LUPRON DEPOT-PED is indicated for the treatment of pediatric patients with central precocious puberty (CPP).

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED is indicated for the treatment of pediatric patients with central precocious puberty (CPP). " }

<div class="scrollingtable"><table> <col width="313"/> <col width="313"/> <tbody class="Headless"> <tr class="First"> <td class="Lrule Rrule Toprule" colspan="2" valign="bottom"><span class="Bold">Table 1. Dos</span><span class="Bold">age</span><span class="Bold"> Recommendations Based on Body Weight for LUPRON DEPOT-PED</span><span class="Bold"> for 1-</span><span class="Bold">M</span><span class="Bold">onth </span><span class="Bold">A</span><span class="Bold">dministration</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">Body Weight</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Once Monthly </span><span class="Bold">Recommended Dos</span><span class="Bold">ag</span><span class="Bold">e</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Less than or equal to 25 kg</td><td align="center" class="Lrule Rrule Toprule">7.5 mg</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Greater than 25 kg up to 37.5 kg</td><td align="center" class="Lrule Rrule Toprule">11.25 mg</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule Toprule">Greater than 37.5 kg</td><td align="center" class="Lrule Rrule Toprule">15 mg</td> </tr> </tbody> </table></div>

1. Visually inspect the LUPRON DEPOT-PED powder and diluent. Do not use the syringe if clumping or caking is evident. A thin layer of powder on the wall of the syringe is considered normal prior to mixing with the diluent. The diluent should appear clear and free from particulate matter. Do not use the diluent if it is not clear or there is particulate matter. 

2. To prepare for injection, screw the white plunger into the end stopper until the stopper begins to turn. (see Figure 1 and Figure 2)

Figure 1

LuproLoc Safety Device should be activated after product injection, refer to Step 9 (Figure 7).

Figure 2

3. Hold the syringe upright. Release the diluent by slowly pushing the plunger for 6 to 8 seconds until the first stopper is at the blue line in the middle of the barrel. (Figure 3)

Figure 3

4. Keep the syringe upright. Mix the powder thoroughly by gently shaking the syringe until the powder forms a uniform suspension. The suspension will appear milky. If the powder adheres to the stopper or caking/clumping is present, tap the syringe with your finger to disperse. Do not use if any of the powder has not gone into suspension. (Figure 4)

Figure 4

5. Hold the syringe upright. With the opposite hand pull the needle cap upward without twisting.

6. Keep the syringe upright. Advance the plunger to expel the air from the syringe.Now the syringe is ready for injection.

7. After cleaning the injection site with an alcohol swab, administer the intramuscular injection by inserting the needle at a 90 degree angle into the deltoid, gluteal area, or anterior thigh. (Figure 5)

Figure 5

NOTE: Aspirated blood would be visible just below the luer lock connection if a blood vessel is accidentally penetrated. If present, blood can be seen through the transparent LuproLoc® safety device. If blood is present remove the needle immediately. Do not inject the medication. (Figure 6)

Figure 6

8. Inject the entire contents of the syringe intramuscularly immediately after reconstitution. The suspension settles very quickly following reconstitution.

9. Withdraw the needle. Once the syringe has been withdrawn, activate immediately the LuproLoc® safety device by pushing the arrow on the lock upward towards the needle tip with the thumb or finger, as illustrated, until the needle cover of the safety device is fully extended over the needle and a click is heard or felt. (Figure 7)

Figure 7

For depot suspension: a white lyophilized powder supplied in a single-dose, prefilled dual-chamber syringe with a colorless diluent is available as: 

{ "type": "p", "children": [], "text": "For depot suspension: a white lyophilized powder supplied in a single-dose, prefilled dual-chamber syringe with a colorless diluent is available as: " }

{ "type": "ul", "children": [ "For 1-month administration: 7.5 mg, 11.25 mg, or 15 mg of leuprolide acetate\n", "For 3-month administration: 11.25 mg or 30 mg of leuprolide acetate\n", "For 6-month administration: 45 mg of leuprolide acetate" ], "text": "" }

{ "type": "ul", "children": [ "Hypersensitivity to GnRH, GnRH agonists or any of the excipients in LUPRON DEPOT-PED. Anaphylactic reactions to synthetic GnRH or GnRH agonists have been reported [see Adverse Reactions (6.2)].\n", "Pregnancy: LUPRON DEPOT-PED may cause fetal harm [see Use in Specific Populations (8.1)]. " ], "text": "" }

During the early phase of therapy or after subsequent doses, gonadotropins and sex steroids may rise above baseline because of a transient stimulatory effect of the drug [see Clinical Pharmacology (12.2)]. Therefore, an increase in clinical signs and symptoms of puberty, including vaginal bleeding, may be observed during the first weeks of therapy or after subsequent doses [see Adverse Reactions (6)]. 

Psychiatric events have been reported in patients taking GnRH agonists, including LUPRON DEPOT-PED. Postmarking reports with this class of drugs include symptoms of emotional lability, such as crying, irritability, impatience, anger and aggression. Monitor for development or worsening of psychiatric symptoms during treatment with LUPRON DEPOT-PED [see Adverse Reactions (6.2)].

Postmarketing reports of convulsions have been observed in patients receiving GnRH agonists, including LUPRON DEPOT-PED. These included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above [see Adverse Reactions (6.2)].

Pseudotumor cerebri (idiopathic intracranial hypertension) have been reported in pediatric patients receiving GnRH agonists, including LUPRON DEPOT-PED. Monitor patients for signs and symptoms of pseudotumor cerebri, including headache, papilledema, blurred vision, diplopia, loss of vision, pain behind the eye or pain with eye movement, tinnitus, dizziness, and nausea.

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

LUPRON DEPOT-PED for 1-month administration

LUPRON DEPOT-PED 1-month administration was evaluated in a pivotal, open label, multicenter study in which 55 (49 female and 6 male) pediatric patients with central precocious puberty were enrolled. The age ranged from 1 to 8 years of age at the beginning of treatment; the mean age for females was 6.8 years (range: 1 to 9 years) and the mean age for males was 7.5 years (range: 4 to 9 years); 61.8% were Caucasian; 20% Black; 1.8% Oriental; and 16.4% Hispanic. 

Adverse reactions that occurred in ≥2% of patients are shown in Table 2.

<div class="scrollingtable"><table> <col width="480"/> <col width="146"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="2" valign="bottom"><span class="Bold">Table 2. Adverse Reactions Occurring in ≥2% </span><span class="Bold">in </span><span class="Bold">Pediatric Patients </span><span class="Bold">with CPP </span><span class="Bold">Receiving</span> <br/> <span class="Bold">LUPRON DEPOT-PED 1-month</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">% </span><span class="Bold">of Patients</span><span class="Bold"> <br/>(N = 421)</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">  Injection Site Reactions Including Abscess*</td><td align="center" class="Lrule Rrule Toprule">9</td> </tr> <tr> <td class="Lrule Rrule Toprule">  Emotional Lability </td><td align="center" class="Lrule Rrule Toprule">5 </td> </tr> <tr> <td class="Lrule Rrule Toprule">  Headache</td><td align="center" class="Lrule Rrule Toprule">3</td> </tr> <tr> <td class="Lrule Rrule Toprule">  General Pain</td><td align="center" class="Lrule Rrule Toprule">3</td> </tr> <tr> <td class="Lrule Rrule Toprule">  Acne/Seborrhea</td><td align="center" class="Lrule Rrule Toprule">3</td> </tr> <tr> <td class="Lrule Rrule Toprule">  Rash Including Erythema Multiforme</td><td align="center" class="Lrule Rrule Toprule">3</td> </tr> <tr> <td class="Lrule Rrule Toprule">  Vaginitis/Vaginal Bleeding/Vaginal Discharge</td><td align="center" class="Lrule Rrule Toprule">3</td> </tr> <tr> <td class="Lrule Rrule Toprule">  Vasodilation</td><td align="center" class="Lrule Rrule Toprule">2</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule" colspan="2">* Most events were mild or moderate in severity.</td> </tr> </tbody> </table></div>

Less Common Adverse Reactions

The following adverse reactions were reported in less than 2% of the patients and are listed below by body system.

Body as a Whole – aggravation of preexisting tumor and decreased vision, allergic reaction, body odor, fever, flu syndrome, hypertrophy, infection;

Cardiovascular System – bradycardia, hypertension, peripheral vascular disorder, syncope; Digestive System – constipation, dyspepsia, dysphagia, gingivitis, increased appetite, nausea/vomiting;

Endocrine System – accelerated sexual maturity, feminization, goiter;

Hemic and Lymphatic System – purpura;

Metabolic and Nutritional Disorders – growth retarded, peripheral edema, weight gain; Musculoskeletal System – arthralgia, joint disorder, myalgia, myopathy;

Nervous System – hyperkinesia, somnolence;

Psychiatric System – depression, nervousness;

Respiratory System – asthma, epistaxis, pharyngitis, rhinitis, sinusitis;

Integumentary System (Skin and Appendages) – alopecia, hair disorder, hirsutism, leukoderma, nail disorder, skin hypertrophy;

Urogenital System – cervix disorder/neoplasm, dysmenorrhea, gynecomastia/breast disorders, menstrual disorder, urinary incontinence.

Laboratory: The following laboratory events were reported as adverse reactions: antinuclear antibody present and increased sedimentation rate.

LUPRON DEPOT-PED for 3-month administration

LUPRON DEPOT-PED for 3-month administration was evaluated in a pivotal, open-label, multicenter, clinical study with 84 randomized pediatric patients with central precocious puberty; 76 (90.5%) were females and 8 (9.5%) were males. The age ranged from 1 to 11 years age at the beginning of treatment; 80/84 (95.2%) were 5 years or older, and female patients were younger than male; the mean age for 11.25 mg and 30 mg groups for females was 7.6 and 7.7 years, and for males 9.3 and 9.4 years, respectively; 58.3% were Caucasian; 22.6% were Black; 7.1% were Asian; 1.2% were Native Hawaiian or Other Pacific Islander; and 10.7% were Multi-race.

Adverse reactions that occurred in ≥2% of patients are shown in Table 3.

<div class="scrollingtable"><table> <col width="241"/> <col width="156"/> <col width="114"/> <col width="115"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="4" valign="bottom"><span class="Bold">Table 3. Adverse Reactions Occurring in ≥2</span><span class="Bold">% in</span><span class="Bold"> Pediatric Patients </span><span class="Bold">with CPP</span><span class="Bold"> <br/>Receiving LUPRON DEPOT-PED for 3-month administration.</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">% </span> <br/> <span class="Bold">11.25 mg </span> <br/> <span class="Bold">every 3 Months</span><span class="Bold"> <br/>N=42</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">% </span> <br/> <span class="Bold">30 mg </span> <br/> <span class="Bold">every 3 Months</span><span class="Bold"> <br/>N=42</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">%</span> <br/> <span class="Bold"> </span><span class="Bold">Overall </span><span class="Bold"> <br/>N = 84</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">Injection site pain</td><td align="center" class="Lrule Rrule Toprule">19</td><td align="center" class="Lrule Rrule Toprule">21</td><td align="center" class="Lrule Rrule Toprule">20</td> </tr> <tr> <td class="Lrule Rrule Toprule">Weight increased</td><td align="center" class="Lrule Rrule Toprule">7</td><td align="center" class="Lrule Rrule Toprule">7</td><td align="center" class="Lrule Rrule Toprule">7</td> </tr> <tr> <td class="Lrule Rrule Toprule">Headache</td><td align="center" class="Lrule Rrule Toprule">2</td><td align="center" class="Lrule Rrule Toprule">7</td><td align="center" class="Lrule Rrule Toprule">5</td> </tr> <tr> <td class="Lrule Rrule Toprule">Mood altered</td><td align="center" class="Lrule Rrule Toprule">5</td><td align="center" class="Lrule Rrule Toprule">5</td><td align="center" class="Lrule Rrule Toprule">5</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule">Injection site swelling</td><td align="center" class="Lrule Rrule Toprule">2</td><td align="center" class="Lrule Rrule Toprule">2</td><td align="center" class="Lrule Rrule Toprule">2</td> </tr> </tbody> </table></div>

Less Common Adverse Reactions

The following adverse reactions were reported in one patient and are listed below by system organ class:

Gastrointestinal Disorders – abdominal pain, nausea;

General Disorders and Administration Site Conditions – asthenia, gait disturbance, injection site abscess sterile, injection site hematoma, injection site induration, injection site warmth, irritability;

Metabolic and Nutritional Disorders – decreased appetite, obesity;

Musculoskeletal and Connective Tissue Disorders - musculoskeletal pain, pain in extremity; Nervous System Disorders – dizziness;

Psychiatric Disorders – crying, tearfulness;

Respiratory, Thoracic and Mediastinal Disorders – cough;

Skin and Subcutaneous Tissue Disorders – hyperhidrosis;

Vascular Disorders – pallor.

LUPRON DEPOT-PED for 6-month administration

LUPRON DEPOT-PED for 6-month administration was evaluated in an open-label, multicenter, clinical study with 45 pediatric patients with central precocious puberty; 41 (91%) were females and 4 (9%) were males. The baseline age ranged from 4 to 10 years. There were 30 (67%) Caucasian; 7 (16%) Black; and 1 (2%) Asian. 

Adverse reactions that occurred in ≥4% of all patients are shown in Table 4.

<div class="scrollingtable"><table> <col width="267"/> <col width="279"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="2" valign="bottom"><span class="Bold">Table 4. Adverse Reactions Occurring in ≥4% in Pediatric Patients with CPP</span><span class="Bold"> <br/>Receiving LUPRON DEPOT-PED for 6-month administration.</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Total</span> <br/> <span class="Bold">(N = 45)</span> <br/> <span class="Bold">n (%)</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">Injection Site Reactions <span class="Sup">a</span> </td><td align="center" class="Lrule Rrule Toprule" valign="bottom">35 (78%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Headache <span class="Sup">b</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">15 (33%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Psychiatric Events <span class="Sup">c</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">10 (22%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Abdominal Pain <span class="Sup">d</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">8 (18%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Diarrhea <span class="Sup">e</span> </td><td align="center" class="Lrule Rrule Toprule" valign="bottom">7 (16%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Hemorrhage <span class="Sup">f</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">6 (13%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Nausea and Vomiting </td><td align="center" class="Lrule Rrule Toprule" valign="bottom">6 (13%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Pyrexia </td><td align="center" class="Lrule Rrule Toprule" valign="bottom">6 (13%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Pruritus <span class="Sup">g</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">5 (11%)</td> </tr> <tr> <td class="Lrule Rrule Toprule">Pain in extremity</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">4 (9%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Rash</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">3 (7%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Back Pain </td><td align="center" class="Lrule Rrule Toprule" valign="bottom">3 (7%)</td> </tr> <tr> <td class="Lrule Rrule Toprule">Ligament sprain</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">3 (7%)</td> </tr> <tr> <td class="Lrule Rrule Toprule">Weight increased</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">3 (7%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Fracture <span class="Sup">h</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">2 (4%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Breast tenderness <span class="Sup">i</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">2 (4%)</td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="bottom">Insomnia <span class="Sup">j</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">2 (4%)</td> </tr> <tr> <td class="Lrule Rrule Toprule">Chest pain</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">2 (4%)</td> </tr> <tr> <td class="Lrule Rrule Toprule">Hyperhidrosis</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">2 (4%)</td> </tr> <tr class="Last"> <td class="Toprule" colspan="2"><span class="Sup">a</span> Injection site reactions includes the preferred terms injection site pain, injection site erythema, injection site <br/>reaction, injection site warmth, injection site bruising, injection site discomfort, and injection site swelling<br/> <span class="Sup">b</span><span class="Sup">-</span>Headache includes the preferred terms headache and cluster headache<br/> <span class="Sup">c</span> Psychiatric events includes the preferred terms affect lability, affective disorder, aggression, crying, <br/>depressed mood, disruptive mood dysregulation disorder, hallucination auditory, mood altered, <br/>mood swings, and trichotillomania<br/> <span class="Sup">d</span> Abdominal pain includes the preferred terms abdominal pain, abdominal pain upper, and abdominal discomfort<br/> <span class="Sup">e</span> Diarrhea includes the preferred terms gastroenteritis and diarrhea <br/> <span class="Sup">f</span> Hemorrhage includes the preferred terms contusion, epistaxis, hematochezia, and injection site bruising<br/> <span class="Sup">g</span> Pruritus includes the preferred terms pruritus, vulvovaginal pruritus, nasal pruritus<br/> <span class="Sup">h</span> Fracture includes the preferred terms ankle fracture and tibia fracture <br/> <span class="Sup">i </span>Breast tenderness includes the preferred terms breast pain and breast tenderness<br/> <span class="Sup">j</span> Insomnia includes the preferred terms initial insomnia and insomnia<br/> </td> </tr> </tbody> </table></div>

The following adverse reactions have been identified during post-approval use of leuprolide acetate or LUPRON DEPOT-PED in pediatric patients. 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. 

Allergic reactions: anaphylactic, rash, urticaria, and photosensitivity reactions. 

General: chest pain, weight increase, decreased appetite, fatigue.

Laboratory Abnormalities: decreased WBC. 

Metabolic: diabetes mellitus. 

Musculoskeletal and Connective Tissue: tenosynovitis-like symptoms, severe muscle pain, arthralgia, epiphysiolysis, muscle spasms, myalgia. 

Published literature and postmarketing reports indicate that bone mineral density may decrease during GnRH therapy in pediatric patients with central precocious puberty.  Published studies indicate that after discontinuation of therapy, subsequent bone mass accrual is preserved and peak bone mass in late adolescence does not seem to be affected.

Neurologic: neuropathy peripheral, convulsion, insomnia, pseudotumor cerebri (idiopathic intracranial hypertension).

Psychiatric Disorders: emotional lability, such as crying, irritability, impatience, anger, and aggression. Depression, including rare reports of suicidal ideation and attempt. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.

Reproductive System: vaginal bleeding, breast enlargement.

Respiratory: dyspnea.

Skin and Subcutaneous Tissue: injection site reactions including induration and abscess, flushing, hyperhidrosis. 

Vascular Disorders: hypertension, hypotension.

No pharmacokinetic-based drug-drug interaction studies have been conducted with LUPRON DEPOT-PED [see Clinical Pharmacology (12.3)].  

Administration of LUPRON DEPOT-PED in therapeutic doses results in suppression of the pituitary-gonadal system. Therefore, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and up to six months after discontinuation of LUPRON DEPOT-PED may be affected. Normal pituitary-gonadal function is usually restored within six months after treatment with LUPRON DEPOT-PED is discontinued. 

Risk Summary

LUPRON DEPOT-PED is contraindicated in pregnancy [see Contraindications (4)]. 

LUPRON DEPOT-PED may cause fetal harm, when administered to a pregnant woman, based on findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology (12.1)]. The available data from published clinical studies and case reports and from the pharmacovigilance database on exposure to LUPRON DEPOT-PED during pregnancy are insufficient to assess the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on animal reproduction studies, LUPRON DEPOT-PED may be associated with an increased risk of pregnancy complications, including early pregnancy loss and fetal harm. In animal reproduction studies, subcutaneous administration of leuprolide acetate to rabbits during the period of organogenesis caused embryo-fetal toxicity, decreased fetal weights and a dose-dependent increase in major fetal abnormalities in animals at doses less than the recommended human dose based on body surface area using an estimated daily dose. A similar rat study also showed increased fetal mortality and decreased fetal weights but no major fetal abnormalities at doses less than the recommended human dose based on body surface area using an estimated daily dose (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% -20%, respectively.

Data

Animal Data

When administered on day 6 of pregnancy at test dosages of 0.00024 mg/kg, 0.0024 mg/kg, and 0.024 mg/kg (doses less than the recommended human dose) to rabbits, leuprolide acetate produced a dose-related increase in malformations comprised primarily of segmental and fusion defects of the skeleton and skull. Similar studies in rats failed to demonstrate an increase in fetal malformations. There was increased fetal mortality and decreased fetal weights with the two higher doses of leuprolide acetate in rabbits and with the highest dose (0.024 mg/kg) in rats.

Risk Summary

There are no data on the presence of leuprolide acetate in either animal or human milk, the effects on the breastfed infants, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LUPRON DEPOT-PED and any potential adverse effects on the breastfed infant from LUPRON DEPOT-PED or from the underlying maternal condition.

Pregnancy Testing 

Exclude pregnancy in women of reproductive potential prior to initiating LUPRON DEPOT-PED if clinically indicated [see Use in Specific Populations (8.1)].

Contraception 

Females 

LUPRON DEPOT-PED may cause embryo-fetal harm when administered during pregnancy. LUPRON DEPOT-PED is not a contraceptive. If contraception is indicated, advise females of reproductive potential to use a non-hormonal method of contraception during treatment with LUPRON DEPOT-PED [see Use in Specific Populations (8.1)].

Infertility

Based on its pharmacodynamic effects of decreasing secretion of gonadal steroids, fertility is expected to be decreased while on treatment with LUPRON DEPOT-PED. Clinical and pharmacologic studies in adults (>18 years) with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks [see Clinical Pharmacology (12.2)].

There is no evidence that pregnancy rates are affected following discontinuation of LUPRON DEPOT-PED. 

Animal studies (prepubertal and adult rats and monkeys) with leuprolide acetate and other GnRH analogs have shown functional recovery of fertility suppression.

The safety and effectiveness of LUPRON DEPOT-PED for the treatment of CPP has been established in pediatric patients 1 years of age and older. Use of LUPRON DEPOT-PED for this indication is supported by evidence from two pivotal, open label clinical studies of 139 pediatric patients with central precocious puberty with an age range of 1 to 11 years [see Clinical Studies (14)]. The safety and effectiveness of LUPRON DEPOT-PED have not been established in pediatric patients less than 1 year old. 

No specific antidotes for LUPRON DEPOT-PED are known. Contact Poison Control (1-800-222-1222) for latest recommendations. 

{ "type": "p", "children": [], "text": "No specific antidotes for LUPRON DEPOT-PED are known. Contact Poison Control (1-800-222-1222) for latest recommendations. " }

In cases of overdosage, standard of care monitoring and management principles should be followed.

{ "type": "p", "children": [], "text": "In cases of overdosage, standard of care monitoring and management principles should be followed." }

LUPRON DEPOT-PED contains active ingredient, leuprolide, in the form of acetate salt, a gonadotropin-releasing hormone (GnRH) agonist. It is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. The chemical name of leuprolide acetate is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate, which has molecular formula of C59H84N16O12.(C2H4O2)n, n=1 or 2, with the following structural formula: 

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED contains active ingredient, leuprolide, in the form of acetate salt, a gonadotropin-releasing hormone (GnRH) agonist. It is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. The chemical name of leuprolide acetate is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate, which has molecular formula of C59H84N16O12.(C2H4O2)n, n=1 or 2, with the following structural formula: " }

LUPRON DEPOT-PED for 1-month administration

{ "type": "p", "children": [], "text": "\nLUPRON DEPOT-PED for 1-month administration\n" }

LUPRON DEPOT-PED is available in a prefilled dual-chamber single-dose syringe containing sterile lyophilized microsphere powder incorporated in a biodegradable lactic acid/glycolid acid copolymer which, when mixed with diluent, becomes a suspension for intramuscular injection. When mixed with 1 milliliter of accompanying diluent, LUPRON DEPOT-PED for 1-month administration is administered as a single-dose intramuscular injection.

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED is available in a prefilled dual-chamber single-dose syringe containing sterile lyophilized microsphere powder incorporated in a biodegradable lactic acid/glycolid acid copolymer which, when mixed with diluent, becomes a suspension for intramuscular injection. When mixed with 1 milliliter of accompanying diluent, LUPRON DEPOT-PED for 1-month administration is administered as a single-dose intramuscular injection." }

The front chamber of LUPRON DEPOT-PED 7.5 mg, 11.25 mg, and 15 mg a prefilled dual-chamber syringe contains leuprolide acetate (7.5 mg equivalent to 6.83-7.15 mg leuprolide / 11.25 mg equivalent to 10.24 – 10.72 mg leuprolide / 15 mg equivalent to 13.65 – 14.30 mg leuprolide), purified gelatin (1.3/1.95/2.6 mg), DL-lactic and glycolic acids copolymer (66.2/99.3/132.4 mg), and D-mannitol (13.2/19.8/26.4 mg). The second chamber of diluent contains carboxymethylcellulose sodium (5 mg), D-mannitol (50 mg), polysorbate 80 (1 mg), water for injection, USP, and glacial acetic acid, USP to control pH.

{ "type": "p", "children": [], "text": "The front chamber of LUPRON DEPOT-PED 7.5 mg, 11.25 mg, and 15 mg a prefilled dual-chamber syringe contains leuprolide acetate (7.5 mg equivalent to 6.83-7.15 mg leuprolide / 11.25 mg equivalent to 10.24 – 10.72 mg leuprolide / 15 mg equivalent to 13.65 – 14.30 mg leuprolide), purified gelatin (1.3/1.95/2.6 mg), DL-lactic and glycolic acids copolymer (66.2/99.3/132.4 mg), and D-mannitol (13.2/19.8/26.4 mg). The second chamber of diluent contains carboxymethylcellulose sodium (5 mg), D-mannitol (50 mg), polysorbate 80 (1 mg), water for injection, USP, and glacial acetic acid, USP to control pH. " }

LUPRON DEPOT-PED for 3-month administration

{ "type": "p", "children": [], "text": "\nLUPRON DEPOT-PED for 3-month administration \n" }

LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration is available in a prefilled dual-chamber single-dose syringe containing sterile lyophilized microsphere powder incorporated in a biodegradable lactic acid/glycolid acid copolymer which, when mixed with diluent, becomes a suspension for intramuscular injection. When mixed with 1.5 milliliters of accompanying diluent, LUPRON DEPOT-PED for 3-month administration is administered as a single-dose intramuscular injection.

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration is available in a prefilled dual-chamber single-dose syringe containing sterile lyophilized microsphere powder incorporated in a biodegradable lactic acid/glycolid acid copolymer which, when mixed with diluent, becomes a suspension for intramuscular injection. When mixed with 1.5 milliliters of accompanying diluent, LUPRON DEPOT-PED for 3-month administration is administered as a single-dose intramuscular injection." }

The front chamber of LUPRON DEPOT-PED 11.25 mg for 3-month administration prefilled dual-chamber syringe contains leuprolide acetate (11.25 mg, equivalent to 10.24 - 10.72 mg leuprolide), D-mannitol (19.45 mg), and polylactic acid (99.3 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH.

{ "type": "p", "children": [], "text": "The front chamber of LUPRON DEPOT-PED 11.25 mg for 3-month administration prefilled dual-chamber syringe contains leuprolide acetate (11.25 mg, equivalent to 10.24 - 10.72 mg leuprolide), D-mannitol (19.45 mg), and polylactic acid (99.3 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH. " }

The front chamber of LUPRON DEPOT-PED 30 mg for 3-month administration prefilled dual-chamber syringe contains leuprolide acetate (30 mg, equivalent to 27.30 - 28.59 mg leuprolide), D-mannitol (51.9 mg), and polylactic acid (264.8 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH.

