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. |
| Molecular Weight | 1209.5 Da |
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 | Contraindicated due to risk of pregnancy loss and congenital anomalies; leuprolide can cause fetal harm when administered to pregnant women. |
| 2nd trimester | Contraindicated; continued exposure may lead to fetal developmental abnormalities. |
| 3rd trimester | Contraindicated; risks of preterm labor and fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for LUPRON DEPOT (LUPRON DEPOT).
| Placental transfer | Leuprolide crosses the placenta; animal studies have demonstrated fetal toxicity. |
| Breastfeeding | It is unknown if leuprolide is excreted in human milk. Due to its hormonal activity and potential for serious adverse effects in nursing infants, breast-feeding is not recommended during therapy. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyHypersensitivity to leuprolide acetate or any component of the formulationUndiagnosed abnormal vaginal bleeding
| 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 |
| Food/Dietary | No significant food interactions reported. Avoid grapefruit products if taking concomitant CYP3A4 substrates, though no specific interaction with leuprolide. |
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| L5 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | For endometriosis, initial flare of symptoms may occur due to transient estrogen surge. In prostate cancer, monitor PSA and testosterone levels. Do not use as monotherapy in prostate cancer beyond 6 months without concomitant antiandrogen to prevent flare. Depot formulations require deep IM injection, not IV or SC. Avoid in pregnancy; confirm negative pregnancy test before starting. |
| Patient Advice | This drug is given as an injection into a muscle, usually in the buttock or thigh, by a healthcare professional. · You may experience hot flashes, sweating, vaginal dryness, or decreased libido due to hormone suppression. · For endometriosis, symptoms may temporarily worsen in the first few weeks of treatment. · Do not become pregnant while on this medication; use effective non-hormonal contraception. · Inform your doctor if you have a history of depression, seizures, or diabetes. · Regular monitoring of bone mineral density may be recommended for long-term use. |