Drug reference

leuprolide

GnRH agonist analogue · Palliative therapy of hormone-responsive tumors, treatment of endometriosis, treatment of uterine fibroids, treatment of central precocious puberty, diagnostic agent

GnRH agonist analoguePalliative therapy of hormone-responsive tumors, treatment of endometriosis, treatment of uterine fibroids, treatment of central precocious puberty, diagnostic agentATC null

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

FDA category + note

Top interactionssee all 12 →

AmiodaroneSevereDatabaseDDInter
AmisulprideSevereDatabaseDDInter
AnagrelideSevereDatabaseDDInter
Arsenic TrioxideSevereDatabaseDDInter

Mechanism

A synthetic agonist congener of GnRH. After a transient stimulation of gonadotropin secretion, it downregulates the GnRH receptor and inhibits gonadotropin secretion. Exhibits enhanced potency and prolonged duration of action compared to native GnRH.

Indications

EndometriosisUterine fibroidsAdvanced prostate cancerCentral precocious pubertyDiagnosis of GnRH-dependent precocious pubertyuterine leiomyomasprecocious pubertymenstrual suppressioncontrolled ovarian hyperstimulationAndrogen deprivation therapy (ADT) for all forms of advanced prostate cancerProstate cancer in conjunction with radiation therapy or in some cases following surgical removal of the prostate gland (for localized intermediate- to high-risk)Adjuvant treatment of breast cancer or metastatic disease for premenopausal women (in combination with tamoxifen or AIs)Suppression of ovarian estrogen and progesterone production in pre- and perimenopausal womenPalliation of carcinoma prostateConditions needing long term Gn suppressionOvarian suppression for premenopausal women with higher risk tumors (in combination with tamoxifen or AI for 5 years)For premenopausal women with ER-positive metastatic breast cancer (with aromatase inhibitor and CDK4/6 inhibitor)For male breast cancer where an AI is indicated (concomitant administration with AI)Concurrent administration with adjuvant chemotherapy for fertility preservation

Dosing

Adult: Subcutaneous (1 mg/day); subcutaneous depot (7.5 mg/month; 22.5 mg/3 months; 30 mg/4 months; 45 mg/6 months); intramuscular depot (3.75 mg/month; 11.25 mg/3 months). For endometriosis, once-monthly injections (3.75 mg) or 3-month injections (11.25 mg) are also copackaged in combination with once-daily norethindrone (a steroidal progestin) 5-mg tablets for oral administration.
Pediatric: Pediatric formulations are approved for central precocious puberty.

Pharmacokinetics

Onset

Initial rise in LH and FSH levels, followed by sustained decrease in serum LH and estrogen (women) or testosterone (men) after 14 to 21 days. Castrate testosterone levels achieved within 3 to 4 weeks in men.

Contraindications

Pregnant women

Side effects

Common

Hot flashesDecreased bone densityVaginal dryness (women)Vaginal atrophy (women)Erectile dysfunction (men)Vasomotor symptoms (hot flashes)Vaginal drynessDecreased libidoOsteoporosisAmenorrheaDyspareuniaVasomotor instabilityImpotenceGynecomastiaFatigueAnemiaWeight gainDecreased insulin sensitivityAltered lipid profilesFracturesLoss of muscle massLoss of libidoEmotional labilityPostmenopausal symptoms

Serious

risk of osteoporosis (with long-term use)
estrogen withdrawal symptoms (e.g., hot flashes)
Testosterone flare (transient rise in testosterone leading to acute stimulation of prostate cancer growth and symptoms, typically lasting 2 to 3 weeks)
Increased risk of diabetes
Increased risk of coronary heart disease
Bone loss