LUPRON DEPOT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LUPRON DEPOT (LUPRON DEPOT).
Gonadotropin-releasing hormone (GnRH) agonist. Continuous administration suppresses pituitary gonadotropin (LH and FSH) secretion, leading to reduced gonadal steroidogenesis (testosterone and estrogen). Initial transient stimulation may occur.
| Metabolism | Primarily hepatic via peptide hydrolysis; not significantly metabolized by cytochrome P450 enzymes. |
| Excretion | Primarily renal (90% as unchanged drug and metabolites); biliary/fecal elimination is minimal. |
| Half-life | Terminal elimination half-life is approximately 3 hours after single subcutaneous dose; with depot formulations, the apparent half-life is prolonged due to slow release (e.g., 1-month depot: 30 days). |
| Protein binding | Approximately 90% bound to serum proteins, primarily sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | Apparent volume of distribution is about 2–3 L/kg, indicating extensive tissue distribution and binding to pituitary and gonadal tissues. |
| Bioavailability | Subcutaneous depot: near 100% bioavailability due to sustained release; oral: negligible (<1%) due to first-pass metabolism and peptide degradation. |
| Onset of Action | Subcutaneous injection: suppression of LH and FSH occurs within 2–4 weeks; peak testosterone suppression in prostate cancer achieved in 2–4 weeks. |
| Duration of Action | Depot formulations provide sustained drug release: 1-month depot (7.5 mg) suppresses testosterone for 28–32 days; 3-month depot (22.5 mg) for up to 90 days; 4-month depot (30 mg) for up to 120 days. |
3.75 mg IM monthly for endometriosis; 3.75 mg IM monthly or 11.25 mg IM every 3 months for central precocious puberty; 7.5 mg IM monthly for prostate cancer.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; limited data in severe renal impairment. |
| Liver impairment | No specific dose adjustment recommended; caution in severe hepatic impairment. |
| Pediatric use | Central precocious puberty: 0.3 mg/kg IM every 28 days (minimum 3.75 mg). |
| Geriatric use | No specific dose adjustment; use with caution due to increased risk of bone loss and cardiovascular effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LUPRON DEPOT (LUPRON DEPOT).
| Breastfeeding | Leuprolide is excreted in human breast milk; M/P ratio is unknown. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Pregnancy Category X. First trimester: High risk of spontaneous abortion and major congenital malformations including central nervous system and cardiovascular defects. Second and third trimesters: Continued risk of fetal harm, including potential for fetal androgen deprivation effects. Contraindicated in women who are or may become pregnant. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to leuprolide or any component","Pregnancy (category X)","Undiagnosed abnormal vaginal bleeding","Breastfeeding (not recommended)","Use in women who may become pregnant without effective contraception"]
| Precautions | ["Tumor flare (transient increase in testosterone/estrogen with potential worsening of symptoms)","Hypersensitivity reactions (anaphylaxis, urticaria)","Pituitary apoplexy (rare, in pituitary adenoma patients)","Bone density loss with prolonged use","QT prolongation risk","Hyperglycemia and diabetes risk (in prostate cancer patients)","Cardiovascular disease risk (in men with prostate cancer)","Convulsions (rare)","Embryo-fetal toxicity"] |
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| Fetal Monitoring | Monitor pregnancy status with serum β-hCG prior to each injection. If exposed during pregnancy, assess fetal development with detailed ultrasound and echocardiography. Monitor maternal bone mineral density due to estrogen suppression. |
| Fertility Effects | Suppresses gonadotropin secretion leading to inhibition of ovulation and spermatogenesis. Reversible after discontinuation; however, delay in return of fertility may occur. Not indicated for use in women desiring pregnancy. |