Lupron Depot Ped Drug Information

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

Dosage and Recommended Monitoring for 1-Month Administration Administer LUPRON DEPOT-PED 7.5 mg, 11.25 mg, or 15 mg for 1-month administration as a single-dose intramuscular injection once every month. The starting dose is based on the patient's weight (see Table 1). The dosage may need to be adjusted with changes in body weight.

If adequate hormonal and clinical suppression is not achieved with the starting dose, increase the dosage to the next available higher dose (e.g., 11.25 mg or 15 mg at the next monthly injection). Monitor response with a GnRH stimulation test, basal luteinizing hormone (LH) or serum concentration of sex steroid levels beginning 1 to 2 months following initiation of therapy, with changing doses, or further as judged clinically appropriate in order to confirm maintenance of efficacy. Monitor response with a GnRH stimulation test, basal LH or serum concentration of sex steroid levels at months 2 to 3, month 6 and further as judged clinically appropriate, to confirm maintenance of efficacy.

Assess height (for calculation of growth rate) and bone age every 6 to 12 months.

Dosage and Recommended Monitoring for 6-Month Administration Use LUPRON DEPOT-PED 45 mg for 6-month administration once every six months (24 weeks) as a single-dose intramuscular injection.

Important Administration Instructions Administer LUPRON

DEPOT-PED as a single-dose intramuscular injection into the gluteal area, anterior thigh, or shoulder. Rotate injection sites within the same region from one injection to the next. Inject immediately after reconstitution.

Discard if not used within 2 hours.

Reconstitution Instructions 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. Figure 2 3.

Hold the syringe upright. 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

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

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.

The baseline age ranged from 4 to 10 years.

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 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.

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.