{ "type": "p", "children": [], "text": "The front chamber of LUPRON DEPOT-PED 30 mg for 3-month administration prefilled dual-chamber syringe contains leuprolide acetate (30 mg, equivalent to 27.30 - 28.59 mg leuprolide), D-mannitol (51.9 mg), and polylactic acid (264.8 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH. " }

LUPRON DEPOT-PED for 6-month administration

{ "type": "p", "children": [], "text": "\nLUPRON DEPOT-PED for 6-month administration\n" }

LUPRON DEPOT-PED 45 mg for 6-month administration is available in a prefilled dual-chamber syringe containing sterile lyophilized microspheres which, when mixed with diluent, become a suspension intended as an intramuscular injection.

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED 45 mg for 6-month administration is available in a prefilled dual-chamber syringe containing sterile lyophilized microspheres which, when mixed with diluent, become a suspension intended as an intramuscular injection. " }

The front chamber of LUPRON DEPOT-PED 45 mg for 6-month administration prefilled dual-chamber syringe contains leuprolide acetate (45 mg, equivalent to 40.95 - 42.89 mg leuprolide), D-mannitol (39.7 mg), polylactic acid (169.9 mg), and stearic acid (10.1 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH.

{ "type": "p", "children": [], "text": "The front chamber of LUPRON DEPOT-PED 45 mg for 6-month administration prefilled dual-chamber syringe contains leuprolide acetate (45 mg, equivalent to 40.95 - 42.89 mg leuprolide), D-mannitol (39.7 mg), polylactic acid (169.9 mg), and stearic acid (10.1 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH." }

Leuprolide acetate, a GnRH agonist, acts as a potent inhibitor of gonadotropin secretion (LH and follicle stimulating hormone (FSH)) when given continuously in therapeutic doses.

Following an initial stimulation of GnRH receptors, chronic administration of leuprolide acetate results in downregulation of GnRH receptors, reduction in release of LH and FSH, and consequent suppression of ovarian and testicular production of estradiol and testosterone, respectively. This inhibitory effect is reversible upon discontinuation of drug therapy.

Absorption

LUPRON DEPOT-PED for 1-month administration

Following a single LUPRON DEPOT-PED 7.5 mg for 1-month administration to adult patients, mean peak leuprolide plasma concentration was almost 20 ng/mL at 4 hours and then declined to 0.36 ng/mL at 4 weeks. However, intact leuprolide and an inactive major metabolite could not be distinguished by the assay which was employed in the study. Nondetectable leuprolide plasma concentrations have been observed during chronic LUPRON DEPOT-PED 7.5 mg administration, but testosterone levels appear to be maintained at castrate levels.

In a study of pediatric patients with CPP, doses of 7.5 mg, 11.25 mg and 15.0 mg of LUPRON DEPOT-PED were given every 4 weeks. In 22 pediatric patients, trough leuprolide plasma levels were determined according to weight categories as summarized below:

<div class="scrollingtable"><table> <col width="132"/> <col width="132"/> <col width="91"/> <col width="270"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Patient Weight</span><span class="Bold"> <br/>Range (kg) </span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Group Weight</span><span class="Bold"> <br/>Average (kg) </span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Dose (mg)</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Trough Plasma Leuprolide Level</span><span class="Bold"> <br/>Mean ±SD (ng/mL)* </span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">20.2 - 27.0</td><td align="center" class="Lrule Rrule Toprule">22.7</td><td align="center" class="Lrule Rrule Toprule">7.5</td><td align="center" class="Lrule Rrule Toprule">0.77±0.033</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">28.4 - 36.8</td><td align="center" class="Lrule Rrule Toprule">32.5</td><td align="center" class="Lrule Rrule Toprule">11.25</td><td align="center" class="Lrule Rrule Toprule">1.25±1.06</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">39.3 - 57.5</td><td align="center" class="Lrule Rrule Toprule">44.2</td><td align="center" class="Lrule Rrule Toprule">15.0</td><td align="center" class="Lrule Rrule Toprule">1.59±0.65</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule" colspan="4">* Group average values determined at Week 4 immediately prior to leuprolide injection. Drug levels at 12 and 24 weeks were similar to respective 4 week levels. </td> </tr> </tbody> </table></div>

LUPRON DEPOT-PED for 3-month administration

Following a single LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration to pediatric patients with CPP, leuprolide concentrations increased with increasing dose with mean peak leuprolide plasma concentration of 19.1 and 52.5 ng/mL at 1 hour for the 11.25 and 30 mg dose levels, respectively. The concentrations then declined to 0.08 and 0.25 ng/mL at 2 weeks after dosing for the 11.25 and 30 mg dose levels. Mean leuprolide plasma concentration remained constant from month 1 to month 3 for both 11.25 and 30 mg doses. The mean leuprolide concentrations 3 months after the first and second injections were similar indicating no accumulation of leuprolide from repeated administration.

LUPRON DEPOT-PED for 6-month administration

Following a single injection of LUPRON DEPOT-PED 45 mg for 6-month administration in 20 pediatric patients with CPP, mean peak plasma concentration increased rapidly to 15.7 ng/mL 1 hour post-dose. Following the initial rise, mean leuprolide plasma concentration declined to 0.03 ng/mL by Week 24. The mean leuprolide concentrations 6 months after the first and second injections were comparable indicating no accumulation of leuprolide from repeated administration.

Distribution

The mean steady-state volume of distribution of leuprolide following intravenous bolus administration to healthy male subjects was 27 L. In vitro binding to human plasma proteins ranged from 43% to 49%.

Elimination

Metabolism

In healthy male subjects given an intravenous 1 mg bolus of leuprolide the mean systemic clearance was 7.6 L/h, with a terminal elimination half-life of approximately 3 hours based on a two-compartment model.

In rats and dogs, administration of 14C-labeled leuprolide was shown to be metabolized to smaller inactive peptides; a pentapeptide (Metabolite I), tripeptides (Metabolites II and III) and a dipeptide (Metabolite IV). These fragments may be further catabolized.

The major metabolite (M-I) plasma concentrations measured in 5 prostate cancer patients reached maximum concentration 2 to 6 hours after dosing and were approximately 6% of the peak parent drug concentration. One week after dosing, mean plasma M-I concentrations were approximately 20% of mean leuprolide concentrations.

Excretion

Following administration of LUPRON DEPOT 3.75 mg to 3 patients, less than 5% of the dose was recovered as parent and M-I metabolite in the urine.

Specific Populations

The pharmacokinetics of LUPRON DEPOT-PED has not been determined in patients with hepatic or renal impairment.

Drug-Drug Interactions

No pharmacokinetic-based drug-drug interaction studies have been conducted with LUPRON DEPOT-PED. Leuprolide acetate is a peptide that is not degraded by cytochrome P-450 enzymes; hence, drug interactions associated with cytochrome P-450 enzymes would not be expected to occur.

A two-year carcinogenicity study was conducted in rats and mice. In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg). There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group). In mice, no leuprolide acetate-induced tumors or pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years.  

Mutagenicity studies have been performed with leuprolide acetate using bacterial and mammalian systems. These studies provided no evidence of a mutagenic potential.

The efficacy of LUPRON DEPOT-PED was evaluated in a pivotal open-label, multicenter clinical trial (NCT00660010) in which 55 pediatric patients with central precocious puberty (49 females and 6 males, naïve to previous GnRHa treatment) were treated with LUPRON DEPOT-PED 1-month formulations until age was appropriate for entry into puberty (see treatment period data below)and a subset of 40 patients were then followed post-treatment (see follow-up period data below). The mean ± SD age at the start of treatment was 7 ± 2 years and the duration of treatment was 4 ± 2 years. Study drug was administered intramuscularly (IM) every 28 days, with incremental adjustments of 3.75mg at each clinic visit, if necessary based on clinical and laboratory results. During the follow-up period, GnRHa stimulation test was performed every 6 months until a pubertal response was observed. 

During the treatment period, LUPRON DEPOT-PED suppressed gonadotropins and sex steroids to prepubertal levels. Suppression of peak stimulated LH concentrations to < 1.75 mIU/mL was achieved in 96% of patients by month 1. Five patients required increased doses of study drug to achieve or retain LH suppression. The number and percentage of patients with suppression of peak stimulated LH < 1.75 mIU/mL and mean ± SD peak stimulated LH over time is shown in Table 5. Six months after the treatment period was finished, the mean peak stimulated LH was 20.6 ± SD 13.7 mIU/mL (n=30).

The following effects have been noted with the chronic administration of leuprolide: cessation of menses (in girls), normalization and stabilization of linear growth and bone age advancement, stabilization of clinical signs and symptoms of puberty. 

<div class="scrollingtable"><table> <col width="113"/> <col width="105"/> <col width="118"/> <col width="133"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="4" valign="bottom"><span class="Bold">Table </span><span class="Bold">5</span><span class="Bold">. The number and percentage of patients with peak</span> <br/> <span class="Bold">stimulated LH &lt; 1.75 mIU/mL and Mean (SD) peak LH at each</span> <br/> <span class="Bold">clinic visit</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Weeks on Study</span></td><td align="center" class="Lrule Rrule Toprule" colspan="2" valign="bottom"><span class="Bold">n with peak stimulated LH &lt; 1.75 mIU/mL/</span><span class="Bold"> <br/>N with a LH measurement for that week</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Mean (SD) peak LH</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"> </td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">n/N</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">%</span></td><td class="Lrule Rrule Toprule"> </td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Baseline</td><td align="center" class="Lrule Rrule Toprule">0/55</td><td align="center" class="Lrule Rrule Toprule">0%</td><td align="center" class="Lrule Rrule Toprule">35.0 (21.32)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 4</td><td align="center" class="Lrule Rrule Toprule">53/55</td><td align="center" class="Lrule Rrule Toprule">96.4%</td><td align="center" class="Lrule Rrule Toprule">0.8 (0.57)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 12</td><td align="center" class="Lrule Rrule Toprule">48/54</td><td align="center" class="Lrule Rrule Toprule">88.9%</td><td align="center" class="Lrule Rrule Toprule">1.1 (1.77)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 24</td><td align="center" class="Lrule Rrule Toprule">48/53</td><td align="center" class="Lrule Rrule Toprule">90.6%</td><td align="center" class="Lrule Rrule Toprule">0.8 (0.79)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 36</td><td align="center" class="Lrule Rrule Toprule">51/54</td><td align="center" class="Lrule Rrule Toprule">94.4%</td><td align="center" class="Lrule Rrule Toprule">0.6 (0.43)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 48</td><td align="center" class="Lrule Rrule Toprule">51/54</td><td align="center" class="Lrule Rrule Toprule">94.4%</td><td align="center" class="Lrule Rrule Toprule">0.6 (0.47)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 72</td><td align="center" class="Lrule Rrule Toprule">52/52</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.5 (0.30)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 96</td><td align="center" class="Lrule Rrule Toprule">46/46</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.4 (0.33)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 120</td><td align="center" class="Lrule Rrule Toprule">40/40</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.4 (0.27)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 144</td><td align="center" class="Lrule Rrule Toprule">36/36</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.4 (0.24)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 168</td><td align="center" class="Lrule Rrule Toprule">27/28</td><td align="center" class="Lrule Rrule Toprule">96.4%</td><td align="center" class="Lrule Rrule Toprule">1.2 (4.58)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 216</td><td align="center" class="Lrule Rrule Toprule">18/19</td><td align="center" class="Lrule Rrule Toprule">94.7%</td><td align="center" class="Lrule Rrule Toprule">0.5 (0.90)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 240</td><td align="center" class="Lrule Rrule Toprule">16/17</td><td align="center" class="Lrule Rrule Toprule">94.1%</td><td align="center" class="Lrule Rrule Toprule">0.4 (0.62)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 264</td><td align="center" class="Lrule Rrule Toprule">14/15</td><td align="center" class="Lrule Rrule Toprule">95.3%</td><td align="center" class="Lrule Rrule Toprule">0.4 (0.41)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 288</td><td align="center" class="Lrule Rrule Toprule">11/11</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.3 (0.22)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 312</td><td align="center" class="Lrule Rrule Toprule">9/9</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.4 (0.20)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 336</td><td align="center" class="Lrule Rrule Toprule">6/6</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.3 (0.10)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 360</td><td align="center" class="Lrule Rrule Toprule">6/6</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.3 (0.13)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 384</td><td align="center" class="Lrule Rrule Toprule">5/5</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.2 (0.10)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 408</td><td align="center" class="Lrule Rrule Toprule">3/3</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.2 (0.09)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 432</td><td align="center" class="Lrule Rrule Toprule">2/2</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.3 (0.04)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 456</td><td align="center" class="Lrule Rrule Toprule">2/2</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.2 (0.04)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Week 480</td><td align="center" class="Lrule Rrule Toprule">1/1</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.2 (NA)</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule Toprule">Week 504</td><td align="center" class="Lrule Rrule Toprule">1/1</td><td align="center" class="Lrule Rrule Toprule">100%</td><td align="center" class="Lrule Rrule Toprule">0.2 (NA)</td> </tr> </tbody> </table></div>

Suppression (defined as regression or no change) of the clinical/physical signs of puberty was achieved in most patients. In females, suppression of breast development ranged from 66.7 to 90.6% of patients during the first 5 years of treatment. The mean stimulated estradiol was 15.1 pg/mL at baseline, decreased to the lower level of detection (5.0 pg/mL) by Week 4 and was maintained there during the first 5 years of treatment. In males, suppression of genitalia development ranged from 60% to 100% of patients during the first 5 years of treatment. The mean stimulated testosterone was 347.7 ng/dL at baseline and was maintained at levels no greater than 25.3 ng/dL during the first 5 years of treatment.

A “flare effect” of transient bleeding or spotting during the first 4 weeks of treatment was observed in 19.4% (7/36) females who had not reached menarche at baseline. After the first 4 weeks and for the remainder of the treatment period, no patients reported menstrual-like bleeding, and only rare spotting was noted.

The mean ratio of bone age to chronological age decreased from 1.5 at baseline to 1.1 by end of treatment. The mean height standard deviation z-score changed from 1.6 at baseline to 0.7 at the end of the treatment phase.

Thirty five (35) females and 5 males participated in a post-treatment follow-up period to assess reproductive function (in females) and final height. At 6 months post-treatment, most patients reverted to pubertal levels of LH (87.9%) and clinical signs of resumption of pubertal progression were evident with increase in breast development in girls (66.7%) and increase in genitalia development in boys (80%).

After stopping treatment, regular menses were reported for all female patients who reached 12 years of age during follow-up; mean time to menses was approximately 1.5 years; mean age of onset of menstruation after stopping treatment was 12.9 years.

Of the 40 patients evaluated in the follow-up, 33 were observed until they reached final or near-final adult height. These patients had a mean increase in final adult height compared to baseline predicted adult height. The mean final adult height standard deviation score was -0.2.

The efficacy was evaluated in a 6-month, randomized, open-label clinical study of LUPRON DEPOT-PED 3-Month formulations (NCT00667446). 84 patients (76 female, 8 male) between 1 and 11 years of age received the LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration formulation. Each dose group had an equal number of treatment-naïve patients who had pubertal LH levels and patients previously treated with GnRHa therapies who had prepubertal LH levels at the time of study entry. The percentage of patients with suppression of peak-stimulated LH to < 4.0 mIU/mL, as determined by assessments at months 2, 3 and 6, is 78.6% in the 11.25 mg dose and 95.2% in the 30 mg dose as shown in Table 6.

<div class="scrollingtable"><table> <col width="183"/> <col width="74"/> <col width="74"/> <col width="74"/> <col width="74"/> <col width="74"/> <col width="74"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="7" valign="bottom"><span class="Bold">Table </span><span class="Bold">6</span><span class="Bold">. Suppression of Peak-Stimulated LH from Month 2 Through Month 6</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom"> </td><td align="center" class="Lrule Rrule Toprule" colspan="3" valign="bottom"><span class="Bold">LUPRON DEPOT-PED </span><span class="Bold"> <br/>11.25 mg every 3 Months</span></td><td align="center" class="Lrule Rrule Toprule" colspan="3" valign="bottom"><span class="Bold">LUPRON DEPOT-PED</span><span class="Bold"> <br/>30 mg every 3 Months</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Parameter</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Naïve</span><span class="Bold"> <br/>N = 21</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Prev Trt</span><span class="Bold"><span class="Sup">a</span></span><span class="Bold"> <br/>N = 21</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Total</span><span class="Bold"> <br/>N = 42</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Naïve </span><span class="Bold"> <br/>N = 21</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Prev Trt</span><span class="Bold"><span class="Sup">a</span></span><span class="Bold"> <br/>N = 21</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Total </span><span class="Bold"> <br/>N = 42</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">Percent with Suppression</td><td align="center" class="Lrule Rrule Toprule">76.2</td><td align="center" class="Lrule Rrule Toprule">81.0</td><td align="center" class="Lrule Rrule Toprule">78.6</td><td align="center" class="Lrule Rrule Toprule">90.5</td><td align="center" class="Lrule Rrule Toprule">100</td><td align="center" class="Lrule Rrule Toprule">95.2</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule">2-sided 95% CI</td><td align="center" class="Lrule Rrule Toprule">52.8, 91.8</td><td align="center" class="Lrule Rrule Toprule">58.1, 94.6</td><td align="center" class="Lrule Rrule Toprule">63.2, 89.7</td><td align="center" class="Lrule Rrule Toprule">69.6, 98.8</td><td align="center" class="Lrule Rrule Toprule">83.9, 100</td><td align="center" class="Lrule Rrule Toprule">83.8, 99.4</td> </tr> </tbody> </table></div>

a. Previously treated with GnRHa for at least 6 months prior to enrollment in pivotal Study L-CP07-167.

The mean peak stimulated LH levels for all visits are shown by dose and subgroup (naïve vs. previously treated patients) in Figures 8 and 9.

Figure 8. Mean Peak Stimulated LH for LUPRON DEPOT-PED 11.25 mg for 3-month administration

Figure 9. Mean Peak Stimulated LH for LUPRON DEPOT-PED 30 mg for 3-month administration

For the LUPRON DEPOT-PED 11.25 mg dose for 3-month administration, 93% (39/42) of patients and for LUPRON DEPOT-PED 30 mg dose for 3-month administration, 100% (42/42) of patients had sex steroid (estradiol or testosterone) suppressed to prepubertal levels at all visits. Clinical suppression of puberty in female patients was observed in 29 of 32 (90.6%) and 28 of 34 (82.4%) of patients in the 11.25 mg and 30 mg groups, respectively, at month 6. Clinical suppression of puberty in males was observed in 1 of 2 (50%) and 2 of 5 (40%) patients in the 11.25 mg and 30 mg groups, respectively, at month 6. In patients with complete data for bone age, 29 of 33 (88%) in the 11.25 mg group and 30 of 40 in the 30 mg group (75%) had a decrease in the ratio of bone age to chronological age at month 6 compared to screening.

The safety and efficacy of LUPRON DEPOT-PED 6-Month formulation was evaluated in an open-label, single-arm, multicenter, clinical trial (NCT03695237).

In the clinical trial, 27 pediatric patients with central precocious puberty (24 females and 3 males) naïve to previous GnRH agonist treatment and 18 pediatric patients with central precocious puberty (17 females and 1 males) previously treated with GnRH agonist therapy (including 1-,3-, 6- and 12- month) received LUPRON DEPOT-PED 45 mg. LUPRON DEPOT-PED 45 mg was administered as an intramuscular injection at two intervals 24 weeks apart.

The primary efficacy endpoint of percentage of patients with suppression of peak-stimulated LH to < 4.0 mIU/mL at Week 24 was achieved in 39/45 (86.7%) patients (Table 7). Of the patients previously treated with other GnRHa formulations 94.4% remained suppressed at Week 24.

<div class="scrollingtable"><table> <col width="228"/> <col width="158"/> <col width="144"/> <col width="121"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="4" valign="bottom"><span class="Bold">Table </span><span class="Bold">7</span><span class="Bold">. Suppression of Peak-Stimulated GnRHa-Stimulated LH at Week 24</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom"> </td><td align="center" class="Lrule Rrule Toprule" colspan="3" valign="bottom"><span class="Bold">LUPRON DEPOT-PED </span><span class="Bold"> <br/>45 mg </span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Parameter</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Naïve</span><span class="Bold"> <br/>N = 27 </span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Prev Trt</span><span class="Bold"><span class="Sup">a</span></span><span class="Bold"> <br/>N = 18 </span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Total</span><span class="Bold"> <br/>N =45</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">Percent with Suppression, n (%)</td><td align="center" class="Lrule Rrule Toprule">22 (81.5)</td><td align="center" class="Lrule Rrule Toprule">17 (94.4)</td><td align="center" class="Lrule Rrule Toprule">39 (86.7)</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule">95% CI</td><td align="center" class="Lrule Rrule Toprule">61.9, 93.7</td><td align="center" class="Lrule Rrule Toprule">72.7, 99.9</td><td align="center" class="Lrule Rrule Toprule">73.2, 95.0</td> </tr> </tbody> </table></div>

The mean peak stimulated LH levels decreased from 17.4 mIU/mL in treatment-naïve patients and from 2.1 mIU/ML in previously treated patients at baseline to 1.6 mIU/mL and 1.5 mIU/mL respectively at Week 4. The levels remained suppressed for all visits up to Week 48. 

The proportion of female patients with suppression of basal estradiol to <20 pg/mL was 97.4% at Week 24 and 100% at Week 48. The proportion of male patients with suppression of testosterone to <30 ng/dL was 100% at Weeks 24 and 48. Suppression (defined as regression or no change) of the physical signs of puberty was achieved in most patients.

In patients with complete data for bone age, 40 of 45 (88.9%) and 42 of 45 (93.3%) had a decrease in the ratio of bone age to chronological age at Weeks 24 and 48, respectively, compared to baseline.

In the extension part of the study (Weeks 49 to 144), 4 of 45 enrolled patients discontinued due to lack of efficacy. Twenty-three patients had complete data available through Week 144; LH suppression was maintained in all 23 patients.

How Supplied

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

LUPRON DEPOT-PED for depot suspension is supplied in a single dose, prefilled dual-chamber syringe containing a white lyophilized powder and a colorless diluent for reconstitution as follows (Table 8):

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED for depot suspension is supplied in a single dose, prefilled dual-chamber syringe containing a white lyophilized powder and a colorless diluent for reconstitution as follows (Table 8):" }

<div class="scrollingtable"><table> <caption> <span>Table 8. LUPRON DEPOT-PED Product Presentations</span> </caption> <col width="127"/> <col width="276"/> <col width="223"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="3" valign="bottom"><span class="Bold">LUPRON DEPOT-PED 7.5 mg, 11.25 mg, or 15 mg for 1-</span><span class="Bold">M</span><span class="Bold">onth</span><span class="Bold"> Administration</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Kit Type</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Strength</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">NDC Number</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">1-month kit <br/> </td><td align="center" class="Lrule Rrule Toprule">7.5 mg</td><td align="center" class="Lrule Rrule Toprule">NDC 0074-2108-03</td> </tr> <tr> <td class="Lrule Rrule"></td><td align="center" class="Lrule Rrule Toprule">11.25 mg</td><td align="center" class="Lrule Rrule Toprule">NDC 0074-2282-03</td> </tr> <tr> <td class="Lrule Rrule"></td><td align="center" class="Lrule Rrule Toprule">15 mg</td><td align="center" class="Lrule Rrule Toprule">NDC 0074-2440-03</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" colspan="3" valign="bottom"><span class="Bold">LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-</span><span class="Bold">M</span><span class="Bold">onth </span><span class="Bold">Administration </span></td> </tr> <tr> <td class="Lrule Rrule Toprule">3-month kit <br/> </td><td align="center" class="Lrule Rrule Toprule">11.25 mg</td><td align="center" class="Lrule Rrule Toprule">NDC 0074-3779-03</td> </tr> <tr> <td class="Lrule Rrule"></td><td align="center" class="Lrule Rrule Toprule">30 mg</td><td align="center" class="Lrule Rrule Toprule">NDC 0074-9694-03</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" colspan="3"><span class="Bold">LUPRON DEPOT-PED 45 mg for 6-Month Administration</span></td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule">6-month kit</td><td align="center" class="Lrule Rrule Toprule">45 mg</td><td align="center" class="Lrule Rrule Toprule">NDC 0074-3575-01</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Table 8. LUPRON DEPOT-PED Product Presentations</span>\n</caption>\n<col width=\"127\"/>\n<col width=\"276\"/>\n<col width=\"223\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"3\" valign=\"bottom\"><span class=\"Bold\">LUPRON DEPOT-PED 7.5 mg, 11.25 mg, or 15 mg for 1-</span><span class=\"Bold\">M</span><span class=\"Bold\">onth</span><span class=\"Bold\"> Administration</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\" valign=\"bottom\"><span class=\"Bold\">Kit Type</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" valign=\"bottom\"><span class=\"Bold\">Strength</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" valign=\"bottom\"><span class=\"Bold\">NDC Number</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">1-month kit <br/>\n</td><td align=\"center\" class=\"Lrule Rrule Toprule\">7.5 mg</td><td align=\"center\" class=\"Lrule Rrule Toprule\">NDC 0074-2108-03</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td align=\"center\" class=\"Lrule Rrule Toprule\">11.25 mg</td><td align=\"center\" class=\"Lrule Rrule Toprule\">NDC 0074-2282-03</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td align=\"center\" class=\"Lrule Rrule Toprule\">15 mg</td><td align=\"center\" class=\"Lrule Rrule Toprule\">NDC 0074-2440-03</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"3\" valign=\"bottom\"><span class=\"Bold\">LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-</span><span class=\"Bold\">M</span><span class=\"Bold\">onth </span><span class=\"Bold\">Administration </span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">3-month kit <br/>\n</td><td align=\"center\" class=\"Lrule Rrule Toprule\">11.25 mg</td><td align=\"center\" class=\"Lrule Rrule Toprule\">NDC 0074-3779-03</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td align=\"center\" class=\"Lrule Rrule Toprule\">30 mg</td><td align=\"center\" class=\"Lrule Rrule Toprule\">NDC 0074-9694-03</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"3\"><span class=\"Bold\">LUPRON DEPOT-PED 45 mg for 6-Month Administration</span></td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule Toprule\">6-month kit</td><td align=\"center\" class=\"Lrule Rrule Toprule\">45 mg</td><td align=\"center\" class=\"Lrule Rrule Toprule\">NDC 0074-3575-01</td>\n</tr>\n</tbody>\n</table></div>" }

Each kit contains:

{ "type": "p", "children": [], "text": "Each kit contains: " }

{ "type": "ul", "children": [ "one single-dose, prefilled dual-chamber syringe containing 23 gauge 1½ inch needle with LuproLoc® safety device \n", "one plunger \n", "two alcohol swabs \n", "population, dose and frequency confirmation insert\n", "a complete prescribing information enclosure" ], "text": "" }

Storage and Handling

{ "type": "p", "children": [], "text": "\nStorage and Handling\n" }

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

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

After reconstitution, use immediately [see Dosage and Administration (2.5, 2.6)].

