduction or alternatives should be considered for the prophylaxis of gout flares in patients with severe renal impairment. Colchicine is not effectively removed by hemodialysis. Patients who are undergoing hemodialysis should be monitored carefully for colchicine toxicity.

No dedicated pharmacokinetic study using GLOPERBA has been conducted in patients with varying degrees of hepatic impairment. Colchicine is known to be metabolized in humans and the presence of severe hepatic impairment has been associated with colchicine toxicity. Hepatic clearance of colchicine may be significantly reduced and plasma half life prolonged in patients with chronic hepatic impairment.

Dose reduction or alternatives should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment.

The dose of colchicine that would induce significant toxicity for an individual is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder adverse reactions such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe adverse reactions, including myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg.

{ "type": "p", "children": [], "text": "The dose of colchicine that would induce significant toxicity for an individual is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder adverse reactions such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe adverse reactions, including myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg." }

{ "type": "ul", "children": [ "The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen.", "Life threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multiorgan failure and its consequences. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery of multiorgan injury may be accompanied by rebound leukocytosis and alopecia starting about one week after the initial ingestion.", "Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent shock. Otherwise, treatment is symptomatic and supportive. No specific antidote is known. Colchicine is not effectively removed by hemodialysis\n \n [see\n \n Clinical Pharmacology (12.3)]\n \n .\n \n " ], "text": "" }

Colchicine is an alkaloid obtained from various species of Colchicum. The chemical name for colchicine is (S)- N-(5,6,7,9-tetrahydro- 1,2,3,10-tetramethoxy-9-oxobenzo[ a]heptalen-7-yl) acetamide with a molecular formula of C 22H 25NO 6and a molecular weight of 399.4.

{ "type": "p", "children": [], "text": "Colchicine is an alkaloid obtained from various species of\n \n Colchicum. The chemical name for colchicine is\n \n (S)-\n \n N-(5,6,7,9-tetrahydro- 1,2,3,10-tetramethoxy-9-oxobenzo[\n \n a]heptalen-7-yl) acetamide with a molecular formula of C\n \n 22H\n \n 25NO\n \n 6and a molecular weight of 399.4.\n\n " }

The structural formula of colchicine is provided in Figure 1.

{ "type": "p", "children": [], "text": "The structural formula of colchicine is provided in Figure 1." }

Figure 1: Colchicine Structural Formula

{ "type": "p", "children": [], "text": "\nFigure 1: Colchicine Structural Formula\n" }

Colchicine consists of pale yellow scales or powder; it darkens on exposure to light. Colchicine is soluble in water, freely soluble in alcohol, and slightly soluble in ether.

{ "type": "p", "children": [], "text": "Colchicine consists of pale yellow scales or powder; it darkens on exposure to light. Colchicine is soluble in water, freely soluble in alcohol, and slightly soluble in ether." }

GLOPERBA is supplied for oral administration as a slightly hazy, red liquid with a cherry odor, containing 0.6 mg/5 mL of the active ingredient colchicine USP. Inactive ingredients: benzyl alcohol, FD&C Red No. 40, artificial cherry flavor, anhydrous citric acid, dibasic sodium phosphate, glycerin, propylene glycol, sucralose, xanthan gum and purified water.

{ "type": "p", "children": [], "text": "GLOPERBA is supplied for oral administration as a slightly hazy, red liquid with a cherry odor, containing 0.6 mg/5 mL of the active ingredient colchicine USP. Inactive ingredients: benzyl alcohol, FD&C Red No. 40, artificial cherry flavor, anhydrous citric acid, dibasic sodium phosphate, glycerin, propylene glycol, sucralose, xanthan gum and purified water." }

Colchicine's effectiveness as a prophylactic treatment for gout has been postulated to be due to its ability to block neutrophil mediated inflammatory responses induced by monosodium urate crystals in synovial fluid. Colchicine disrupts the polymerization of β-tubulin into microtubules, thereby preventing the activation, degranulation and migration of neutrophils to sites of inflammation. Colchicine also interferes with the inflammasome complex found in neutrophils and monocytes that mediates interleukin-1β (IL-1β) activation.

The pharmacodynamics of colchicine are unknown.

Absorption

In healthy adults, GLOPERBA reached a mean C maxof 2.16 ± 0.87 ng/mL in 1 hour (range 0.5 to 2 hours) after a single dose administered under fasting conditions. A minimal food effect was observed when GLOPERBA was administered following a high fat, high calorie meal. A slight decrease in C maxwas observed; however, the overall extent of absorption based on AUC 0-tand AUC 0-inf, was similar in the fed and fasted states. The absolute bioavailability of colchicine is reported to be approximately 45%. Mean pharmacokinetic parameter values for GLOPERBA in healthy adults are shown in Table 1.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Mean Pharmacokinetic Parameter Estimates for GLOPERBA in Healthy Adults</span> </caption> <col align="left" valign="middle" width="33%"/> <col align="left" valign="middle" width="34%"/> <col align="left" valign="middle" width="33%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule">Parameter</th><th align="left" class="Rrule">GLOPERBA, 0.6 mg <br/> (0.12 mg/mL, 5 mL) <br/> Fasted (N=34) </th><th align="left" class="Rrule">GLOPERBA, 0.6 mg <br/> (0.12 mg/mL, 5 mL) <br/> Fed (N=34) </th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">C <span class="Sub">max</span>(ng/mL) </td><td align="left" class="Rrule">2.16 (0.87)</td><td align="left" class="Rrule">1.68 (0.39)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">AUC <span class="Sub">0-t</span>(h∙ng/mL) </td><td align="left" class="Rrule">18.59 (4.64)</td><td align="left" class="Rrule">17.20 (4.23)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">AUC <span class="Sub">0-inf</span>(h∙ng/mL) </td><td align="left" class="Rrule">19.90 (4.74)</td><td align="left" class="Rrule">18.47 (4.29)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">T <span class="Sub">max</span>(h) (Min-Max) </td><td align="left" class="Rrule">1.00 (0.50: 2.00)</td><td align="left" class="Rrule">2.00 (1.00: 4.00)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">t <span class="Sub">1/2</span>(h) </td><td align="left" class="Rrule">31.04 (5.99)</td><td align="left" class="Rrule">30.54 (5.22)</td> </tr> </tbody> </table></div>

Distribution

The mean apparent volume of distribution (Vz/F) of GLOPERBA in healthy adults was approximately 1420 L. Colchicine binding to serum protein is reported to be low (39%) primarily due to albumin regardless of concentration.

Colchicine crosses the placenta (plasma levels in the fetus are reported to be approximately 15% of the maternal concentration) [see Use in Specific Populations (8.1)] . Colchicine also distributes into breast milk at concentrations similar to those found in the maternal serum [see Use in Specific Populations (8.2)] .

Metabolism

In vitrostudies using human liver microsomes have shown that CYP3A4 is involved in the metabolism of colchicine to 2- O-demethylcolchicine (2-DMC) and 3- O-demethylcolchicine (3-DMC). Glucuronidation is also believed to be a metabolic pathway for colchicine.

Elimination

The mean elimination half-life of GLOPERBA in healthy adults is 31 hours (± 6 hours). In a published study in healthy adults approximately 40 to 65% of a single 1-mg oral dose of colchicine was reported to be recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are postulated to play a role in colchicine elimination. Colchicine is also a substrate of P-gp, and P-gp efflux is postulated to play an important role in colchicine disposition.

Specific Populations

There is no difference between men and women in the pharmacokinetic disposition of colchicine.

Pediatric Patients:Pharmacokinetics of colchicine were not evaluated in pediatric patients.

Geriatric Patients:Pharmacokinetics of GLOPERBA have not been determined in elderly patients. A published report described the pharmacokinetics of a 1 mg oral colchicine tablet dose in four elderly women compared to six young healthy males. The mean age of the four elderly women was 83 years (range 75 to 93), mean weight was 47 kg (38 to 61 kg) and mean creatinine clearance was 46 mL/minute (range 25 to 75 mL/minute). Mean peak plasma levels and AUC of colchicine were two times higher in elderly subjects compared to young healthy males. It is possible that the higher exposure in the elderly subjects was due to decreased renal function.

Patients with Renal Impairment:Pharmacokinetics of colchicine in patients with mild and moderate renal impairment is not known. A published report described the disposition of colchicine (1 mg) in young adult men and women patients who had end stage renal disease requiring dialysis compared to patients with normal renal function. Patients with end stage renal disease had 75% lower colchicine clearance (0.17 vs. 0.73 L/hr/kg) and prolonged plasma elimination half-life (18.8 hours vs. 4.4 hours) as compared to subjects with normal renal function [see Use in Specific Populations (8.6)] .

Patients with Hepatic Impairment:Published reports on the pharmacokinetics of intravenous colchicine in patients with severe chronic liver disease, as well as those with alcoholic or primary biliary cirrhosis, and normal renal function suggest wide inter-patient variability. In some subjects with mild to moderate cirrhosis, the clearance of colchicine is significantly reduced and plasma half-life prolonged compared to healthy subjects. In subjects with primary biliary cirrhosis, no consistent trends were noted [see Use in Specific Populations (8.7)] . No pharmacokinetic data are available for patients with severe hepatic impairment (Child Pugh C).

Drug Interactions

Pharmacokinetics studies evaluating changes in systemic levels of colchicine when co-administered with CYP3A4 and P-gp inhibitors in healthy subjects have been conducted with GOLPERBA. Carvedilol 20 to 40 mg QD (considered a P-gp inhibitor), amlodipine 5 to 10 mg QD (considered a weak inhibitor of CYP3A4) and ciprofloxacin 500 mg BID (considered a moderate CYP3A4 inhibitor) did not cause any significant changes in colchicine systemic levels. Co-administration with posaconazole 300 mg QD (considered a strong CYP3A4 inhibitor) increased AUC by approximately 3-fold.

These results should not be extrapolated to other inhibitors as colchicine is known to be a substrate for CYP3A4 and P-gp, and case reports of colchicine toxicity associated with the co-administration of CYP3A4 and P-gp inhibitors (i.e., clarithromycin) have been published.

Fatal drug interactions have been reported when colchicine is administered with clarithromycin, a dual inhibitor of CYP3A4 and P-gp. Toxicities have also been reported when colchicine is administered with inhibitors of CYP3A4 that may not be potent inhibitors of P-gp (e.g., grapefruit juice), or inhibitors of P-gp that may not be potent inhibitors of CYP3A4 (e.g., cyclosporine). If treatment with a P-gp and CYP3A4 inhibitor is required in patients with normal renal and hepatic function, the patients' dose of colchicine may need to be reduced or interrupted.

Carcinogenesis

Carcinogenicity studies of colchicine have not been conducted. Due to the potential for colchicine to produce aneuploid cells (cells with an unequal number of chromosomes), colchicine presents a theoretical increased risk of malignancy.

Mutagenesis

Colchicine was negative for mutagenicity in the bacterial reverse mutation assay. In a chromosomal aberration assay in cultured human white blood cells, colchicine treatment resulted in the formation of micronuclei. Since published studies demonstrated that colchicine induces aneuploidy from the process of mitotic nondisjunction without structural DNA changes, colchicine is not considered clastogenic, although micronuclei are formed.

Impairment of Fertility

There were no studies conducted of the effects of GLOPERBA on fertility. Published nonclinical studies have demonstrated that colchicine induced disruption of microtubule formation affects meiosis and mitosis. Published colchicine reproductive studies have reported abnormal sperm morphology and reduced sperm counts in males and interference with sperm penetration, second meiotic division and normal cleavage in females.

The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate-lowering therapy. In both trials, treatment with colchicine decreased the frequency of gout flares.

{ "type": "p", "children": [], "text": "The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate-lowering therapy. In both trials, treatment with colchicine decreased the frequency of gout flares." }

GLOPERBA (colchicine) Oral Solution is a slightly hazy, red liquid with a cherry odor and the strength of 0.6 mg/5 mL. GLOPERBA (150 mL) is provided in a white, oblong, high density polyethylene bottle with a child-resistant cap.

150 mL: NDC 69557-222-01

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

Dosing Instructions

Patients should be advised to take GLOPERBA as prescribed, even if they are feeling better. Patients should not alter the dose or discontinue treatment without consulting with their doctor. If a dose of GLOPERBA is missed, take the dose as soon as possible and then return to the normal dosing schedule. However, if a dose is skipped the patient should not double the next dose.

Advise patients and caregivers to measure GLOPERBA with an accurate milliliter measuring device. A household teaspoon is not an accurate measuring device. Advise patients and caregivers to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.

Fatal Overdose

Instruct patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine. GLOPERBA should be kept out of the reach of children.

Blood Dyscrasias

Patients should be informed that bone marrow depression with agranulocytosis, aplastic anemia and thrombocytopenia may occur with GLOPERBA.

Drug and Food Interactions

Advise patients that many drugs or other substances may interact with GLOPERBA and some interactions could be fatal. Therefore, patients should report to their healthcare provider all of the current medications they are taking and check with their healthcare provider before starting any new medications, including short term medications such as antibiotics. Patients should also be advised to report the use of nonprescription medication or herbal products. Grapefruit and grapefruit juice may also interact and should not be consumed during GLOPERBA treatment.

Neuromuscular Toxicity

Patients should be informed that muscle pain or weakness, tingling or numbness in fingers or toes may occur with GLOPERBA alone or when it is used with certain other drugs. Patients developing any of these signs or symptoms must discontinue GLOPERBA and seek medical evaluation immediately.

Infertility

Advise males of reproductive potential that GLOPERBA may rarely and transiently impair fertility [see Use in Specific Populations (8.3)] .

