Leuprolide acetate

Indications

Leuprolide acetate is used for: Uterine fibroids, Endometriosis, Prostate cancer

Adult Dose

Advanced Prostate Cancer Recommended Dose: 1 mg (0.2 mL) administered as a single daily SC injection. Endometriosis 3.75 mg IM monthly for up to 6 months or 11.25 mg IM every 3 months for 2 doses (6 months total) Recommended duration of treatment is 6 months; may treat again for additional 6 months, but with concomitant administration of norethindrone Uterine Leiomyomata (Fibroids) 3.75 mg IM monthly for up to 3 months or 11.25 mg IM once Use concomitant iron treatment

Child Dose

Central Precocious Puberty Indicated when signs of sexual maturity begin to develop in girls <8 years old and boys <9 years old; may be discontinued at appropriate age of onset of puberty (eg, 11 years in females and 12 years in males), at physician's discretion 50 mcg/kg/day SC; may be titrated upward by 10 mcg/kg/day if downregulation not achieved <2 years old: Safety and efficacy not established

Renal Dose

Administration

Contra Indications

Pregnancy, lactation; hypersensitivity to GnRH, GnRH agonist analogs or product excipients; undiagnosed abnormal vaginal bleeding.

Precautions

Vary inj site periodically. May cause transient elevation of testosterone levels during the first 1-2 wk, which may lead to worsening or onset of new symptoms (e.g. bone pain, neuropathy, haematuria) in prostate cancer patients. Ureteral obstruction and spinal cord compression have been reported; closely monitor patients with urinary obstruction and/or metastatic vertebral lesion. Leuprorelin is associated with increased risk of diabetes and certain CV diseases (heart attack, sudden cardiac death, stroke) when used in men for treatment of prostate cancer. For prostate cancer, monitor response by testosterone and prostate-specific antigen (PSA) levels. For precocious puberty in children, monitor response by GnRH stimulation test sex steroid levels 1-2 month after treatment initiation. Leuprorelin usually inhibits ovulation and stops menstruation in women, but does not incur contraception, non-hormonal contraception should be used as pregnancy is contraindicated. May cause adverse reactions associated with hypoestrogenism and loss in bone density. Lactation: Contraindicated; not known if drug is excreted in breast milk; make decision to either discontinue nursing or discontinue drug, taking into account risk and benefits to the mother

Pregnancy-Lactation

Pregnancy There are no available data in pregnant women to inform the drug-associated risk Based on findings in animal studies and mechanism of action, therapy may cause fetal harm when administered to a pregnant woman Advise pregnant patients and females of reproductive potential of the potential risk to the fetus Based on findings in animals and mechanism of action, therapy may impair fertility in males of reproductive potential Animal data 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 Lactation The safety and efficacy of therapy have not been established in females; there is no information regarding presence of drug in human milk, the effects on breastfed child, or on milk production; because many drugs are excreted in human milk and because of potential for serious adverse reactions in a breastfed child from therapy, a decision should be made to discontinue breastfeeding or discontinue drug, taking into account importance of drug to mother

Interactions

Adverse Effects

Side effects of Leuprolide acetate : >10% Hot flashes (57%), Cardiovascular changes or ischemia (19%), Fatigue (18%), Pain (13%), Peripheral edema (12%) 1-10% Asthenia (10%), Gynocomastia (7%), Headache (7%), Testicular atrophy (7%), Anorexia (6%), Anemia (5%), Bone pain (5%), Constipation (7%), Urinary frequency (6%), Dermatitis (5%), Dizziness (5%), Nausea and vomiting (5%), Gastroenteritis (3%), Myalgia (3%), UTI (3%), Dyspnea (2%) Frequency Not Defined Convulsion, Depression, Neuropathy, Decreased bone density, Hematuria, Obstruction of ureter or bladder, Impotence, Sweating, Implant site reactions (pain, bruising, edema), Spinal cord compression (rare)

Mechanism of Action

Leuprorelin is a gonadotropin-releasing hormone (GnRH) analogue. Following an initial stimulation of gonadotrophins, continuous admin of Leuprorelin leads to down regulation of GnRH receptors and subsequently reduces pituitary gonadotrophin secretion. Reduced gonadotrophin levels lead to inhibition of sex hormone (testosterone and oestrogen) production. Within 2-4 wk after treatment initiation, testosterone levels in male may be reduced to below castrate threshold.