{ "type": "p", "children": [], "text": "After reconstitution, use immediately [see Dosage and Administration (2.5, 2.6)].\n" }

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). " }

Symptoms After Initial LUPRON DEPOT-PED Administration

{ "type": "p", "children": [], "text": "\nSymptoms After Initial LUPRON DEPOT-PED Administration\n" }

Inform patients and caregivers that during the early phase of therapy with LUPRON DEPOT-PED, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug. Therefore, an increase in clinical signs and symptoms of puberty may be observed. Instruct patients and caregivers to notify the physician if these symptoms continue beyond the second month after LUPRON DEPOT-PED administration [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Inform patients and caregivers that during the early phase of therapy with LUPRON DEPOT-PED, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug. Therefore, an increase in clinical signs and symptoms of puberty may be observed. Instruct patients and caregivers to notify the physician if these symptoms continue beyond the second month after LUPRON DEPOT-PED administration [see Warnings and Precautions (5.1)].\n" }

Psychiatric Events

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

Inform patients and caregivers that psychiatric events have been reported in patients taking GnRH agonists, including leuprolide acetate. Events include emotional lability, such as crying, irritability, impatience, anger, and aggression. Instruct patients and caregivers to monitor for development or worsening of psychiatric symptoms including depression during treatment with LUPRON DEPOT-PED [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Inform patients and caregivers that psychiatric events have been reported in patients taking GnRH agonists, including leuprolide acetate. Events include emotional lability, such as crying, irritability, impatience, anger, and aggression. Instruct patients and caregivers to monitor for development or worsening of psychiatric symptoms including depression during treatment with LUPRON DEPOT-PED [see Warnings and Precautions (5.2)].\n" }

Convulsions

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

Inform patients and caregivers that reports of convulsions have been observed in patients receiving GnRH agonists, including leuprolide acetate. Patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions may be at increased risk [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform patients and caregivers that reports of convulsions have been observed in patients receiving GnRH agonists, including leuprolide acetate. Patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and patients on concomitant medications that have been associated with convulsions may be at increased risk [see Warnings and Precautions (5.3)].\n" }

Pseudotumor Cerebri (Idiopathic Intracranial Hypertension)

{ "type": "p", "children": [], "text": "\nPseudotumor Cerebri (Idiopathic Intracranial Hypertension)\n" }

Inform patients and caregivers that reports of pseudotumor cerebri (idiopathic intracranial hypertension) have been observed in pediatric patients receiving GnRH agonists, including LUPRON DEPOT-PED. Advise patients and caregivers to monitor for headache and vision issues such as blurred vision, double vision, loss of vision, pain behind the eye or pain with eye movement, ringing in the ears, dizziness, and nausea. Advise patients and caregivers to contact their healthcare provider if the patient develops any of these symptoms [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Inform patients and caregivers that reports of pseudotumor cerebri (idiopathic intracranial hypertension) have been observed in pediatric patients receiving GnRH agonists, including LUPRON DEPOT-PED. Advise patients and caregivers to monitor for headache and vision issues such as blurred vision, double vision, loss of vision, pain behind the eye or pain with eye movement, ringing in the ears, dizziness, and nausea. Advise patients and caregivers to contact their healthcare provider if the patient develops any of these symptoms [see Warnings and Precautions (5.4)].\n" }

Injection Site Reactions

{ "type": "p", "children": [], "text": "\nInjection Site Reactions\n" }

Inform patients and caregivers that injection site related adverse reactions may occur such as transient burning/stinging, pain, bruising, and redness. Advise patients to contact their healthcare provider if they experience rash or severe injection site reactions [see Adverse Reactions (6.1)].

{ "type": "p", "children": [], "text": "Inform patients and caregivers that injection site related adverse reactions may occur such as transient burning/stinging, pain, bruising, and redness. Advise patients to contact their healthcare provider if they experience rash or severe injection site reactions [see Adverse Reactions (6.1)].\n" }

Pregnancy

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

LUPRON DEPOT-PED is contraindicated in pregnancy. If the patient becomes pregnant while taking the drug, the patient should be informed of the potential risk to the fetus [see Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED is contraindicated in pregnancy. If the patient becomes pregnant while taking the drug, the patient should be informed of the potential risk to the fetus [see Use in Specific Populations (8.1)].\n" }

Compliance with the Dosing Schedule

{ "type": "p", "children": [], "text": "\nCompliance with the Dosing Schedule\n" }

Inform caregivers about the importance of adherence to the LUPRON DEPOT-PED dosing schedule [see Dosage and Administration (2.2, 2.3, 2.4)].

{ "type": "p", "children": [], "text": "Inform caregivers about the importance of adherence to the LUPRON DEPOT-PED dosing schedule [see Dosage and Administration (2.2, 2.3, 2.4)]. " }

Manufactured forAbbVie Inc.North Chicago, IL 60064by Takeda Pharmaceutical Company LimitedOsaka, Japan 540-8645

{ "type": "p", "children": [], "text": "Manufactured forAbbVie Inc.North Chicago, IL 60064by Takeda Pharmaceutical Company LimitedOsaka, Japan 540-8645 " }

20093338

{ "type": "p", "children": [], "text": "20093338" }

<div class="scrollingtable"><table> <col width="252"/> <col width="72"/> <col width="84"/> <col width="48"/> <col width="180"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule" colspan="5"><span class="Bold">MEDICATION GUIDE</span><span class="Bold"> <br/>LUPRON DEPOT-PED</span><span class="Bold"><span class="Sup">®</span></span><span class="Bold"> (loo-pron depo peed) </span><span class="Bold"> <br/>(leuprolide acetate for depot suspension) </span></td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">What is the most important information I should know about LUPRON DEPOT-PED?</span> <br/> <ul> <li> <span class="Bold">During the first 2 to 4 weeks of treatment, LUPRON DEPOT-PED can cause an increase in some hormones.</span> During this time you may notice more signs of puberty in your child, including vaginal bleeding. <span class="Bold">Call your doctor if these signs continue after the second month of treatment with LUPRON DEPOT-PED.</span> <br/> </li> <li> <span class="Bold">Some people taking gonadotropin releasing hormone (GnRH) agonists like LUPRON DEPOT-PED have had new or worsened mental (psychiatric) problems.</span> Mental (psychiatric) problems may include emotional symptoms such as:<br/>◦ crying<br/>◦ irritability<br/>◦ restlessness (impatience)<br/>◦ anger<br/>◦ acting aggressive</li> </ul> <span class="Bold">Call your child’s doctor right away if your child has any new or worsening mental symptoms or problems while taking LUPRON DEPOT-PED.</span> <br/> <ul> <li> <span class="Bold">Some people taking GnRH agonists like LUPRON DEPOT-PED have had seizures. The risk of seizures may be higher in people who:</span> <br/>◦ have a history of seizures<br/>◦ have a history of epilepsy<br/>◦ have a history of brain or brain vessel (cerebrovascular) problems or tumors<br/>◦ are taking a medicine that has been connected to seizures such as bupropion or selective serotonin reuptake inhibitors (SSRIs)</li> </ul>Seizures have also happened in people who have not had any of these problems. <span class="Bold">Call your child’s doctor right away if your child has a seizure while taking LUPRON DEPOT-PED</span>. <ul class="Disc"> <li> <span class="Bold">increased pressure in the fluid around the brain can happen in children taking gonadotropin releasing hormone (GnRH) agonist medicines including LUPRON DEPOT-PED. Call your child’s doctor right away if your child has any of the following symptoms during treatment with LUPRON DEPOT-PED:</span> </li> </ul> </td> </tr> <tr> <td class="Lrule" colspan="2">      ◦ headache<br/>      ◦ eye problems, including blurred vision, double vision and decreased eyesight<br/>      ◦ eye pain</td><td class="Rrule" colspan="3">◦ ringing in the ears<br/>◦ dizziness<br/>◦ nausea<br/> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">What is LUPRON DEPOT-PED? </span> <ul> <li>LUPRON DEPOT-PED is an injectable prescription gonadotropin releasing hormone (GnRH) medicine used for the treatment of children with central precocious puberty (CPP). <br/> </li> <li>It is not known if LUPRON DEPOT-PED is safe and effective in children less than 1 year old.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">LUPRON DEPOT-PED should not be taken if your child is:</span> <ul> <li>allergic to GnRH, GnRH agonist medicines, or any ingredients in LUPRON DEPOT-PED. See the end of this Medication Guide for a complete list of ingredients in LUPRON DEPOT-PED. <br/> </li> <li>pregnant or becomes pregnant. LUPRON DEPOT-PED can cause birth defects or loss of the baby. If your child becomes pregnant call your doctor. </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">Before your child receives LUPRON DEPOT-PED, tell their doctor about all of your child’s medical conditions including if they:</span> <br/> <ul> <li>have a history of mental (psychiatric) problems.<br/> </li> <li>have a history of seizures.<br/> </li> <li>have a history of epilepsy.<br/> </li> <li>have a history of brain or brain vessel (cerebrovascular) problems or tumors.<br/> </li> <li>are taking a medicine that has been connected to seizures such as bupropion or selective serotonin reuptake inhibitors (SSRIs).<br/> </li> <li>are breastfeeding or plans to breastfeed. It is not known if LUPRON DEPOT-PED passes into the breast milk.</li> </ul> <span class="Bold">Tell your doctor about all the medicines your child takes,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">How will your child receive LUPRON DEPOT-PED?</span> <ul> <li>Your child’s doctor should do tests to make sure your child has CPP before treating them with LUPRON DEPOT-PED.<br/> </li> <li>LUPRON DEPOT-PED is given as a single-dose injection into your child’s muscle each month, every 3 months, or every 6 months by a doctor or trained nurse. Your doctor will decide how often your child will receive the injection. <br/> </li> <li>Keep all scheduled visits to the doctor. If a scheduled dose is missed, your child may start having signs of puberty again. The doctor will do regular exams and blood tests to check for signs of puberty. </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">What are the possible side effects of LUPRON DEPOT-PED?</span> <br/> <span class="Bold">LUPRON DEPOT-PED may cause serious side effects. See “What is the most important information I should know about LUPRON DEPOT-PED?”</span> <br/> <span class="Bold">The most common side effects of LUPRON DEPOT-PED received 1 time each month include:</span> <br/> <ul> <li>injection site reactions such as pain, swelling, and abscess<br/> </li> <li>weight gain<br/> </li> <li>pain throughout body<br/> </li> <li>headache<br/> </li> <li>acne or red, itchy, rash, and white scales (seborrhea)<br/> </li> <li>serious skin rash (erythema multiforme)<br/> </li> <li>mood changes<br/> </li> <li>swelling of vagina (vaginitis), vaginal bleeding, and vaginal discharge</li> </ul> <span class="Bold">The most common side effects of LUPRON DEPOT-PED received every 3 months include:</span> <br/> <ul> <li>injection site reactions such as pain and swelling<br/> </li> <li>weight gain<br/> </li> <li>headache<br/> </li> <li>mood changes</li> </ul> <span class="Bold">The most common side effects of LUPRON DEPOT-PED received every 6 months include:</span></td> </tr> <tr> <td class="Lrule"> <ul> <li>injection site reactions such as pain, swelling, and abscess<br/> </li> <li>headache<br/> </li> <li>mood changes<br/> </li> <li>upper stomach pain<br/> </li> <li>diarrhea<br/> </li> <li>bleeding</li> </ul> </td><td colspan="2"> <ul> <li>nausea and vomiting<br/> </li> <li>fever<br/> </li> <li>itching<br/> </li> <li>pain in extremity<br/> </li> <li>rash<br/> </li> <li>back pain<br/> </li> <li>ligament sprain</li> </ul> </td><td class="Rrule" colspan="2"> <ul> <li>weight gain<br/> </li> <li>fracture<br/> </li> <li>breast tenderness<br/> </li> <li>difficulty sleeping<br/> </li> <li>chest pain<br/> </li> <li>excessive sweating</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="5"> <br/>These are not all the possible side effects of LUPRON DEPOT-PED. <span class="Bold">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span></td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">How should I store LUPRON DEPOT-PED INJECTION?</span> <ul> <li>Store LUPRON DEPOT-PED INJECTION at room temperature between 68<span class="Sup">○</span>F to 77<span class="Sup">○</span>F (20<span class="Sup">○</span>C to 25<span class="Sup">○</span>C). <br/> </li> <li> <span class="Bold">Keep LUPRON DEPOT-PED INJECTION and all medicines out of the reach of children.</span> </li> </ul> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">General information about the safe and effective use of LUPRON DEPOT-PED.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use LUPRON DEPOT-PED for a condition for which it was not prescribed. <br/>This Medication Guide summarizes the most important information about LUPRON DEPOT-PED. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about LUPRON DEPOT-PED that is written for doctors or trained nurses. </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"><span class="Bold">What are the ingredients in LUPRON DEPOT-PED?</span> <br/> <span class="Bold">LUPRON DEPOT-PED 7.5 mg, 11.25 mg or 15 mg for 1-month administration:</span> <br/> <span class="Bold">Active Ingredients:</span> leuprolide acetate for depot suspension <br/> <span class="Bold">Inactive Ingredients:</span> purified gelatin, DL-lactic and glycolic acids copolymer, D-mannitol, carboxymethylcellulose sodium, polysorbate 80, water for injection, USP, and glacial acetic acid, USP to control pH. <br/> <span class="Bold">LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration:</span> <br/> <span class="Bold">Active Ingredients:</span> leuprolide acetate for depot suspension <br/> <span class="Bold">Inactive Ingredients:</span> polylactic acid, D-mannitol, carboxymethylcellulose sodium, polysorbate 80, water for injection, USP, and glacial acetic acid, USP to control pH.<br/> <span class="Bold">LUPRON DEPOT-PED 45 mg for 6-month administration:</span> <br/> <span class="Bold">Active Ingredients:</span> leuprolide acetate for depot suspension<br/> <span class="Bold">Inactive Ingredients: </span>polylactic acid, D-mannitol, and stearic acid, carboxymethylcellulose sodium, D-mannitol, polysorbate 80, water for injection, USP, and glacial acetic acid, USP to control pH. <br/>Manufactured for: <br/>AbbVie Inc. <br/>North Chicago, IL 60064 <br/>By Takeda Pharmaceutical Company Limited <br/>Osaka, Japan 540-8645 <br/>For more information, go to www.lupronped.com or call 1-800-633-9110. </td> </tr> <tr class="Last"> <td class="Lrule Toprule" colspan="4">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td><td align="right" class="Rrule Toprule">Revised: May 2025</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col width=\"252\"/>\n<col width=\"72\"/>\n<col width=\"84\"/>\n<col width=\"48\"/>\n<col width=\"180\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">MEDICATION GUIDE</span><span class=\"Bold\">\n<br/>LUPRON DEPOT-PED</span><span class=\"Bold\"><span class=\"Sup\">®</span></span><span class=\"Bold\"> (loo-pron depo peed) </span><span class=\"Bold\">\n<br/>(leuprolide acetate for depot suspension) </span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">What is the most important information I should know about LUPRON DEPOT-PED?</span>\n<br/>\n<ul>\n<li>\n<span class=\"Bold\">During the first 2 to 4 weeks of treatment, LUPRON DEPOT-PED can cause an increase in some hormones.</span> During this time you may notice more signs of puberty in your child, including vaginal bleeding. <span class=\"Bold\">Call your doctor if these signs continue after the second month of treatment with LUPRON DEPOT-PED.</span>\n<br/>\n</li>\n<li>\n<span class=\"Bold\">Some people taking gonadotropin releasing hormone (GnRH) agonists like LUPRON DEPOT-PED have had new or worsened mental (psychiatric) problems.</span> Mental (psychiatric) problems may include emotional symptoms such as:<br/>◦ crying<br/>◦ irritability<br/>◦ restlessness (impatience)<br/>◦ anger<br/>◦ acting aggressive</li>\n</ul>\n<span class=\"Bold\">Call your child’s doctor right away if your child has any new or worsening mental symptoms or problems while taking LUPRON DEPOT-PED.</span>\n<br/>\n<ul>\n<li>\n<span class=\"Bold\">Some people taking GnRH agonists like LUPRON DEPOT-PED have had seizures. The risk of seizures may be higher in people who:</span>\n<br/>◦ have a history of seizures<br/>◦ have a history of epilepsy<br/>◦ have a history of brain or brain vessel (cerebrovascular) problems or tumors<br/>◦ are taking a medicine that has been connected to seizures such as bupropion or selective serotonin reuptake inhibitors (SSRIs)</li>\n</ul>Seizures have also happened in people who have not had any of these problems. <span class=\"Bold\">Call your child’s doctor right away if your child has a seizure while taking LUPRON DEPOT-PED</span>. <ul class=\"Disc\">\n<li>\n<span class=\"Bold\">increased pressure in the fluid around the brain can happen in children taking gonadotropin releasing hormone (GnRH) agonist medicines including LUPRON DEPOT-PED. Call your child’s doctor right away if your child has any of the following symptoms during treatment with LUPRON DEPOT-PED:</span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"2\">      ◦ headache<br/>      ◦ eye problems, including blurred vision, double vision and decreased eyesight<br/>      ◦ eye pain</td><td class=\"Rrule\" colspan=\"3\">◦ ringing in the ears<br/>◦ dizziness<br/>◦ nausea<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">What is LUPRON DEPOT-PED? </span>\n<ul>\n<li>LUPRON DEPOT-PED is an injectable prescription gonadotropin releasing hormone (GnRH) medicine used for the treatment of children with central precocious puberty (CPP). <br/>\n</li>\n<li>It is not known if LUPRON DEPOT-PED is safe and effective in children less than 1 year old.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">LUPRON DEPOT-PED should not be taken if your child is:</span> <ul>\n<li>allergic to GnRH, GnRH agonist medicines, or any ingredients in LUPRON DEPOT-PED. See the end of this Medication Guide for a complete list of ingredients in LUPRON DEPOT-PED. <br/>\n</li>\n<li>pregnant or becomes pregnant. LUPRON DEPOT-PED can cause birth defects or loss of the baby. If your child becomes pregnant call your doctor. </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">Before your child receives LUPRON DEPOT-PED, tell their doctor about all of your child’s medical conditions including if they:</span> <br/>\n<ul>\n<li>have a history of mental (psychiatric) problems.<br/>\n</li>\n<li>have a history of seizures.<br/>\n</li>\n<li>have a history of epilepsy.<br/>\n</li>\n<li>have a history of brain or brain vessel (cerebrovascular) problems or tumors.<br/>\n</li>\n<li>are taking a medicine that has been connected to seizures such as bupropion or selective serotonin reuptake inhibitors (SSRIs).<br/>\n</li>\n<li>are breastfeeding or plans to breastfeed. It is not known if LUPRON DEPOT-PED passes into the breast milk.</li>\n</ul>\n<span class=\"Bold\">Tell your doctor about all the medicines your child takes,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements. </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">How will your child receive LUPRON DEPOT-PED?</span>\n<ul>\n<li>Your child’s doctor should do tests to make sure your child has CPP before treating them with LUPRON DEPOT-PED.<br/>\n</li>\n<li>LUPRON DEPOT-PED is given as a single-dose injection into your child’s muscle each month, every 3 months, or every 6 months by a doctor or trained nurse. Your doctor will decide how often your child will receive the injection. <br/>\n</li>\n<li>Keep all scheduled visits to the doctor. If a scheduled dose is missed, your child may start having signs of puberty again. The doctor will do regular exams and blood tests to check for signs of puberty. </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">What are the possible side effects of LUPRON DEPOT-PED?</span>\n<br/>\n<span class=\"Bold\">LUPRON DEPOT-PED may cause serious side effects. See “What is the most important information I should know about LUPRON DEPOT-PED?”</span>\n<br/>\n<span class=\"Bold\">The most common side effects of LUPRON DEPOT-PED received 1 time each month include:</span>\n<br/>\n<ul>\n<li>injection site reactions such as pain, swelling, and abscess<br/>\n</li>\n<li>weight gain<br/>\n</li>\n<li>pain throughout body<br/>\n</li>\n<li>headache<br/>\n</li>\n<li>acne or red, itchy, rash, and white scales (seborrhea)<br/>\n</li>\n<li>serious skin rash (erythema multiforme)<br/>\n</li>\n<li>mood changes<br/>\n</li>\n<li>swelling of vagina (vaginitis), vaginal bleeding, and vaginal discharge</li>\n</ul>\n<span class=\"Bold\">The most common side effects of LUPRON DEPOT-PED received every 3 months include:</span>\n<br/>\n<ul>\n<li>injection site reactions such as pain and swelling<br/>\n</li>\n<li>weight gain<br/>\n</li>\n<li>headache<br/>\n</li>\n<li>mood changes</li>\n</ul>\n<span class=\"Bold\">The most common side effects of LUPRON DEPOT-PED received every 6 months include:</span></td>\n</tr>\n<tr>\n<td class=\"Lrule\">\n<ul>\n<li>injection site reactions such as pain, swelling, and abscess<br/>\n</li>\n<li>headache<br/>\n</li>\n<li>mood changes<br/>\n</li>\n<li>upper stomach pain<br/>\n</li>\n<li>diarrhea<br/>\n</li>\n<li>bleeding</li>\n</ul>\n</td><td colspan=\"2\">\n<ul>\n<li>nausea and vomiting<br/>\n</li>\n<li>fever<br/>\n</li>\n<li>itching<br/>\n</li>\n<li>pain in extremity<br/>\n</li>\n<li>rash<br/>\n</li>\n<li>back pain<br/>\n</li>\n<li>ligament sprain</li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\">\n<ul>\n<li>weight gain<br/>\n</li>\n<li>fracture<br/>\n</li>\n<li>breast tenderness<br/>\n</li>\n<li>difficulty sleeping<br/>\n</li>\n<li>chest pain<br/>\n</li>\n<li>excessive sweating</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\">\n<br/>These are not all the possible side effects of LUPRON DEPOT-PED. <span class=\"Bold\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">How should I store LUPRON DEPOT-PED INJECTION?</span>\n<ul>\n<li>Store LUPRON DEPOT-PED INJECTION at room temperature between 68<span class=\"Sup\">○</span>F to 77<span class=\"Sup\">○</span>F (20<span class=\"Sup\">○</span>C to 25<span class=\"Sup\">○</span>C). <br/>\n</li>\n<li>\n<span class=\"Bold\">Keep LUPRON DEPOT-PED INJECTION and all medicines out of the reach of children.</span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">General information about the safe and effective use of LUPRON DEPOT-PED.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use LUPRON DEPOT-PED for a condition for which it was not prescribed. <br/>This Medication Guide summarizes the most important information about LUPRON DEPOT-PED. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about LUPRON DEPOT-PED that is written for doctors or trained nurses. </td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\"><span class=\"Bold\">What are the ingredients in LUPRON DEPOT-PED?</span>\n<br/>\n<span class=\"Bold\">LUPRON DEPOT-PED 7.5 mg, 11.25 mg or 15 mg for 1-month administration:</span>\n<br/>\n<span class=\"Bold\">Active Ingredients:</span> leuprolide acetate for depot suspension <br/>\n<span class=\"Bold\">Inactive Ingredients:</span> purified gelatin, DL-lactic and glycolic acids copolymer, D-mannitol, carboxymethylcellulose sodium, polysorbate 80, water for injection, USP, and glacial acetic acid, USP to control pH. <br/>\n<span class=\"Bold\">LUPRON DEPOT-PED 11.25 mg or 30 mg for 3-month administration:</span> <br/>\n<span class=\"Bold\">Active Ingredients:</span> leuprolide acetate for depot suspension <br/>\n<span class=\"Bold\">Inactive Ingredients:</span> polylactic acid, D-mannitol, carboxymethylcellulose sodium, polysorbate 80, water for injection, USP, and glacial acetic acid, USP to control pH.<br/>\n<span class=\"Bold\">LUPRON DEPOT-PED 45 mg for 6-month administration:</span>\n<br/>\n<span class=\"Bold\">Active Ingredients:</span> leuprolide acetate for depot suspension<br/>\n<span class=\"Bold\">Inactive Ingredients: </span>polylactic acid, D-mannitol, and stearic acid, carboxymethylcellulose sodium, D-mannitol, polysorbate 80, water for injection, USP, and glacial acetic acid, USP to control pH. <br/>Manufactured for: <br/>AbbVie Inc. <br/>North Chicago, IL 60064 <br/>By Takeda Pharmaceutical Company Limited <br/>Osaka, Japan 540-8645 <br/>For more information, go to www.lupronped.com or call 1-800-633-9110. </td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Toprule\" colspan=\"4\">This Medication Guide has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\" class=\"Rrule Toprule\">Revised: May 2025</td>\n</tr>\n</tbody>\n</table></div>" }

20093338

{ "type": "p", "children": [], "text": "20093338" }

NDC 0074-2108-03

{ "type": "p", "children": [], "text": "NDC 0074-2108-03 " }

PEDIATRIC USE ONLY 7.5 mg for 1-month administration

{ "type": "p", "children": [], "text": "PEDIATRIC USE ONLY 7.5 mg for 1-month administration " }

Single Dose Administration Kit with prefilled dual-chamber syringe.

{ "type": "p", "children": [], "text": "Single Dose Administration Kit with prefilled dual-chamber syringe. " }

LUPRON DEPOT-PED®

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED®\n" }

(Leuprolide Acetate for Depot Suspension)

{ "type": "p", "children": [], "text": "(Leuprolide Acetate for Depot Suspension) " }

Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "Dispense the accompanying Medication Guide to each patient. " }

7.5 mg for 1-month administration

{ "type": "p", "children": [], "text": "7.5 mg for 1-month administration " }

FOR INTRAMUSCULAR INJECTION

{ "type": "p", "children": [], "text": "FOR INTRAMUSCULAR INJECTION " }

The front chamber contains: leuprolide acetate 7.5 mg۰purified gelatin 1.3 mg۰DL-lactic & glycolic acids copolymer 66.2 mg۰D-mannitol 13.2 mg

{ "type": "p", "children": [], "text": "\nThe front chamber contains: leuprolide acetate 7.5 mg۰purified gelatin 1.3 mg۰DL-lactic & glycolic acids copolymer 66.2 mg۰D-mannitol 13.2 mg " }

The second chamber contains: D-mannitol 50 mg۰ carboxymethylcellulose sodium 5 mg۰polysorbate 80 1 mg۰water for injection, USP and glacial acetic acid, USP to control pH

{ "type": "p", "children": [], "text": "\nThe second chamber contains: D-mannitol 50 mg۰ carboxymethylcellulose sodium 5 mg۰polysorbate 80 1 mg۰water for injection, USP and glacial acetic acid, USP to control pH " }

Rx only

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

NDC 0074-2282-03

{ "type": "p", "children": [], "text": "NDC 0074-2282-03 " }

PEDIATRIC USE ONLY 11.25 mg for 1-month administration

{ "type": "p", "children": [], "text": "PEDIATRIC USE ONLY 11.25 mg for 1-month administration " }

Single Dose Administration Kit with prefilled dual-chamber syringe.