Rx ONLY

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

Manufactured for: SCILEX Pharmaceuticals, Inc. Palo Alto, California Rev 03/23 GL0-00052

{ "type": "p", "children": [], "text": "\nManufactured for:\n SCILEX Pharmaceuticals, Inc. \n Palo Alto, California \n Rev 03/23 \n GL0-00052\n\n " }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="18%"/> <col align="left" valign="top" width="18%"/> <col align="left" valign="top" width="18%"/> <col align="left" valign="top" width="44%"/> <thead> <tr> <th align="center" class="Lrule Rrule Toprule" colspan="5">MEDICATION GUIDE</th> </tr> <tr class="Botrule"> <th align="center" class="Lrule Rrule" colspan="5">GLOPERBA <span class="Sup">®</span>(Glow per' bah) <br/> (colchicine) Oral Solution </th> </tr> </thead> <tbody> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What is the most important information I should know about GLOPERBA?</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">GLOPERBA can cause serious side effects or death if levels of GLOPERBA are too high in your body. <ul class="Disc"> <li>Taking certain medicines with GLOPERBA can cause your level of GLOPERBA to be too high, especially if you have kidney or liver problems.</li> <li>Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of GLOPERBA may need to be changed.</li> <li>Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.</li> <li>Medicines that you take for a short period of time, such as antibiotics, can interact with GLOPERBA and cause serious side effects or death.</li> <li>Talk to your healthcare provider or pharmacist before taking any new medicine.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What is GLOPERBA?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">GLOPERBA is a prescription medicine used to prevent gout flares in adults.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">It is not known if GLOPERBA is safe and effective for the treatment of sudden (acute) gout flares.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">GLOPERBA is not a pain medicine, and it should not be taken to treat pain related to other medical conditions unless specifically prescribed for those conditions.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">It is not known if GLOPERBA is safe and effective in children.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Do not take GLOPERBA if you:</span> <ul class="Disc"> <li>have liver or kidney problems and you take certain other medicines, unless directed to by a healthcare provider. Serious side effects, including death, have happened in people even when GLOPERBA is taken as directed.</li> <li>have liver and kidney problems.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">See <span class="Bold">" <a href="#important">What is the most important information that I should know about GLOPERBA?</a>" </span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Before taking GLOPERBA, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>are pregnant or plan to become pregnant. It is not known if GLOPERBA can harm your unborn baby.</li> <li>are breastfeeding or plan to breastfeed. GLOPERBA can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take GLOPERBA.</li> <li>are a <span class="Bold">male</span>with a female partner who can become pregnant. Receiving treatment with GLOPERBA may be related to infertility in some men that is reversible when treatment is stopped. </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">Tell your healthcare provider about all the medicines you take, including prescription, over-the-counter medicines, vitamins, and herbal supplements. <ul class="Disc"> <li>Using GLOPERBA with certain other medicines can affect each other, causing serious side effects or death.</li> <li> <span class="Bold">Do not</span>take GLOPERBA with other medicines unless your healthcare provider tells you to. </li> <li>Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine.</li> <li>Especially tell your healthcare provider if you take: <ul class="Circle"> <li>medicines that may affect how your liver works (CYP3A4 inhibitors)</li> <li>a medicine called cyclosporine (Noeral, Gengraf, Sandimmune)</li> <li>cholesterol lowering medicines, or</li> <li>antibiotics</li> </ul> </li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can affect GLOPERBA.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">How should I take GLOPERBA?</span> <ul class="Disc"> <li>Take GLOPERBA exactly as your healthcare provider tells you to take it. If you are not sure about your dosing, call your healthcare provider.</li> <li>Measure GLOPERBA with an accurate milliliter measuring device. <span class="Bold">A household teaspoon is not an accurate measuring device.</span>Ask your pharmacist to recommend a measuring device and for instructions on how to measure the correct dose. </li> <li>GLOPERBA can be taken with or without food.</li> <li>If you take too much GLOPERBA, call your healthcare provider or go to the nearest hospital emergency room right away.</li> <li> <span class="Bold">Do not stop taking GLOPERBA unless your healthcare provider tells you.</span> </li> <li>If you miss a dose of GLOPERBA, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What should I avoid while taking GLOPERBA?</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">Avoid eating grapefruit or drinking grapefruit juice while taking GLOPERBA. It can increase your chances of having serious side effects.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What are the possible side effects of GLOPERBA?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">GLOPERBA can cause serious side effects, including:</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">See <span class="Bold">" <a href="#important">What is the most important information that I should know about GLOPERBA?</a>" </span> <ul class="Disc"> <li> <span class="Bold">Blood problems.</span>Blood problems have happened in some people taking GLOPERBA. Get medical help right away if you have any of these symptoms: </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="3"> <ul class="Circle"> <li>pale or gray color to your lips, tongue or palms of your hands.</li> <li>unusual bleeding or bruising</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>feel weak or tired</li> <li>increased infections</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"> <ul class="Disc"> <li> <span class="Bold">Muscle weakness (neuromuscular toxicity).</span>Muscle weakness has happened in some people taking GLOPERBA. Get medical help right away if you have any of these symptoms: </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" colspan="3"> <ul class="Circle"> <li>muscle weakness or pain</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>numbness or tingling in your fingers or toes</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">The most common side effects of GLOPERBA include:</td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left"> <ul class="Circle"> <li>diarrhea</li> </ul> </td><td align="left"> <ul class="Circle"> <li>nausea</li> </ul> </td><td align="left"> <ul class="Circle"> <li>vomiting</li> </ul> </td><td align="left" class="Rrule"> <ul class="Circle"> <li>abdominal (stomach) pain</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">These are not all of the possible side effects of GLOPERBA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">How should I store GLOPERBA?</span> <ul class="Disc"> <li>Store GLOPERBA between 20°-25°C (68° - 77°F); excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature.]</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Keep GLOPERBA and all medicines out of the reach of children.</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">General information about the safe and effective use of GLOPERBA.</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5">Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use GLOPERBA for a condition for which it was not prescribed. Do not give GLOPERBA to other people, even if they have the same symptoms that you have. It may harm them.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5">If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about GLOPERBA that is written for healthcare professionals.</td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">What are the ingredients in GLOPERBA?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Active Ingredient:</span>colchicine </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Inactive Ingredients:</span>benzyl alcohol, FD&amp;C Red No. 40, artificial cherry flavor, anhydrous citric acid, dibasic sodium phosphate, glycerin, propylene glycol, sucralose, xanthan gum and purified water. </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Rx ONLY</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Manufactured for:</span> <br/> SCILEX Pharmaceuticals, Inc. <br/> Palo Alto, California <br/> For more information, visit scilexholding.com or call 1-866-SCILEX3. </td> </tr> <tr> <td align="left" colspan="4">This Medication Guide has been approved by the U.S Food and Drug Administration</td><td align="right"><span class="Bold">Issued: 7/2019</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"18%\"/>\n<col align=\"left\" valign=\"top\" width=\"18%\"/>\n<col align=\"left\" valign=\"top\" width=\"18%\"/>\n<col align=\"left\" valign=\"top\" width=\"44%\"/>\n<thead>\n<tr>\n<th align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"5\">MEDICATION GUIDE</th>\n</tr>\n<tr class=\"Botrule\">\n<th align=\"center\" class=\"Lrule Rrule\" colspan=\"5\">GLOPERBA\n \n <span class=\"Sup\">®</span>(Glow per' bah) \n <br/> (colchicine) Oral Solution\n \n </th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What is the most important information I should know about GLOPERBA?</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">GLOPERBA can cause serious side effects or death if levels of GLOPERBA are too high in your body.\n \n <ul class=\"Disc\">\n<li>Taking certain medicines with GLOPERBA can cause your level of GLOPERBA to be too high, especially if you have kidney or liver problems.</li>\n<li>Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of GLOPERBA may need to be changed.</li>\n<li>Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.</li>\n<li>Medicines that you take for a short period of time, such as antibiotics, can interact with GLOPERBA and cause serious side effects or death.</li>\n<li>Talk to your healthcare provider or pharmacist before taking any new medicine.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What is GLOPERBA?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">GLOPERBA is a prescription medicine used to prevent gout flares in adults.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">It is not known if GLOPERBA is safe and effective for the treatment of sudden (acute) gout flares.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">GLOPERBA is not a pain medicine, and it should not be taken to treat pain related to other medical conditions unless specifically prescribed for those conditions.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">It is not known if GLOPERBA is safe and effective in children.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Do not take GLOPERBA if you:</span>\n<ul class=\"Disc\">\n<li>have liver or kidney problems and you take certain other medicines, unless directed to by a healthcare provider. Serious side effects, including death, have happened in people even when GLOPERBA is taken as directed.</li>\n<li>have liver and kidney problems.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">See\n \n <span class=\"Bold\">\"\n \n <a href=\"#important\">What is the most important information that I should know about GLOPERBA?</a>\"\n \n </span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Before taking GLOPERBA, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>are pregnant or plan to become pregnant. It is not known if GLOPERBA can harm your unborn baby.</li>\n<li>are breastfeeding or plan to breastfeed. GLOPERBA can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take GLOPERBA.</li>\n<li>are a\n \n <span class=\"Bold\">male</span>with a female partner who can become pregnant. Receiving treatment with GLOPERBA may be related to infertility in some men that is reversible when treatment is stopped.\n \n </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">Tell your healthcare provider about all the medicines you take, including prescription, over-the-counter medicines, vitamins, and herbal supplements.\n \n <ul class=\"Disc\">\n<li>Using GLOPERBA with certain other medicines can affect each other, causing serious side effects or death.</li>\n<li>\n<span class=\"Bold\">Do not</span>take GLOPERBA with other medicines unless your healthcare provider tells you to.\n \n </li>\n<li>Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine.</li>\n<li>Especially tell your healthcare provider if you take:\n \n <ul class=\"Circle\">\n<li>medicines that may affect how your liver works (CYP3A4 inhibitors)</li>\n<li>a medicine called cyclosporine (Noeral, Gengraf, Sandimmune)</li>\n<li>cholesterol lowering medicines, or</li>\n<li>antibiotics</li>\n</ul>\n</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can affect GLOPERBA.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">How should I take GLOPERBA?</span>\n<ul class=\"Disc\">\n<li>Take GLOPERBA exactly as your healthcare provider tells you to take it. If you are not sure about your dosing, call your healthcare provider.</li>\n<li>Measure GLOPERBA with an accurate milliliter measuring device.\n \n <span class=\"Bold\">A household teaspoon is not an accurate measuring device.</span>Ask your pharmacist to recommend a measuring device and for instructions on how to measure the correct dose.\n \n </li>\n<li>GLOPERBA can be taken with or without food.</li>\n<li>If you take too much GLOPERBA, call your healthcare provider or go to the nearest hospital emergency room right away.</li>\n<li>\n<span class=\"Bold\">Do not stop taking GLOPERBA unless your healthcare provider tells you.</span>\n</li>\n<li>If you miss a dose of GLOPERBA, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What should I avoid while taking GLOPERBA?</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">Avoid eating grapefruit or drinking grapefruit juice while taking GLOPERBA. It can increase your chances of having serious side effects.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What are the possible side effects of GLOPERBA?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">GLOPERBA can cause serious side effects, including:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">See\n \n <span class=\"Bold\">\"\n \n <a href=\"#important\">What is the most important information that I should know about GLOPERBA?</a>\"\n \n </span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Blood problems.</span>Blood problems have happened in some people taking GLOPERBA. Get medical help right away if you have any of these symptoms:\n \n </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"3\">\n<ul class=\"Circle\">\n<li>pale or gray color to your lips, tongue or palms of your hands.</li>\n<li>unusual bleeding or bruising</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>feel weak or tired</li>\n<li>increased infections</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Muscle weakness (neuromuscular toxicity).</span>Muscle weakness has happened in some people taking GLOPERBA. Get medical help right away if you have any of these symptoms:\n \n </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" colspan=\"3\">\n<ul class=\"Circle\">\n<li>muscle weakness or pain</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>numbness or tingling in your fingers or toes</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">The most common side effects of GLOPERBA include:</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\">\n<ul class=\"Circle\">\n<li>diarrhea</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Circle\">\n<li>nausea</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Circle\">\n<li>vomiting</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\">\n<ul class=\"Circle\">\n<li>abdominal (stomach) pain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">These are not all of the possible side effects of GLOPERBA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">How should I store GLOPERBA?</span>\n<ul class=\"Disc\">\n<li>Store GLOPERBA between 20°-25°C (68° - 77°F); excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature.]</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Keep GLOPERBA and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">General information about the safe and effective use of GLOPERBA.</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use GLOPERBA for a condition for which it was not prescribed. Do not give GLOPERBA to other people, even if they have the same symptoms that you have. It may harm them.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\">If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about GLOPERBA that is written for healthcare professionals.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">What are the ingredients in GLOPERBA?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Active Ingredient:</span>colchicine\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Inactive Ingredients:</span>benzyl alcohol, FD&amp;C Red No. 40, artificial cherry flavor, anhydrous citric acid, dibasic sodium phosphate, glycerin, propylene glycol, sucralose, xanthan gum and purified water.\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Rx ONLY</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"5\"><span class=\"Bold\">Manufactured for:</span>\n<br/> SCILEX Pharmaceuticals, Inc. \n <br/> Palo Alto, California \n <br/> For more information, visit scilexholding.com or call 1-866-SCILEX3.\n \n </td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"4\">This Medication Guide has been approved by the U.S Food and Drug Administration</td><td align=\"right\"><span class=\"Bold\">Issued: 7/2019</span></td>\n</tr>\n</tbody>\n</table></div>" }

NDC 69557-222-01

{ "type": "p", "children": [], "text": "NDC 69557-222-01" }

GLOPERBA ® (colchicine) oral solution

{ "type": "p", "children": [], "text": "GLOPERBA\n \n ®\n (colchicine) oral solution\n\n " }

0.6 mg/5 mL

{ "type": "p", "children": [], "text": "0.6 mg/5 mL" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

150 mL

{ "type": "p", "children": [], "text": "150 mL" }

Colchicine capsules are indicated for prophylaxis of gout flares in adults.

{ "type": "p", "children": [], "text": "Colchicine capsules are indicated for prophylaxis of gout flares in adults." }

Limitations of Use: The safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied.

{ "type": "p", "children": [], "text": "\nLimitations of Use: The safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied.\n " }

Colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes.

{ "type": "p", "children": [], "text": "Colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes." }

For prophylaxis of gout flares, the recommended dosage of colchicine capsules is 0.6 mg once or twice daily. The maximum dosage is 1.2 mg per day.

Colchicine capsules are administered orally, without regard to meals.

0.6 mg capsules – No. 4 Dark Blue/Light Blue Hard Gelatin Capsules printed “West-ward 118” in white ink.

{ "type": "p", "children": [], "text": "0.6 mg capsules \n – No. 4 Dark Blue/Light Blue Hard Gelatin Capsules printed “West-ward 118” in white ink.\n " }

Patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4 inhibitors [see Drug Interactions (7)]. Combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life-threatening or fatal colchicine toxicity.

{ "type": "p", "children": [], "text": "Patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4 inhibitors \n [see \n Drug Interactions (7)]. \n Combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life-threatening or fatal colchicine toxicity.\n " }

Patients with both renal and hepatic impairment should not be given colchicine capsules.

{ "type": "p", "children": [], "text": "Patients with both renal and hepatic impairment should not be given colchicine capsules." }

Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Overdosage (10)]. Colchicine capsules should be kept out of the reach of children.

Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia have been reported with colchicine used in therapeutic doses.

Because colchicine is a substrate for both the CYP3A4 metabolizing enzyme and the P-glycoprotein efflux transporter, inhibition of either of these pathways may lead to colchicine-related toxicity. Inhibition of both CYP3A4 and P-gp by dual inhibitors such as clarithromycin has been reported to produce life-threatening or fatal colchicine toxicity due to significant increases in systemic colchicine levels. Therefore, concomitant use of colchicine capsules and inhibitors of CYP3A4 or P-glycoprotein should be avoided [see Drug Interactions (7)]. If avoidance is not possible, reduced daily dose should be considered and the patient should be monitored closely for colchicine toxicity. Use of colchicine capsules in conjunction with drugs that inhibit both P-gp and CYP3A4 is contraindicated in patients with renal or hepatic impairment [see Contraindications (4)].

Neuromuscular toxicity and rhabdomyolysis have been reported from chronic treatment with colchicine in therapeutic doses, especially in combination with other drugs known to cause this effect. Patients with impaired renal function and elderly patients (even those with normal renal and hepatic function) are at increased risk. Once colchicine treatment is ceased, the symptoms generally resolve within 1 week to several months.

Gastrointestinal disorders are the most common adverse reactions with colchicine. They are often the first signs of toxicity and may indicate that the colchicine dosage needs to be reduced or therapy stopped. These include diarrhea, nausea, vomiting, and abdominal pain.

{ "type": "p", "children": [], "text": "Gastrointestinal disorders are the most common adverse reactions with colchicine. They are often the first signs of toxicity and may indicate that the colchicine dosage needs to be reduced or therapy stopped. These include diarrhea, nausea, vomiting, and abdominal pain." }

Colchicine has been reported to cause neuromuscular toxicity, which may present as muscle pain or weakness [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Colchicine has been reported to cause neuromuscular toxicity, which may present as muscle pain or weakness \n [see \n Warnings and Precautions (5.4)]. \n \n" }

Toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation, and injury to cells in the renal, hepatic, circulatory, and central nervous system. These most often occur with excessive accumulation or overdosage [see Overdosage (10)].

