leuprolide acetate

Clinical summary

Indications and usage INDICATIONS AND USAGE Leuprolide acetate injection is indicated in the palliative treatment of advanced prostatic cancer. Dosage and administration DOSAGE AND ADMINISTRATION The recommended dose is 1 mg (0.2 mL or 20 unit mark) administered as a single daily subcutaneous injection. As with other drugs administered chronically by subcutaneous injection, the injection site should be varied periodically. Each 0.2 mL contains 1 mg of leuprolide acetate, sodium chloride for tonicity adjustment, 1.8 mg of benzyl alcohol as preservative and water for injection. The pH may have been adjusted with sodium hydroxide and/or glacial acetic acid. Follow the pictorial directions on the reverse side of this package insert for administration. NOTE: As with all parenteral products, inspect the solution for discoloration and particulate matter before each use. Warnings and cautions WARNINGS Initially, leuprolide acetate injection, like other LH-RH agonists, causes increases in serum levels of testosterone. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostate cancer, may occasionally develop during the first few weeks of leuprolide acetate injection treatment. A small number of patients may experience a temporary increase in bone pain, which can be managed symptomatically. As with other LH-RH agonists, isolated cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications. Safe use of leuprolide acetate in pregnancy has not been established clinically. Leuprolide acetate injection may cause fetal harm. Periodic monitoring of serum testosterone and prostate-specific antigen (PSA) levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. It should be noted that 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. Severe Cutaneous Adverse Reactions Leuprolide acetate injection can cause severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). SCARs, including SJS/TEN, DRESS, and AGEP, occurred in patients receiving leuprolide acetate injection; including cases with visceral involvement and/or requiring skin grafts [see Adverse Reactions ]. Monitor patients for the development of SCARs. If a SCAR is suspected, interrupt leuprolide acetate injection 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 leuprolide acetate injection. Drug interactions Drug Interactions See CLINICAL PHARMACOLOGY , Pharmacokinetics section. Pregnancy Pregnancy Risk Summary Based on findings in animal studies and mechanism of action, leuprolide acetate injection may cause fetal harm when administered to a pregnant woman. 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 acetate 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 the monthly formulation of leuprolide acetate administered on day 6 of pregnancy at test dosages of 0.00024 mg/kg, 0.0024 mg/kg, and 0.024 mg/kg (approximately 1/600 to 1/6 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 acetate in rabbits and with the highest dose in rats.