{ "type": "p", "children": [], "text": "Single Dose Administration Kit with prefilled dual-chamber syringe. " }

LUPRON DEPOT-PED®

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED®\n" }

(Leuprolide Acetate for Depot Suspension)

{ "type": "p", "children": [], "text": "(Leuprolide Acetate for Depot Suspension) " }

Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "Dispense the accompanying Medication Guide to each patient. " }

11.25 mg for 1-month administration

{ "type": "p", "children": [], "text": "11.25 mg for 1-month administration " }

FOR INTRAMUSCULAR INJECTION

{ "type": "p", "children": [], "text": "FOR INTRAMUSCULAR INJECTION " }

The front chamber contains: leuprolide acetate 11.25 mg۰purified gelatin 1.95 mg۰DL-lactic & glycolic acids copolymer 99.3 mg۰D-mannitol 19.8 mg

{ "type": "p", "children": [], "text": "\nThe front chamber contains: leuprolide acetate 11.25 mg۰purified gelatin 1.95 mg۰DL-lactic & glycolic acids copolymer 99.3 mg۰D-mannitol 19.8 mg " }

The second chamber contains: D-mannitol 50 mg۰carboxymethylcellulose sodium 5 mg۰polysorbate 80 1 mg۰water for injection, USP, and glacial acetic acid, USP to control pH

{ "type": "p", "children": [], "text": "\nThe second chamber contains: D-mannitol 50 mg۰carboxymethylcellulose sodium 5 mg۰polysorbate 80 1 mg۰water for injection, USP, and glacial acetic acid, USP to control pH " }

Rx only

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

NDC 0074-2440-03

{ "type": "p", "children": [], "text": "NDC 0074-2440-03 " }

PEDIATRIC USE ONLY 15 mg for 1-month administration

{ "type": "p", "children": [], "text": "PEDIATRIC USE ONLY 15 mg for 1-month administration " }

Single Dose Administration Kit with prefilled dual-chamber syringe.

{ "type": "p", "children": [], "text": "Single Dose Administration Kit with prefilled dual-chamber syringe. " }

LUPRON DEPOT-PED®

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED®\n" }

(Leuprolide Acetate for Depot Suspension)

{ "type": "p", "children": [], "text": "(Leuprolide Acetate for Depot Suspension) " }

Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "Dispense the accompanying Medication Guide to each patient. " }

15 mg for 1-month administration

{ "type": "p", "children": [], "text": "15 mg for 1-month administration " }

FOR INTRAMUSCULAR INJECTION

{ "type": "p", "children": [], "text": "FOR INTRAMUSCULAR INJECTION " }

The front chamber contains: leuprolide acetate 15 mg۰purified gelatin 2.6 mg۰DL-lactic & glycolic acids copolymer 132.4 mg۰D-mannitol 26.4 mg

{ "type": "p", "children": [], "text": "\nThe front chamber contains: leuprolide acetate 15 mg۰purified gelatin 2.6 mg۰DL-lactic & glycolic acids copolymer 132.4 mg۰D-mannitol 26.4 mg " }

The second chamber contains: D-mannitol 50 mg۰ carboxymethylcellulose sodium 5 mg۰polysorbate 80 1 mg۰water for injection, USP and glacial acetic acid, USP to control pH

{ "type": "p", "children": [], "text": "\nThe second chamber contains: D-mannitol 50 mg۰ carboxymethylcellulose sodium 5 mg۰polysorbate 80 1 mg۰water for injection, USP and glacial acetic acid, USP to control pH " }

Rx only

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

NDC 0074-3779-03

{ "type": "p", "children": [], "text": "NDC 0074-3779-03 " }

PEDIATRIC USE ONLY 11.25 mg for 3-month administration

{ "type": "p", "children": [], "text": "PEDIATRIC USE ONLY 11.25 mg for 3-month administration " }

Single Dose Administration Kit with prefilled dual-chamber syringe.

{ "type": "p", "children": [], "text": "Single Dose Administration Kit with prefilled dual-chamber syringe. " }

LUPRON DEPOT-PED® (Leuprolide Acetate for Depot Suspension)

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED® (Leuprolide Acetate for Depot Suspension) " }

Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "Dispense the accompanying Medication Guide to each patient. " }

11.25 mg for 3-month administration

{ "type": "p", "children": [], "text": "11.25 mg for 3-month administration " }

FOR INTRAMUSCULAR INJECTION

{ "type": "p", "children": [], "text": "FOR INTRAMUSCULAR INJECTION " }

The front chamber contains: leuprolide acetate 11.25 mg۰polylactic acid 99.3 mg۰D-mannitol 19.45 mg

{ "type": "p", "children": [], "text": "\nThe front chamber contains: leuprolide acetate 11.25 mg۰polylactic acid 99.3 mg۰D-mannitol 19.45 mg " }

The second chamber contains: carboxymethylcellulose sodium 7.5 mg۰D-mannitol 75.0 mg۰polysorbate 80 1.5 mg۰water for injection, USP, and glacial acetic acid, USP to control pH

{ "type": "p", "children": [], "text": "\nThe second chamber contains: carboxymethylcellulose sodium 7.5 mg۰D-mannitol 75.0 mg۰polysorbate 80 1.5 mg۰water for injection, USP, and glacial acetic acid, USP to control pH " }

Rx only

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

NDC 0074-9694-03

{ "type": "p", "children": [], "text": "NDC 0074-9694-03 " }

PEDIATRIC USE ONLY 30 mg for 3-month administration

{ "type": "p", "children": [], "text": "PEDIATRIC USE ONLY 30 mg for 3-month administration " }

Single Dose Administration Kit with prefilled dual-chamber syringe

{ "type": "p", "children": [], "text": "Single Dose Administration Kit with prefilled dual-chamber syringe " }

LUPRON DEPOT-PED®

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED®\n" }

(Leuprolide Acetate for Depot Suspension)

{ "type": "p", "children": [], "text": "(Leuprolide Acetate for Depot Suspension) " }

Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "Dispense the accompanying Medication Guide to each patient. " }

30 mg for 3-month administration

{ "type": "p", "children": [], "text": "30 mg for 3-month administration " }

FOR INTRAMUSCULAR INJECTION

{ "type": "p", "children": [], "text": "FOR INTRAMUSCULAR INJECTION " }

The front chamber contains: leuprolide acetate 30 mg۰polylactic acid 264.8 mg۰D-mannitol 51.9 mg

{ "type": "p", "children": [], "text": "\nThe front chamber contains: leuprolide acetate 30 mg۰polylactic acid 264.8 mg۰D-mannitol 51.9 mg " }

The second chamber contains: carboxymethylcellulose sodium 7.5 mg۰D-mannitol 75.0 mg۰polysorbate 80 1.5 mg۰water for injection, USP, and glacial acetic acid, USP to control pH

{ "type": "p", "children": [], "text": "\nThe second chamber contains: carboxymethylcellulose sodium 7.5 mg۰D-mannitol 75.0 mg۰polysorbate 80 1.5 mg۰water for injection, USP, and glacial acetic acid, USP to control pH " }

Rx only

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

NDC 0074-3575-01 

{ "type": "p", "children": [], "text": "NDC 0074-3575-01 " }

PEDIATRIC USE ONLY 45 mg for 6-month administration

{ "type": "p", "children": [], "text": "PEDIATRIC USE ONLY 45 mg for 6-month administration " }

Single Dose Administration Kit with prefilled dual-chamber syringe

{ "type": "p", "children": [], "text": "Single Dose Administration Kit with prefilled dual-chamber syringe " }

LUPRON DEPOT-PED®

{ "type": "p", "children": [], "text": "LUPRON DEPOT-PED®\n" }

(Leuprolide Acetate for Depot Suspension)

{ "type": "p", "children": [], "text": "(Leuprolide Acetate for Depot Suspension) " }

Dispense the accompanying Medication Guide to each patient.

{ "type": "p", "children": [], "text": "Dispense the accompanying Medication Guide to each patient." }

45 mg for 6-month administration

{ "type": "p", "children": [], "text": "45 mg for 6-month administration " }

FOR INTRAMUSCULAR INJECTION

{ "type": "p", "children": [], "text": "FOR INTRAMUSCULAR INJECTION " }

The front chamber contains: leuprolide acetate 45 mg۰polylactic acid 169.9 mg۰D-mannitol 39.7 mg۰stearic acid 10.1 mg

{ "type": "p", "children": [], "text": "\nThe front chamber contains: leuprolide acetate 45 mg۰polylactic acid 169.9 mg۰D-mannitol 39.7 mg۰stearic acid 10.1 mg " }

The second chamber contains: carboxymethylcellulose sodium 7.5 mg۰D-mannitol 75.0 mg۰polysorbate 80 1.5 mg۰water for injection, USP, and glacial acetic acid, USP to control pH

{ "type": "p", "children": [], "text": "\nThe second chamber contains: carboxymethylcellulose sodium 7.5 mg۰D-mannitol 75.0 mg۰polysorbate 80 1.5 mg۰water for injection, USP, and glacial acetic acid, USP to control pH " }

Rx only

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

CAMCEVI is indicated for the treatment of adult patients with advanced prostate cancer.

{ "type": "p", "children": [], "text": "CAMCEVI is indicated for the treatment of adult patients with advanced prostate cancer." }

The recommended dose of CAMCEVI is 42 mg administered subcutaneously once every 6 months.

CAMCEVI must be administered by a healthcare provider.

Important:Read the instructions completely before you administer Camcevi for the first time. Do NOT substitute any of the components from the kit for administration.

CAMCEVI is packaged in a blister in the kit. Check to make sure the kit contains:

Follow the detailed instructions to ensure correct preparation of CAMCEVI prior to administration:

<div class="scrollingtable"><table> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 1 <br/> <br/> Remove CAMCEVI kit from refrigerator. <br/> <br/> Keep the contents in their original, sealed blister carton and allow to sit at room temperature for 30 minutes before use. <br/> <br/> Return to refrigerator after 30 minutes if not used. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><img alt="camcevi-inj-image-2-terumo-needle" src="/dailymed/image.cfm?name=camcevi-inj-image-2-terumo-needle.jpg&amp;setid=cbff25e5-6fe8-4e44-b10a-8397b3349905"/></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 2 <br/> <br/> On a clean, dry surface, open carton and remove the contents. Examine all contents of the package. Do not use if any component is damaged. <br/> <br/> Check the expiration date on the syringe. Do not use if the expiration date has passed. <br/> <br/> The use of gloves is recommended during syringe assembly and administration. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><img alt="camcevi-inj-image-3-terumo-needle" src="/dailymed/image.cfm?name=camcevi-inj-image-3-terumo-needle.jpg&amp;setid=cbff25e5-6fe8-4e44-b10a-8397b3349905"/></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 3 <br/> <br/> Remove pre-filled syringe (A) from the blister tray and open the safety needle (B) package by peeling back the paper tab. <br/> <br/> The safety needle (B) package is located beneath the blister tray. <br/> <br/> Visually inspect the syringe for particulate matter prior to administration. The emulsion should appear off-white to pale yellow, viscous, and opalescent. Do not use if particulate matter is observed prior to administration. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><img alt="camcevi-inj-image-4-terumo-needle" src="/dailymed/image.cfm?name=camcevi-inj-image-4-terumo-needle.jpg&amp;setid=cbff25e5-6fe8-4e44-b10a-8397b3349905"/></td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">STEP 4 <br/> <br/> Remove the gray cap from the syringe (A). <br/> <br/> Attach the needle (B) to the end of the syringe (A) by gently screwing clockwise with approximately a three-quarter turn until the needle is secure . <span class="Bold">Do not overtighten, as the needle hub may become damaged resulting in leakage of the product during injection. The safety sheath may also be damaged if the needle is overtightened onto the syringe.</span> <br/> <br/> See figure of assembled pre-filled syringe below. </p> <p> <img alt="camcevi-inj-image-9-terumo-needle" src="/dailymed/image.cfm?name=camcevi-inj-image-9-terumo-needle.jpg&amp;setid=cbff25e5-6fe8-4e44-b10a-8397b3349905"/></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><img alt="camcevi-inj-image-5-terumo-needle.jpg" src="/dailymed/image.cfm?name=camcevi-inj-image-5-terumo-needle.jpg&amp;setid=cbff25e5-6fe8-4e44-b10a-8397b3349905"/></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 5 <br/> <br/> Choose an injection site on the upper- or mid-abdominal area with sufficient soft or loose subcutaneous tissue that has not recently been used. <br/> <br/> Clean the injection site with an alcohol swab. <br/> <br/> Do <span class="Bold">NOT</span>inject in areas with brawny or fibrous subcutaneous tissue or locations that can be rubbed or compressed (i.e., with a belt or clothing waistband). In addition, avoid applying heat directly to the site of Camcevi injection. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><img alt="camcevi-inj-image-6-terumo-needle" src="/dailymed/image.cfm?name=camcevi-inj-image-6-terumo-needle.jpg&amp;setid=cbff25e5-6fe8-4e44-b10a-8397b3349905"/></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 6 <br/> <br/> (1) Move the safety sheath away from the needle and towards the syringe and (2) remove the clear needle cover immediately before injection. <br/> <br/> <span class="Bold">Note:</span>Should the needle hub appear to be damaged, or leak, the product should NOT be used. The damaged needle should NOT be replaced and the product should NOT be injected. In the event of damage to the needle hub, use a new replacement CAMCEVI kit. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><img alt="camcevi-inj-image-7-terumo-needle" src="/dailymed/image.cfm?name=camcevi-inj-image-7-terumo-needle.jpg&amp;setid=cbff25e5-6fe8-4e44-b10a-8397b3349905"/></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 7 <br/> <br/> Use standard aseptic technique when performing the injection. <br/> <br/> Grab and bunch the skin around the injection site with one hand. <br/> <br/> Insert the needle at a 90° angle to the skin surface, and then release the bunched skin. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 8 <br/> <br/> Inject the full contents of the syringe with a slow and steady push on the plunger, and then withdraw the needle at the same 90° angle used for insertion. </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><img alt="camcevi-inj-image-8-terumo-needle" src="/dailymed/image.cfm?name=camcevi-inj-image-8-terumo-needle.jpg&amp;setid=cbff25e5-6fe8-4e44-b10a-8397b3349905"/></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 9 <br/> <br/> Immediately following the withdrawal of the needle, activate the safety sheath using a finger/thumb or flat surface and push until it completely covers the needle tip and locks into place. <br/> <br/> An audible and tactile “click” verifies a locked position. <br/> <br/> Check to confirm the safety sheath is fully engaged. </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule" colspan="2">STEP 10 <br/> <br/> After use, discard all components safely in a suitable sharps container. Dispose of the syringe and contaminated products according to local regulations/procedures. </td> </tr> </tbody> </table></div>

Injectable emulsion: 42 mg leuprolide (equivalent to approximately 48 mg leuprolide mesylate) as a sterile, off-white to pale yellow, viscous, and opalescent emulsion in a single-dose, pre-filled syringe for subcutaneous injection.

{ "type": "p", "children": [], "text": "Injectable emulsion: 42 mg leuprolide (equivalent to approximately 48 mg leuprolide mesylate) as a sterile, off-white to pale yellow, viscous, and opalescent emulsion in a single-dose, pre-filled syringe for subcutaneous injection." }

CAMCEVI is contraindicated in patients known to be hypersensitive to GnRH, GnRH agonist analogs, or any of the excipients in CAMCEVI. Anaphylactic reactions to GnRH agonist analogs have been reported in the medical literature.

{ "type": "p", "children": [], "text": "CAMCEVI is contraindicated in patients known to be hypersensitive to GnRH, GnRH agonist analogs, or any of the excipients in CAMCEVI. Anaphylactic reactions to GnRH agonist analogs have been reported in the medical literature." }

CAMCEVI, like other GnRH agonists, causes a transient increase in serum levels of testosterone during the first week of treatment, declining thereafter to baseline levels or below by the end of the second week of treatment. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostate cancer, may develop during the first few weeks of CAMCEVI treatment. Patients treated with CAMCEVI may experience a temporary increase in bone pain, which can be managed symptomatically.

Cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications.

Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy.

Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent the development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.

Increased risk of developing myocardial infarction, sudden cardiac death, and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

Convulsions have been reported in patients receiving GnRH agonists, like CAMCEVI [see Adverse Reactions ( 6.2)]. Manage patients receiving a GnRH agonist who experience convulsions according to current clinical practice.

Monitor serum levels of testosterone following injection of CAMCEVI. In the majority of patients treated with CAMCEVI, testosterone levels increased above baseline during the first week, and then declined thereafter to castration levels (<50 ng/dL) within 4 weeks [see Clinical Studies ( 14) and Adverse Reactions ( 6)].

Based on findings in animal studies and mechanism of action, CAMCEVI can cause fetal harm when administered to a pregnant woman. In animal developmental and reproductive toxicology studies, administration of a monthly formulation of leuprolide on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-fetal toxicity in animals at doses less than the human dose based on body surface area using an estimated daily dose. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus [see Use in Specific Population ( 8.1), Clinical Pharmacology ( 12.1)].

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

FP01C-13-001

The safety of CAMCEVI was evaluated in an open-label, single-arm, international clinical trial (FP01C-13-001) in patients with advanced prostate cancer. Patients received CAMCEVI administered subcutaneously at a dose of 42 mg on Day 0 and Day 168. Of 137 patients enrolled, 93% received both doses of CAMCEVI.

Serious adverse reactions occurred in 15% of patients who received CAMCEVI, including 1% of patients who experienced subdural hematoma. Fatal adverse reactions occurred in 2% of patients, including cerebrovascular accident (0.7%) and pulmonary embolism (0.7%).

The most common adverse reactions (≥10%) occurring during a median follow-up duration of 336 days were hot flush, hypertension, injection site reactions, upper respiratory tract infections, musculoskeletal pain, fatigue, and pain in extremity.

Table 1 summarizes the adverse reactions in FP01C-13-001.

                                    Table 1. Adverse Reactions Occurring in ≥5% of CAMCEVI in Advanced Prostate Cancer Patients - FP01C-13-001

<div class="scrollingtable"><table width="70%"> <tbody class="Headless"> <tr class="First"> <td class="Lrule Rrule Toprule"><span class="Underline"><span class="Bold">Adverse Reaction</span></span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Underline"><span class="Bold">CAMCEVI <br/> N=137 </span></span></td> </tr> <tr> <td class="Lrule Rrule"></td><td align="center" class="Lrule Rrule Toprule"><span class="Underline"><span class="Bold">All Grades <br/> (%) </span></span></td><td align="center" class="Lrule Rrule Toprule"><span class="Underline"><span class="Bold">Grade 3-4 <br/> (%) </span></span></td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="3">Vascular disorders</td> </tr> <tr> <td class="Lrule Rrule Toprule">    Hot flushes <span class="Sup">a</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">50</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule">    Hypertension <span class="Sup">b</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">15</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="3">General disorders and administration site conditions</td> </tr> <tr> <td class="Lrule Rrule Toprule">    Injection site reactions <span class="Sup">c</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">11</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule">    Fatigue <span class="Sup">d</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">10</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="3">Infections and infestations</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Upper respiratory tract infection <span class="Sup">e</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">11</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="3">Musculoskeletal and connective tissue disorders</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Musculoskeletal pain <span class="Sup">f</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">11</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Pain in extremity</td><td align="center" class="Lrule Rrule Toprule" valign="top">10</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule">    Arthralgia</td><td align="center" class="Lrule Rrule Toprule" valign="top">7</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="3">Renal and urinary disorders</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Micturition urgency <span class="Sup">g</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">6</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule">     Nocturia</td><td align="center" class="Lrule Rrule Toprule" valign="top">6</td><td align="center" class="Lrule Rrule Toprule" valign="top">0</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="3">Nervous system disorders</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule">     Dizziness <span class="Sup">h</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">5</td><td align="center" class="Lrule Rrule Toprule" valign="top">0.7</td> </tr> </tbody> </table></div>

aincludes hot flush and flushing bincludes hypertension, essential hypertension, and blood pressure increased cincludes injection site pain, injection site erythema, injection site hemorrhage, injection site nodule, injection site paraesthesia, injection site pruritus, and injection site warmth dincludes fatigue and asthenia eincludes upper respiratory tract infection, sinusitis, and nasopharyngitis fincludes musculoskeletal pain, back pain, and bone pain gincludes micturition urgency and dysuria hincludes dizziness, dizziness postural, vertigo, and vertigo positional.

The following adverse reactions have been identified during post approval use of CAMCEVI or leuprolide. 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.

During postmarketing surveillance, which includes other dosage forms and other patient populations, the following adverse reactions were reported.

Allergic Conditions: hypersensitivity reactions including anaphylaxis, rash, urticaria, and photosensitivity reactions

Cardiovascular System:hypotension, myocardial infarction, pulmonary embolism

Central/Peripheral Nervous System:convulsion, peripheral neuropathy, spinal fracture/paralysis

Endocrine System:pituitary apoplexy, diabetes

Hepato-biliary disorder:drug-induced liver injury

Hematologic:leukopenia

Psychiatric:mood swings, including depression, suicidal ideation and attempt

Respiratory, thoracic and mediastinal disorder:interstitial lung disease

Musculoskeletal System:decreased bone density, tenosynovitis-like symptoms, fibromyalgia

Skin and Subcutaneous:injection site induration or swelling

Urogenital System:prostate pain

Risk Summary

Based on findings in animal studies and mechanism of action, CAMCEVI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1)]. There are no available data in pregnant women to inform the drug-associated risk. In animal developmental and reproductive toxicology studies, administration of a monthly formulation of leuprolide on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-fetal toxicity in animals at doses less than the human dose based on body surface area using an estimated daily dose (see data). Advise pregnant patients and females of reproductive potential of the potential risk to the fetus.

Data

Animal Data

Major fetal malformations were observed in developmental and reproductive toxicology studies in rabbits after a single administration of a monthly formulation of leuprolide administered on day 6 of pregnancy at test dosages of 0.00024, 0.0024, and 0.024 mg/kg (approximately 1/1500 to 1/15 the human dose based on body surface area using an estimated daily dose in animals and humans). Since a depot formulation was utilized in the study, a sustained exposure to leuprolide was expected throughout the period of organogenesis and to the end of gestation. Similar studies in rats did not demonstrate an increase in fetal malformations, however, there was increased fetal mortality and decreased fetal weights with the two higher doses of the monthly formulation of leuprolide in rabbits and with the highest dose in rats.

Risk Summary

The safety and efficacy of CAMCEVI have not been established in females. There is no information regarding the presence of leuprolide in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in a breastfed child, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Infertility

Males

Based on findings in animals and mechanism of action, CAMCEVI may impair fertility in males of reproductive potential [seeClinical Pharmacology ( 12.1), Nonclinical Toxicology ( 13.1) ].

The safety and efficacy of CAMCEVI in pediatric patients have not been established.

Of the 137 patients who received CAMCEVI in the FP01C-13-001 study, 74% were 65 years of age or older, while 37% were 75 years of age or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

CAMCEVI is a sterile formulation of leuprolide mesylate for subcutaneous injection. CAMCEVI is designed to deliver approximately 42 mg of leuprolide over 6 months.

{ "type": "p", "children": [], "text": "CAMCEVI is a sterile formulation of leuprolide mesylate for subcutaneous injection. CAMCEVI is designed to deliver approximately 42 mg of leuprolide over 6 months." }

Leuprolide mesylate is a synthetic nonapeptide analog of naturally occurring GnRH and is a GnRH agonist. The analog possesses greater potency than the natural hormone. The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide mesylate (salt) with the following structural formula. The pH of 50 mg/mL solution of leuprolide mesylate in water is approximately 5.7.

{ "type": "p", "children": [], "text": "Leuprolide mesylate is a synthetic nonapeptide analog of naturally occurring GnRH and is a GnRH agonist. The analog possesses greater potency than the natural hormone. The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide mesylate (salt) with the following structural formula. The pH of 50 mg/mL solution of leuprolide mesylate in water is approximately 5.7." }

CAMCEVI is supplied as a kit with a pre-filled, single-dose, sterile syringe for subcutaneous injection. Each pre-filled syringe delivers 42 mg leuprolide (equivalent to approximately 48 mg leuprolide mesylate), poly(D, L-lactide) (184 mg) polymer and N-methyl-2-pyrrolidone (136 mg).

{ "type": "p", "children": [], "text": "CAMCEVI is supplied as a kit with a pre-filled, single-dose, sterile syringe for subcutaneous injection. Each pre-filled syringe delivers 42 mg leuprolide (equivalent to approximately 48 mg leuprolide mesylate), poly(D, L-lactide) (184 mg) polymer and\n \n N-methyl-2-pyrrolidone (136 mg).\n\n " }

Leuprolide, a GnRH agonist, acts as an inhibitor of gonadotropin secretion. Animal and human studies indicate that following an initial stimulation of gonadotropins, chronic administration of leuprolide results in suppression of ovarian and testicular steroidogenesis. This effect is reversible upon discontinuation of drug therapy.

Mean serum testosterone concentrations transiently increased, then fell to below castrate threshold levels (≤ 50 ng/dL) within 3 weeks following administration of the dose of leuprolide, and generally remained below castrate thresholds levels throughout treatment.

In humans, subcutaneous administration of single daily doses of leuprolide result in an initial increase in circulating levels of LH and FSH, leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestosterone in males). However, continuous daily administration of leuprolide results in decreased levels of LH and FSH. In males, testosterone is reduced to below castration levels. These decreases generally occur within 2 to 4 weeks after initiation of treatment, and castration levels of testosterone in prostatic cancer patients have been demonstrated for periods of up to 5 years.

Leuprolide concentration is variable, exhibiting an initial rapid increase followed by a rapid decline over the first 3 days before reaching steady concentrations for the duration of the dosing interval. The mean serum leuprolide C maxwas 94.5 and 99 ng/mL following the first and second doses of CAMCEVI, respectively. The mean serum concentration was maintained at 0.497–2.57 and 0.507–2.39 ng/ml after Day 3 post the first and second doses, respectively. The mean AUC 0-6 monwas 224 and 268 day.ng/mL following the first and second doses of CAMCEVI, respectively.

Absorption

The median T maxof leuprolide was 3.2 and 2.1 hours following the first and second doses of CAMCEVI, respectively

Distribution

The mean steady-state volume of distribution of leuprolide was 27 L following an intravenous bolus in healthy male volunteers. Protein binding of leuprolide ranged from 43% to 49% in vitro.