{ "type": "p", "children": [], "text": "Toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation, and injury to cells in the renal, hepatic, circulatory, and central nervous system. These most often occur with excessive accumulation or overdosage \n [see \n Overdosage (10)]. \n \n" }

The following reactions have been reported with colchicine. These have been generally reversible by interrupting treatment or lowering the dose of colchicine:

{ "type": "p", "children": [], "text": "The following reactions have been reported with colchicine. These have been generally reversible by interrupting treatment or lowering the dose of colchicine:" }

Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting

{ "type": "p", "children": [], "text": "\nDigestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting\n " }

Neurological: sensory motor neuropathy

{ "type": "p", "children": [], "text": "\nNeurological: sensory motor neuropathy\n " }

Dermatological: alopecia, maculopapular rash, purpura, rash

{ "type": "p", "children": [], "text": "\nDermatological: alopecia, maculopapular rash, purpura, rash\n " }

Hematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia

{ "type": "p", "children": [], "text": "\nHematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia\n " }

Hepatobiliary: elevated AST, elevated ALT

{ "type": "p", "children": [], "text": "\nHepatobiliary: elevated AST, elevated ALT\n " }

Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis

{ "type": "p", "children": [], "text": "\nMusculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis\n " }

Reproductive: azoospermia, oligospermia

{ "type": "p", "children": [], "text": "\nReproductive: azoospermia, oligospermia\n " }

The concomitant use of colchicine capsules and CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, grapefruit juice, erythromycin, verapamil, etc.) should be avoided due to the potential for serious and life-threatening toxicity [see Warnings and Precautions (5.3) and Clinical Pharmacology (12)] .

If co-administration of colchicine capsules and a CYP3A4 inhibitor is necessary, the dose of colchicine capsules should be adjusted by either reducing the daily dose or reducing the dose frequency, and the patient should be monitored carefully for colchicine toxicity [see Clinical Pharmacology (12)].

The concomitant use of colchicine capsules and inhibitors of P-glycoprotein (e.g. clarithromycin, ketoconazole, cyclosporine, etc.) should be avoided due to the potential for serious and life-threatening toxicity [see Warnings and Precautions (5.3) and Clinical Pharmacology (12)] .

If co-administration of colchicine capsules and a P-gp inhibitor is necessary, the dose of colchicine capsules should be adjusted by either reducing the daily dose or reducing the dose frequency, and the patient should be monitored carefully for colchicine toxicity [see Clinical Pharmacology (12)] .

Some drugs such as HMG-CoA reductase inhibitors and fibrates may increase the risk of myopathy when combined with colchicine capsules. Complaints of muscle pain or weakness could be an indication to check serum creatinine kinase levels for signs of myopathy.

Four pharmacokinetic studies evaluated the effects of co-administration of voriconazole (200 mg BID), fluconazole (200 mg QD), cimetidine (800 mg BID), and propafenone (225 mg BID) on systemic levels of colchicine. Colchicine can be administered with these drugs at the tested doses without a need for dose adjustment. However, these results should not be extrapolated to other co-administered drugs [see Drug Interactions (7.1, 7.2) and Pharmacokinetics (12.3)].

Risk Summary: Available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or other adverse maternal or fetal outcomes (see Data). Colchicine crosses the human placenta. Although animal reproductive and developmental studies were not conducted with colchicine capsules, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity, and altered postnatal development at exposures within or above the clinical therapeutic range.

The background risk of major birth defects and miscarriage for the indicated population is 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.

Data: Human Data: Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, Behcet’s disease, or Familial Mediterranean Fever (FMF)) treated with colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.

Risk Summary: Colchicine is present in human milk (see Data). Adverse events in breastfed infants have not been reported in the published literature after administration of colchicine to lactating women. There are no data on the effects of colchicine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for colchicine capsules and any potential adverse effects on the breastfed child from colchicine or from the underlying maternal condition.

Data: Human data:Limited published data from case reports and a small lactation study demonstrate that colchicine is present in breastmilk. A systematic review of literature reported no adverse effects in 149 breastfed children. In a prospective observational cohort study, no gastrointestinal or other symptoms were reported in 38 colchicine-exposed breastfed infants.

Infertility: Case reports and epidemiology studies in human male subjects on colchicine therapy indicated that infertility from colchicine is rare and may be reversible.

Gout is rare in pediatric patients; the safety and effectiveness of colchicine capsules in pediatric patients has not been evaluated in controlled studies.

Because of the increased incidence of decreased renal function in the elderly population, and the higher incidence of other co-morbid conditions in the elderly population requiring the use of other medications, reducing the dosage of colchicine when elderly patients are treated with colchicine should be carefully considered.

No dedicated pharmacokinetic study has been conducted using colchicine capsules in patients with varying degrees of renal impairment. Colchicine is known to be excreted in urine in humans and the presence of severe renal impairment has been associated with colchicine toxicity. Urinary clearance of colchicine and its metabolites may be decreased in patients with impaired renal function. Dose reduction or alternatives should be considered for the prophylaxis of gout flares in patients with severe renal impairment. Colchicine is not effectively removed by hemodialysis. Patients who are undergoing hemodialysis should be monitored carefully for colchicine toxicity.

No dedicated pharmacokinetic study using colchicine capsules has been conducted in patients with varying degrees of hepatic impairment. Colchicine is known to be metabolized in humans and the presence of severe hepatic impairment has been associated with colchicine toxicity. Hepatic clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment.

Dose reduction or alternatives should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment.

Tolerance, abuse, or dependence from colchicine has not been reported.

{ "type": "p", "children": [], "text": "Tolerance, abuse, or dependence from colchicine has not been reported." }

The dose of colchicine that would induce significant toxicity for an individual is unknown. Fatalities have been reported in patients after ingesting a dose as low as 7 mg over a 4-day period, while other patients have reportedly survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder adverse reactions, such as gastrointestinal symptoms, whereas those who ingested from 0.5 to 0.8 mg/kg had more severe adverse reactions, including myelosuppression. There was 100% mortality among patients who ingested more than 0.8 mg/kg.

{ "type": "p", "children": [], "text": "The dose of colchicine that would induce significant toxicity for an individual is unknown. Fatalities have been reported in patients after ingesting a dose as low as 7 mg over a 4-day period, while other patients have reportedly survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder adverse reactions, such as gastrointestinal symptoms, whereas those who ingested from 0.5 to 0.8 mg/kg had more severe adverse reactions, including myelosuppression. There was 100% mortality among patients who ingested more than 0.8 mg/kg." }

{ "type": "ul", "children": [ "The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea, and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen.", "Life-threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multi-organ failure and its associated consequences. Death usually results from respiratory depression and cardiovascular collapse. If the patient survives, recovery of multi-organ injury may be accompanied by rebound leukocytosis and alopecia starting about 1 week after the initial ingestion.", "Treatment of colchicine overdose should begin with gastric lavage and measures to prevent shock. Otherwise, treatment is symptomatic and supportive. No specific antidote is known. Colchicine is not effectively removed by hemodialysis\n \n [see\n \n Pharmacokinetics (12.3)].\n \n \n" ], "text": "" }

Colchicine is an alkaloid obtained from the plant colchicum autumnale.

{ "type": "p", "children": [], "text": "Colchicine is an alkaloid obtained from the plant \n colchicum autumnale.\n " }

The chemical name for colchicine is (S) -N-(5,6,7,9- tetrahydro-1,2,3,10-tetramethoxy-9 oxobenzol[a]heptalen-7-yl) acetamide. The structural formula is represented below:

{ "type": "p", "children": [], "text": "The chemical name for colchicine is (S)\n -N-(5,6,7,9- tetrahydro-1,2,3,10-tetramethoxy-9 oxobenzol[a]heptalen-7-yl) acetamide. The structural formula is represented below:\n " }

Colchicine consists of pale yellow scales or powder; it darkens on exposure to light. Colchicine is soluble in water, freely soluble in alcohol, and slightly soluble in ether.

{ "type": "p", "children": [], "text": "Colchicine consists of pale yellow scales or powder; it darkens on exposure to light. Colchicine is soluble in water, freely soluble in alcohol, and slightly soluble in ether." }

Colchicine capsules are supplied for oral administration. Each capsule contains 0.6 mg colchicine, USP and the following inactive ingredients: colloidal silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The capsule shell contains gelatin, purified water, titanium dioxide, erythrosine, Brilliant Blue FCF, and may contain D&C Red No. 28, FD&C Red No. 40 and Quinoline Yellow.

{ "type": "p", "children": [], "text": "Colchicine capsules are supplied for oral administration. Each capsule contains 0.6 mg colchicine, USP and the following inactive ingredients: colloidal silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The capsule shell contains gelatin, purified water, titanium dioxide, erythrosine, Brilliant Blue FCF, and may contain D&C Red No. 28, FD&C Red No. 40 and Quinoline Yellow." }

Colchicine’s effectiveness as a treatment for gout has been postulated to be due to its ability to block neutrophil-mediated inflammatory responses induced by monosodium urate crystals in synovial fluid. Colchicine disrupts the polymerization of β-tubulin into microtubules, thereby preventing the activation, degranulation, and migration of neutrophils to sites of inflammation. Colchicine also interferes with the inflammasome complex found in neutrophils and monocytes that mediates interleukin-1β (IL-1β) activation.

Absorption: In healthy adults, colchicine capsules when given orally reached a mean C max of 3 ng/mL in 1.3 h (range 0.7 to 2.5 h) after 0.6 mg single dose administration.

Absolute bioavailability is reported to be approximately 45%.

Administration with food has no effect on the rate or extent of colchicine absorption.

Colchicine is not effectively removed by hemodialysis.

Distribution: Colchicine has a mean apparent volume of distribution in healthy young volunteers of approximately 5 to 8 L/kg. Colchicine binding to serum protein is about 39%, primarily to albumin. Colchicine crosses the placenta and distributes into breast milk [see Pregnancy (8.1) and Lactation (8.2)] .

Metabolism: A published in vitro human liver microsome study showed that about 16% of colchicine is metabolized to 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC, respectively) by CYP3A4. Glucuronidation is also believed to be a metabolic pathway for colchicine.

Excretion: In a published study in healthy volunteers, 40 to 65% of the total absorbed dose of colchicine (1 mg administered orally) was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also believed to play a role in colchicine elimination. Colchicine is a substrate of P-gp and P-gp efflux is postulated to play an important role in colchicine disposition. Elimination half-life in humans was found to be 31 h (range 21.7 to 49.9 h).

Special Populations: There is no difference between men and women in the pharmacokinetic disposition of colchicine.

Pediatric Patients: Pharmacokinetics of colchicine was not evaluated in pediatric patients.

Elderly: Pharmacokinetics of colchicine have not been determined in elderly patients. A published report described the pharmacokinetics of 1 mg oral colchicine tablet in four elderly women compared to six young healthy males. The mean age of the four elderly women was 83 years (range 75 to 93), mean weight was 47 kg (38 to 61 kg) and mean creatinine clearance was 46 mL/min (range 25 to 75 mL/min). Mean peak plasma levels and AUC of colchicine were two times higher in elderly subjects compared to young healthy males. It is possible that the higher exposure in the elderly subjects was due to decreased renal function.

Renal impairment: Pharmacokinetics of colchicine in patients with mild and moderate renal impairment is not known. A published report described the disposition of colchicine (1 mg) in young adult men and women patients who had end-stage renal disease requiring dialysis compared to patients with normal renal function. Patients with end-stage renal disease had 75% lower colchicine clearance (0.17 vs. 0.73 L/hr/kg) and prolonged plasma elimination half-life (18.8 hrs vs. 4.4 hrs) as compared to subjects with normal renal function [see Renal Impairment (8.6)] .

Hepatic impairment: Published reports on the pharmacokinetics of intravenous colchicine in patients with severe chronic liver disease, as well as those with alcoholic or primary biliary cirrhosis, and normal renal function suggest wide inter-patient variability. In some subjects with mild to moderate cirrhosis, the clearance of colchicine is significantly reduced and plasma half-life prolonged compared to healthy subjects. In subjects with primary biliary cirrhosis, no consistent trends were noted [see Hepatic Impairment (8.7)] . No pharmacokinetic data are available for patients with severe hepatic impairment (Child-Pugh C).

Drug Interactions: Pharmacokinetic studies evaluating changes in systemic levels of colchicine when co-administered with CYP3A4 inhibitors in healthy volunteers have been conducted with colchicine capsules. While voriconazole 200 mg BID for 5 days (considered a strong CYP3A4 inhibitor) and cimetidine 800 mg BID for 5 days (considered a weak CYP3A4 inhibitor) did not cause any changes in colchicine systemic levels, fluconazole 200 mg QD for 4 days with a 400 mg loading dose (considered a moderate CYP3A4 inhibitor) increased colchicine AUC by 40%. As voriconazole, cimetidine, and fluconazole are known as CYP3A4 inhibitors that do not inhibit P-gp, these studies show that CYP3A4 inhibition by itself may not lead to clinically significant increases in colchicine systemic levels in humans, and P-gp inhibition in addition to CYP3A4 inhibition may be necessary for clinically meaningful interactions of colchicine. However, based on published case reports that indicate the presence of colchicine toxicity when colchicine is co-administered with strong to moderate CYP3A4 inhibitors such as clarithromycin, erythromycin, grapefruit juice, etc., as well as the 40% increase in systemic levels of colchicine observed with concomitantly administered fluconazole (a moderate CYP3A4 inhibitor that is not known to inhibit P-gp) in a drug-drug interaction study, the drug-drug interaction potential of colchicine with strong or moderate CYP3A4 inhibitors that do not inhibit P-gp cannot be ruled out completely.

Co-administration of colchicine capsules with propafenone (a P-gp inhibitor) at 225 mg BID for 5 days, in a pharmacokinetic study in healthy volunteers, did not cause any changes in systemic levels of colchicine. This indicates that propafenone can be administered with colchicine capsules without any dose adjustment. However, these results should not be extrapolated to other P-gp inhibitors as colchicine is known to be a substrate for P‑gp and case reports of colchicine toxicity associated with the co-administration of P-gp inhibitors such as cyclosporine have been published.

Carcinogenesis Carcinogenicity studies of colchicine have not been conducted. Due to the potential for colchicine to produce aneuploid cells (cells with an unequal number of chromosomes), colchicine presents a theoretical increased risk of malignancy.

Mutagenesis Published studies demonstrated that colchicine was negative for mutagenicity in the bacterial reverse mutation assay. However, in vitrochromosomal aberration assays demonstrated the formation of micronuclei following colchicine treatment. Because published studies demonstrated that colchicine induces aneuploidy through the process of mitotic nondisjunction without structural DNA changes, colchicine is not considered clastogenic, although micronuclei are formed.

Impairment of Fertility There were no studies of the effects of colchicine capsules on fertility. However, published nonclinical studies have demonstrated that colchicine-induced disruption of microtubule formation affects meiosis and mitosis. Published reproductive studies with colchicine reported abnormal sperm morphology and reduced sperm counts in males, and interference with sperm penetration, second meiotic division, and normal cleavage in females.

Case reports and epidemiology studies in human male subjects on colchicine therapy indicate that infertility from colchicine is rare. A case report indicated that azoospermia was reversed when therapy was stopped. Case reports and epidemiology studies in female subjects on colchicine therapy have not established a clear relationship between colchicine use and female infertility.

