LUPRON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LUPRON (LUPRON).
Gonadotropin-releasing hormone (GnRH) agonist. Chronic administration suppresses pituitary gonadotropin secretion, leading to decreased testosterone and estradiol levels.
| Metabolism | Primarily metabolized by peptidases in the liver and kidneys; no significant CYP450 involvement. |
| Excretion | Renal (primarily as metabolites), <5% unchanged; fecal ~5% |
| Half-life | Terminal half-life approximately 3 hours after subcutaneous administration; in patients with renal impairment, half-life may be prolonged |
| Protein binding | Approximately 40-50% bound to plasma proteins (mainly albumin) |
| Volume of Distribution | 0.3-0.5 L/kg; distributes mainly into extracellular fluid; higher Vd in elderly |
| Bioavailability | Subcutaneous: ~90-100%; intramuscular: ~100%; intranasal: only investigative (not approved) |
| Onset of Action | Subcutaneous: suppression of LH and FSH within 2-4 weeks; intramuscular: similar; initial transient stimulation phase lasts about 1 week |
| Duration of Action | Subcutaneous depot formulations: 1-4 months depending on formulation; IM depot: 1-3 months; clinical effects persist for duration of dosing |
3.75 mg intramuscularly once monthly or 11.25 mg intramuscularly once every 3 months. For endometriosis, 3.75 mg intramuscularly monthly for up to 6 months. For central precocious puberty, 0.3 mg/kg intramuscularly every 28 days.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | For central precocious puberty: Weight-based dosing. Body weight ≤25 kg: 7.5 mg intramuscularly every 28 days; >25 to 37.5 kg: 11.25 mg intramuscularly every 28 days. Alternatively, 0.3 mg/kg intramuscularly every 28 days. |
| Geriatric use | No specific dose adjustment; use with caution due to potential increased sensitivity in elderly patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LUPRON (LUPRON).
| Breastfeeding | Leuprolide (LUPRON) is excreted in human breast milk. M/P ratio not specifically reported. Due to potential for serious adverse reactions in nursing infants, including hormonal effects, breastfeeding is not recommended during treatment and for at least 1 month after last dose. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: High risk of spontaneous abortion and major congenital malformations, including neural tube defects and cardiovascular anomalies. Second/third trimesters: Continued risk of fetal harm, including potential for delayed fetal development and endocrine disruption. Contraindicated in pregnancy. |
■ FDA Black Box Warning
WARNING: LUPRON has been associated with an increased risk of myocardial infarction, sudden cardiac death, and stroke in men with prostate cancer. Androgen deprivation therapy may contribute to cardiovascular risk.
| Serious Effects |
["Hypersensitivity to leuprolide acetate or any component","Pregnancy (Category X; risk of fetal harm)","Undiagnosed abnormal vaginal bleeding","Use in women who are or may become pregnant"]
| Precautions | ["Cardiovascular disease risk (MI, stroke, sudden cardiac death)","Hyperglycemia and diabetes risk","Bone density loss and osteoporosis","QT prolongation risk","Seizure risk in patients with CNS disorders","Tumor flare reaction initially in prostate cancer","Hypersensitivity reactions","Spinal cord compression in prostate cancer"] |
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| Fetal Monitoring | Pregnancy test before initiating therapy; confirm non-pregnant status. Monitor for signs of pregnancy during treatment (e.g., missed menses). If pregnancy occurs, discontinue immediately and assess fetal wellbeing via ultrasound and maternal serum markers. Monitor maternal bone mineral density if prolonged use. |
| Fertility Effects | Suppresses pituitary-ovarian axis, inhibiting ovulation and potentially impairing fertility during treatment. Effects are reversible upon discontinuation. May cause temporary infertility. In females, resumption of ovulation typically occurs within weeks to months after cessation. |