Elimination

The mean systemic clearance was 7.6 L/h and terminal elimination half-life of approximately 3 hours following an intravenous bolus of leuprolide in healthy male volunteers.

Metabolism

Administration of radiolabeled leuprolide was metabolized to smaller inactive peptides which may then be further catabolized.

Excretion

Excretion of leuprolide has not been evaluated with CAMCEVI.

Specific Populations

No clinically significant differences in the systemic exposure of leuprolide were observed based on age (51 to 88 years), race/ethnicity (White, Black, Asian), or body weight (54 to 134 kg). The effect of renal or hepatic impairment on the pharmacokinetics of leuprolide has not been evaluated.

Two-year carcinogenicity studies were conducted with leuprolide in rats and mice. In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg). There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group). In mice, no pituitary abnormalities were observed at a dose as high as 60 mg/kg for 2 years. Patients have been treated with leuprolide for up to 3 years with doses as high as 10 mg/day and for 2 years with doses as high as 20 mg/day without demonstrable pituitary abnormalities.

Mutagenicity studies have been performed with leuprolide using bacterial and mammalian systems. These studies provided no evidence of mutagenic potential.

Leuprolide may reduce male and female fertility. Administration of leuprolide to male and female rats at doses of 0.024, 0.24, and 2.4 mg/kg as monthly depot formulation for up to 3 months (approximately as low as 1/30 of the human dose based on body surface area using an estimated daily dose in animals and humans) caused atrophy of the reproductive organs, and suppression of reproductive function. These changes were reversible upon cessation of treatment.

The efficacy of CAMCEVI was evaluated in an open label, single arm, multinational study FP01C-13-001 ( NCT02234115) in patients with advanced prostate carcinoma who have a baseline morning serum testosterone level >150 ng/dL and Eastern Cooperative Oncology Group performance status ≤ 2. CAMCEVI was administered subcutaneously at a dose of 42 mg initially on Day 0 and on Week 24.

{ "type": "p", "children": [], "text": "The efficacy of CAMCEVI was evaluated in an open label, single arm, multinational study FP01C-13-001 (\n \n NCT02234115) in patients with advanced prostate carcinoma who have a baseline morning serum testosterone level >150 ng/dL and Eastern Cooperative Oncology Group performance status ≤ 2. CAMCEVI was administered subcutaneously at a dose of 42 mg initially on Day 0 and on Week 24.\n\n " }

The population (n = 137) had a median age of 71 years (range 51 to 88) and was 90% White, 6% Black, and 4% Asian. Disease stage was distributed as follows: 23% metastatic (M1), 27% locally advanced (T3/4 NX M0 or any T N1 M0), 26% localized (T1 or T2 N0 M0), and 24% not classifiable. The median testosterone concentration at baseline was 440 ng/dL.

{ "type": "p", "children": [], "text": "The population (n = 137) had a median age of 71 years (range 51 to 88) and was 90% White, 6% Black, and 4% Asian. Disease stage was distributed as follows: 23% metastatic (M1), 27% locally advanced (T3/4 NX M0 or any T N1 M0), 26% localized (T1 or T2 N0 M0), and 24% not classifiable. The median testosterone concentration at baseline was 440 ng/dL." }

The major efficacy outcome measure was medical castration rate, defined as achieving and maintaining serum testosterone suppression to ≤ 50 ng/dL by Week 4 through Week 48 of treatment. Following the first injection of CAMCEVI, serum testosterone levels were suppressed to ≤ 50 ng/dL by Week 4 (+/-7 days) in 98.5% of the patients; and from Week 4 through Week 48 in 97.0% of patients (95% CI: 92.2-98.9) estimated using the Kaplan-Meier method. The time course of percent change from baseline in testosterone suppression are shown in Figure 1. The percentage of patients with testosterone suppression to ≤ 20 ng/dL was 69.3% on Day 28.

{ "type": "p", "children": [], "text": "The major efficacy outcome measure was medical castration rate, defined as achieving and maintaining serum testosterone suppression to ≤ 50 ng/dL by Week 4 through Week 48 of treatment. Following the first injection of CAMCEVI, serum testosterone levels were suppressed to ≤ 50 ng/dL by Week 4 (+/-7 days) in 98.5% of the patients; and from Week 4 through Week 48 in 97.0% of patients (95% CI: 92.2-98.9) estimated using the Kaplan-Meier method. The time course of percent change from baseline in testosterone suppression are shown in Figure 1. The percentage of patients with testosterone suppression to ≤ 20 ng/dL was 69.3% on Day 28." }

Figure 1 CAMCEVI Mean (95% CI) Percentage Change from Baseline in Serum Testosterone Concentration Over Time (N =137)

{ "type": "p", "children": [], "text": "\nFigure 1 CAMCEVI Mean (95% CI) Percentage Change from Baseline in Serum Testosterone Concentration Over Time (N =137)\n" }

In the clinical trial, PSA levels were monitored and were lowered on average by 51% after 4 weeks after administration of CAMCEVI, 83% after 3 months and remained suppressed throughout the 48 weeks of treatment. These PSA results should be interpreted with caution because of the heterogeneity of the patient population studied. No evidence has shown that the rapidity of PSA decline correlates with clinical benefit.

{ "type": "p", "children": [], "text": "In the clinical trial, PSA levels were monitored and were lowered on average by 51% after 4 weeks after administration of CAMCEVI, 83% after 3 months and remained suppressed throughout the 48 weeks of treatment. These PSA results should be interpreted with caution because of the heterogeneity of the patient population studied. No evidence has shown that the rapidity of PSA decline correlates with clinical benefit." }

CAMCEVI is a sterile, off-white to pale yellow, viscous and opalescent injectable emulsion supplied in a kit as a single-dose, pre-filled syringe. CAMCEVI is available as follows:

{ "type": "p", "children": [], "text": "CAMCEVI is a sterile, off-white to pale yellow, viscous and opalescent injectable emulsion supplied in a kit as a single-dose, pre-filled syringe. CAMCEVI is available as follows:" }

<div class="scrollingtable"><table cellpadding="0" cellspacing="0" width="60%"> <col width="500px"/> <col width="450px"/> <tbody class="Headless"> <tr class="First"> <td class="Lrule Toprule"> <p class="First">Kit Contents</p> </td><td class="Lrule Rrule Toprule"> <p class="First">NDC</p> </td> </tr> <tr class="Last"> <td class="Lrule Toprule"> <p class="First">Injectable emulsion in a pre-filled syringe containing 42 mg leuprolide for subcutaneous injection, a sterile 18-gauge SurGuard <span class="Sup">®</span>3 safety needle, and Prescribing Information. </p> </td><td class="Lrule Rrule Toprule" valign="top"> <p class="First">69448-023-63</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"0\" cellspacing=\"0\" width=\"60%\">\n<col width=\"500px\"/>\n<col width=\"450px\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Lrule Toprule\">\n<p class=\"First\">Kit Contents</p>\n</td><td class=\"Lrule Rrule Toprule\">\n<p class=\"First\">NDC</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Toprule\">\n<p class=\"First\">Injectable emulsion in a pre-filled syringe containing 42 mg leuprolide for subcutaneous injection, a sterile 18-gauge SurGuard\n \n <span class=\"Sup\">®</span>3 safety needle, and Prescribing Information.\n \n </p>\n</td><td class=\"Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">69448-023-63</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Store CAMCEVI at 2°C–8°C (36°F–46°F). Protect CAMCEVI from light by storing in the original package until time of use. Do not freeze or shake.

{ "type": "p", "children": [], "text": "Store CAMCEVI at 2°C–8°C (36°F–46°F). Protect CAMCEVI from light by storing in the original package until time of use. Do not freeze or shake." }

The rubber used in syringe tip cap and plunger stopper is not made of natural rubber latex.

{ "type": "p", "children": [], "text": "The rubber used in syringe tip cap and plunger stopper is not made of natural rubber latex." }

Hypersensitivity

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

{ "type": "ul", "children": [ "Inform patients that if they have experienced hypersensitivity with other GnRH agonist drugs like CAMCEVI, CAMCEVI is contraindicated\n \n [see Contraindications (\n \n 4)].\n \n \n" ], "text": "" }

Tumor Flare

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

{ "type": "ul", "children": [ "Inform patients that CAMCEVI can cause tumor flare during the first weeks of treatment. Inform patients that the increase in testosterone can cause an increase in urinary symptoms or pain. Advise patients to contact their healthcare provider if uretral obstruction, spinal cord compression, paralysis, or new or worsened symptoms occur after beginning CAMCEVI treatment\n \n [see Warnings and Precautions (\n \n 5.1)]\n \n .\n \n " ], "text": "" }

Hyperglycemia and Diabetes

{ "type": "p", "children": [], "text": "\nHyperglycemia and Diabetes\n" }

{ "type": "ul", "children": [ "Advise patients that there is an increased risk of hyperglycemia and diabetes with CAMCEVI therapy. Inform patients that periodic monitoring for hyperglycemia and diabetes is required when being treated with CAMCEVI\n \n [see Warnings and Precautions (\n \n 5.2)]\n \n .\n \n " ], "text": "" }

Cardiovascular Diseases

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

{ "type": "ul", "children": [ "Inform patients that there is an increased risk of myocardial infarction, sudden cardiac death, and stroke with CAMCEVI treatment. Advise patients to immediately report signs and symptoms associated with these events to their healthcare provider for evaluation\n \n [see Warnings and Precautions (\n \n 5.3)].\n \n \n" ], "text": "" }

QT/QTc Prolongation

{ "type": "p", "children": [], "text": "\nQT/QTc Prolongation\n" }

{ "type": "ul", "children": [ "Inform patients that CAMCEVI can cause QT/QTc prolongation. Advise patients to immediately contact their healthcare provider in the event of syncope, presyncopal symptoms, or cardiac palpitations\n \n [see Warnings and Precautions (\n \n 5.4)].\n \n \n" ], "text": "" }

Convulsions

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

{ "type": "ul", "children": [ "Inform patients that there is an increased risk of convulsions with CAMCEVI treatment. Advise patients to immediately contact their healthcare provider if they experience convulsions\n \n [see Warnings and Precautions (\n \n 5.5)].\n \n \n" ], "text": "" }

Injection Site Reactions

{ "type": "p", "children": [], "text": "\nInjection Site Reactions\n" }

{ "type": "ul", "children": [ "Inform patients that injection site related adverse reactions may occur such as transient burning/stinging, pain, bruising, and redness. Advise patients to contact their healthcare provider if they experience rash or severe injection site reactions\n \n [see Adverse Reactions (\n \n 6.1)].\n \n \n" ], "text": "" }

Urogenital Disorders

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

{ "type": "ul", "children": [ "Advise patients that CAMCEVI may cause impotence." ], "text": "" }

Infertility

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

{ "type": "ul", "children": [ "Inform patients that CAMCEVI may cause infertility\n \n [see Use In Specific Populations (\n \n 8.3)].\n \n \n" ], "text": "" }

Manufactured for: Accord BioPharma Inc. 8041 Arco Corporate Drive, Suite 200 Raleigh, NC 27617, USA

{ "type": "p", "children": [], "text": "Manufactured for: \n Accord BioPharma Inc. \n 8041 Arco Corporate Drive, Suite 200 \n Raleigh, NC 27617, USA\n " }

By: Fareva Pau Fareva Pau 1, Avenue du Bearn, IDRON, 64320, France

{ "type": "p", "children": [], "text": "By: \n Fareva Pau \n Fareva Pau 1, Avenue du Bearn, IDRON, 64320, France \n \n" }

ELIGARD is indicated for the treatment of advanced prostate cancer.

{ "type": "p", "children": [], "text": "ELIGARD is indicated for the treatment of advanced prostate cancer. " }

ELIGARD is administered subcutaneously and provides continuous release of leuprolide acetate over a one-, three-, four-, or six-month treatment period (Table 1). ELIGARD must be administered by a healthcare provider. The injection delivers the dose of leuprolide acetate incorporated in a polymer formulation.

Table 1. ELIGARD Recommended Dosing

<div class="scrollingtable"><table width="55%"> <col/> <col width="90px"/> <col width="106px"/> <col width="106px"/> <col width="106px"/> <tbody class="Headless"> <tr class="First"> <td class="Toprule"> <p class="First"> <span class="Bold">Dosage</span> </p> </td><td class="Lrule Toprule"> <p class="First"> <span class="Bold">7.5 mg</span> </p> </td><td class="Lrule Toprule"> <p class="First"> <span class="Bold">22.5 mg</span> </p> </td><td class="Lrule Toprule"> <p class="First"> <span class="Bold">30 mg</span> </p> </td><td class="Lrule Toprule"><span class="Bold">45 mg</span></td> </tr> <tr class="Last"> <td class="Botrule Toprule"> <p class="First"> <span class="Bold">Recommended dose</span> </p> </td><td class="Botrule Lrule Toprule"> <p class="First">1 injection every<br/> month</p> </td><td class="Botrule Lrule Toprule"> <p class="First">1 injection every<br/> 3 months</p> </td><td class="Botrule Lrule Toprule"> <p class="First">1 injection every<br/> 4 months</p> </td><td class="Botrule Lrule Toprule">1 injection every<br/> 6 months</td> </tr> </tbody> </table></div>

As with other drugs administered by subcutaneous injection, the injection site should vary periodically.  The specific injection location should be an area with sufficient soft or loose subcutaneous tissue.  In clinical trials, the injections were administered in the upper- or mid-abdominal area.  Avoid areas with brawny or fibrous subcutaneous tissue or locations that could be rubbed or compressed (i.e., with a belt or clothing waistband).

In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of metastatic castration-resistant prostate cancer.

Use aseptic technique throughout the procedure.  As with other similar agents, the use of gloves is recommended during mixing and administration.  Allow the product to reach room temperature before mixing.  Once mixed, the product must be administered within 30 minutes or it should be discarded.

ELIGARD is packaged in a carton containing:

Follow the detailed instructions below to ensure correct preparation of ELIGARD prior to administration:

<div class="scrollingtable"><table> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Step 1</span> </p> On a clean field open the tray by tearing off the foil from the corner and remove the contents. Discard the desiccant pack. Remove the pre-connected syringe system from the tray. Open the sterile safety needle package by peeling back the paper tab. <span class="Bold">Note:</span> Syringe A and Syringe B should not be lined-up yet. The product should only be administered with the co-packaged, sterile safety needle.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <img alt="mixing" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-1.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <span class="Bold">Step 2</span> <p class="First">Grasp the latching button on the coupling device with your finger and thumb and press until you hear a snapping sound. The two syringes will be aligned.<br/> <br/> </p> Do not bend the pre-connected syringe system.</td><td class="Botrule Lrule Rrule Toprule"><img alt="step2" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-2.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">  <p class="First"> <span class="Bold">Step 3</span> </p> <p>Holding the syringes in a horizontal position, transfer the liquid contents of Syringe A into the leuprolide acetate powder contained in Syringe B. <span class="Bold">Thoroughly mix the product for 60 cycles by pushing the contents back and forth between both syringes to obtain a uniform suspension.</span> </p> <ul class="Disk"> <li> <span class="Bold">A cycle is one push of the Syringe A plunger and one push of the Syringe B plunger.</span> </li> <li>When thoroughly mixed, the suspension will appear light tan to tan (ELIGARD 7.5 mg) or colorless to pale yellow (ELIGARD 22.5 mg, 30 mg, and 45 mg).</li> </ul> <span class="Bold">Note: </span>Product must be mixed as described; shaking will NOT provide adequate mixing. Do not bend.</td><td class="Botrule Lrule Rrule Toprule"> <img alt="step3" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-3.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">  <p class="First"> <span class="Bold">Step 4</span> </p> After mixing, hold the syringes vertically (upright) with Syringe B (wide syringe) on the bottom. The syringes should remain securely coupled. Transfer all of the mixed product into Syringe B by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger.</td><td class="Botrule Lrule Rrule Toprule"> <img alt="step4" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-4.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">  <p class="First"> <span class="Bold">Step 5</span> </p> <p>While ensuring the Syringe A plunger is fully pushed down, hold the coupling device and unscrew Syringe B. This will disconnect Syringe B from the coupling device. Syringe A will remain attached to the coupling device.</p> <p> <span class="Bold">Note:</span> Small air bubbles will remain in the formulation – this is acceptable.</p> <span class="Bold">Do not purge the air bubbles from Syringe B as product may be lost!</span></td><td class="Botrule Lrule Rrule Toprule"> <img alt="step5" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-5.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">  <p class="First"> <span class="Bold">Step 6</span> </p> <p>Continue to hold Syringe B upright with the open end at the top. Hold back the white plunger on Syringe B to prevent loss of the product, and attach the safety needle and cap (the safety needle is located under the tray). Gently screw clockwise with approximately a three-quarter turn until the safety needle and cap are secure.</p> <p> <span class="Bold">Do not overtighten, as the needle hub may become damaged which could result in leakage of the product during injection. </span>The safety shield may also be damaged if the safety needle and cap are screwed with too much force.</p> </td><td class="Botrule Lrule Rrule Toprule"> <img alt="step6" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-6.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">  <p class="First"> <span class="Bold">Step 7</span> </p> <p>Move the safety shield away from the needle and towards the syringe.</p> <p>Pull off the cap immediately prior to administration.</p> </td><td class="Botrule Lrule Rrule Toprule"> <img alt="step7" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-7.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> </tbody> </table></div>

Note: Should the needle hub appear to be damaged, or leak, the product should NOT be used. The damaged safety needle and cap should NOT be replaced and the product should NOT be injected. In the event of damage to the needle hub, use a new replacement ELIGARD carton.

<div class="scrollingtable"><table> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">1. Select an injection site on the abdomen, upper buttocks, or another location with adequate amounts of subcutaneous tissue that does not have excessive pigment, nodules, lesions, or hair and hasn’t recently been used.</p> <p>2. Cleanse the injection-site area with an alcohol swab (not enclosed).</p> <p>3. Using the thumb and forefinger, grab and bunch the area of skin around the injection site.</p> </td><td class="Botrule Lrule Rrule Toprule"><img alt="admin1" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-8.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">4. Using your dominant hand, insert the needle quickly at a 90° angle to the skin surface. The depth of penetration will depend on the amount and fullness of the subcutaneous tissue and the length of the needle. After the needle is inserted, release the skin. <p class="First">5. Inject the drug using a slow, steady push and press down on the plunger until the syringe is empty.</p> <p> <span class="Bold">Make sure all the drug has been injected before removing the needle.</span> </p> <p>6. Withdraw the needle quickly at the same 90° angle used for insertion.</p> </td><td class="Botrule Lrule Rrule Toprule"> <img alt="admin" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-9.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> 7. Immediately following the withdrawal of the needle, activate the safety shield using a finger/thumb or flat surface and push until it completely covers the needle tip and locks into place.</p> <p>8. An audible and tactile “click” verifies a locked position.</p> <p>9. Check to confirm the safety shield is fully engaged. Discard all components safely in an appropriate biohazard container.</p> </td><td class="Botrule Lrule Rrule Toprule"> <img alt="admin" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-10.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> </tbody> </table></div>

ELIGARD is an injectable suspension of leuprolide acetate available in a pre-connected syringe system and packaged with a sterile safety needle and cap (Table 2), a desiccant, prescribing information and instructions for use. The pre-connected syringe system consists of syringe A and syringe B connected using a coupling device.  Syringe A contains the in situ polymeric extended release technology and the syringe B contains leuprolide acetate powder. When reconstituted, ELIGARD is administered as a single dose. Refer to Table 10 for details of the description of the dosage form before and after mixing [see How Supplied/Storage and Handling (16)].

{ "type": "p", "children": [], "text": "ELIGARD is an injectable suspension of leuprolide acetate available in a pre-connected syringe system and packaged with a sterile safety needle and cap (Table 2), a desiccant, prescribing information and instructions for use. The pre-connected syringe system consists of syringe A and syringe B connected using a coupling device.  Syringe A contains the in situ polymeric extended release technology and the syringe B contains leuprolide acetate powder. When reconstituted, ELIGARD is administered as a single dose. Refer to Table 10 for details of the description of the dosage form before and after mixing [see How Supplied/Storage and Handling (16)]." }

Table 2. Specifications for ELIGARD Sterile Safety Needle and Cap

{ "type": "p", "children": [], "text": "\nTable 2. Specifications for ELIGARD Sterile Safety Needle and Cap\n" }

<div class="scrollingtable"><table width="40%"> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Toprule"><span class="Bold">ELIGARD strength</span> </td><td class="Lrule Toprule"><span class="Bold">Gauge</span> </td><td class="Lrule Toprule"><span class="Bold">Length</span> </td> </tr> <tr> <td class="Botrule Toprule"> <span class="Bold">7.5 mg</span></td><td class="Botrule Lrule Toprule">20-gauge</td><td class="Botrule Lrule Toprule">5/8-inch</td> </tr> <tr> <td class="Botrule Toprule"> <span class="Bold">22.5 mg</span></td><td class="Botrule Lrule Toprule">20-gauge</td><td class="Botrule Lrule Toprule">5/8-inch</td> </tr> <tr> <td class="Botrule Toprule"> <span class="Bold">30 mg</span></td><td class="Botrule Lrule Toprule">20-gauge</td><td class="Botrule Lrule Toprule">5/8-inch</td> </tr> <tr class="Last"> <td class="Botrule Toprule"> <span class="Bold">45 mg</span></td><td class="Botrule Lrule Toprule">18-gauge</td><td class="Botrule Lrule Toprule">5/8-inch</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"40%\">\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Toprule\"><span class=\"Bold\">ELIGARD strength</span> </td><td class=\"Lrule Toprule\"><span class=\"Bold\">Gauge</span> </td><td class=\"Lrule Toprule\"><span class=\"Bold\">Length</span> </td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\"> <span class=\"Bold\">7.5 mg</span></td><td class=\"Botrule Lrule Toprule\">20-gauge</td><td class=\"Botrule Lrule Toprule\">5/8-inch</td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\"> <span class=\"Bold\">22.5 mg</span></td><td class=\"Botrule Lrule Toprule\">20-gauge</td><td class=\"Botrule Lrule Toprule\">5/8-inch</td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\"> <span class=\"Bold\">30 mg</span></td><td class=\"Botrule Lrule Toprule\">20-gauge</td><td class=\"Botrule Lrule Toprule\">5/8-inch</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Toprule\"> <span class=\"Bold\">45 mg</span></td><td class=\"Botrule Lrule Toprule\">18-gauge</td><td class=\"Botrule Lrule Toprule\">5/8-inch</td>\n</tr>\n</tbody>\n</table></div>" }

Hypersensitivity

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

ELIGARD is contraindicated in patients with hypersensitivity to GnRH, GnRH agonist analogs or any of the components of ELIGARD. Anaphylactic reactions to synthetic GnRH or GnRH agonist analogs have been reported in the literature.

{ "type": "p", "children": [], "text": "ELIGARD is contraindicated in patients with hypersensitivity to GnRH, GnRH agonist analogs or any of the components of ELIGARD. Anaphylactic reactions to synthetic GnRH or GnRH agonist analogs have been reported in the literature." }

ELIGARD 7.5 mg, 22.5 mg, and 30 mg like other GnRH agonists, causes a transient increase in serum concentrations of testosterone during the first week of treatment. ELIGARD 45 mg causes a transient increase in serum concentrations of testosterone during the first two weeks of treatment. Patients may experience worsening of symptoms or onset of new signs and symptoms during the first few weeks of treatment, including bone pain, neuropathy, hematuria, or bladder outlet obstruction. 

Cases of ureteral obstruction and/or spinal cord compression, which may contribute to paralysis with or without fatal complications, have been observed in the treatment of advanced prostate cancer using GnRH agonists.

Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy. If spinal cord compression or ureteral obstruction develops, standard treatment of these complications should be instituted.

Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

Postmarketing reports of convulsions have been observed in patients on leuprolide acetate therapy. These included patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications that have been associated with convulsions such as bupropion and SSRIs. Convulsions have also been reported in patients in the absence of any of the conditions mentioned above. Patients receiving a GnRH agonist who experience convulsion should be managed according to current clinical practice.

Severe cutaneous adverse reactions (SCARs), including Steve-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and erythema multiforme, occurred in patients receiving ELIGARD [see Adverse Reactions (6.2)].

Monitor patients for the development of SCARs. Advise patients of the signs and symptoms of SCARs (e.g., a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy).

If a SCAR is suspected, interrupt ELIGARD until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, or for other grade 4 skin reactions, permanently discontinue ELIGARD.

Monitor ELIGARD response by periodic measurement of serum concentrations of testosterone and prostate specific antigen.

In the majority of patients, testosterone levels increased above Baseline during the first week, declining thereafter to Baseline levels or below by the end of the second or third week.  Castrate levels were generally reached within two to four weeks.

Castrate testosterone levels were maintained for the duration of the treatment with ELIGARD 7.5 mg.  No increases to above the castrate level occurred in any of the patients.

Castrate levels were generally maintained for the duration of treatment with ELIGARD 22.5 mg.

Once castrate levels were achieved with ELIGARD 30 mg, most (86/89) patients remained suppressed throughout the study.

Once castrate levels were achieved with ELIGARD 45 mg, one patient (< 1%) experienced a breakthrough, with testosterone levels > 50 ng/dL.

Results of testosterone determinations are dependent on assay methodology.  It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.

Drug/Laboratory Test Interactions:  Therapy with ELIGARD results in suppression of the pituitary-gonadal system.  Results of diagnostic tests of pituitary gonadotropic and gonadal functions conducted during and after ELIGARD therapy may be affected.

Based on findings in animal studies and mechanism of action, ELIGARD may cause fetal harm when administered to a pregnant woman. In animal developmental and reproductive studies, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation in rats. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1)].

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

The safety of all ELIGARD formulations was evaluated in clinical trials involving patients with advanced prostate cancer.  In addition, the safety of ELIGARD 7.5 mg was evaluated in 8 surgically castrated males (Table 4).  ELIGARD, like other GnRH analogs, caused a transient increase in serum testosterone concentrations during the first one to two weeks of treatment. 

Therefore, potential exacerbations of signs and symptoms of the disease during the first weeks of treatment are of concern in patients with vertebral metastases and/or urinary obstruction or hematuria.  If these conditions are aggravated, it may lead to neurological problems such as weakness and/or paresthesia of the lower limbs or worsening of urinary symptoms [see Warnings and Precautions (5.7)].

During the clinical trials, injection sites were closely monitored.  Refer to Table 3 for a summary of reported injection site adverse reactions.