The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate lowering therapy. In both trials, treatment with colchicine decreased the frequency of gout flares.

{ "type": "p", "children": [], "text": "The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate lowering therapy. In both trials, treatment with colchicine decreased the frequency of gout flares." }

Colchicine capsules, 0.6 mg are No. 4 Dark Blue/Light Blue Hard Gelatin Capsules printed “West-ward 118” in white ink.

Unit dose packages of 30 (5 x 6) NDC 60687-358-25

Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature]. Protect from light and moisture.

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Hikma Pharmaceuticals USA Inc. as follows: (0.6 mg / 30 UD) NDC 60687-358-25 packaged from NDC 0143-3018

Distributed by: American Health Packaging Columbus, OH 43217

8435825/0425F

8435825/0425F

{ "type": "p", "children": [], "text": "\n8435825/0425F\n" }

Colchicine (kol’ chi seen) Capsules

{ "type": "p", "children": [], "text": "\nColchicine (kol’ chi seen) Capsules\n" }

What is the most important information I should know about colchicine capsules? Colchicine capsules can cause serious side effects or death if levels of colchicine are too high in your body.

{ "type": "p", "children": [], "text": "\nWhat is the most important information I should know about colchicine capsules?\n\nColchicine capsules can cause serious side effects or death if levels of colchicine are too high in your body.\n " }

{ "type": "ul", "children": [ "Taking certain medicines with colchicine capsules can cause your level of colchicine to be too high, especially if you have kidney or liver problems.", "Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of colchicine capsules may need to be changed.", "Even medicines that you take for a short period of time, such as antibiotics, can interact with colchicine capsules and cause serious side effects or death." ], "text": "" }

What are colchicine capsules? Colchicine capsules are a prescription medication used to prevent gout flares in adults.

{ "type": "p", "children": [], "text": "\nWhat are colchicine capsules?\n\nColchicine capsules are a prescription medication used to prevent gout flares in adults.\n " }

It is not known if colchicine capsules are safe and effective for the treatment of:

{ "type": "p", "children": [], "text": "It is not known if colchicine capsules are safe and effective for the treatment of:" }

{ "type": "ul", "children": [ "acute gout flares" ], "text": "" }

Colchicine capsules are not a pain medicine and it should not be taken to treat pain related to other conditions unless specifically for those conditions.

{ "type": "p", "children": [], "text": "Colchicine capsules are not a pain medicine and it should not be taken to treat pain related to other conditions unless specifically for those conditions." }

It is not known if colchicine capsules are safe and effective in children.

{ "type": "p", "children": [], "text": "It is not known if colchicine capsules are safe and effective in children." }

Who should not take colchicine capsules? Do not take colchicine capsules if you have liver and kidney problems and you take certain other medicines. Serious side effects, including death, have been reported in these people even when taken as directed. See “What is the most important information I should know about colchicine capsules?”

{ "type": "p", "children": [], "text": "\nWho should not take colchicine capsules?\n\nDo not take colchicine capsules if you have liver and kidney problems and you take certain other medicines. Serious side effects, including death, have been reported in these people even when taken as directed. See \n “What is the most important information I should know about colchicine capsules?”\n" }

What should I tell my healthcare provider before taking colchicine capsules? Before you take colchicine capsules, tell your healthcare provider:

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

{ "type": "ul", "children": [ "about all of your medical conditions", "if you have kidney or liver problems", "if you are pregnant or plan to become pregnant. It is not known if colchicine capsules can harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.", "if you are breastfeeding or plan to breastfeed. Colchicine can pass into your breast milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take colchicine capsules.", "if you are a male with a female partner who can become pregnant. Receiving treatment with colchicine capsules maybe related to infertility in some men that is reversible whentreatment is stopped." ], "text": "" }

Tell your healthcare provider about all the medicines you take, including prescription, over-the-counter medicines, vitamins, or herbal supplements.

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take, including prescription, over-the-counter medicines, vitamins, or herbal supplements.\n " }

{ "type": "ul", "children": [ "Using colchicine capsules with certain other medicines can affect each other causing serious side effects and/or death.", "Do not take colchicine capsules with other medicines unless your healthcare provider tells you to.", "Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine.", "Especially tell your healthcare provider if you take:\n\t\n \nmedicines that may affect how your liver works (CYP3A4 inhibitors)\ncyclosporine (Neoral, Gengraf, Sandimmune)\ncholesterol lowering medicines\nantibiotics\n\n" ], "text": "" }

Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can affect colchicine capsules.

{ "type": "p", "children": [], "text": "Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can affect colchicine capsules." }

How should I take colchicine capsules?

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

{ "type": "ul", "children": [ "Take colchicine capsules exactly as your healthcare provider tells you to take it.", "Colchicine capsules can be taken with or without food.", "If you take too much colchicine capsules, call your healthcare provider or go to the nearest hospital emergency room right away.", "Do not stop taking colchicine capsules unless your healthcare provider tells you to.", "If you miss a dose of colchicine capsules, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time.", "If you have a gout flare while taking colchicine capsules, tell your healthcare provider." ], "text": "" }

What should I avoid while taking colchicine capsules?

{ "type": "p", "children": [], "text": "\nWhat should I avoid while taking colchicine capsules?\n" }

{ "type": "ul", "children": [ "Avoid eating grapefruit or drinking grapefruit juice while taking colchicine capsules. It can increase your chances of getting serious side effects." ], "text": "" }

What are the possible side effects of colchicine capsules? Colchicine capsules can cause serious side effects or death.

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of colchicine capsules?\n\nColchicine capsules can cause serious side effects or death.\n " }

See “What is the most important information I should know about colchicine capsules?” Get medical help right away, if you have:

{ "type": "p", "children": [], "text": "\nSee “What is the most important information I should know about colchicine capsules?”\n\nGet medical help right away, if you have:\n " }

{ "type": "ul", "children": [ "unusual bleeding or bruising", "increased infections", "weakness or fatigue", "muscle weakness or pain", "numbness or tingling in your fingers or toes", "pale or gray color to your lips, tongue, or palms of your hands", "severe diarrhea or vomiting" ], "text": "" }

The most common side effects of colchicine capsules include abdominal pain, diarrhea, nausea, and vomiting.

{ "type": "p", "children": [], "text": "The most common side effects of colchicine capsules include abdominal pain, diarrhea, nausea, and vomiting." }

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

{ "type": "p", "children": [], "text": "Tell your healthcare provider if you have any side effect that bothers you or that does not go away." }

These are not all of the possible side effects of colchicine capsules. For more information ask your healthcare provider or pharmacist.

{ "type": "p", "children": [], "text": "These are not all of the possible side effects of colchicine 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": "Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088." }

How should I store colchicine capsules?

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

{ "type": "ul", "children": [ "Store colchicine capsules at room temperature between 68°F to 77°F (20°C to 25°C).", "Keep colchicine capsules out of the light and away from moisture." ], "text": "" }

Keep colchicine capsules and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep colchicine capsules and all medicines out of the reach of children.\n" }

General information about the safe and effective use of colchicine capsules. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take colchicine capsules for a condition for which it was not prescribed. Do not give colchicine capsules to other people, even if they have the same symptoms that you have. It may harm them.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of colchicine capsules.\n\nMedicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take colchicine capsules for a condition for which it was not prescribed. Do not give colchicine capsules to other people, even if they have the same symptoms that you have. It may harm them.\n " }

This Medication Guide summarizes the most important information about colchicine capsules. If you would like more information, talk to your pharmacist or healthcare provider for information about colchicine capsules that is written for health professionals.

{ "type": "p", "children": [], "text": "This Medication Guide summarizes the most important information about colchicine capsules. If you would like more information, talk to your pharmacist or healthcare provider for information about colchicine capsules that is written for health professionals." }

For more information about the drug product, go to www.hikma.com or call 1-800-962-8364.

{ "type": "p", "children": [], "text": "For more information about the drug product, go to \n www.hikma.com or call 1-800-962-8364.\n " }

For more information about the packaging or labeling, call American Health Packaging at 1‐800‐707‐4621.

{ "type": "p", "children": [], "text": "For more information about the packaging or labeling, call American Health Packaging at 1‐800‐707‐4621." }

What are the ingredients in colchicine capsules? Active Ingredient: Colchicine, USP Inactive Ingredients:colloidal silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline cellulose and sodium starch glycolate. The capsule shell contains gelatin, purified water, titanium dioxide, erythrosine, Brilliant Blue FCF, and may contain D&C Red No. 28, FD&C Red No. 40 and Quinoline Yellow.

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in colchicine capsules?\n\nActive Ingredient: Colchicine, USP\n \nInactive Ingredients:colloidal silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline cellulose and sodium starch glycolate. The capsule shell contains gelatin, purified water, titanium dioxide, erythrosine, Brilliant Blue FCF, and may contain D&C Red No. 28, FD&C Red No. 40 and Quinoline Yellow.\n " }

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." }

Distributed by: American Health Packaging Columbus, OH 43217

{ "type": "p", "children": [], "text": "Distributed by:\n \nAmerican Health Packaging\n\nColumbus, OH 43217\n " }

8435825/0425F

{ "type": "p", "children": [], "text": "\n8435825/0425F\n" }

NDC 60687- 358-25

{ "type": "p", "children": [], "text": "NDC 60687-\n 358-25\n " }

Colchicine Capsules

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

0.6 mg

{ "type": "p", "children": [], "text": "\n0.6 mg\n" }

30 Capsules (5 x 6)            Rx Only

{ "type": "p", "children": [], "text": "\n30 Capsules (5 x 6)            Rx Only\n" }

PHARMACIST: Dispense with Medication Guide to each patient.

{ "type": "p", "children": [], "text": "\nPHARMACIST: Dispense with Medication Guide to\n \neach patient.\n " }

Each Capsule Contains: Colchicine, USP............................................................0.6 mg

{ "type": "p", "children": [], "text": "\nEach Capsule Contains:\n\nColchicine, USP............................................................0.6 mg\n " }

Usual Adult Dosage: See package full prescribing information.

{ "type": "p", "children": [], "text": "\nUsual Adult Dosage: See package full prescribing information.\n " }

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

{ "type": "p", "children": [], "text": "\nStore at 20° to 25°C (68° to 77°F); excursions permitted\n \nbetween 15° to 30°C (59° to 86°F) [see USP Controlled\n \nRoom Temperature].\n \nPROTECT FROM LIGHT AND MOISTURE.\n" }

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

{ "type": "p", "children": [], "text": "\nFOR YOUR PROTECTION: Do not use if blister is torn\n \nor broken.\n " }

The drug product contained in this package is from NDC # 0143-3018, Hikma Pharmaceuticals USA Inc.

{ "type": "p", "children": [], "text": "The drug product contained in this package is from\n \nNDC # 0143-3018, Hikma Pharmaceuticals USA Inc.\n " }

Distributed by: American Health Packaging, Columbus, Ohio 43217

{ "type": "p", "children": [], "text": "Distributed by: American Health Packaging, Columbus,\n \nOhio 43217\n " }

735825 0435825/0324

{ "type": "p", "children": [], "text": "735825\n \n0435825/0324\n " }

Colchicine Capsule

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

0.6 mg

{ "type": "p", "children": [], "text": "\n0.6 mg\n" }

Colchicine tablets are indicated for prophylaxis and the treatment of acute gout flares.

Colchicine tablets are indicated in adults and children four years or older for treatment of familial Mediterranean fever (FMF).

The recommended dosage of colchicine tablets for prophylaxis of gout flares for adults and adolescents older than 16 years of age is 0.6 mg once or twice daily. The maximum recommended dose for prophylaxis of gout flares is 1.2 mg/day.

An increase in gout flares may occur after initiation of uric acid-lowering therapy, including pegloticase, febuxostat and allopurinol, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Colchicine tablets are recommended upon initiation of gout flare prophylaxis with uric acid-lowering therapy. Prophylactic therapy may be beneficial for at least the first six months of uric acid-lowering therapy.

The recommended dose of colchicine tablets for treatment of a gout flare is 1.2 mg (two tablets) at the first sign of the flare followed by 0.6 mg (one tablet) one hour later. Higher doses have not been found to be more effective. The maximum recommended dose for treatment of gout flares is 1.8 mg over a 1-hour period. Colchicine tablets may be administered for treatment of a gout flare during prophylaxis at doses not to exceed 1.2 mg (two tablets) at the first sign of the flare followed by 0.6 mg (one tablet) one hour later. Wait 12 hours and then resume the prophylactic dose.

The recommended dosage of colchicine tablets for FMF in adults is 1.2 mg to 2.4 mg daily.

Colchicine tablets should be increased as needed to control disease and as tolerated in increments of 0.3 mg/day to a maximum recommended daily dose. If intolerable side effects develop, the dose should be decreased in increments of 0.3 mg/day. The total daily colchicine tablets dose may be administered in one to two divided doses.

Colchicine tablets are not recommended for pediatric use in prophylaxis or treatment of gout flares.

The recommended dosage of colchicine tablets for FMF in pediatric patients 4 years of age and older is based on age. The following daily doses may be given as a single or divided dose twice daily:

Coadministration of colchicine tablets with drugs known to inhibit CYP3A4 and/or P-glycoprotein (P-gp) increases the risk of colchicine-induced toxic effects (Table 1). If patients are taking or have recently completed treatment with drugs listed in Table 1 within the prior 14 days, the dose adjustments are as shown in the table below [see Drug Interactions (7)].

