Lupron Depot Ped Drug Information

DEPOT-PED is indicated for the treatment of pediatric patients with central precocious puberty (CPP). LUPRON DEPOT-PED is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of pediatric patients with central precocious puberty.

Clinical Trials Experience

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. Table 2. Adverse Reactions Occurring in ≥2% in Pediatric Patients with CPP Receiving LUPRON DEPOT-PED 1-month % of Patients (N = 421) Injection Site Reactions Including Abscess* 9 Emotional Lability 5 Headache 3 General Pain 3 Acne/Seborrhea 3 Rash Including Erythema Multiforme 3 Vaginitis/Vaginal Bleeding/Vaginal Discharge 3 Vasodilation 2 * Most events were mild or moderate in severity. 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. Table 3. Adverse Reactions Occurring in ≥2 % in Pediatric Patients with CPP Receiving LUPRON DEPOT-PED for 3-month administration. % 11.25 mg every 3 Months N=42 % 30 mg every 3 Months N=42 % Overall N = 84 Injection site pain 19 21 20 Weight increased 7 7 7 Headache 2 7 5 Mood altered 5 5 5 Injection site swelling 2 2 2 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. Table 4. Adverse Reactions Occurring in ≥4% in Pediatric Patients with CPP Receiving LUPRON DEPOT-PED for 6-month administration. Total (N = 45) n (%) Injection Site Reactions a 35 (78%) Headache b 15 (33%) Psychiatric Events c 10 (22%) Abdominal Pain d 8 (18%) Diarrhea e 7 (16%) Hemorrhage f 6 (13%) Nausea and Vomiting 6 (13%) Pyrexia 6 (13%) Pruritus g 5 (11%) Pain in extremity 4 (9%) Rash 3 (7%) Back Pain 3 (7%) Ligament sprain 3 (7%) Weight increased 3 (7%) Fracture h 2 (4%) Breast tenderness i 2 (4%) Insomnia j 2 (4%) Chest pain 2 (4%) Hyperhidrosis 2 (4%) a Injection site reactions includes the preferred terms injection site pain, injection site erythema, injection site reaction, injection site warmth, injection site bruising, injection site discomfort, and injection site swelling b - Headache includes the preferred terms headache and cluster headache c Psychiatric events includes the preferred terms affect lability, affective disorder, aggression, crying, depressed mood, disruptive mood dysregulation disorder, hallucination auditory, mood altered, mood swings, and trichotillomania d Abdominal pain includes the preferred terms abdominal pain, abdominal pain upper, and abdominal discomfort e Diarrhea includes the preferred terms gastroenteritis and diarrhea f Hemorrhage includes the preferred terms contusion, epistaxis, hematochezia, and injection site bruising g Pruritus includes the preferred terms pruritus, vulvovaginal pruritus, nasal pruritus h Fracture includes the preferred terms ankle fracture and tibia fracture i Breast tenderness includes the preferred terms breast pain and breast tenderness j Insomnia includes the preferred terms initial insomnia and insomnia

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of LUPRON DEPOT-PED or GnRH agonists 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 disorders and administration site conditions : chest pain, weight increase, decreased appetite, fatigue, injection site reactions including induration, abscess, and necrosis. Laboratory Abnormalities : decreased WBC. Metaboli c : 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 : flushing, hyperhidrosis, erythema multiforme, bullous dermatitis, dermatitis exfoliative, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome and toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. Vascular Disorders : hypertension, hypotension.

Drug Interactions No pharmacokinetic-based drug-drug interaction studies have been conducted with

LUPRON DEPOT-PED .

Drug-Laboratory Test Interactions

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.

Pregnancy Risk Summary LUPRON DEPOT-PED is contraindicated in pregnancy. 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. 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.

Pediatric Use 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 . The safety and effectiveness of LUPRON DEPOT-PED have not been established in pediatric patients less than 1 year old.

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 . Pregnancy: LUPRON DEPOT-PED may cause fetal harm . Hypersensitivity reactions to GnRH, GnRH agonists or any of the excipients in LUPRON DEPOT-PED Pregnancy

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.