Table 3. Reported Injection Site Adverse Reactions

<div class="scrollingtable"><table width="100%"> <col width="1px"/> <col width="1px"/> <col width="1px"/> <col width="1px"/> <col width="1px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">ELIGARD</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">7.5 mg </span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">22.5 mg </span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">30 mg </span> </p> </td><td class="Botrule Rrule Toprule"> <span class="Bold">45 mg</span></td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Study number</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">AGL9904</p> </td><td class="Botrule Rrule Toprule"> <p class="First">AGL9909</p> </td><td class="Botrule Rrule Toprule"> <p class="First">AGL0001</p> </td><td class="Botrule Rrule Toprule"> AGL0205</td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Number of patients</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">120</p> </td><td class="Botrule Rrule Toprule"> <p class="First">117       </p> </td><td class="Botrule Rrule Toprule"> <p class="First">90</p> </td><td class="Botrule Rrule Toprule"> 111</td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Treatment</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">1 injection every month up to 6 months                   </p> </td><td class="Botrule Rrule Toprule"> <p class="First">1 injection every 3 months up to 6 months</p> </td><td class="Botrule Rrule Toprule"> <p class="First">1 injection every 4 months up to 8 months</p> </td><td class="Botrule Rrule Toprule">1 injection every 6 months up to 12 months</td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Number of injections</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">716</p> </td><td class="Botrule Rrule Toprule"> <p class="First">230</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">175</p> </td><td class="Botrule Lrule Rrule Toprule">217</td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Transient burning/<br/> stinging</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">248 (34.6%) injections; 84% reported as mild</p> </td><td class="Botrule Rrule Toprule"> <p class="First">50 (21.7%) injections; 86% reported as mild</p> </td><td class="Botrule Rrule Toprule"> <p class="First">35 (20%) injections; 100% reported as mild3</p> </td><td class="Botrule Rrule Toprule">35 (16%) injections; 91.4% reported as mild</td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Pain (generally brief and mild)</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">4.3% of injections (18.3% of patients)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">3.5% of injections<br/> (6.0% of patients)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">2.3% of injections2<br/> (3.3% of patients)</p> </td><td class="Botrule Rrule Toprule">  <p class="First">4.6% of injections<span class="Sup">4</span> </p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"><span class="Bold">Erythema (generally brief and mild)</span></td><td class="Botrule Rrule Toprule">2.6% of injections (12.5% of patients) </td><td class="Botrule Rrule Toprule">0.9% of injections<span class="Sup">1 </span> <br/> (1.7% of patients)</td><td class="Botrule Rrule Toprule">1.1% of injections <br/> (2.2% of patients)</td><td class="Botrule Rrule Toprule"> -</td> </tr> <tr> <td class="Botrule Rrule Toprule"><span class="Bold">Bruising (mild)</span></td><td class="Botrule Rrule Toprule">2.5% of injections (11.7% of patients)</td><td class="Botrule Rrule Toprule">1.7% of injections<br/> (3.4% of patients)</td><td class="Botrule Rrule Toprule"> -</td><td class="Botrule Rrule Toprule">  <p class="First">2.3% of injections<span class="Sup">5</span> </p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"><span class="Bold">Pruritus</span></td><td class="Botrule Rrule Toprule">1.4% of injections (9.2% of patients)</td><td class="Botrule Rrule Toprule">0.4% of injections <br/> (0.9% of patients)</td><td class="Botrule Rrule Toprule"> -</td><td class="Botrule Rrule Toprule"> -</td> </tr> <tr> <td class="Botrule Rrule Toprule"><span class="Bold">Induration</span></td><td class="Botrule Rrule Toprule">0.4% of injections (2.5% of patients)</td><td class="Botrule Rrule Toprule"> -</td><td class="Botrule Rrule Toprule"> -</td><td class="Botrule Rrule Toprule"> -</td> </tr> <tr> <td class="Botrule Rrule Toprule"><span class="Bold">Ulceration</span></td><td class="Botrule Rrule Toprule">0.1% of injections<br/> (&gt; 0.8% of patients)</td><td class="Botrule Rrule Toprule"> -</td><td class="Botrule Rrule Toprule"> -</td><td class="Botrule Rrule Toprule"> -</td> </tr> <tr class="Last"> <td class="Botrule Toprule" colspan="5"> <ol class="Arabic"> <li>Erythema was reported following 2 injections of ELIGARD 22.5 mg. One report characterized the erythema as mild and it resolved within 7 days. The other report characterized the erythema as moderate and it resolved within 15 days. Neither patient experienced erythema at multiple injection times.</li> <li>A single reaction reported as moderate pain resolved within two minutes and all 3 mild pain reactions resolved within several days following injection of ELIGARD 30 mg.</li> <li>Following injection of ELIGARD 30 mg, three of the 35 burning/stinging reactions were reported as moderate.</li> <li>Transient pain was reported as mild in intensity in nine of ten (90%) events and moderate in intensity in one of ten (10%) events following injection of ELIGARD 45 mg.</li> <li>Mild bruising was reported following 5 (2.3%) study injections and moderate bruising was reported following 2 (&lt;1%) study injections of ELIGARD 45 mg.</li> </ol> </td> </tr> </tbody> </table></div>

These localized adverse reactions were non-recurrent over time.  No patient discontinued therapy due to an injection site adverse reaction.

The following possibly or probably related systemic adverse reactions occurred during clinical trials with ELIGARD, and were reported in > 2% of patients (Table 4).  Reactions considered not drug-related are excluded.

Table 4. Summary of Possible or Probably Related Systemic Adverse Reactions Reported by > 2% of Patients Treated with ELIGARD

<div class="scrollingtable"><table> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">ELIGARD</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">7.5 mg</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">7.5 mg </span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">22.5 mg </span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">30 mg </span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <span class="Bold">45 mg</span></td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">Study number</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">AGL9904</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">AGL9802</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">AGL9909</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">AGL0001</p> </td><td class="Botrule Lrule Rrule Toprule">AGL0205</td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">Number of patients</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">120                                             </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">8                                                   </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">117                                                  </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">90</p> </td><td class="Botrule Lrule Rrule Toprule">111</td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="4"> <p class="First"> <span class="Bold">Treatment</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 injection <br/> every month <br/> up to 6 months</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 injection<br/> (surgically castrated<br/> patients)          </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 injection every 3 months up to 6 months</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 injection<br/> every 4 months up <br/> to 8 months</p> </td><td class="Botrule Lrule Rrule Toprule">1 injection every 6 months up to 12 months</td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"><span class="Bold">Body system</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Adverse Reaction</span></td><td align="center" class="Botrule Lrule Toprule" colspan="4"> <span class="Bold">Number (percent)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> </td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"><span class="Bold">Body as a whole</span></td><td class="Botrule Lrule Rrule Toprule">Malaise and fatigue</td><td class="Botrule Lrule Rrule Toprule">21 (17.5%)   </td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule"> 7 (6.0%)</td><td align="center" class="Botrule Lrule Rrule Toprule">12 (13.3%)</td><td align="center" class="Botrule Lrule Rrule Toprule">13 (11.7%) </td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"> </td><td class="Botrule Lrule Rrule Toprule"> Weakness</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">- </td><td align="center" class="Botrule Lrule Rrule Toprule">- </td><td align="center" class="Botrule Lrule Rrule Toprule">4 (3.6%)  </td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"><span class="Bold">Nervous system</span></td><td class="Botrule Lrule Rrule Toprule">Dizziness</td><td class="Botrule Lrule Rrule Toprule">4 (3.3%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (4.4%) </td><td align="center" class="Botrule Lrule Rrule Toprule"> - </td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"><span class="Bold">Vascular</span></td><td class="Botrule Lrule Rrule Toprule">Hot flashes/sweats</td><td class="Botrule Lrule Rrule Toprule">68 (56.7%)<span class="Sup">*</span></td><td align="center" class="Botrule Lrule Rrule Toprule">2 (25.0%)*</td><td align="center" class="Botrule Lrule Rrule Toprule">66 (56.4%)<span class="Sup">*</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First">66 (73.3%)<span class="Sup">*</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule">64 (57.7%)*</td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3" rowspan="2"><span class="Bold">Renal/urinary</span> <br/>  </td><td class="Botrule Lrule Rrule Toprule">Urinary frequency</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (2.6%) </td><td align="center" class="Botrule Lrule Rrule Toprule">2 (2.2%) </td><td align="center" class="Botrule Lrule Rrule Toprule">- </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Nocturia</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (2.2%) </td><td align="center" class="Botrule Lrule Rrule Toprule">- </td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3" rowspan="2"><span class="Bold">Gastrointestinal</span></td><td class="Botrule Lrule Rrule Toprule">Nausea</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (3.4%) </td><td align="center" class="Botrule Lrule Rrule Toprule">2 (2.2%) </td><td align="center" class="Botrule Lrule Rrule Toprule">- </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Gastroenteritis/colitis</td><td class="Botrule Lrule Rrule Toprule">3 (2.5%)</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-<br/> </td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3" rowspan="4"><span class="Bold">Skin </span></td><td class="Botrule Lrule Rrule Toprule">Pruritus</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (2.6%)</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">- </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Clamminess</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (4.4%)<span class="Sup">*</span></td><td align="center" class="Botrule Lrule Rrule Toprule">- </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Night sweats</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (3.3%)<span class="Sup">*</span></td><td align="center" class="Botrule Lrule Rrule Toprule"> 3 (2.7%)<span class="Sup">*</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Alopecia</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (2.2%) </td><td align="center" class="Botrule Lrule Rrule Toprule">- </td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3" rowspan="3"> <span class="Bold">Musculoskeletal</span></td><td class="Botrule Lrule Rrule Toprule">Arthralgia</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">4 (3.4%)  </td><td align="center" class="Botrule Lrule Rrule Toprule">- </td><td align="center" class="Botrule Lrule Rrule Toprule">- </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Myalgia</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (2.2%) </td><td align="center" class="Botrule Lrule Rrule Toprule">5 (4.5%) </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Pain in limb</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">- </td><td align="center" class="Botrule Lrule Rrule Toprule">- </td><td align="center" class="Botrule Lrule Rrule Toprule">3 (2.7%) </td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3" rowspan="3"> <span class="Bold">Reproductive</span></td><td class="Botrule Lrule Rrule Toprule">Testicular atrophy</td><td class="Botrule Lrule Rrule Toprule">6 (5.0%)*</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center">4 (4.4%)*</td><td align="center" class="Rrule">8 (7.2%)<span class="Sup">*</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Gynecomastia</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Botrule Lrule Rrule Toprule">-</td><td align="center" class="Lrule Rrule Toprule">2 (2.2%)* </td><td align="center" class="Lrule Rrule Toprule"> 4 (3.6%)<span class="Sup">*</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Testicular pain </td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">- </td><td align="center" class="Botrule Lrule Rrule Toprule">2 (2.2%) </td><td align="center" class="Botrule Lrule Rrule Toprule">-</td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"> <span class="Bold">Psychiatric</span></td><td class="Botrule Lrule Rrule Toprule">Decreased libido</td><td class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule"> -</td><td align="center" class="Botrule Lrule Rrule Toprule">- </td><td align="center" class="Botrule Lrule Rrule Toprule">3 (3.3%)<span class="Sup">*</span></td><td align="center" class="Botrule Lrule Rrule Toprule">- </td> </tr> <tr> <td colspan="8"> </td><td> </td> </tr> <tr class="Last"> <td colspan="9"> <p class="First">*Expected pharmacological consequences of testosterone suppression.</p> <p>In the patient populations studied with ELIGARD 7.5 mg, a total of 86 hot flashes/sweats adverse reactions were reported in 70 patients. Of these, 71 reactions (83%) were mild; 14 (16%) were moderate; 1 (1%) was severe. <br/> In the patient population studied with ELIGARD 22.5 mg, a total of 84 hot flashes/sweats adverse reactions were reported in 66 patients. Of these, 73 reactions (87%) were mild; 11 (13%) were moderate; none were severe. <br/> In the patient population studied with ELIGARD 30 mg, a total of 75 hot flash adverse reactions were reported in 66 patients. Of these, 57 reactions (76%) were mild; 16 (21%) were moderate; 2 (3%) were severe.<br/> In the patient population studied with ELIGARD 45 mg, a total of 89 hot flash adverse reactions were reported in 64 patients.  Of these, 62 reactions (70%) were mild; 27 (30%) were moderate; none were severe.</p> </td> </tr> </tbody> </table></div>

In addition, the following possibly or probably related systemic adverse reactions were reported by < 2% of the patients treated with ELIGARD in these clinical studies.

<div class="scrollingtable"><table width="100%"> <col width="1px"/> <col width="1px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Body system</span> </p> </td><td class="Botrule Toprule"> <p class="First"> <span class="Bold">Adverse Reactions</span> </p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">General</p> </td><td class="Botrule Toprule"> <p class="First">Sweating, insomnia, syncope, rigors, weakness, lethargy</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Gastrointestinal</p> </td><td class="Botrule Toprule"> <p class="First">Flatulence, constipation, dyspepsia</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Hematologic</p> </td><td class="Botrule Toprule"> <p class="First">Decreased red blood cell count, hematocrit and hemoglobin</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Metabolic</p> </td><td class="Botrule Toprule"> <p class="First">Weight gain</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Musculoskeletal</p> </td><td class="Botrule Toprule"> <p class="First">Tremor, backache, joint pain, muscle atrophy, limb pain</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Nervous</p> </td><td class="Botrule Toprule"> <p class="First">Disturbance of smell and taste, depression, vertigo</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Psychiatric</p> </td><td class="Botrule Toprule"> <p class="First">Insomnia, depression, loss of libido*</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Renal/urinary</p> </td><td class="Botrule Toprule"> <p class="First">Difficulties with urination, pain on urination, scanty urination, bladder spasm, blood in urine, urinary retention, urinary urgency, incontinence, nocturia, nocturia aggravated</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Reproductive/<br/> Urogenital</p> </td><td class="Botrule Toprule"> <p class="First">Testicular soreness/pain, impotence*, decreased libido*, gynecomastia*, breast soreness/tenderness*, testicular atrophy*, erectile dysfunction, penile disorder*, reduced penis size</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Skin</p> </td><td class="Botrule Toprule"> <p class="First">Alopecia, clamminess, night sweats*, sweating increased*</p> </td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Vascular</p> </td><td class="Botrule Toprule"> <p class="First">Hypertension, hypotension</p> </td> </tr> <tr class="Last"> <td class="Botrule Toprule" colspan="2"> <p class="First">* Expected pharmacological consequences of testosterone suppression.</p> </td> </tr> </tbody> </table></div>

Changes in Bone Density:  Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist analog.  It can be anticipated that long periods of medical castration in men will have effects on bone density.

The following adverse reactions have been identified during post-approval use of ELIGARD. 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.

Pituitary apoplexy- During postmarketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

Nervous System- Convulsions

Respiratory System- Interstitial lung disease

Skin reactions- Erythema multiforme, SJS/TEN

Risk Summary Based on findings in animal studies and mechanism of action, ELIGARD may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data in pregnant women to inform the drug-associated risk. Expected hormonal changes that occur with ELIGARD treatment increase the risk for pregnancy loss. In animal developmental and reproductive studies, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation in rats. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus (see Data).

Data

Animal Data In animal developmental and reproductive studies, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation.  There were increased fetal mortality and decreased fetal weights in rats and rabbits.  The effects of fetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug.

The safety and efficacy of ELIGARD have not been established in females. There is no information regarding the presence of ELIGARD in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in a breastfed child from ELIGARD, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Infertility Males Based on mechanism of action, ELIGARD may impair fertility in males of reproductive potential [see Clinical Pharmacology (12.1)].

The safety and effectiveness of ELIGARD in pediatric patients have not been established.

The majority of the patients (approximately 70%) studied in the clinical trials were age 70 and older.  Clinical studies of ELIGARD did not include sufficient numbers of younger adult patients to determine if patients 65 years of age and older respond differently than younger adult patients.

ELIGARD is a sterile polymeric matrix formulation of leuprolide acetate, a GnRH agonist, for subcutaneous injection.  It is designed to deliver leuprolide acetate at a controlled rate over a one-, three-, four, or six-month therapeutic period.

{ "type": "p", "children": [], "text": "ELIGARD is a sterile polymeric matrix formulation of leuprolide acetate, a GnRH agonist, for subcutaneous injection.  It is designed to deliver leuprolide acetate at a controlled rate over a one-, three-, four, or six-month therapeutic period. " }

Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin releasing hormone (GnRH) that, when given continuously, inhibits pituitary gonadotropin secretion and suppresses testicular and ovarian steroidogenesis.  The analog possesses greater potency than the natural hormone.  The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt) with the following structural formula:

{ "type": "p", "children": [], "text": "Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin releasing hormone (GnRH) that, when given continuously, inhibits pituitary gonadotropin secretion and suppresses testicular and ovarian steroidogenesis.  The analog possesses greater potency than the natural hormone.  The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt) with the following structural formula:" }

ELIGARD is supplied as a pre-connected syringe system comprised of two prefilled syringes (syringe A and syringe B) connected using a coupling device.  Immediately prior to administration, the contents of the pre-connected syringe system are mixed until homogenous.  ELIGARD is administered subcutaneously, where it forms a solid drug delivery depot.

{ "type": "p", "children": [], "text": "ELIGARD is supplied as a pre-connected syringe system comprised of two prefilled syringes (syringe A and syringe B) connected using a coupling device.  Immediately prior to administration, the contents of the pre-connected syringe system are mixed until homogenous.  ELIGARD is administered subcutaneously, where it forms a solid drug delivery depot." }

Syringe A contains the in situ polymeric extended release technology consisting of a biodegradable poly (DL-lactide-co-glycolide) (PLGH or PLG) polymer formulation dissolved in a biocompatible solvent, N-methyl-2-pyrrolidone (NMP) and syringe B contains leuprolide acetate.

{ "type": "p", "children": [], "text": "Syringe A contains the in situ polymeric extended release technology consisting of a biodegradable poly (DL-lactide-co-glycolide) (PLGH or PLG) polymer formulation dissolved in a biocompatible solvent, N-methyl-2-pyrrolidone (NMP) and syringe B contains leuprolide acetate." }

Refer to Table 5 for the delivery system composition and reconstituted product formulation for each ELIGARD product.

{ "type": "p", "children": [], "text": "Refer to Table 5 for the delivery system composition and reconstituted product formulation for each ELIGARD product." }

Table 5.  ELIGARD Delivery System Composition and Reconstituted Product Formulation

{ "type": "p", "children": [], "text": "\nTable 5.  ELIGARD Delivery System Composition and Reconstituted Product Formulation\n" }

<div class="scrollingtable"><table> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">ELIGARD</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">7.5 mg</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">22.5 mg</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">30 mg</span> </p> </td><td class="Botrule Rrule Toprule"> <span class="Bold">45 mg</span></td> </tr> <tr> <td class="Botrule Toprule" rowspan="3"> <p class="First"> <span class="Bold">In situ polymeric extended release technology</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Polymer</p> </td><td class="Botrule Rrule Toprule"> <p class="First">PLGH</p> </td><td class="Botrule Rrule Toprule"> <p class="First">PLG</p> </td><td class="Botrule Rrule Toprule"> <p class="First">PLG</p> </td><td class="Botrule Rrule Toprule"> PLG</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Polymer description</p> </td><td class="Botrule Rrule Toprule"> <p class="First">Copolymer containing carboxyl endgroups</p> </td><td class="Botrule Rrule Toprule"> <p class="First">Copolymer with hexanediol</p> </td><td class="Botrule Rrule Toprule"> <p class="First">Copolymer with hexanediol</p> </td><td class="Botrule Rrule Toprule"> Copolymer with hexanediol</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Polymer DL-lactide to glycolide<br/> molar ratio</p> </td><td class="Botrule Rrule Toprule"> <p class="First">50:50</p> </td><td class="Botrule Rrule Toprule"> <p class="First">75:25</p> </td><td class="Botrule Rrule Toprule"> <p class="First">75:25</p> </td><td class="Botrule Rrule Toprule"> 85:15</td> </tr> <tr> <td class="Botrule Toprule" rowspan="6"> <p class="First"> <span class="Bold">Reconstituted product</span> </p> <br/> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Polymer delivered</p> </td><td class="Botrule Rrule Toprule"> <p class="First">82.5 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">158.6 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">211.5 mg</p> </td><td class="Botrule Rrule Toprule"> 165 mg</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">NMP delivered</p> </td><td class="Botrule Rrule Toprule"> <p class="First">160.0 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">193.9 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">258.5 mg</p> </td><td class="Botrule Rrule Toprule"> 165 mg</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Leuprolide acetate delivered</p> </td><td class="Botrule Rrule Toprule"> <p class="First">7.5 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">22.5 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">30 mg</p> </td><td class="Botrule Rrule Toprule"> 45 mg</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Approximate Leuprolide free<br/> base equivalent</p> </td><td class="Botrule Rrule Toprule"> <p class="First">7.0 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">21 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">28 mg</p> </td><td class="Botrule Rrule Toprule"> 42 mg</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Approximate administered formulation weight</p> </td><td class="Botrule Rrule Toprule"> <p class="First">250 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">375 mg</p> </td><td class="Botrule Rrule Toprule"> <p class="First">500 mg</p> </td><td class="Botrule Rrule Toprule"> 375 mg</td> </tr> <tr class="Last"> <td class="Botrule Lrule"> <p class="First">Approximate injection volume</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0.25 mL</p> </td><td class="Botrule Rrule Toprule"> <p class="First">0.375 mL</p> </td><td class="Botrule Rrule Toprule"> <p class="First">0.5 mL</p> </td><td class="Botrule Rrule Toprule"> 0.375 mL</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">ELIGARD</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">7.5 mg</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">22.5 mg</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">30 mg</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\"> <span class=\"Bold\">45 mg</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\" rowspan=\"3\">\n<p class=\"First\">\n<span class=\"Bold\">In situ polymeric extended release technology</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Polymer</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">PLGH</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">PLG</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">PLG</p>\n</td><td class=\"Botrule Rrule Toprule\"> PLG</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Polymer description</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">Copolymer containing carboxyl endgroups</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">Copolymer with hexanediol</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">Copolymer with hexanediol</p>\n</td><td class=\"Botrule Rrule Toprule\"> Copolymer with hexanediol</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Polymer DL-lactide to glycolide<br/>\n molar ratio</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">50:50</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">75:25</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">75:25</p>\n</td><td class=\"Botrule Rrule Toprule\"> 85:15</td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\" rowspan=\"6\">\n<p class=\"First\">\n<span class=\"Bold\">Reconstituted product</span>\n</p>\n<br/>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Polymer delivered</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">82.5 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">158.6 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">211.5 mg</p>\n</td><td class=\"Botrule Rrule Toprule\"> 165 mg</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">NMP delivered</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">160.0 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">193.9 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">258.5 mg</p>\n</td><td class=\"Botrule Rrule Toprule\"> 165 mg</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Leuprolide acetate delivered</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">7.5 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">22.5 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">30 mg</p>\n</td><td class=\"Botrule Rrule Toprule\"> 45 mg</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Approximate Leuprolide free<br/>\n base equivalent</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">7.0 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">21 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">28 mg</p>\n</td><td class=\"Botrule Rrule Toprule\"> 42 mg</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Approximate administered formulation weight</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">250 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">375 mg</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">500 mg</p>\n</td><td class=\"Botrule Rrule Toprule\"> 375 mg</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule\">\n<p class=\"First\">Approximate injection volume</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">0.25 mL</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">0.375 mL</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">0.5 mL</p>\n</td><td class=\"Botrule Rrule Toprule\"> 0.375 mL</td>\n</tr>\n</tbody>\n</table></div>" }

Leuprolide acetate, a gonadotropin releasing hormone (GnRH) agonist, acts as an inhibitor of gonadotropin secretion when given continuously in therapeutic doses.  Animal and human studies indicate that after an initial stimulation, chronic administration of leuprolide acetate results in suppression of testicular and ovarian steroidogenesis.  This effect is reversible upon discontinuation of drug therapy.

Following initial administration, ELIGARD causes an initial increase in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels with subsequent increases in serum levels of testosterone.  Administration of ELIGARD leads to sustained suppression of pituitary gonadotropins, and serum levels of testosterone consequently fall into the range normally seen in surgically castrated men approximately 21 days after initiation of therapy. Continuation of therapy with leuprolide acetate in patients with prostate cancer maintained testosterone below the castrate level for up to five years.

Following the first dose of ELIGARD, mean serum testosterone concentrations transiently increased, then fell to below castrate threshold (< 50 ng/dL) within three weeks, and generally remained below castrate threshold levels throughout treatment for all ELIGARD concentrations. Mean serum testosterone concentrations fell to < 20 ng/dL within five weeks for all ELIGARD concentrations.

Absorption ELIGARD 7.5 mg Following a single injection of ELIGARD 7.5 mg for 1-month administration in patients, the mean peak plasma concentration was 25.3 ng/mL (Cmax) at 5 hours;at the end of the 4 week dosing interval the mean concentration declined to 0.42 ng/mL.

ELIGARD 22.5 mg Following a single injection of ELIGARD 22.5 mg for 3-month administration in patients, the mean peak plasma concentration was 127 ng/mL (Cmax) at 5 hours; at the end of the 12 week dosing interval the mean concentration declined to 0.34 ng/mL.

ELIGARD 30 mg Following a single injection of ELIGARD 30 mg for 4-month administration in patients, the mean peak plasma concentration was 150 ng/mL (Cmax) at 3.3 hours; at the end of the 16 week dosing interval the mean concentration declined to 0.1 ng/mL.

ELIGARD 45 mg Following a single injection of ELIGARD 45 mg for 6-month administration in patients, the mean peak plasma concentration was 82 ng/mL at 4.5 hours (Cmax); at the end of the 24 week dosing interval the mean concentration declined to 0.2 ng/mL.

There was no evidence of significant accumulation during repeated dosing. 

Distribution The mean steady-state volume of distribution of leuprolide following intravenous bolus administration to healthy male volunteers was 27 L. In vitro binding to human plasma proteins ranged from 43% to 49%.

Elimination After the initial increase following each subcutaneous injection, serum concentration range was 0.1 – 2.00 ng/mL.

In healthy male volunteers, a 1-mg bolus of leuprolide administered intravenously revealed that the mean systemic clearance was 8.34 L/h, with a terminal elimination half-life of approximately 3 hours based on a two compartment model.

Metabolism No drug metabolism study was conducted with ELIGARD.  Upon administration with different leuprolide acetate formulations, the major metabolite of leuprolide acetate is a pentapeptide (M-1) metabolite.

Excretion No drug excretion study was conducted with ELIGARD.

Specific Populations Geriatrics [see Use in Specific Populations (8.5)]

Race In patients studied, mean serum leuprolide concentrations were similar regardless of race.  Refer to Table 6 for distribution of study patients by race.