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1. Colchicine Tablets Dose Adjustment for Coadministration with Interacting Drugs if No Alternative Available<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></span> </caption> <col width="14%"/> <col width="15%"/> <col width="13%"/> <col width="12%"/> <col width="12%"/> <col width="10%"/> <col width="12%"/> <col width="10%"/> <tfoot> <tr> <td align="left" colspan="8"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>For magnitude of effect on colchicine plasma concentrations <span class="Italics">[see <a href="#_RefID_a392eae1-2105-4c56-b004-d983ccf8e">Clinical Pharmacology (12.3)</a>]</span> </dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd>Patients with renal or hepatic impairment should not be given colchicine tablets in conjunction with strong CYP3A4 or P-gp inhibitors <span class="Italics">[see <a href="#_RefID_f5c9c8c7-d821-448e-9972-e67a940b2">Contraindications (4)</a>]</span> </dd> <dt> <a href="#footnote-reference-3" name="footnote-3">‡</a> </dt> <dd>When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors <span class="Italics">[see <a href="#_RefID_f5c9c8c7-d821-448e-9972-e67a940b2">Contraindications (4)</a>]</span> </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="8" valign="top"> <p class="First"> <span class="Bold">Strong CYP3A4 Inhibitors</span><a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="bottom"></td><td class="Lrule Rrule" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule" colspan="4" valign="bottom"> <p class="First"> <span class="Bold">Gout Flares</span> </p> </td><td class="Lrule" valign="bottom"></td><td class="Rrule" valign="bottom"></td> </tr> <tr> <td class="Lrule Rrule" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Noted or Anticipated Outcome</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Prophylaxis of Gout Flares</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Treatment of Gout Flares</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">FMF</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dose</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Atazanavir</p> <p>Clarithromycin</p> <p>Darunavir/</p> <p>Ritonavir<a class="Sup" href="#footnote-3" name="footnote-reference-3">‡</a> </p> <p>Indinavir</p> <p>Itraconazole</p> <p>Ketoconazole</p> <p>Lopinavir/</p> <p>Ritonavir </p> <p>Nefazodone</p> <p>Nelfinavir</p> <p>Ritonavir</p> <p>Saquinavir</p> <p>Telithromycin</p> <p>Tipranavir/</p> <p>Ritonavir </p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Significant increase in colchicine plasma levels; fatal colchicine toxicity has been reported with clarithromycin, a strong CYP3A4 inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other strong CYP3A4 inhibitors</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day </p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">1.2 mg </p> <p>(2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p> (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Maximum daily dose of 1.2 mg - 2.4 mg</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="8" valign="top"> <p class="First"> <span class="Bold">Moderate CYP3A4 Inhibitors</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="bottom"></td><td class="Lrule Rrule" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule" colspan="4" valign="bottom"> <p class="First"> <span class="Bold">Gout Flares</span> </p> </td><td class="Lrule" valign="bottom"></td><td class="Rrule" valign="bottom"></td> </tr> <tr> <td class="Lrule Rrule" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Note or Anticipated Outcome</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Prophylaxis of Gout Flares</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Treatment of Gout Flares</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">FMF</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dosage</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Amprenavir </p> <p>Aprepitant</p> <p>Diltiazem</p> <p>Erythromycin</p> <p>Fluconazole</p> <p>Fosamprenavir (prodrug of Amprenavir)</p> <p>Grapefruit juice</p> <p>Verapamil</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Significant increase in colchicine plasma concentration is anticipated. Neuromuscular toxicity has been reported with diltiazem and verapamil interactions.</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg twice a day or 0.6 mg once a day</p> <p>0.3 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">1.2 mg </p> <p>(2 tablets) followed by 0.6 mg (1 tablet) </p> <p>1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">1.2 mg </p> <p>(2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Maximum daily dose of 1.2 mg - 2.4 mg</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="8" valign="top"> <p class="First"> <span class="Bold">P-gp Inhibitors</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="bottom"></td><td class="Lrule Rrule" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule" colspan="4" valign="bottom"> <p class="First"> <span class="Bold">Gout Flares</span> </p> </td><td class="Lrule" valign="bottom"></td><td class="Rrule" valign="bottom"></td> </tr> <tr> <td class="Lrule Rrule" valign="bottom"></td><td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Note or Anticipated Outcome</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Prophylaxis of Gout Flares</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Treatment of Gout Flares</span> </p> </td><td align="center" class="Botrule Lrule Rrule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">FMF</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Original Intended Dosage</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Adjusted Dosage</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Cyclosporine</p> <p>Ranolazine</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Significant increase in colchicine plasma levels; fatal colchicine toxicity has been reported with cyclosporine, a P-gp inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other </p> <p>P-gp inhibitors.</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">1.2 mg </p> <p>(2 tablets) followed by 0.6 mg </p> <p>(1 tablet) </p> <p>1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg </p> <p>(1 tablet) x </p> <p>1 dose. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Maximum daily dose of 1.2 mg - 2.4 mg</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2. Colchicine Tablets Dose Adjustment for Coadministration with Protease Inhibitors</span> </caption> <col width="16%"/> <col width="18%"/> <col width="15%"/> <col width="18%"/> <col width="17%"/> <col width="17%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Protease Inhibitor</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Clinical Comment</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">w/ Colchicine - Prophylaxis of Gout Flares</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">w/o Colchicine – Treatment of Gout Flares</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">w/Colchicine – Treatment of FMF</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Atazanavir</p> <p>sulfate</p> <p>(Reyataz)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Reyataz.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original</span> </p> <p> <span class="Bold">dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted</span> </p> <p> <span class="Bold">dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Darunavir (Prezista)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Prezista/ritonavir.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Fosamprenavir (Lexiva) with Ritonavir</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Fosamprenavir (Lexiva)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg twice a day or 0.6 mg once a day</p> <p>0.3 mg once a day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Indinavir (Crixivan)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Crixivan.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Lopinavir/</p> <p>Ritonavir</p> <p>(Kaletra)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Kaletra.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Nelfinavir mesylate (Viracept)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Viracept.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Ritonavir (Norvir)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Norvir.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Saquinavir mesylate (Invirase)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Invirase/ritonavir.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Tipranavir (Aptivus)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Patients with renal or hepatic impairment should not be given colchicine with Aptivus/ritonavir.</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Original dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Adjusted dose</span> </p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days.</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg twice a day</p> <p>0.6 mg once a day</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">0.3 mg once a day</p> <p>0.3 mg once every other day</p> </td> </tr> </tbody> </table></div>

Treatment of gout flares with colchicine tablets is not recommended in patients receiving prophylactic dose of colchicine tablets and CYP3A4 inhibitors.

Colchicine dosing must be individualized according to the patient's renal function [see Use in Specific Populations (8.6)].

Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula:

For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Clcr] 50 to 80 mL/min) to moderate (Clcr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg/day and any increase in dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring [see Clinical Pharmacology (12.3), Use in Specific Populations (8.6)].

For treatment of gout flares in patients with mild (Clcr 50 to 80 mL/min) to moderate (Clcr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks. For patients with gout flares requiring repeated courses, consideration should be given to alternate therapy. For patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). For these patients, the treatment course should not be repeated more than once every two weeks [see Clinical Pharmacology (12.3), Use in Specific Populations (8.6)].

Treatment of gout flares with colchicine tablets is not recommended in patients with renal impairment who are receiving colchicine tablets for prophylaxis.

Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing dialysis. For these patients, the dosage should be reduced [see Clinical Pharmacology (12.3)]. Patients with mild (Clcr 50 to 80 mL/min) and moderate (Clcr 30 to 50 mL/min) renal impairment should be monitored closely for adverse effects of colchicine tablets. Dose reduction may be necessary. For patients with severe renal failure (Clcr less than 30 mL/min), start with 0.3 mg/day; any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine [see Use in Specific Populations (8.6)]. For patients undergoing dialysis, the total recommended starting dose should be 0.3 mg (half tablet) per day. Dosing can be increased with close monitoring. Any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine [see Clinical Pharmacology (12.3), Use in Specific Populations (8.6)].

For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment [see Use in Specific Populations (8.7)].

For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, a treatment course should be repeated no more than once every two weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Use in Specific Populations (8.7)].

Treatment of gout flares with colchicine tablets is not recommended in patients with hepatic impairment who are receiving colchicine tablets for prophylaxis.

Patients with mild to moderate hepatic impairment should be monitored closely for adverse effects of colchicine. Dose reduction should be considered in patients with severe hepatic impairment [see Use in Specific Populations (8.7)].

Colchicine Tablets USP, 0.6 mg — purple color, film-coated, capsule shaped tablets debossed with ‘372’ on one side and score line on the other side of the tablet.

{ "type": "p", "children": [], "text": "Colchicine Tablets USP, 0.6 mg — purple color, film-coated, capsule shaped tablets debossed with ‘372’ on one side and score line on the other side of the tablet." }

Patients with renal or hepatic impairment should not be given colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir). In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses.

{ "type": "p", "children": [], "text": "Patients with renal or hepatic impairment should not be given colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir). In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses." }

Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Overdosage (10)]. Colchicine tablets should be kept out of the reach of children.

Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported with colchicine used in therapeutic doses.

Colchicine is a P-gp and CYP3A4 substrate. Life-threatening and fatal drug interactions have been reported in patients treated with colchicine given with P-gp and strong CYP3A4 inhibitors. If treatment with a P-gp or strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, the patient’s dose of colchicine may need to be reduced or interrupted [see Drug Interactions (7)]. Use of colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir) is contraindicated in patients with renal or hepatic impairment [see Contraindications (4)].

Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses. Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk. Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, gemfibrozil, fenofibrate, fenofibric acid or benzafibrate (themselves associated with myotoxicity) or cyclosporine with colchicine tablets may potentiate the development of myopathy [see Drug Interactions (7)]. Once colchicine is stopped, the symptoms generally resolve within one week to several months.

Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.

In a randomized, double-blind, placebo-controlled trial in patients with a gout flare, gastrointestinal adverse reactions occurred in 26% of patients using the recommended dose (1.8 mg over one hour) of colchicine tablets compared to 77% of patients taking a nonrecommended high dose (4.8 mg over six hours) of colchicine and 20% of patients taking placebo. Diarrhea was the most commonly reported drug-related gastrointestinal adverse event. As shown in Table 3, diarrhea is associated with colchicine tablets treatment. Diarrhea was more likely to occur in patients taking the high-dose regimen than the low-dose regimen. Severe diarrhea occurred in 19% and vomiting occurred in 17% of patients taking the nonrecommended high-dose colchicine regimen but did not occur in the recommended low-dose colchicine tablets regimen.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3. Number (%) of Patients with at Least One Drug-Related Treatment-Emergent Adverse Event with an Incidence of ≥ 2% of Patients in Any Treatment Group</span> </caption> <col width="25%"/> <col width="25%"/> <col width="25%"/> <col width="25%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">MedDRA System Organ Class MedDRA Preferred Term</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">Colchicine Tablets Dose</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">(N = 59)</span> </p> <p> <span class="Bold">n (%)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">High (N= 52)</span> </p> <p> <span class="Bold">n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">Low (N = 74)</span> </p> <p> <span class="Bold">n (%)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Number of Patients with at Least One Drug-Related TEAE</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">40 (77)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">27 (37)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">16 (27)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Gastrointestinal Disorders</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">40 (77)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">19 (26)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">12 (20)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Diarrhea</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">40 (77)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">17 (23)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">8 (14)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Nausea</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">9 (17)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3 (4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3 (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" valign="middle"> <p class="First">9 (17)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Abdominal Discomfort</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 (3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">General Disorders and Administration Site Conditions</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">4 (8)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Fatigue</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 (4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Metabolic and Nutrition Disorders</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3 (4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 (3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Gout</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3 (4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Nervous System Disorders</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (1.4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 (3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Headache</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 (3)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Respiratory Thoracic Mediastinal Disorders</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 (3)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Pharyngolaryngeal Pain</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1 (2)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2 (3)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0</p> </td> </tr> </tbody> </table></div>

Serious toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation and injury to cells in the renal, hepatic, circulatory and central nervous systems. These most often occur with excessive accumulation or overdosage [see Overdosage (10)].

The following adverse reactions have been identified with colchicine. These have been generally reversible upon temporarily interrupting treatment or lowering the dose of colchicine. 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.

Neurological: sensory motor neuropathy

Dermatological: alopecia, maculopapular rash, purpura, rash

Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting

Hematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia

Hepatobiliary: elevated AST, elevated ALT

Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis

Reproductive: azoospermia, oligospermia

Colchicine is a substrate of the efflux transporter P-glycoprotein (P-gp). Of the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the metabolism of colchicine. If colchicine tablets are administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely. Fatal drug interactions have been reported.

{ "type": "p", "children": [], "text": "Colchicine is a substrate of the efflux transporter P-glycoprotein (P-gp). Of the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the metabolism of colchicine. If colchicine tablets are administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely. Fatal drug interactions have been reported." }

Physicians should ensure that patients are suitable candidates for treatment with colchicine tablets and remain alert for signs and symptoms of toxicities related to increased colchicine exposure as a result of a drug interaction. Signs and symptoms of colchicine tablets toxicity should be evaluated promptly and, if toxicity is suspected, colchicine tablets should be discontinued immediately.

{ "type": "p", "children": [], "text": "Physicians should ensure that patients are suitable candidates for treatment with colchicine tablets and remain alert for signs and symptoms of toxicities related to increased colchicine exposure as a result of a drug interaction. Signs and symptoms of colchicine tablets toxicity should be evaluated promptly and, if toxicity is suspected, colchicine tablets should be discontinued immediately." }

Table 4 provides recommendations as a result of other potentially significant drug interactions. Table 1 provides recommendations for strong and moderate CYP3A4 inhibitors and P-gp inhibitors.

{ "type": "p", "children": [], "text": "Table 4 provides recommendations as a result of other potentially significant drug interactions. Table 1 provides recommendations for strong and moderate CYP3A4 inhibitors and P-gp inhibitors." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4. Other Potentially Significant Drug Interactions</span> </caption> <col width="35%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Concomitant Drug Class or Food</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Noted or Anticipated Outcome</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Clinical Comment</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">HMG-CoA Reductase Inhibitors:</span> </p> <p>atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin</p> </td><td class="Botrule Lrule Rrule" rowspan="3" valign="top"> <p class="First">Pharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis (including a fatality)</p> </td><td class="Botrule Lrule Rrule" rowspan="2" valign="top"> <p class="First">Weigh the potential benefits and risks and carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy; monitoring CPK (creatine phosphokinase) will not necessarily prevent the occurrence of severe myopathy.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Other Lipid-Lowering Drugs:</span> </p> <p>fibrates, gemfibrozil</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Digitalis Glycosides: </span> </p> <p>digoxin</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">P-gp substrate; rhabdomyolysis has been reported</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 4. Other Potentially Significant Drug Interactions</span>\n</caption>\n<col width=\"35%\"/>\n<col width=\"33%\"/>\n<col width=\"33%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Concomitant Drug Class or Food</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Noted or Anticipated Outcome</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Clinical Comment</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\">HMG-CoA Reductase Inhibitors:</span>\n</p>\n<p>atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin</p>\n</td><td class=\"Botrule Lrule Rrule\" rowspan=\"3\" valign=\"top\">\n<p class=\"First\">Pharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis (including a fatality)</p>\n</td><td class=\"Botrule Lrule Rrule\" rowspan=\"2\" valign=\"top\">\n<p class=\"First\">Weigh the potential benefits and risks and carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy; monitoring CPK (creatine phosphokinase) will not necessarily prevent the occurrence of severe myopathy.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Other Lipid-Lowering Drugs:</span>\n</p>\n<p>fibrates, gemfibrozil</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Digitalis Glycosides: </span>\n</p>\n<p>digoxin</p>\n</td><td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">P-gp substrate; rhabdomyolysis has been reported</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Colchicine crosses the human placenta. Although animal reproductive and developmental studies were not conducted with colchicine tablets, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity and altered postnatal development at exposures within or above the clinical therapeutic range.

The estimated background risk of major birth defects and miscarriage for the indicated population is 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.

Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, Behcet’s disease, or familial Mediterranean fever (FMF) treated with colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.

Colchicine is present in human milk (see Data). Adverse events in breastfed infants have not been reported in the published literature after administration of colchicine to lactating women. There are no data on the effects of colchicine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for colchicine tablets and any potential adverse effects on the breastfed child from colchicine tablets or from the underlying maternal condition.

Limited published data from case reports and a small lactation study demonstrate that colchicine is present in breastmilk. A systematic review of literature reported no adverse effects in 149 breastfed children. In a prospective observational cohort study, no gastrointestinal or other symptoms were reported in 38 colchicine-exposed breastfed infants.

Case reports and epidemiology studies in human male subjects on colchicine therapy indicated that infertility from colchicine is rare and may be reversible. A case report indicated that azoospermia was reversed when therapy was stopped. Case reports and epidemiology studies in female subjects on colchicine therapy have not established a clear relationship between colchicine use and female infertility. However, since the progression of FMF without treatment may result in infertility, the use of colchicine needs to be weighed against the potential risks [see Nonclinical Toxicology (13.1)].

The safety and efficacy of colchicine in children of all ages with FMF has been evaluated in uncontrolled studies. There does not appear to be an adverse effect on growth in children with FMF treated long-term with colchicine.

Safety and effectiveness of colchicine in pediatric patients with gout has not been established.

Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)].

Colchicine is significantly excreted in urine in healthy subjects. Clearance of colchicine is decreased in patients with impaired renal function. Total body clearance of colchicine was reduced by 75% in patients with end-stage renal disease undergoing dialysis.

For prophylaxis of gout flares in patients with mild (estimated creatinine clearance Clcr 50 to 80 mL/min) to moderate (Clcr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg per day and any increase in dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring [see Dosage and Administration (2.5)].

For treatment of gout flares in patients with mild (Clcr 50 to 80 mL/min) to moderate (Clcr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine tablets. However, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks. For patients with gout flares requiring repeated courses, consideration should be given to alternate therapy. For patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). For these patients, the treatment course should not be repeated more than once every two weeks [see Dosage and Administration (2.5)].

Although pharmacokinetics of colchicine in patients with mild (Clcr 50 to 80 mL/min) and moderate (Clcr 30 to 50 mL/min) renal impairment is not known, these patients should be monitored closely for adverse effects of colchicine. Dose reduction may be necessary. In patients with severe renal failure (Clcr less than 30 mL/min) and end-stage renal disease requiring dialysis, colchicine tablets may be started at the dose of 0.3 mg/day. Any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine tablets [see Clinical Pharmacology (12.3), Dosage and Administration (2.5)].

The clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment compared to healthy subjects [see Clinical Pharmacology (12.3)].

For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment [see Dosage and Administration (2.6)].

For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended colchicine tablets dose is not required, but patients should be monitored closely for adverse effects of colchicine tablets. However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, the treatment course should be repeated no more than once every two weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Dosage and Administration (2.6)].

In patients with severe hepatic disease, dose reduction should be considered with careful monitoring [see Clinical Pharmacology (12.3), Dosage and Administration (2.6)].

Tolerance, abuse or dependence with colchicine has not been reported.

{ "type": "p", "children": [], "text": "Tolerance, abuse or dependence with colchicine has not been reported." }

The exact dose of colchicine that produces significant toxicity is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder toxicities such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe reactions such as myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg.

{ "type": "p", "children": [], "text": "The exact dose of colchicine that produces significant toxicity is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder toxicities such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe reactions such as myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg." }

The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen. Life-threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multiorgan failure and its consequences. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery of multiorgan injury may be accompanied by rebound leukocytosis and alopecia starting about one week after the initial ingestion.

{ "type": "p", "children": [], "text": "The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen. Life-threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multiorgan failure and its consequences. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery of multiorgan injury may be accompanied by rebound leukocytosis and alopecia starting about one week after the initial ingestion." }

Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent shock. Otherwise, treatment is symptomatic and supportive. No specific antidote is known. Colchicine is not effectively removed by dialysis [see Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent shock. Otherwise, treatment is symptomatic and supportive. No specific antidote is known. Colchicine is not effectively removed by dialysis [see Clinical Pharmacology (12.3)]." }

Colchicine is an alkaloid chemically described as (S)N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo [alpha] heptalen-7-yl) acetamide with a molecular formula of C22H25NO6 and a molecular weight of 399.4. The structural formula of colchicine is given below.

{ "type": "p", "children": [], "text": "Colchicine is an alkaloid chemically described as (S)N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo [alpha] heptalen-7-yl) acetamide with a molecular formula of C22H25NO6 and a molecular weight of 399.4. The structural formula of colchicine is given below." }

Colchicine, USP occurs as a white to pale yellow powder that is very soluble in water, freely soluble in alcohol and chloroform, slightly soluble in ether, practically insoluble in cyclohexane.

{ "type": "p", "children": [], "text": "Colchicine, USP occurs as a white to pale yellow powder that is very soluble in water, freely soluble in alcohol and chloroform, slightly soluble in ether, practically insoluble in cyclohexane." }

Colchicine Tablets, USP are supplied for oral administration as purple color, film-coated, capsule shaped tablets debossed with ‘372’ on one side and score line on the other side of the tablet. Each tablet contains 0.6 mg of the active ingredient colchicine USP.

{ "type": "p", "children": [], "text": "Colchicine Tablets, USP are supplied for oral administration as purple color, film-coated, capsule shaped tablets debossed with ‘372’ on one side and score line on the other side of the tablet. Each tablet contains 0.6 mg of the active ingredient colchicine USP." }

Inactive ingredients: FD&C BLUE #2, FD&C RED #40, hypromellose, lactose monohydrate, macrogol, magnesium stearate, microcrystalline cellulose, polydextrose, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin.

{ "type": "p", "children": [], "text": "Inactive ingredients: FD&C BLUE #2, FD&C RED #40, hypromellose, lactose monohydrate, macrogol, magnesium stearate, microcrystalline cellulose, polydextrose, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin." }

The mechanism by which colchicine tablets exert its beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β. Additionally, colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules and consequently prevents the activation, degranulation and migration of neutrophils thought to mediate some gout symptoms.

In healthy adults, colchicine tablets are absorbed when given orally, reaching a mean Cmax of 2.5 ng/mL (range 1.1 to 4.4 ng/mL) in one to two hours (range 0.5 to 3 hours) after a single dose administered under fasting conditions.

Following oral administration of colchicine tablets given as 1.8 mg colchicine over one hour to healthy, young adults under fasting conditions, colchicine appears to be readily absorbed, reaching mean maximum plasma concentrations of 6.2 ng/mL at a median 1.81 hours (range: 1.0 to 2.5 hours). Following administration of the nonrecommended high-dose regimen (4.8 mg over six hours), mean maximal plasma concentrations were 6.8 ng/mL, at a median 4.47 hours (range: 3.1 to 7.5 hours).

After ten days on a regimen of 0.6 mg twice daily, peak concentrations are 3.1 to 3.6 ng/mL (range 1.6 to 6.0 ng/mL), occurring 1.3 to 1.4 hours postdose (range 0.5 to 3.0 hours). Mean pharmacokinetic parameter values in healthy adults are shown in Table 5.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 5. Mean (% CV) Pharmacokinetic Parameters in Healthy Adults Given Colchicine Tablets</span> </caption> <col width="30%"/> <col width="21%"/> <col width="17%"/> <col width="17%"/> <col width="16%"/> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-4" name="footnote-4">*</a> </dt> <dd>T<span class="Sub">max</span> mean (range)<br/>CL = Dose/AUC<span class="Sub">0-t</span> (calculated from mean values)<br/>Vd = CL/Ke (calculated from mean values)</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> </p> <p> <span class="Bold">(Colchicine ng/mL)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">T<span class="Sub">max</span></span><a class="Sup" href="#footnote-4" name="footnote-reference-4">*</a> </p> <p> <span class="Bold">(h)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Vd/F</span> </p> <p> <span class="Bold">(L)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">CL/F</span> </p> <p> <span class="Bold">(L/hr)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">t<span class="Sub">1/2</span></span> </p> <p> <span class="Bold">(h)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Colchicine Tablets 0.6 mg Single Dose (N = 13)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2.5</p> <p>(28.7)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.5</p> <p>(1.0 - 3.0)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">341.5</p> <p>(54.4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">54.1</p> <p>(31.0)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">--</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="5" valign="top"> <p class="First"> <span class="Bold">Colchicine Tablets 0.6 mg Twice Daily x 10 Days (N = 13)</span> </p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3.6</p> <p>(23.7)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1.3</p> <p>(0.5 - 3.0)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1150</p> <p>(18.7)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">30.3</p> <p>(19.0)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">26.6</p> <p>(16.3)</p> </td> </tr> </tbody> </table></div>

In some subjects, secondary colchicine peaks are seen, occurring between three and 36 hours postdose and ranging from 39 to 155% of the height of the initial peak. These observations are attributed to intestinal secretion and reabsorption and/or biliary recirculation.

Absolute bioavailability is reported to be approximately 45%.

Administration of colchicine tablets with food has no effect on the rate of colchicine absorption but does decrease the extent of colchicine by approximately 15%. This is without clinical significance.

The mean apparent volume of distribution in healthy young volunteers is approximately 5 to 8 L/kg.

Colchicine binding to serum protein is low, 39 ± 5%, primarily to albumin regardless of concentration.

Colchicine crosses the placenta (plasma levels in the fetus are reported to be approximately 15% of the maternal concentration). Colchicine also distributes into breast milk at concentrations similar to those found in the maternal serum [see Use in Specific Populations (8.1, 8.2)].

Colchicine is demethylated to two primary metabolites, 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC, respectively) and one minor metabolite, 10-O-demethylcolchicine (also known as colchicine). In vitro studies using human liver microsomes have shown that CYP3A4 is involved in the metabolism of colchicine to 2- and 3-DMC. Plasma levels of these metabolites are minimal (less than 5% of parent drug).

In healthy volunteers (n = 12), 40 to 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination. Following multiple oral doses (0.6 mg twice daily), the mean elimination half-lives in young healthy volunteers (mean age 25 to 28 years of age) is 26.6 to 31.2 hours. Colchicine is a substrate of P-gp.

Colchicine is not removed by hemodialysis.

There is no difference between men and women in the pharmacokinetic disposition of colchicine.

Pharmacokinetics of colchicine was not evaluated in pediatric patients.

A published report described the pharmacokinetics of 1 mg oral colchicine tablet in four elderly women compared to six young healthy males. The mean age of the four elderly women was 83 years (range 75 to 93), mean weight was 47 kg (38 to 61 kg) and mean creatinine clearance was 46 mL/min (range 25 to 75 mL/min). Mean peak plasma levels and AUC of colchicine were two times higher in elderly subjects compared to young healthy males.

A pharmacokinetic study using a single oral dose of one 0.6 mg colchicine tablet was conducted in young healthy subjects (n = 20) between the ages of 18 and 30 years and elderly subjects (n = 18) between the ages of 60 and 70 years. Elderly subjects in this study had a median age of 62 years and a mean (± SD) age of 62.83 ± 2.83 years. A statistically significant difference in creatinine clearance (mean ± SD) was found between the two age groups (132.56 ± 23.16 mL/min for young vs 87.02 ± 17.92 mL/min for elderly subjects, respectively). The following pharmacokinetic parameter values (mean ± SD) were observed for colchicine in the young and elderly subjects, respectively: AUC0-inf (ng/hr/mL) 22.39 ± 6.95 and 25.01 ± 6.92; Cmax (ng/mL) 2.61 ± 0.71 and 2.56 ± 0.97; Tmax (hr) 1.38 ± 0.42 and 1.25 ± 0.43; apparent elimination half-life (hr) 24.92 ± 5.34 and 30.06 ± 10.78; and clearance (mL/min) 0.0321 ± 0.0091 and 0.0292 ± 0.0071.

Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see Dosage and Administration (2.4), Use in Specific Populations (8.5)].

Pharmacokinetics of colchicine in patients with mild and moderate renal impairment is not known. A published report described the disposition of colchicine (1 mg) in young adult men and women with FMF who had normal renal function or end-stage renal disease requiring dialysis. Patients with end-stage renal disease had 75% lower colchicine clearance (0.17 vs 0.73 L/hr/kg) and prolonged plasma elimination half-life (18.8 vs 4.4 hours) as compared to subjects with FMF and normal renal function [see Dosage and Administration (2.5), Use in Specific Populations (8.6)].

Published reports on the pharmacokinetics of IV colchicine in patients with severe chronic liver disease, as well as those with alcoholic or primary biliary cirrhosis and normal renal function suggest wide interpatient variability. In some subjects with mild to moderate cirrhosis, the clearance of colchicine is significantly reduced and plasma half-life prolonged compared to healthy subjects. In subjects with primary biliary cirrhosis, no consistent trends were noted [see Dosage and Administration (2.6), Use in Specific Populations (8.7)]. No pharmacokinetic data are available for patients with severe hepatic impairment (Child-Pugh C).

In vitro studies in human liver microsomes have shown that colchicine is not an inhibitor or inducer of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 activity.

The effects of coadministration of other drugs with colchicine tablets on Cmax, AUC and Cmin are summarized in Table 6 (effect of other drugs on colchicine) and Table 7 (effect of colchicine on other drugs). For information regarding clinical recommendations, see Table 1 in Dose Modification for Coadministration of Interacting Drugs [see Dosage and Administration (2.4)].

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 6. Drug Interactions: Pharmacokinetic Parameters for Colchicine Tablets in the Presence of the Coadministered Drug</span> </caption> <col width="17%"/> <col width="21%"/> <col width="16%"/> <col width="7%"/> <col width="17%"/> <col width="21%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Coadministered Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Coadministered Drug (mg)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Colchicine Tablets (mg)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">% Change in Colchicine Concentrations from Baseline</span> </p> <p> <span class="Bold">(Range: Min – Max)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">AUC<span class="Sub">0-t</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Cyclosporine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">100 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">23</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">270.0</p> <p>(62.0 to 606.9)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">259.0</p> <p>(75.8 to 511.9)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Clarithromycin</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">250 mg twice daily, 7 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">23</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">227.2</p> <p>(65.7 to 591.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">281.5</p> <p>(88.7 to 851.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Ketoconazole</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">200 mg twice daily, 5 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">24</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">101.7</p> <p>(19.6 to 219.0)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">212.2</p> <p>(76.7 to 419.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Ritonavir</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">100 mg twice daily, 5 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">184.4</p> <p>(79.2 to 447.4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">296.0</p> <p>(53.8 to 924.4)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Verapamil</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">240 mg daily, 5 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">24</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">40.1</p> <p>(-47.1 to 149.5)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">103.3</p> <p>(-9.8 to 217.2)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Diltiazem</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">240 mg daily, 7 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">20</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">44.2</p> <p>(-46.0 to 318.3)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">93.4</p> <p>(-30.2 to 338.6)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Azithromycin</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">500 mg x 1 day, then</p> <p>250 mg x 4 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">21</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">21.6</p> <p>(-41.7 to 222.0)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">57.1</p> <p>(-24.3 to 241.1)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Grapefruit juice</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">240 mL twice daily, 4 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.6 mg</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">21</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.55</p> <p>(-53.4 to 55.0)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">-2.36</p> <p>(-46.4 to 62.2)</p> </td> </tr> </tbody> </table></div>

Estrogen-containing oral contraceptives: In healthy female volunteers given ethinyl estradiol and norethindrone (Ortho-Novum® 1/35) coadministered with colchicine tablets (0.6 mg twice daily × 14 days), hormone concentrations are not affected.

In healthy volunteers given theophylline coadministered with colchicine tablets (0.6 mg twice daily × 14 days), theophylline concentrations were not affected.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 7. Drug Interactions: Pharmacokinetic Parameters for Coadministration of Drug in the Presence of Colchicine Tablets </span> </caption> <col width="18%"/> <col width="20%"/> <col width="16%"/> <col width="6%"/> <col width="20%"/> <col width="20%"/> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-5" name="footnote-5">*</a> </dt> <dd>Conducted in healthy adult females</dd> <dt> <a href="#footnote-reference-6" name="footnote-6">†</a> </dt> <dd>AUC<span class="Sub">Ʈ</span> </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Coadministered Drug</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Coadministered Drug (mg)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Dose of Colchicine Tablets (mg)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="bottom"> <p class="First"> <span class="Bold">% Change in Coadministered Drug Concentrations from Baseline</span> </p> <p> <span class="Bold">(Range: Min – Max)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="bottom"> <p class="First"> <span class="Bold">AUC<span class="Sub">0-t</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Theophylline</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">300 mg (elixir)</p> <p>single dose</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.6 mg twice daily x 14 days</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">27</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1.6</p> <p>(-30.4 to 23.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1.6</p> <p>(-28.5 to 27.1)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Ethinyl Estradiol (Ortho-Novum<span class="Sup">®</span> 1/35)</p> </td><td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="middle"> <p class="First">21-day cycle (active treatment)</p> <p>+</p> <p>7-day placebo</p> </td><td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="middle"> <p class="First">0.6 mg twice daily x 14 days</p> </td><td align="center" class="Botrule Lrule Rrule" rowspan="2" valign="middle"> <p class="First">27<a class="Sup" href="#footnote-5" name="footnote-reference-5">*</a> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">-6.7</p> <p>(-40.3 to 44.7)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">-3.0<a class="Sup" href="#footnote-6" name="footnote-reference-6">†</a> </p> <p>(-25.3 to 24.9)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Norethindrone (Ortho-Novum<span class="Sup">®</span> 1/35)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">0.94</p> <p>(-37.3 to 59.4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">-1.6 </p> <p>(-32.0 to 33.7)</p> </td> </tr> </tbody> </table></div>

Two year studies were conducted in mice and rats to assess the carcinogenic potential of colchicine. No evidence of colchicine-related tumorigenicity was observed in mice or rats at colchicine oral doses up to 3 and 2 mg/kg/day, respectively (approximately six and eight times, respectively, the maximum recommended human dose of 2.4 mg on a mg/m2 basis).