Table 6.  Race Characterization of ELIGARD Study Patients (n)

<div class="scrollingtable"><table width="70%"> <col width="1px"/> <col width="1px"/> <col width="1px"/> <col width="1px"/> <col width="1px"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">Race</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">ELIGARD<br/> 7.5 mg</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">ELIGARD<br/> 22.5 mg </span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">ELIGARD<br/> 30 mg</span> </p> </td><td class="Botrule Rrule Toprule"><span class="Bold">ELIGARD<br/> 45 mg</span></td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">White</p> </td><td class="Botrule Rrule Toprule"> <p class="First">26</p> </td><td class="Botrule Rrule Toprule"> <p class="First">19</p> </td><td class="Botrule Rrule Toprule"> <p class="First">18</p> </td><td class="Botrule Rrule Toprule"> 17</td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">Black</p> </td><td class="Botrule Rrule Toprule"> <p class="First">-</p> </td><td class="Botrule Rrule Toprule"> <p class="First">4</p> </td><td class="Botrule Rrule Toprule"> <p class="First">4</p> </td><td class="Botrule Rrule Toprule"> 7</td> </tr> <tr class="Last"> <td class="Botrule Rrule Toprule"> <p class="First">Hispanic</p> </td><td class="Botrule Rrule Toprule"> <p class="First">2</p> </td><td class="Botrule Rrule Toprule"> <p class="First">2</p> </td><td class="Botrule Rrule Toprule"> <p class="First">2</p> </td><td class="Botrule Rrule Toprule"> 3</td> </tr> </tbody> </table></div>

Renal and Hepatic Insufficiency The pharmacokinetics of ELIGARD in hepatically and renally impaired patients have not been determined.

Two-year carcinogenicity studies were conducted with leuprolide acetate in rats and mice.  In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg).  There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group).  In mice, no leuprolide acetate-induced tumors or pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years. Patients have been treated with leuprolide acetate for up to three years with doses as high as 10 mg/day and for two years with doses as high as 20 mg/day without demonstrable pituitary abnormalities. No carcinogenicity studies have been conducted with ELIGARD.

Mutagenicity studies have been performed with leuprolide acetate using bacterial and mammalian systems and with ELIGARD 7.5 mg in bacterial systems.  These studies provided no evidence of a mutagenic potential.

One open-label, multicenter study was conducted with each ELIGARD formulation (7.5 mg, 22.5 mg, 30 mg, and 45 mg) in patients with Jewett stage A though D prostate cancer who were treated with at least a single injection of study drug (Table 7).  The efficacy outcome measure was medical castration rate, defined as achieving and maintaining serum testosterone suppression to ≤ 50 ng/dL (Figures 1-4).

{ "type": "p", "children": [], "text": "One open-label, multicenter study was conducted with each ELIGARD formulation (7.5 mg, 22.5 mg, 30 mg, and 45 mg) in patients with Jewett stage A though D prostate cancer who were treated with at least a single injection of study drug (Table 7).  The efficacy outcome measure was medical castration rate, defined as achieving and maintaining serum testosterone suppression to ≤ 50 ng/dL (Figures 1-4). " }

During the AGL9904 study using ELIGARD 7.5 mg, once testosterone suppression below 50 ng/dL was achieved, no patients (0%) demonstrated breakthrough (concentration > 50 ng/dL) at any time in the study.

{ "type": "p", "children": [], "text": "During the AGL9904 study using ELIGARD 7.5 mg, once testosterone suppression below 50 ng/dL was achieved, no patients (0%) demonstrated breakthrough (concentration > 50 ng/dL) at any time in the study." }

During the AGL9909 study using ELIGARD 22.5 mg, once testosterone suppression below 50 ng/dL was achieved, one patient (< 1%) demonstrated breakthrough following the initial injection; that patient remained below 50 ng/dL following the second injection.

{ "type": "p", "children": [], "text": "During the AGL9909 study using ELIGARD 22.5 mg, once testosterone suppression below 50 ng/dL was achieved, one patient (< 1%) demonstrated breakthrough following the initial injection; that patient remained below 50 ng/dL following the second injection." }

During the AGL0001 study using ELIGARD 30 mg, once testosterone suppression below 50 ng/dL was achieved, three patients (3%) demonstrated breakthrough.  In the first of these patients, a single serum testosterone concentration of 53 ng/dL was reported on the day after the second injection.  In this patient, suppression below 50 ng/dL was reported for all other time points.  In the second patient, a serum testosterone concentration of 66 ng/dL was reported immediately prior to the second injection.  This rose to a maximum concentration of 147 ng/dL on the second day after the second injection.  In this patient, suppression below 50 ng/dL was again reached on the seventh day after the second injection and was maintained thereafter.  In the final patient, serum testosterone concentrations > 50 ng/dL were reported at 2 and at 8 hours after the second injection.  Serum testosterone concentration rose to a maximum of 110 ng/dL on the third day after the second injection.  In this patient, suppression below 50 ng/dL was again reached eighteen days after the second injection and was maintained until the final day of the study, when a single serum testosterone concentration of 55 ng/dL was reported.

{ "type": "p", "children": [], "text": "During the AGL0001 study using ELIGARD 30 mg, once testosterone suppression below 50 ng/dL was achieved, three patients (3%) demonstrated breakthrough.  In the first of these patients, a single serum testosterone concentration of 53 ng/dL was reported on the day after the second injection.  In this patient, suppression below 50 ng/dL was reported for all other time points.  In the second patient, a serum testosterone concentration of 66 ng/dL was reported immediately prior to the second injection.  This rose to a maximum concentration of 147 ng/dL on the second day after the second injection.  In this patient, suppression below 50 ng/dL was again reached on the seventh day after the second injection and was maintained thereafter.  In the final patient, serum testosterone concentrations > 50 ng/dL were reported at 2 and at 8 hours after the second injection.  Serum testosterone concentration rose to a maximum of 110 ng/dL on the third day after the second injection.  In this patient, suppression below 50 ng/dL was again reached eighteen days after the second injection and was maintained until the final day of the study, when a single serum testosterone concentration of 55 ng/dL was reported." }

During the AGL0205 study using ELIGARD 45 mg, once testosterone suppression below 50 ng/dL was achieved, one patient (<1%) demonstrated breakthrough.  This patient reached castrate suppression below 50 ng/dL at Day 21 and remained suppressed until Day 308 when his testosterone level rose to 112 ng/dL.  At Month 12 (Day 336), his testosterone was 210 ng/dL.

{ "type": "p", "children": [], "text": "During the AGL0205 study using ELIGARD 45 mg, once testosterone suppression below 50 ng/dL was achieved, one patient (<1%) demonstrated breakthrough.  This patient reached castrate suppression below 50 ng/dL at Day 21 and remained suppressed until Day 308 when his testosterone level rose to 112 ng/dL.  At Month 12 (Day 336), his testosterone was 210 ng/dL. " }

Table 7.  Summary of Patients in ELIGARD Clinical Studies

{ "type": "p", "children": [], "text": "\nTable 7.  Summary of Patients in ELIGARD Clinical Studies\n" }

<div class="scrollingtable"><table> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" colspan="3"> <p class="First"> <span class="Bold">ELIGARD</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">7.5 mg </span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">22.5 mg </span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First"> <span class="Bold">30 mg </span> </p> </td><td class="Botrule Rrule Toprule"> <span class="Bold">45 mg</span></td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"> <p class="First"> <span class="Bold">Study number</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">AGL9904</p> </td><td class="Botrule Rrule Toprule"> <p class="First">AGL9909</p> </td><td class="Botrule Rrule Toprule"> <p class="First">AGL0001</p> </td><td class="Botrule Rrule Toprule"> AGL0205</td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"> <p class="First"> <span class="Bold">Total number of patients</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">120 (117 completed)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">117<span class="Sup">2</span> (111 completed<span class="Sup">3</span>)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">90 (82 completed<span class="Sup">4</span>)</p> </td><td class="Botrule Rrule Toprule">111 (103 completed<span class="Sup">5</span>)</td> </tr> <tr> <td class="Botrule Toprule" rowspan="4"> <p class="First"> <span class="Bold">Jewett stages</span> </p> </td><td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Stage A</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">‑</p> </td><td class="Botrule Rrule Toprule"> <p class="First">2</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">2</p> </td><td class="Botrule Lrule Rrule Toprule">5</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Stage B</p> </td><td class="Botrule Rrule Toprule"> <p class="First">‑</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">19</p> </td><td class="Botrule Rrule Toprule"> <p class="First">38</p> </td><td class="Botrule Rrule Toprule">43</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Stage C</p> </td><td class="Botrule Rrule Toprule"> <p class="First">89</p> </td><td class="Botrule Rrule Toprule"> <p class="First">60</p> </td><td class="Botrule Rrule Toprule"> <p class="First">16</p> </td><td class="Botrule Rrule Toprule">19</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First">Stage D</p> </td><td class="Botrule Rrule Toprule"> <p class="First">31</p> </td><td class="Botrule Rrule Toprule"> <p class="First">36</p> </td><td class="Botrule Rrule Toprule"> <p class="First">34</p> </td><td class="Botrule Rrule Toprule">44</td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3" rowspan="2"> <p class="First"> <span class="Bold">Treatment</span> </p> </td><td class="Botrule Rrule Toprule" rowspan="2"> <p class="First">6 monthly injections</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 injection (4 patients)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">1 injection (5 patients)</p> </td><td class="Botrule Rrule Toprule">1 injection (5 patients)</td> </tr> <tr> <td class="Botrule Rrule Toprule"> <p class="First">2 injections, one every three months (113 patients)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">2 injections, one every four months (85 patients)</p> </td><td class="Botrule Rrule Toprule">2 injections, one every six months (106 patients)</td> </tr> <tr> <td class="Botrule Rrule Toprule" colspan="3"> <p class="First"> <span class="Bold">Duration of therapy</span> </p> </td><td class="Botrule Rrule Toprule"> <p class="First">6 months</p> </td><td class="Botrule Rrule Toprule"> <p class="First">6 months</p> </td><td class="Botrule Rrule Toprule"> <p class="First">8 months</p> </td><td class="Botrule Rrule Toprule">12 months</td> </tr> <tr> <td class="Botrule Toprule" colspan="2" rowspan="5"> <p class="First"> <span class="Bold">Mean testosterone concentration (ng/dL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Baseline</p> </td><td class="Botrule Rrule Toprule"> <p class="First">361.3</p> </td><td class="Botrule Rrule Toprule"> <p class="First">367.1</p> </td><td class="Botrule Rrule Toprule"> <p class="First">385.5</p> </td><td class="Botrule Rrule Toprule">367.7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Day 2</p> </td><td class="Botrule Rrule Toprule"> <p class="First">574.6 (Day 3)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">588.0</p> </td><td class="Botrule Rrule Toprule"> <p class="First">610.0</p> </td><td class="Botrule Rrule Toprule">588.6</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Day 14</p> </td><td class="Botrule Rrule Toprule"> <p class="First">Below Baseline (Day 10)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">Below Baseline</p> </td><td class="Botrule Rrule Toprule"> <p class="First">Below Baseline</p> </td><td class="Botrule Rrule Toprule">Below Baseline</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Day 28</p> </td><td class="Botrule Rrule Toprule"> <p class="First">21.8</p> </td><td class="Botrule Rrule Toprule"> <p class="First">27.7 (Day 21)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">17.2</p> </td><td class="Botrule Rrule Toprule">16.7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Conclusion</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">6.1</p> </td><td class="Botrule Rrule Toprule"> <p class="First">10.1</p> </td><td class="Botrule Rrule Toprule"> <p class="First">12.4</p> </td><td class="Botrule Rrule Toprule">12.6</td> </tr> <tr> <td class="Botrule Toprule" colspan="2" rowspan="4"> <p class="First"> <span class="Bold">Number of patients with testosterone </span><span class="Bold"><span class="Bold">≤</span></span><span class="Bold"> 50 ng/dL</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Day 28</p> </td><td class="Botrule Rrule Toprule"> <p class="First">112 of 119 (94.1%)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">115 of 116 (99%)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">85 of 89 (96%)</p> </td><td class="Botrule Rrule Toprule">108 of 109 (99.1%) </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Day 35</p> </td><td class="Botrule Rrule Toprule"> <p class="First">‑</p> </td><td class="Botrule Rrule Toprule"> <p class="First">116 (100%)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">‑</p> </td><td class="Botrule Rrule Toprule"> -</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Day 42</p> </td><td class="Botrule Rrule Toprule"> <p class="First">118 (100%)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">‑</p> </td><td class="Botrule Rrule Toprule"> <p class="First">89 (100%)</p> </td><td class="Botrule Rrule Toprule"> -</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Conclusion</p> </td><td class="Botrule Rrule Toprule"> <p class="First">117<span class="Sup">1</span> (100%)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">111 (100%)</p> </td><td class="Botrule Rrule Toprule"> <p class="First">81 (99%)</p> </td><td class="Botrule Rrule Toprule"> 102 (99%)</td> </tr> <tr> <td class="Botrule Toprule" colspan="2"><span class="Bold">Number of patients with testosterone <br/> ≤ 20 ng/dL</span></td><td class="Botrule Lrule Rrule Toprule"> Day 28</td><td class="Botrule Rrule Toprule"> 90 of 119 (76%)</td><td class="Botrule Rrule Toprule"> 94 of 116 (81%)</td><td class="Botrule Rrule Toprule"> 60 of 89 (67%)</td><td class="Botrule Rrule Toprule"> 87 of 109 (80%)</td> </tr> <tr class="Last"> <td class="Botrule Toprule" colspan="7"> <ol class="Arabic"> <li>Two patients withdrew for reasons unrelated to drug.</li> <li>One patient received less than a full dose at Baseline, never attained castration, and was withdrawn at Day 73 and given an alternate treatment.</li> <li>All non-evaluable patients who attained castration by Day 28 maintained castration at each time point up to and including the time of withdrawal. </li> <li>One patient withdrew on Day 14. All 7 non-evaluable patients who had achieved castration by Day 28 maintained castration at each time point, up to and including the time of withdrawal.</li> <li>Two patients were withdrawn prior to the Month 1 blood draw.  One patient did not achieve castration and was withdrawn on Day 85.  All 5 non-evaluable patients who attained castration by Day 28, maintained castration at each time point up to and including the time of withdrawal.</li> </ol> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Rrule Toprule\" colspan=\"3\">\n<p class=\"First\">\n<span class=\"Bold\">ELIGARD</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">7.5 mg </span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">22.5 mg </span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">30 mg </span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\"> <span class=\"Bold\">45 mg</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Rrule Toprule\" colspan=\"3\">\n<p class=\"First\">\n<span class=\"Bold\">Study number</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">AGL9904</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">AGL9909</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">AGL0001</p>\n</td><td class=\"Botrule Rrule Toprule\"> AGL0205</td>\n</tr>\n<tr>\n<td class=\"Botrule Rrule Toprule\" colspan=\"3\">\n<p class=\"First\">\n<span class=\"Bold\">Total number of patients</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">120 (117 completed)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">117<span class=\"Sup\">2</span> (111 completed<span class=\"Sup\">3</span>)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">90 (82 completed<span class=\"Sup\">4</span>)</p>\n</td><td class=\"Botrule Rrule Toprule\">111 (103 completed<span class=\"Sup\">5</span>)</td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\" rowspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">Jewett stages</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">Stage A</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">‑</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">2</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">2</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">5</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">Stage B</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">‑</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">19</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">38</p>\n</td><td class=\"Botrule Rrule Toprule\">43</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">Stage C</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">89</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">60</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">16</p>\n</td><td class=\"Botrule Rrule Toprule\">19</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">Stage D</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">31</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">36</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">34</p>\n</td><td class=\"Botrule Rrule Toprule\">44</td>\n</tr>\n<tr>\n<td class=\"Botrule Rrule Toprule\" colspan=\"3\" rowspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Treatment</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" rowspan=\"2\">\n<p class=\"First\">6 monthly injections</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">1 injection (4 patients)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">1 injection (5 patients)</p>\n</td><td class=\"Botrule Rrule Toprule\">1 injection (5 patients)</td>\n</tr>\n<tr>\n<td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">2 injections, one every three months (113 patients)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">2 injections, one every four months (85 patients)</p>\n</td><td class=\"Botrule Rrule Toprule\">2 injections, one every six months (106 patients)</td>\n</tr>\n<tr>\n<td class=\"Botrule Rrule Toprule\" colspan=\"3\">\n<p class=\"First\">\n<span class=\"Bold\">Duration of therapy</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">6 months</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">6 months</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">8 months</p>\n</td><td class=\"Botrule Rrule Toprule\">12 months</td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\" colspan=\"2\" rowspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">Mean testosterone concentration (ng/dL)</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Baseline</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">361.3</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">367.1</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">385.5</p>\n</td><td class=\"Botrule Rrule Toprule\">367.7</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Day 2</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">574.6 (Day 3)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">588.0</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">610.0</p>\n</td><td class=\"Botrule Rrule Toprule\">588.6</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Day 14</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">Below Baseline (Day 10)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">Below Baseline</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">Below Baseline</p>\n</td><td class=\"Botrule Rrule Toprule\">Below Baseline</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Day 28</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">21.8</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">27.7 (Day 21)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">17.2</p>\n</td><td class=\"Botrule Rrule Toprule\">16.7</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Conclusion</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">6.1</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">10.1</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">12.4</p>\n</td><td class=\"Botrule Rrule Toprule\">12.6</td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\" colspan=\"2\" rowspan=\"4\">\n<p class=\"First\">\n<span class=\"Bold\">Number of patients with testosterone </span><span class=\"Bold\"><span class=\"Bold\">≤</span></span><span class=\"Bold\"> 50 ng/dL</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Day 28</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">112 of 119 (94.1%)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">115 of 116 (99%)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">85 of 89 (96%)</p>\n</td><td class=\"Botrule Rrule Toprule\">108 of 109 (99.1%) </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Day 35</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">‑</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">116 (100%)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">‑</p>\n</td><td class=\"Botrule Rrule Toprule\"> -</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Day 42</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">118 (100%)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">‑</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">89 (100%)</p>\n</td><td class=\"Botrule Rrule Toprule\"> -</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Conclusion</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">117<span class=\"Sup\">1</span> (100%)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">111 (100%)</p>\n</td><td class=\"Botrule Rrule Toprule\">\n<p class=\"First\">81 (99%)</p>\n</td><td class=\"Botrule Rrule Toprule\"> 102 (99%)</td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\" colspan=\"2\"><span class=\"Bold\">Number of patients with testosterone <br/>\n ≤ 20 ng/dL</span></td><td class=\"Botrule Lrule Rrule Toprule\"> Day 28</td><td class=\"Botrule Rrule Toprule\"> 90 of 119 (76%)</td><td class=\"Botrule Rrule Toprule\"> 94 of 116 (81%)</td><td class=\"Botrule Rrule Toprule\"> 60 of 89 (67%)</td><td class=\"Botrule Rrule Toprule\"> 87 of 109 (80%)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Toprule\" colspan=\"7\">\n<ol class=\"Arabic\">\n<li>Two patients withdrew for reasons unrelated to drug.</li>\n<li>One patient received less than a full dose at Baseline, never attained castration, and was withdrawn at Day 73 and given an alternate treatment.</li>\n<li>All non-evaluable patients who attained castration by Day 28 maintained castration at each time point up to and including the time of withdrawal. </li>\n<li>One patient withdrew on Day 14. All 7 non-evaluable patients who had achieved castration by Day 28 maintained castration at each time point, up to and including the time of withdrawal.</li>\n<li>Two patients were withdrawn prior to the Month 1 blood draw.  One patient did not achieve castration and was withdrawn on Day 85.  All 5 non-evaluable patients who attained castration by Day 28, maintained castration at each time point up to and including the time of withdrawal.</li>\n</ol>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Figure 1.  ELIGARD 7.5 mg Mean Serum Testosterone Concentrations (n=117)

{ "type": "p", "children": [], "text": "\nFigure 1.  ELIGARD 7.5 mg Mean Serum Testosterone Concentrations (n=117)\n" }

Figure 2.  ELIGARD 22.5 mg Mean Serum Testosterone Concentrations (n=111)

{ "type": "p", "children": [], "text": "\nFigure 2.  ELIGARD 22.5 mg Mean Serum Testosterone Concentrations (n=111)\n" }

Figure 3.  ELIGARD 30 mg Mean Serum Testosterone Concentrations (n=90)

{ "type": "p", "children": [], "text": "\nFigure 3.  ELIGARD 30 mg Mean Serum Testosterone Concentrations (n=90)\n" }

Figure 4.  ELIGARD 45 mg Mean Serum Testosterone Concentrations (n=103)

{ "type": "p", "children": [], "text": "\nFigure 4.  ELIGARD 45 mg Mean Serum Testosterone Concentrations (n=103)\n" }

Serum PSA decreased in all patients in all studies whose Baseline values were elevated above the normal limit.  Refer to Table 8 for a summary of the effectiveness of ELIGARD in reducing serum PSA values.

{ "type": "p", "children": [], "text": "Serum PSA decreased in all patients in all studies whose Baseline values were elevated above the normal limit.  Refer to Table 8 for a summary of the effectiveness of ELIGARD in reducing serum PSA values." }

Table 8. Effect of ELIGARD on Patient Serum PSA Values

{ "type": "p", "children": [], "text": "\nTable 8. Effect of ELIGARD on Patient Serum PSA Values\n" }

<div class="scrollingtable"><table width="80%"> <col width="93.5pt"/> <col width="93.5pt"/> <col width="93.5pt"/> <col width="93.5pt"/> <col width="93.5pt"/> <tbody class="Headless"> <tr class="First"> <td> <p class="First"> <span class="Bold">ELIGARD</span> </p> </td><td class="Lrule"><span class="Bold">7.5 mg</span></td><td class="Lrule"><span class="Bold">22.5 mg</span></td><td class="Lrule"><span class="Bold">30 mg</span></td><td class="Lrule"><span class="Bold">45 mg</span></td> </tr> <tr> <td class="Toprule"> <p class="First">Mean PSA reduction at study conclusion</p> </td><td class="Lrule Toprule">94%</td><td class="Lrule Toprule">98%</td><td class="Lrule Toprule">86%</td><td class="Lrule Toprule"> 97%</td> </tr> <tr> <td class="Toprule"> <p class="First">Patients with normal PSA at study conclusion*</p> </td><td class="Lrule Toprule">94%</td><td class="Lrule Toprule">91%</td><td class="Lrule Toprule">93%</td><td class="Lrule Toprule"> 95%</td> </tr> <tr class="Last"> <td class="Toprule" colspan="4"> <p class="First">*Among patients who presented with elevated levels at Baseline</p> </td><td class="Toprule"> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"80%\">\n<col width=\"93.5pt\"/>\n<col width=\"93.5pt\"/>\n<col width=\"93.5pt\"/>\n<col width=\"93.5pt\"/>\n<col width=\"93.5pt\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">\n<span class=\"Bold\">ELIGARD</span>\n</p>\n</td><td class=\"Lrule\"><span class=\"Bold\">7.5 mg</span></td><td class=\"Lrule\"><span class=\"Bold\">22.5 mg</span></td><td class=\"Lrule\"><span class=\"Bold\">30 mg</span></td><td class=\"Lrule\"><span class=\"Bold\">45 mg</span></td>\n</tr>\n<tr>\n<td class=\"Toprule\">\n<p class=\"First\">Mean PSA reduction at study conclusion</p>\n</td><td class=\"Lrule Toprule\">94%</td><td class=\"Lrule Toprule\">98%</td><td class=\"Lrule Toprule\">86%</td><td class=\"Lrule Toprule\"> 97%</td>\n</tr>\n<tr>\n<td class=\"Toprule\">\n<p class=\"First\">Patients with normal PSA at study conclusion*</p>\n</td><td class=\"Lrule Toprule\">94%</td><td class=\"Lrule Toprule\">91%</td><td class=\"Lrule Toprule\">93%</td><td class=\"Lrule Toprule\"> 95%</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Toprule\" colspan=\"4\">\n<p class=\"First\">*Among patients who presented with elevated levels at Baseline</p>\n</td><td class=\"Toprule\"> </td>\n</tr>\n</tbody>\n</table></div>" }

Other secondary efficacy endpoints evaluated included WHO performance status, bone pain, urinary pain and urinary signs and symptoms.  Refer to Table 9 for a summary of these endpoints.