Colchicine was negative for mutagenicity in the bacterial reverse mutation assay. In a chromosomal aberration assay in cultured human white blood cells, colchicine treatment resulted in the formation of micronuclei. Since published studies demonstrated that colchicine induces aneuploidy from the process of mitotic nondisjunction without structural DNA changes, colchicine is not considered clastogenic, although micronuclei are formed.

No studies of colchicine effects on fertility were conducted with colchicine tablets. However, published nonclinical studies demonstrated that colchicine-induced disruption of microtubule formation affects meiosis and mitosis. Reproductive studies also reported abnormal sperm morphology and reduced sperm counts in males, and interference with sperm penetration, second meiotic division and normal cleavage in females when exposed to colchicine. Colchicine administered to pregnant animals resulted in fetal death and teratogenicity. These effects were dose-dependent, with the timing of exposure critical for the effects on embryofetal development. The nonclinical doses evaluated were generally higher than an equivalent human therapeutic dose, but safety margins for reproductive and developmental toxicity could not be determined.

The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate-lowering therapy. In both trials, treatment with colchicine decreased the frequency of gout flares.

{ "type": "p", "children": [], "text": "The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature. Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate-lowering therapy. In both trials, treatment with colchicine decreased the frequency of gout flares." }

The efficacy of a low-dosage regimen of oral colchicine (colchicine tablets total dose 1.8 mg over one hour) for treatment of gout flares was assessed in a multicenter, randomized, double-blind, placebo-controlled, parallel group, one week, dose-comparison study. Patients meeting American College of Rheumatology criteria for gout were randomly assigned to three groups: high-dose colchicine (1.2 mg, then 0.6 mg hourly x 6 hours [4.8 mg total]); low-dose colchicine (1.2 mg, then 0.6 mg in one hour [1.8 mg total] followed by five placebo doses hourly); or placebo (two capsules, then one capsule hourly x six hours). Patients took the first dose within 12 hours of the onset of the flare and recorded pain intensity (11-point Likert scale) and adverse events over 72 hours. The efficacy of colchicine was measured based on response to treatment in the target joint, using patient self-assessment of pain at 24 hours following the time of first dose as recorded in the diary. A responder was one who achieved at least a 50% reduction in pain score at the 24-hour postdose assessment relative to the pretreatment score and did not use rescue medication prior to the actual time of 24-hour postdose assessment.

{ "type": "p", "children": [], "text": "The efficacy of a low-dosage regimen of oral colchicine (colchicine tablets total dose 1.8 mg over one hour) for treatment of gout flares was assessed in a multicenter, randomized, double-blind, placebo-controlled, parallel group, one week, dose-comparison study. Patients meeting American College of Rheumatology criteria for gout were randomly assigned to three groups: high-dose colchicine (1.2 mg, then 0.6 mg hourly x 6 hours [4.8 mg total]); low-dose colchicine (1.2 mg, then 0.6 mg in one hour [1.8 mg total] followed by five placebo doses hourly); or placebo (two capsules, then one capsule hourly x six hours). Patients took the first dose within 12 hours of the onset of the flare and recorded pain intensity (11-point Likert scale) and adverse events over 72 hours. The efficacy of colchicine was measured based on response to treatment in the target joint, using patient self-assessment of pain at 24 hours following the time of first dose as recorded in the diary. A responder was one who achieved at least a 50% reduction in pain score at the 24-hour postdose assessment relative to the pretreatment score and did not use rescue medication prior to the actual time of 24-hour postdose assessment. " }

Rates of response were similar for the recommended low-dose treatment group (38%) and the nonrecommended high-dose group (33%) but were higher as compared to the placebo group (16%) as shown in Table 8.

{ "type": "p", "children": [], "text": "Rates of response were similar for the recommended low-dose treatment group (38%) and the nonrecommended high-dose group (33%) but were higher as compared to the placebo group (16%) as shown in Table 8." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 8. Number (%) of Responders Based on Target Joint Pain Score at 24 Hours Post First Dose</span> </caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Colchicine Tablets Dose</span> </p> <p> <span class="Bold">Responders n (%)</span> </p> <p> <span class="Bold">Low-Dose High-Dose</span> </p> <p> <span class="Bold">(n = 74) (n = 52)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">n (%)</span> </p> <p> <span class="Bold">(n = 58)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First">% Differences in Proportion</p> <p>Low-Dose High-Dose</p> <p>vs Placebo vs Placebo</p> <p>(95% Cl) (95% Cl)</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">28 (38%) 17 (33%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">9 (16%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">22 (8, 37) 17 (1, 33)</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 8. Number (%) of Responders Based on Target Joint Pain Score at 24 Hours Post First Dose</span>\n</caption>\n<col width=\"33%\"/>\n<col width=\"33%\"/>\n<col width=\"33%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"bottom\">\n<p class=\"First\">\n<span class=\"Bold\">Colchicine Tablets Dose</span>\n</p>\n<p>\n<span class=\"Bold\">Responders n (%)</span>\n</p>\n<p>\n<span class=\"Bold\">Low-Dose High-Dose</span>\n</p>\n<p>\n<span class=\"Bold\">(n = 74) (n = 52)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"bottom\">\n<p class=\"First\">\n<span class=\"Bold\">Placebo</span>\n</p>\n<p>\n<span class=\"Bold\">n (%)</span>\n</p>\n<p>\n<span class=\"Bold\">(n = 58)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"bottom\">\n<p class=\"First\">% Differences in Proportion</p>\n<p>Low-Dose High-Dose</p>\n<p>vs Placebo vs Placebo</p>\n<p>(95% Cl) (95% Cl)</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"middle\">\n<p class=\"First\">28 (38%) 17 (33%)</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"middle\">\n<p class=\"First\">9 (16%)</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"middle\">\n<p class=\"First\">22 (8, 37) 17 (1, 33)</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Figure 1 shows the percentage of patients achieving varying degrees of improvement in pain from baseline at 24 hours.

{ "type": "p", "children": [], "text": "Figure 1 shows the percentage of patients achieving varying degrees of improvement in pain from baseline at 24 hours." }

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

The evidence for the efficacy of colchicine in patients with FMF is derived from the published literature. Three randomized, placebo-controlled studies were identified. The three placebo-controlled studies randomized a total of 48 adult patients diagnosed with FMF and reported similar efficacy endpoints as well as inclusion and exclusion criteria.

{ "type": "p", "children": [], "text": "The evidence for the efficacy of colchicine in patients with FMF is derived from the published literature. Three randomized, placebo-controlled studies were identified. The three placebo-controlled studies randomized a total of 48 adult patients diagnosed with FMF and reported similar efficacy endpoints as well as inclusion and exclusion criteria." }

One of the studies randomized 15 patients with FMF to a six month crossover study during which five patients discontinued due to study noncompliance. The ten patients completing the study experienced five attacks over the course of 90 days while treated with colchicine compared to 59 attacks over the course of 90 days while treated with placebo. Similarly, the second study randomized 22 patients with FMF to a four month crossover study during which nine patients discontinued due to lack of efficacy while receiving placebo or study noncompliance. The 13 patients completing the study experienced 18 attacks over the course of 60 days while treated with colchicine compared to 68 attacks over the course of 60 days while treated with placebo. The third study was discontinued after an interim analysis of six of the 11 patients enrolled had completed the study; results could not be confirmed.

{ "type": "p", "children": [], "text": "One of the studies randomized 15 patients with FMF to a six month crossover study during which five patients discontinued due to study noncompliance. The ten patients completing the study experienced five attacks over the course of 90 days while treated with colchicine compared to 59 attacks over the course of 90 days while treated with placebo. Similarly, the second study randomized 22 patients with FMF to a four month crossover study during which nine patients discontinued due to lack of efficacy while receiving placebo or study noncompliance. The 13 patients completing the study experienced 18 attacks over the course of 60 days while treated with colchicine compared to 68 attacks over the course of 60 days while treated with placebo. The third study was discontinued after an interim analysis of six of the 11 patients enrolled had completed the study; results could not be confirmed." }

Open-label experience with colchicine in adults and children with FMF is consistent with the randomized, controlled trial experience and was utilized to support information on the safety profile of colchicine and for dosing recommendations.

{ "type": "p", "children": [], "text": "Open-label experience with colchicine in adults and children with FMF is consistent with the randomized, controlled trial experience and was utilized to support information on the safety profile of colchicine and for dosing recommendations." }

Colchicine Tablets USP, 0.6 mg are purple colored, film-coated, capsule shaped tablets debossed with ‘372’ on one side and score line on the other side of the tablet.

Bottles of 10 NDC 71205-687-10

Bottles of 21 NDC 71205-687-21

Bottles of 30 NDC 71205-687-30

Bottles of 60 NDC 71205-687-60

Bottles of 90 NDC 71205-687-90

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Protect from light.

DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.

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)." }

Dosing Instructions: Patients should be advised to take colchicine tablets as prescribed, even if they are feeling better. Patients should not alter the dose or discontinue treatment without consulting with their doctor. If a dose of colchicine tablets is missed:

{ "type": "p", "children": [], "text": "\nDosing Instructions: Patients should be advised to take colchicine tablets as prescribed, even if they are feeling better. Patients should not alter the dose or discontinue treatment without consulting with their doctor. If a dose of colchicine tablets is missed:" }

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

Fatal Overdose: Instruct patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine. Colchicine tablets should be kept out of the reach of children.

{ "type": "p", "children": [], "text": "\nFatal Overdose: Instruct patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine. Colchicine tablets should be kept out of the reach of children." }

Blood Dyscrasias: Patients should be informed that bone marrow depression with agranulocytosis, aplastic anemia and thrombocytopenia may occur with colchicine tablets.

{ "type": "p", "children": [], "text": "\nBlood Dyscrasias: Patients should be informed that bone marrow depression with agranulocytosis, aplastic anemia and thrombocytopenia may occur with colchicine tablets." }

Drug and Food Interactions: Patients should be advised that many drugs or other substances may interact with colchicine tablets and some interactions could be fatal. Therefore, patients should report to their healthcare provider all of the current medications they are taking and check with their healthcare provider before starting any new medications, particularly antibiotics. Patients should also be advised to report the use of nonprescription medication or herbal products. Grapefruit and grapefruit juice may also interact and should not be consumed during colchicine tablets treatment.

{ "type": "p", "children": [], "text": "\nDrug and Food Interactions: Patients should be advised that many drugs or other substances may interact with colchicine tablets and some interactions could be fatal. Therefore, patients should report to their healthcare provider all of the current medications they are taking and check with their healthcare provider before starting any new medications, particularly antibiotics. Patients should also be advised to report the use of nonprescription medication or herbal products. Grapefruit and grapefruit juice may also interact and should not be consumed during colchicine tablets treatment." }

Neuromuscular Toxicity: Patients should be informed that muscle pain or weakness, tingling or numbness in fingers or toes may occur with colchicine tablets alone or when it is used with certain other drugs. Patients developing any of these signs or symptoms must discontinue colchicine tablets and seek medical evaluation immediately.

{ "type": "p", "children": [], "text": "\nNeuromuscular Toxicity: Patients should be informed that muscle pain or weakness, tingling or numbness in fingers or toes may occur with colchicine tablets alone or when it is used with certain other drugs. Patients developing any of these signs or symptoms must discontinue colchicine tablets and seek medical evaluation immediately." }

Infertility: Advise males of reproductive potential that colchicine tablets may rarely and transiently impair fertility [see Use in Specific Populations (8.3)].

{ "type": "p", "children": [], "text": "\nInfertility: Advise males of reproductive potential that colchicine tablets may rarely and transiently impair fertility [see Use in Specific Populations (8.3)]." }