{ "type": "p", "children": [], "text": "Other secondary efficacy endpoints evaluated included WHO performance status, bone pain, urinary pain and urinary signs and symptoms.  Refer to Table 9 for a summary of these endpoints." }

Table 9. Secondary Efficacy Endpoints

{ "type": "p", "children": [], "text": "\nTable 9. Secondary Efficacy Endpoints\n" }

<div class="scrollingtable"><table> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Rrule Toprule" colspan="2"><span class="Bold">ELIGARD</span></td><td class="Botrule Toprule"> <span class="Bold">7.5 mg </span></td><td class="Botrule Lrule Rrule Toprule"> <span class="Bold">22.5 mg</span></td><td class="Botrule Toprule"> <span class="Bold">30 mg </span></td><td class="Botrule Lrule Toprule"> <span class="Bold">45 mg</span></td> </tr> <tr> <td class="Rrule Toprule" rowspan="5" valign="top"> <p class="First"> <span class="Bold">Baseline</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">WHO Status = 0<span class="Sup">1</span> </p> </td><td class="Botrule Toprule"> <p class="First">88%</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">94%</p> </td><td class="Botrule Toprule"> <p class="First">90%</p> </td><td class="Botrule Lrule Toprule">90%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">WHO Status = 1<span class="Sup">2</span></td><td class="Botrule Toprule"> <p class="First">11%</p> </td><td class="Botrule Lrule Rrule Toprule">6%</td><td class="Botrule Toprule">10%</td><td class="Botrule Lrule Toprule">7%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">WHO Status = 2<span class="Sup">3</span></td><td class="Botrule Toprule">-</td><td class="Botrule Lrule Rrule Toprule">-</td><td class="Botrule Lrule Rrule Toprule">-</td><td class="Botrule Lrule Rrule Toprule">3%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mean bone pain<span class="Sup">4</span> <br/> (range)</p> </td><td class="Botrule Toprule"> <p class="First">1.22 (1-9)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.20 (1-9)</p> </td><td class="Botrule Toprule"> <p class="First">1.20 (1-7)</p> </td><td class="Botrule Lrule Toprule">1.38 (1-7)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mean urinary pain (range)</p> </td><td class="Botrule Toprule"> <p class="First">1.12 (1-5)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.02 (1-2)</p> </td><td class="Botrule Toprule"> <p class="First">1.01 (1-2)</p> </td><td class="Botrule Lrule Toprule">1.22 (1-8)</td> </tr> <tr> <td class="Botrule Rrule" rowspan="2"> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Mean urinary signs and symptoms (range)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Low</p> </td><td class="Botrule Toprule"> <p class="First">1.09 (1-4)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Low</p> </td><td class="Botrule Lrule Rrule Toprule">Low</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Number of patients with prostate abnormalities</p> </td><td class="Botrule Toprule"> <p class="First">102 (85%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">96 (82%)</p> </td><td class="Botrule Toprule"> <p class="First">66 (73%)</p> </td><td class="Botrule Lrule Toprule">89 (80%)</td> </tr> <tr> <td class="Botrule Toprule"></td><td></td><td> <p class="First"> <span class="Bold">Month 6</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Month 6</span> </p> </td><td class="Botrule Toprule"> <p class="First"> <span class="Bold">Month 8</span> </p> </td><td class="Botrule Lrule Toprule"> <span class="Bold">Month 12</span></td> </tr> <tr> <td class="Rrule Toprule" rowspan="2" valign="top"> <p class="First"> <span class="Bold">Follow-up</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">WHO status = 0</p> </td><td class="Botrule Toprule"> <p class="First">Unchanged</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">96%</p> </td><td class="Botrule Toprule"> <p class="First">87%</p> </td><td class="Botrule Lrule Toprule">94%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">WHO status = 1</p> </td><td class="Botrule Toprule"> <p class="First">Unchanged</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">4%</p> </td><td class="Botrule Toprule"> <p class="First">12%</p> </td><td class="Botrule Lrule Toprule">5%</td> </tr> <tr> <td class="Rrule" rowspan="2"> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">WHO status = 2</p> </td><td class="Botrule Toprule">-</td><td class="Botrule Lrule Rrule Toprule">-</td><td class="Botrule Lrule Rrule Toprule">1%</td><td class="Botrule Lrule Rrule Toprule"> 1%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mean bone pain (range)</p> </td><td class="Botrule Toprule"> <p class="First">1.26 (1-7)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.22 (1-5)</p> </td><td class="Botrule Toprule"> <p class="First">1.19 (1-8)</p> </td><td class="Botrule Lrule Toprule">1.31 (1-8)</td> </tr> <tr> <td class="Botrule Rrule" rowspan="3"> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Mean urinary pain (range)</p> </td><td class="Botrule Toprule"> <p class="First">1.07 (1-8)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.10 (1-8)</p> </td><td class="Botrule Toprule"> <p class="First">1.00 (1-1)</p> </td><td class="Botrule Lrule Toprule">1.07 (1-5)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Mean urinary signs and symptoms (range)</p> </td><td class="Botrule Toprule"> <p class="First">Modestly decreased</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1.18 (1-7)</p> </td><td class="Botrule Toprule"> <p class="First">Modestly decreased</p> </td><td class="Botrule Lrule Toprule">Modestly decreased</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Number of patients with prostate abnormalities</p> </td><td class="Botrule Toprule"> <p class="First">77 (64%)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">76 (65%)</p> </td><td class="Botrule Toprule"> <p class="First">54 (60%)</p> </td><td class="Botrule Lrule Toprule">60 (58%)</td> </tr> <tr class="Last"> <td class="Botrule Toprule" colspan="5"> <ol class="Arabic"> <li> <p class="First">WHO status = 0 classified as “fully active.” </p> </li> <li> <p class="First">WHO status = 1 classified as “restricted in strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.” </p> </li> <li> <p class="First">WHO status = 2 classified as “ambulatory but unable to carry out work activities.” </p> </li> <li> <p class="First">Pain score scale: 1 (no pain) to 10 (worst pain possible).</p> </li> </ol> </td><td class="Botrule Toprule"> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">ELIGARD</span></td><td class=\"Botrule Toprule\"> <span class=\"Bold\">7.5 mg </span></td><td class=\"Botrule Lrule Rrule Toprule\"> <span class=\"Bold\">22.5 mg</span></td><td class=\"Botrule Toprule\"> <span class=\"Bold\">30 mg </span></td><td class=\"Botrule Lrule Toprule\"> <span class=\"Bold\">45 mg</span></td>\n</tr>\n<tr>\n<td class=\"Rrule Toprule\" rowspan=\"5\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Baseline</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">WHO Status = 0<span class=\"Sup\">1</span>\n</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">88%</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">94%</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">90%</p>\n</td><td class=\"Botrule Lrule Toprule\">90%</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">WHO Status = 1<span class=\"Sup\">2</span></td><td class=\"Botrule Toprule\">\n<p class=\"First\">11%</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">6%</td><td class=\"Botrule Toprule\">10%</td><td class=\"Botrule Lrule Toprule\">7%</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">WHO Status = 2<span class=\"Sup\">3</span></td><td class=\"Botrule Toprule\">-</td><td class=\"Botrule Lrule Rrule Toprule\">-</td><td class=\"Botrule Lrule Rrule Toprule\">-</td><td class=\"Botrule Lrule Rrule Toprule\">3%</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Mean bone pain<span class=\"Sup\">4</span>\n<br/>\n (range)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.22 (1-9)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">1.20 (1-9)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.20 (1-7)</p>\n</td><td class=\"Botrule Lrule Toprule\">1.38 (1-7)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Mean urinary pain (range)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.12 (1-5)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">1.02 (1-2)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.01 (1-2)</p>\n</td><td class=\"Botrule Lrule Toprule\">1.22 (1-8)</td>\n</tr>\n<tr>\n<td class=\"Botrule Rrule\" rowspan=\"2\"> </td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Mean urinary signs and symptoms (range)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Low</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.09 (1-4)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Low</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">Low</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Number of patients with prostate abnormalities</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">102 (85%)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">96 (82%)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">66 (73%)</p>\n</td><td class=\"Botrule Lrule Toprule\">89 (80%)</td>\n</tr>\n<tr>\n<td class=\"Botrule Toprule\"></td><td></td><td>\n<p class=\"First\">\n<span class=\"Bold\">Month 6</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Month 6</span>\n</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Month 8</span>\n</p>\n</td><td class=\"Botrule Lrule Toprule\"> <span class=\"Bold\">Month 12</span></td>\n</tr>\n<tr>\n<td class=\"Rrule Toprule\" rowspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Follow-up</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">WHO status = 0</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">Unchanged</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">96%</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">87%</p>\n</td><td class=\"Botrule Lrule Toprule\">94%</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">WHO status = 1</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">Unchanged</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">4%</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">12%</p>\n</td><td class=\"Botrule Lrule Toprule\">5%</td>\n</tr>\n<tr>\n<td class=\"Rrule\" rowspan=\"2\"> </td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">WHO status = 2</p>\n</td><td class=\"Botrule Toprule\">-</td><td class=\"Botrule Lrule Rrule Toprule\">-</td><td class=\"Botrule Lrule Rrule Toprule\">1%</td><td class=\"Botrule Lrule Rrule Toprule\"> 1%</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Mean bone pain (range)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.26 (1-7)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">1.22 (1-5)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.19 (1-8)</p>\n</td><td class=\"Botrule Lrule Toprule\">1.31 (1-8)</td>\n</tr>\n<tr>\n<td class=\"Botrule Rrule\" rowspan=\"3\"> </td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Mean urinary pain (range)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.07 (1-8)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">1.10 (1-8)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">1.00 (1-1)</p>\n</td><td class=\"Botrule Lrule Toprule\">1.07 (1-5)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Mean urinary signs and symptoms (range)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">Modestly decreased</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">1.18 (1-7)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">Modestly decreased</p>\n</td><td class=\"Botrule Lrule Toprule\">Modestly decreased</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Number of patients with prostate abnormalities</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">77 (64%)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">76 (65%)</p>\n</td><td class=\"Botrule Toprule\">\n<p class=\"First\">54 (60%)</p>\n</td><td class=\"Botrule Lrule Toprule\">60 (58%)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Toprule\" colspan=\"5\">\n<ol class=\"Arabic\">\n<li>\n<p class=\"First\">WHO status = 0 classified as “fully active.” </p>\n</li>\n<li>\n<p class=\"First\">WHO status = 1 classified as “restricted in strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.” </p>\n</li>\n<li>\n<p class=\"First\">WHO status = 2 classified as “ambulatory but unable to carry out work activities.” </p>\n</li>\n<li>\n<p class=\"First\">Pain score scale: 1 (no pain) to 10 (worst pain possible).</p>\n</li>\n</ol>\n</td><td class=\"Botrule Toprule\"> </td>\n</tr>\n</tbody>\n</table></div>" }

How Supplied

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

ELIGARD is supplied as a single-dose, two syringe-mixing system with a sterile safety needle and cap. ELIGARD is available as follows (Table 10):

{ "type": "p", "children": [], "text": "ELIGARD is supplied as a single-dose, two syringe-mixing system with a sterile safety needle and cap. ELIGARD is available as follows (Table 10):" }

Table 10.  ELIGARD Product Presentations

{ "type": "p", "children": [], "text": "\nTable 10.  ELIGARD Product Presentations\n" }

<div class="scrollingtable"><table width="80%"> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">ELIGARD strength</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">NDC number</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Description of Syringe A<br/> with the delivery system</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Description of Syringe B<br/> with leuprolide acetate</span></td><td class="Botrule Lrule Rrule Toprule"><span class="Bold">Description of the<br/> suspension after mixing</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">7.5 mg</td><td class="Botrule Lrule Rrule Toprule">62935-756-80</td><td class="Botrule Lrule Rrule Toprule">Light tan to tan, clear,<br/> viscous solution</td><td class="Botrule Lrule Rrule Toprule">White to off white powder</td><td class="Botrule Lrule Rrule Toprule">Light tan to tan</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">22.5 mg</td><td class="Botrule Lrule Rrule Toprule">62935-227-10</td><td class="Botrule Lrule Rrule Toprule">Colorless to pale yellow,<br/> clear viscous solution</td><td class="Botrule Lrule Rrule Toprule">White to off white powder</td><td class="Botrule Lrule Rrule Toprule">Colorless to pale yellow</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">30 mg</td><td class="Botrule Lrule Rrule Toprule">62935-306-40</td><td class="Botrule Lrule Rrule Toprule">Colorless to pale yellow,<br/> clear viscous solution</td><td class="Botrule Lrule Rrule Toprule">White to off white powder</td><td class="Botrule Lrule Rrule Toprule">Colorless to pale yellow<br/> <br/> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">45 mg</td><td class="Botrule Lrule Rrule Toprule"> 62935-461-50</td><td class="Botrule Lrule Rrule Toprule"> Colorless to pale yellow, clear viscous solution</td><td class="Botrule Lrule Rrule Toprule">White to off white powder</td><td class="Botrule Lrule Rrule Toprule"> Colorless to pale yellow</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"80%\">\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">ELIGARD strength</span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">NDC number</span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Description of Syringe A<br/>\n with the delivery system</span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Description of Syringe B<br/>\n with leuprolide acetate</span></td><td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Description of the<br/>\n suspension after mixing</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">7.5 mg</td><td class=\"Botrule Lrule Rrule Toprule\">62935-756-80</td><td class=\"Botrule Lrule Rrule Toprule\">Light tan to tan, clear,<br/>\n viscous solution</td><td class=\"Botrule Lrule Rrule Toprule\">White to off white powder</td><td class=\"Botrule Lrule Rrule Toprule\">Light tan to tan</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">22.5 mg</td><td class=\"Botrule Lrule Rrule Toprule\">62935-227-10</td><td class=\"Botrule Lrule Rrule Toprule\">Colorless to pale yellow,<br/>\n clear viscous solution</td><td class=\"Botrule Lrule Rrule Toprule\">White to off white powder</td><td class=\"Botrule Lrule Rrule Toprule\">Colorless to pale yellow</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">30 mg</td><td class=\"Botrule Lrule Rrule Toprule\">62935-306-40</td><td class=\"Botrule Lrule Rrule Toprule\">Colorless to pale yellow,<br/>\n clear viscous solution</td><td class=\"Botrule Lrule Rrule Toprule\">White to off white powder</td><td class=\"Botrule Lrule Rrule Toprule\">Colorless to pale yellow<br/>\n<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">45 mg</td><td class=\"Botrule Lrule Rrule Toprule\"> 62935-461-50</td><td class=\"Botrule Lrule Rrule Toprule\"> Colorless to pale yellow, clear viscous solution</td><td class=\"Botrule Lrule Rrule Toprule\">White to off white powder</td><td class=\"Botrule Lrule Rrule Toprule\"> Colorless to pale yellow</td>\n</tr>\n</tbody>\n</table></div>" }

Storage

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

Store at 2°C to 8°C (36°F to 46°F)

{ "type": "p", "children": [], "text": "Store at 2°C to 8°C (36°F to 46°F)" }

Once outside the refrigerator this product may be stored in its original packaging at room temperature 15°C to 30°C (59°F to 86°F) for up to eight weeks prior to mixing and administration.

{ "type": "p", "children": [], "text": "Once outside the refrigerator this product may be stored in its original packaging at room temperature 15°C to 30°C (59°F to 86°F) for up to eight weeks prior to mixing and administration." }

Hypersensitivity

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

{ "type": "ul", "children": [ "Inform patients that if they have experienced hypersensitivity with other GnRH agonist drugs like ELIGARD, ELIGARD is contraindicated [see Contraindications (4)]. \n" ], "text": "" }

Tumor Flare

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

{ "type": "ul", "children": [ "Inform patients that ELIGARD can cause tumor flare during the first weeks of treatment. Inform patients that the increase in testosterone can cause an increase in urinary symptoms or pain. Advise patients to contact their healthcare provider if ureteral obstruction, spinal cord compression, paralysis, or new or worsened symptoms occur after beginning ELIGARD treatment [see Warnings and Precautions (5.1)].\n" ], "text": "" }

Hyperglycemia and Diabetes

{ "type": "p", "children": [], "text": "\nHyperglycemia and Diabetes\n" }

{ "type": "ul", "children": [ "Advise patients that there is an increased risk of hyperglycemia and diabetes with ELIGARD therapy.  Inform patients that periodic monitoring for hyperglycemia and diabetes is required when being treated with ELIGARD [see Warnings and Precautions (5.2)].\n" ], "text": "" }

Cardiovascular Disease

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

{ "type": "ul", "children": [ "Inform patients that there is an increased risk of myocardial infarction, sudden cardiac death, and stroke with ELIGARD treatment. Advise patients to immediately report signs and symptoms associated with these events to their healthcare provider for evaluation [see Warnings and Precautions (5.3)].\n" ], "text": "" }

Severe Cutaneous Adverse Reactions

{ "type": "p", "children": [], "text": "\nSevere Cutaneous Adverse Reactions\n" }

{ "type": "ul", "children": [ "Inform patients that severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which may be life threatening or fatal, may occur during treatment with ELIGARD. Advise patients to contact their healthcare provider or seek medical attention right away if they experience signs or symptoms of SCARs [see Warnings and Precautions (5.6)].\n" ], "text": "" }

Injection Site Reactions

{ "type": "p", "children": [], "text": "\nInjection Site Reactions\n" }

{ "type": "ul", "children": [ "Inform patients that injection site related adverse reactions may occur such as transient burning/stinging, pain, bruising, and redness.  Advise patients to contact their healthcare provider if they experience rash or severe injection site reactions [see Adverse Reactions (6.1)].\n" ], "text": "" }

Urogenital Disorders

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

{ "type": "ul", "children": [ "Advise patients that ELIGARD may cause impotence.\n" ], "text": "" }

Infertility

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

{ "type": "ul", "children": [ "Inform patients that ELIGARD may cause infertility [see Use In Specific Populations (8.3)].\n" ], "text": "" }

Continuation of ELIGARD Treatment:

{ "type": "p", "children": [], "text": "\nContinuation of ELIGARD Treatment:\n" }

{ "type": "ul", "children": [ " Inform patients that ELIGARD is usually continued, often with additional medication, after the development of non-metastatic and metastatic castration-resistant prostate cancer [see Dosage and Administration (2.1)].\n" ], "text": "" }

Manufactured by: Tolmar, Fort Collins, CO 80526

{ "type": "p", "children": [], "text": "Manufactured by: Tolmar, Fort Collins, CO 80526" }

©2025 Tolmar

{ "type": "p", "children": [], "text": "©2025 Tolmar" }

04006512 Rev. 5 02/2025

{ "type": "p", "children": [], "text": "04006512 Rev. 5 02/2025" }

Follow the detailed instructions below to ensure correct preparation of ELIGARD prior to administration:

{ "type": "p", "children": [], "text": "\nFollow the detailed instructions below to ensure correct preparation of ELIGARD prior to administration:\n" }

<div class="scrollingtable"><table> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Bold">Step 1</span> </p> <p>Use aseptic technique throughout the procedure.  Gloves are recommended during mixing and administration. </p> <p>Allow the product to reach room temperature before mixing.  Once mixed, the product must be administered within 30 minutes or it should be discarded.</p> <p>On a clean field open the tray by tearing off the foil from the corner and remove the contents. Discard the desiccant pack. Remove the pre-connected syringe system from the tray. Open the sterile safety needle package by peeling back the paper tab. <span class="Bold">Note:</span> Syringe A and Syringe B should not be lined-up yet. The product should only be administered with the co-packaged, sterile safety needle.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2"><img alt="mixing" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-16.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/><br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Step 2</span> <p class="First">Grasp the latching button on the coupling device with your finger and thumb and press until you hear a snapping sound. The two syringes will be aligned.<br/> <br/> </p> Do not bend the pre-connected syringe system.</td><td class="Botrule Lrule Rrule Toprule"><img alt="step 2" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-17.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 3</span> </p> <p>Holding the syringes in a horizontal position, transfer the liquid contents of Syringe A into the leuprolide acetate powder contained in Syringe B. <span class="Bold">Thoroughly mix the product for 60 cycles by pushing the contents back and forth between both syringes to obtain a uniform suspension.</span> </p> <ul class="Disk"> <li> <span class="Bold">A cycle is one push of the Syringe A plunger and one push of the Syringe B plunger.</span> </li> <li>When thoroughly mixed, the suspension will appear light tan to tan (ELIGARD 7.5 mg) or colorless to pale yellow (ELIGARD 22.5 mg, 30 mg, and 45 mg).</li> </ul> <span class="Bold">Note: </span>Product must be mixed as described; shaking will NOT provide adequate mixing. Do not bend.</td><td class="Botrule Lrule Rrule Toprule"><img alt="step 3" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-18.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 4</span> </p> After mixing, hold the syringes vertically (upright) with Syringe B (wide syringe) on the bottom. The syringes should remain securely coupled. Transfer all of the mixed product into Syringe B by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger.</td><td class="Botrule Lrule Rrule Toprule"><img alt="step 4" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-19.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/><br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 5</span> </p> <p>While ensuring the Syringe A plunger is fully pushed down, hold the coupling device and unscrew Syringe B. This will disconnect Syringe B from the coupling device. Syringe A will remain attached to the coupling device.</p> <p> <span class="Bold">Note: </span>Small air bubbles will remain in the formulation – this is acceptable.</p> <span class="Bold">Do not purge the air bubbles from Syringe B as product may be lost!</span></td><td class="Botrule Lrule Rrule Toprule"><img alt="step 5" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-20.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/><br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 6</span> </p> <p>Continue to hold Syringe B upright with the open end at the top. Hold back the white plunger on Syringe B to prevent loss of the product, and attach the safety needle and cap (the safety needle is located under the tray). Gently screw clockwise with approximately a three-quarter turn until the safety needle and cap are secure.</p> <p> <span class="Bold">Do not overtighten, as the needle hub may become damaged which could result in leakage of the product during injection. </span>The safety shield may also be damaged if the safety needle and cap are screwed with too much force.</p> </td><td class="Botrule Lrule Rrule Toprule"><img alt="step 6" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-21.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/><br/> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 7</span> </p> <p>Move the safety shield away from the needle and towards the syringe.</p> Pull off the cap immediately prior to administration.</td><td class="Botrule Lrule Rrule Toprule"> <img alt="step 7" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-22.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Step 1</span>\n</p>\n<p>Use aseptic technique throughout the procedure.  Gloves are recommended during mixing and administration. </p>\n<p>Allow the product to reach room temperature before mixing.  Once mixed, the product must be administered within 30 minutes or it should be discarded.</p>\n<p>On a clean field open the tray by tearing off the foil from the corner and remove the contents. Discard the desiccant pack. Remove the pre-connected syringe system from the tray. Open the sterile safety needle package by peeling back the paper tab. <span class=\"Bold\">Note:</span> Syringe A and Syringe B should not be lined-up yet. The product should only be administered with the co-packaged, sterile safety needle.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><img alt=\"mixing\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-16.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/><br/>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Step 2</span>\n<p class=\"First\">Grasp the latching button on the coupling device with your finger and thumb and press until you hear a snapping sound. The two syringes will be aligned.<br/>\n<br/>\n</p>\n Do not bend the pre-connected syringe system.</td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"step 2\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-17.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 3</span>\n</p>\n<p>Holding the syringes in a horizontal position, transfer the liquid contents of Syringe A into the leuprolide acetate powder contained in Syringe B. <span class=\"Bold\">Thoroughly mix the product for 60 cycles by pushing the contents back and forth between both syringes to obtain a uniform suspension.</span>\n</p>\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">A cycle is one push of the Syringe A plunger and one push of the Syringe B plunger.</span>\n</li>\n<li>When thoroughly mixed, the suspension will appear light tan to tan (ELIGARD 7.5 mg) or colorless to pale yellow (ELIGARD 22.5 mg, 30 mg, and 45 mg).</li>\n</ul>\n<span class=\"Bold\">Note: </span>Product must be mixed as described; shaking will NOT provide adequate mixing. Do not bend.</td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"step 3\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-18.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 4</span>\n</p>\n After mixing, hold the syringes vertically (upright) with Syringe B (wide syringe) on the bottom. The syringes should remain securely coupled. Transfer all of the mixed product into Syringe B by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger.</td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"step 4\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-19.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/><br/>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 5</span>\n</p>\n<p>While ensuring the Syringe A plunger is fully pushed down, hold the coupling device and unscrew Syringe B. This will disconnect Syringe B from the coupling device. Syringe A will remain attached to the coupling device.</p>\n<p>\n<span class=\"Bold\">Note: </span>Small air bubbles will remain in the formulation – this is acceptable.</p>\n<span class=\"Bold\">Do not purge the air bubbles from Syringe B as product may be lost!</span></td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"step 5\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-20.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/><br/>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 6</span>\n</p>\n<p>Continue to hold Syringe B upright with the open end at the top. Hold back the white plunger on Syringe B to prevent loss of the product, and attach the safety needle and cap (the safety needle is located under the tray). Gently screw clockwise with approximately a three-quarter turn until the safety needle and cap are secure.</p>\n<p>\n<span class=\"Bold\">Do not overtighten, as the needle hub may become damaged which could result in leakage of the product during injection. </span>The safety shield may also be damaged if the safety needle and cap are screwed with too much force.</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"step 6\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-21.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/><br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 7</span>\n</p>\n<p>Move the safety shield away from the needle and towards the syringe.</p>\n Pull off the cap immediately prior to administration.</td><td class=\"Botrule Lrule Rrule Toprule\"> <img alt=\"step 7\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-22.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/></td>\n</tr>\n</tbody>\n</table></div>" }

Note: Should the needle hub appear to be damaged, or leak, the product should NOT be used. The damaged safety needle and cap should NOT be replaced and the product should NOT be injected. In the event of damage to the needle hub, use a new replacement ELIGARD carton.

{ "type": "p", "children": [], "text": "\nNote: Should the needle hub appear to be damaged, or leak, the product should NOT be used. The damaged safety needle and cap should NOT be replaced and the product should NOT be injected. In the event of damage to the needle hub, use a new replacement ELIGARD carton.\n\n" }

Follow the detailed instructions below to ensure correct administration of ELIGARD:

{ "type": "p", "children": [], "text": "\nFollow the detailed instructions below to ensure correct administration of ELIGARD:\n" }

<div class="scrollingtable"><table> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">1. Select an injection site on the abdomen, upper buttocks, or another location with adequate amounts of subcutaneous tissue that does not have excessive pigment, nodules, lesions, or hair and hasn’t recently been used.</p> <p>2. Cleanse the injection-site area with an alcohol swab (not enclosed).</p> <p>3. Using the thumb and forefinger, grab and bunch the area of skin around the injection site.</p> </td><td class="Botrule Lrule Rrule Toprule"> <img alt="admin 1" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-23.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">4. Using your dominant hand, insert the needle quickly at a 90° angle to the skin surface. The depth of penetration will depend on the amount and fullness of the subcutaneous tissue and the length of the needle. After the needle is inserted, release the skin. <p class="First">5. Inject the drug using a slow, steady push and press down on the plunger until the syringe is empty.</p> <p> <span class="Bold">Make sure all the drug has been injected before removing the needle.</span> </p> <p>6. Withdraw the needle quickly at the same 90° angle used for insertion.</p> </td><td class="Botrule Lrule Rrule Toprule"> <img alt="admin" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-24.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">7. Immediately following the withdrawal of the needle, activate the safety shield using a finger/thumb or flat surface and push until it completely covers the needle tip and locks into place.</p> <p>8. An audible and tactile “click” verifies a locked position.</p> <p>9. Check to confirm the safety shield is fully engaged. Discard all components safely in an appropriate biohazard container.</p> </td><td class="Botrule Lrule Rrule Toprule"><img alt="admin" src="/dailymed/image.cfm?name=eligard-pss-all-strengths-25.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc"/><br/> <br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">1. Select an injection site on the abdomen, upper buttocks, or another location with adequate amounts of subcutaneous tissue that does not have excessive pigment, nodules, lesions, or hair and hasn’t recently been used.</p>\n<p>2. Cleanse the injection-site area with an alcohol swab (not enclosed).</p>\n<p>3. Using the thumb and forefinger, grab and bunch the area of skin around the injection site.</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\"> <img alt=\"admin 1\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-23.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">4. Using your dominant hand, insert the needle quickly at a 90° angle to the skin surface. The depth of penetration will depend on the amount and fullness of the subcutaneous tissue and the length of the needle. After the needle is inserted, release the skin.\n <p class=\"First\">5. Inject the drug using a slow, steady push and press down on the plunger until the syringe is empty.</p>\n<p>\n<span class=\"Bold\">Make sure all the drug has been injected before removing the needle.</span>\n</p>\n<p>6. Withdraw the needle quickly at the same 90° angle used for insertion.</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\"> <img alt=\"admin\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-24.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/></td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">7. Immediately following the withdrawal of the needle, activate the safety shield using a finger/thumb or flat surface and push until it completely covers the needle tip and locks into place.</p>\n<p>8. An audible and tactile “click” verifies a locked position.</p>\n<p>9. Check to confirm the safety shield is fully engaged. Discard all components safely in an appropriate biohazard container.</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\"><img alt=\"admin\" src=\"/dailymed/image.cfm?name=eligard-pss-all-strengths-25.jpg&amp;setid=b7b679a9-6823-4ef8-8d31-3ab5058ffcfc\"/><br/>\n<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

©2025 Tolmar

{ "type": "p", "children": [], "text": "©2025 Tolmar " }

Manufactured by: Tolmar, Fort Collins, CO 80526     04006512 Rev. 5 02/2025

{ "type": "p", "children": [], "text": " Manufactured by: Tolmar, Fort Collins, CO 80526     04006512 Rev. 5 02/2025" }