<div class="scrollingtable"><table width="100%"> <col width="50%"/> <col width="50%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Colchicine Tablets, USP</span> </p> <p> <span class="Bold">(KOL-chi-seen)</span> </p> <p> <span class="Bold">for oral use</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Read the Medication Guide that comes with colchicine tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about colchicine tablets when you start taking it and at regular checkups.</p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What is the most important information that I should know about colchicine tablets? </span> </p> <p>Colchicine tablets can cause serious side effects or death if levels of colchicine are too high in your body. </p> <dl> <dt>•</dt> <dd>Taking certain medicines with colchicine tablets can cause your level of colchicine to be too high, especially if you have kidney or liver problems. </dd> <dt>•</dt> <dd>Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of colchicine tablets may need to be changed. </dd> <dt>•</dt> <dd>Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. </dd> <dt>•</dt> <dd>Even medicines that you take for a short period of time, such as antibiotics, can interact with colchicine tablets and cause serious side effects or death. </dd> <dt>•</dt> <dd>Talk to your healthcare provider or pharmacist before taking any new medicine. </dd> <dt>•</dt> <dd>Especially tell your healthcare provider if you take: </dd> </dl> </td> </tr> <tr> <td class="Lrule" valign="top"> <dl> <dt>•</dt> <dd>atazanavir sulfate (Reyataz)</dd> <dt>•</dt> <dd>cyclosporine (Neoral, Gengraf, Sandimmune)</dd> <dt>•</dt> <dd>fosamprenavir (Lexiva) with ritonavir</dd> <dt>•</dt> <dd>indinavir (Crixivan)</dd> <dt>•</dt> <dd>ketoconazole (Nizoral)</dd> <dt>•</dt> <dd>nefazodone (Serzone)</dd> <dt>•</dt> <dd>ritonavir (Norvir)</dd> <dt>•</dt> <dd>telithromycin (Ketek)</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>•</dt> <dd>clarithromycin (Biaxin)</dd> <dt>•</dt> <dd>darunavir (Prezista)</dd> <dt>•</dt> <dd>fosamprenavir (Lexiva)</dd> <dt>•</dt> <dd>itraconazole (Sporanox)</dd> <dt>•</dt> <dd>lopinavir/ritonavir (Kaletra)</dd> <dt>•</dt> <dd>nelfinavir mesylate (Viracept)</dd> <dt>•</dt> <dd>saquinavir mesylate (Invirase)</dd> <dt>•</dt> <dd>tipranavir (Aptivus)</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can interact with colchicine tablets. </p> <dl> <dt>•</dt> <dd>Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. </dd> <dt>•</dt> <dd>Keep colchicine tablets out of the reach of children.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What are colchicine tablets? </span> </p> <p>Colchicine tablets are a prescription medicine used to: </p> <dl> <dt>•</dt> <dd>prevent and treat gout flares in adults</dd> <dt>•</dt> <dd>treat familial Mediterranean fever (FMF) in adults and children age 4 or older </dd> </dl> <p>Colchicine tablets are not a pain medicine, and it should not be taken to treat pain related to other conditions unless specifically prescribed for those conditions.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Who should not take colchicine tablets? </span> </p> <p>Do not take colchicine tablets if you have liver or kidney problems and you take certain other medicines. Serious side effects, including death, have been reported in these patients even when taken as directed. See <span class="Bold">“What is the most important information that I should know about colchicine tablets?” </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What should I tell my healthcare provider before starting colchicine tablets? </span>See <span class="Bold">“What is the most important information that I should know about colchicine tablets?” </span> </p> <p> </p> <p>Before you take colchicine tablets, tell your healthcare provider about all your medical conditions, including if you: </p> <dl> <dt>•</dt> <dd>have liver or kidney problems. </dd> <dt>•</dt> <dd>are pregnant or plan to become pregnant. It is not known if colchicine tablets will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. </dd> <dt>•</dt> <dd>are a male with a female partner who can become pregnant. Receiving treatment with colchicine tablets may be related to infertility in some men that is reversible when treatment is stopped. </dd> <dt>•</dt> <dd>are breastfeeding or plan to breastfeed. Colchicine passes into your breast milk. You and your healthcare provider should decide if you will take colchicine tablets while breastfeeding. If you take colchicine tablets and breastfeed, you should talk to your child’s healthcare provider about how to watch for side effects in your child. </dd> </dl> <p>Tell your healthcare provider about all the medicines you take, including ones that you may only be taking for a short time, such as antibiotics. See <span class="Bold">“What is the most important information that I should know about colchicine tablets?” </span> <br/> <br/>Do not start a new medicine without talking to your healthcare provider. </p> <p> </p> <p>Using colchicine tablets with certain other medicines, such as cholesterol-lowering medications and digoxin, can affect each other, causing serious side effects. Your healthcare provider may need to change your dose of colchicine tablets. Talk to your healthcare provider about whether the medications you are taking might interact with colchicine tablets and what side effects to look for. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">How should I take colchicine tablets? </span> </p> <dl> <dt>•</dt> <dd>Take colchicine tablets exactly as your healthcare provider tells you to take it. <span class="Bold">If you are not sure about your dosing</span>, call your healthcare provider. </dd> <dt>•</dt> <dd>Colchicine tablets can be taken with or without food. </dd> <dt>•</dt> <dd>If you take too many colchicine tablets, go to the nearest hospital emergency room right away. </dd> <dt>•</dt> <dd>Do not stop taking colchicine tablets even if you start to feel better, unless your healthcare provider tells you. </dd> <dt>•</dt> <dd>Your healthcare provider may do blood tests while you take colchicine tablets. </dd> <dt>•</dt> <dd>If you take colchicine tablets daily and you miss a dose, then 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. <dl> <dt>o</dt> <dd>If you have a gout flare while taking colchicine tablets daily, report this to your healthcare provider.</dd> </dl> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What should I avoid while taking colchicine tablets? </span> </p> <p>Avoid eating grapefruit or drinking grapefruit juice while taking colchicine tablets. It can increase your chances of getting serious side effects. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of colchicine tablets? </span> </p> <p>Colchicine tablets can cause serious side effects or even cause death. See <span class="Bold">“What is the most important information that I should know about colchicine tablets?” </span> </p> <p>Get medical help right away if you have: </p> <dl> <dt>•</dt> <dd>Muscle weakness or pain </dd> <dt>•</dt> <dd>Numbness or tingling in your fingers or toes </dd> <dt>•</dt> <dd>Unusual bleeding or bruising </dd> <dt>•</dt> <dd>Increased infections </dd> <dt>•</dt> <dd>Feel weak or tired </dd> <dt>•</dt> <dd>Pale or gray color to your lips, tongue or palms of your hands </dd> <dt>•</dt> <dd>Severe diarrhea or vomiting </dd> </dl> <p> <span class="Bold">Gout Flares:</span> The most common side effect of colchicine tablets in people who have gout flares is diarrhea.</p> <p> </p> <p> <span class="Bold">FMF: </span>The most common side effects of colchicine tablets in people who have FMF are abdominal pain, diarrhea, nausea and vomiting. </p> <p> </p> <p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of colchicine tablets. 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="2" valign="top"> <p class="First"> <span class="Bold">How should I store colchicine tablets? </span> </p> <dl> <dt>•</dt> <dd>Store colchicine tablets at room temperature between 20° to 25°C (68° to 77°F). </dd> <dt>•</dt> <dd>Keep colchicine tablets in a tightly closed container. </dd> <dt>•</dt> <dd>Keep colchicine tablets out of the light. </dd> </dl> <p> <span class="Bold">Keep colchicine tablets and all medicines out of the reach of children. </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">General Information about colchicine tablets </span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use colchicine tablets for a condition for which it was not prescribed. Do not give colchicine tablets to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about colchicine tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about colchicine tablets that is written for healthcare professionals. </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in colchicine tablets? </span> </p> <p> <span class="Bold"> </span> </p> <p> <span class="Bold">Active Ingredient: </span>colchicine. </p> <p> </p> <p> <span class="Bold">Inactive Ingredients: </span>FD&amp;C BLUE #2, FD&amp;C RED #40, hypromellose, lactose monohydrate, macrogol, magnesium stearate, microcrystalline cellulose, polydextrose, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin.<br/> <br/> <br/> <br/>All other trademarks are the property of their respective owners. <br/> <br/>For more information, call Dr. Reddy’s Laboratories, Inc. at 1-888-375-3784.<br/> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Rx Only <br/> <br/>Distributor:<br/> <span class="Bold">Dr. Reddy’s Laboratories Inc.,</span> <br/>Princeton, NJ 08540 <br/> <br/> <span class="Bold">Made in India</span> </p> <p>Repackaged and Relabeled by:<br/> <span class="Bold">Proficient Rx LP</span> <br/>Thousand Oaks, CA 91320 <br/> </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"50%\"/>\n<col width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Colchicine Tablets, USP</span>\n</p>\n<p>\n<span class=\"Bold\">(KOL-chi-seen)</span>\n</p>\n<p>\n<span class=\"Bold\">for oral use</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Read the Medication Guide that comes with colchicine tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about colchicine tablets when you start taking it and at regular checkups.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information that I should know about colchicine tablets? </span>\n</p>\n<p>Colchicine tablets can cause serious side effects or death if levels of colchicine are too high in your body. </p>\n<dl>\n<dt>•</dt>\n<dd>Taking certain medicines with colchicine tablets can cause your level of colchicine to be too high, especially if you have kidney or liver problems. </dd>\n<dt>•</dt>\n<dd>Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of colchicine tablets may need to be changed. </dd>\n<dt>•</dt>\n<dd>Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. </dd>\n<dt>•</dt>\n<dd>Even medicines that you take for a short period of time, such as antibiotics, can interact with colchicine tablets and cause serious side effects or death. </dd>\n<dt>•</dt>\n<dd>Talk to your healthcare provider or pharmacist before taking any new medicine. </dd>\n<dt>•</dt>\n<dd>Especially tell your healthcare provider if you take: </dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>atazanavir sulfate (Reyataz)</dd>\n<dt>•</dt>\n<dd>cyclosporine (Neoral, Gengraf, Sandimmune)</dd>\n<dt>•</dt>\n<dd>fosamprenavir (Lexiva) with ritonavir</dd>\n<dt>•</dt>\n<dd>indinavir (Crixivan)</dd>\n<dt>•</dt>\n<dd>ketoconazole (Nizoral)</dd>\n<dt>•</dt>\n<dd>nefazodone (Serzone)</dd>\n<dt>•</dt>\n<dd>ritonavir (Norvir)</dd>\n<dt>•</dt>\n<dd>telithromycin (Ketek)</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>clarithromycin (Biaxin)</dd>\n<dt>•</dt>\n<dd>darunavir (Prezista)</dd>\n<dt>•</dt>\n<dd>fosamprenavir (Lexiva)</dd>\n<dt>•</dt>\n<dd>itraconazole (Sporanox)</dd>\n<dt>•</dt>\n<dd>lopinavir/ritonavir (Kaletra)</dd>\n<dt>•</dt>\n<dd>nelfinavir mesylate (Viracept)</dd>\n<dt>•</dt>\n<dd>saquinavir mesylate (Invirase)</dd>\n<dt>•</dt>\n<dd>tipranavir (Aptivus)</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can interact with colchicine tablets. </p>\n<dl>\n<dt>•</dt>\n<dd>Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. </dd>\n<dt>•</dt>\n<dd>Keep colchicine tablets out of the reach of children.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are colchicine tablets? </span>\n</p>\n<p>Colchicine tablets are a prescription medicine used to: </p>\n<dl>\n<dt>•</dt>\n<dd>prevent and treat gout flares in adults</dd>\n<dt>•</dt>\n<dd>treat familial Mediterranean fever (FMF) in adults and children age 4 or older </dd>\n</dl>\n<p>Colchicine tablets are not a pain medicine, and it should not be taken to treat pain related to other conditions unless specifically prescribed for those conditions.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not take colchicine tablets? </span>\n</p>\n<p>Do not take colchicine tablets if you have liver or kidney problems and you take certain other medicines. Serious side effects, including death, have been reported in these patients even when taken as directed. See <span class=\"Bold\">“What is the most important information that I should know about colchicine tablets?” </span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I tell my healthcare provider before starting colchicine tablets? </span>See <span class=\"Bold\">“What is the most important information that I should know about colchicine tablets?” </span>\n</p>\n<p> </p>\n<p>Before you take colchicine tablets, tell your healthcare provider about all your medical conditions, including if you: </p>\n<dl>\n<dt>•</dt>\n<dd>have liver or kidney problems. </dd>\n<dt>•</dt>\n<dd>are pregnant or plan to become pregnant. It is not known if colchicine tablets will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. </dd>\n<dt>•</dt>\n<dd>are a male with a female partner who can become pregnant. Receiving treatment with colchicine tablets may be related to infertility in some men that is reversible when treatment is stopped. </dd>\n<dt>•</dt>\n<dd>are breastfeeding or plan to breastfeed. Colchicine passes into your breast milk. You and your healthcare provider should decide if you will take colchicine tablets while breastfeeding. If you take colchicine tablets and breastfeed, you should talk to your child’s healthcare provider about how to watch for side effects in your child. </dd>\n</dl>\n<p>Tell your healthcare provider about all the medicines you take, including ones that you may only be taking for a short time, such as antibiotics. See <span class=\"Bold\">“What is the most important information that I should know about colchicine tablets?” </span>\n<br/>\n<br/>Do not start a new medicine without talking to your healthcare provider. </p>\n<p> </p>\n<p>Using colchicine tablets with certain other medicines, such as cholesterol-lowering medications and digoxin, can affect each other, causing serious side effects. Your healthcare provider may need to change your dose of colchicine tablets. Talk to your healthcare provider about whether the medications you are taking might interact with colchicine tablets and what side effects to look for. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I take colchicine tablets? </span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Take colchicine tablets exactly as your healthcare provider tells you to take it. <span class=\"Bold\">If you are not sure about your dosing</span>, call your healthcare provider. </dd>\n<dt>•</dt>\n<dd>Colchicine tablets can be taken with or without food. </dd>\n<dt>•</dt>\n<dd>If you take too many colchicine tablets, go to the nearest hospital emergency room right away. </dd>\n<dt>•</dt>\n<dd>Do not stop taking colchicine tablets even if you start to feel better, unless your healthcare provider tells you. </dd>\n<dt>•</dt>\n<dd>Your healthcare provider may do blood tests while you take colchicine tablets. </dd>\n<dt>•</dt>\n<dd>If you take colchicine tablets daily and you miss a dose, then 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. <dl>\n<dt>o</dt>\n<dd>If you have a gout flare while taking colchicine tablets daily, report this to your healthcare provider.</dd>\n</dl>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I avoid while taking colchicine tablets? </span>\n</p>\n<p>Avoid eating grapefruit or drinking grapefruit juice while taking colchicine tablets. It can increase your chances of getting serious side effects. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of colchicine tablets? </span>\n</p>\n<p>Colchicine tablets can cause serious side effects or even cause death. See <span class=\"Bold\">“What is the most important information that I should know about colchicine tablets?” </span>\n</p>\n<p>Get medical help right away if you have: </p>\n<dl>\n<dt>•</dt>\n<dd>Muscle weakness or pain </dd>\n<dt>•</dt>\n<dd>Numbness or tingling in your fingers or toes </dd>\n<dt>•</dt>\n<dd>Unusual bleeding or bruising </dd>\n<dt>•</dt>\n<dd>Increased infections </dd>\n<dt>•</dt>\n<dd>Feel weak or tired </dd>\n<dt>•</dt>\n<dd>Pale or gray color to your lips, tongue or palms of your hands </dd>\n<dt>•</dt>\n<dd>Severe diarrhea or vomiting </dd>\n</dl>\n<p>\n<span class=\"Bold\">Gout Flares:</span> The most common side effect of colchicine tablets in people who have gout flares is diarrhea.</p>\n<p> </p>\n<p>\n<span class=\"Bold\">FMF: </span>The most common side effects of colchicine tablets in people who have FMF are abdominal pain, diarrhea, nausea and vomiting. </p>\n<p> </p>\n<p>Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of colchicine tablets. 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=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store colchicine tablets? </span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Store colchicine tablets at room temperature between 20° to 25°C (68° to 77°F). </dd>\n<dt>•</dt>\n<dd>Keep colchicine tablets in a tightly closed container. </dd>\n<dt>•</dt>\n<dd>Keep colchicine tablets out of the light. </dd>\n</dl>\n<p>\n<span class=\"Bold\">Keep colchicine tablets 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=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General Information about colchicine tablets </span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use colchicine tablets for a condition for which it was not prescribed. Do not give colchicine tablets to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about colchicine tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about colchicine tablets that is written for healthcare professionals. </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in colchicine tablets? </span>\n</p>\n<p>\n<span class=\"Bold\"> </span>\n</p>\n<p>\n<span class=\"Bold\">Active Ingredient: </span>colchicine. </p>\n<p> </p>\n<p>\n<span class=\"Bold\">Inactive Ingredients: </span>FD&amp;C BLUE #2, FD&amp;C RED #40, hypromellose, lactose monohydrate, macrogol, magnesium stearate, microcrystalline cellulose, polydextrose, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin.<br/>\n<br/>\n<br/>\n<br/>All other trademarks are the property of their respective owners. <br/>\n<br/>For more information, call Dr. Reddy’s Laboratories, Inc. at 1-888-375-3784.<br/>\n</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Rx Only <br/>\n<br/>Distributor:<br/>\n<span class=\"Bold\">Dr. Reddy’s Laboratories Inc.,</span>\n<br/>Princeton, NJ 08540 <br/>\n<br/>\n<span class=\"Bold\">Made in India</span>\n</p>\n<p>Repackaged and Relabeled by:<br/>\n<span class=\"Bold\">Proficient Rx LP</span>\n<br/>Thousand Oaks, CA 91320 <br/>\n</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

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: 03/2021

{ "type": "p", "children": [], "text": "Revised: 03/2021\n" }

Colchicine Tablets USP, 0.6 mg - 30's Count

{ "type": "p", "children": [], "text": "Colchicine Tablets USP, 0.6 mg - 30's Count" }