Introduction
Lupron Depot (leuprolide acetate) is a gonadotropin-releasing hormone (GnRH) agonist manufactured by AbbVie. It is available as a long-acting depot formulation administered via intramuscular or subcutaneous injection. This medication is primarily used to suppress sex hormone production through its action on the pituitary gland, making it valuable in treating various hormone-dependent conditions.
Mechanism of Action
Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH). Initially, it stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. However, with continuous administration, it causes downregulation of GnRH receptors in the pituitary, leading to suppressed secretion of FSH and LH. This results in markedly reduced production of testosterone in men and estrogen in women.
Indications
FDA-approved indications include:
- Treatment of advanced prostate cancer
- Management of central precocious puberty (CPP)
- Endometriosis management (typically limited to 6 months)
- Uterine fibroid management (preoperative with iron therapy)
- Assisted reproductive technology (ovarian suppression)
Dosage and Administration
Prostate cancer:- 7.5 mg IM monthly
- 22.5 mg IM every 3 months
- 30 mg IM every 4 months
- 45 mg IM every 6 months
- 0.3 mg/kg IM every 4 weeks (minimum 7.5 mg)
- Dose adjustment based on clinical response and hormonal levels
- 3.75 mg IM monthly for up to 6 months
- 11.25 mg IM every 3 months for up to 6 months
Administration requires proper reconstitution with provided diluent. Injection sites should be rotated. Dosage adjustments may be necessary in hepatic impairment.
Pharmacokinetics
Absorption: Slowly released from depot formulation over weeks to months Distribution: Widely distributed throughout body Metabolism: Undergoes hydrolysis in the liver Elimination: Half-life approximately 3 hours; primarily excreted renally Onset of action: Initial gonadotropin surge within first week, followed by suppression within 2-4 weeksContraindications
- Hypersensitivity to GnRH agonists or any product components
- Undiagnosed abnormal vaginal bleeding
- Pregnancy (Category X)
- Breastfeeding
- Women who may become pregnant during treatment
Warnings and Precautions
Initial Disease Flare: May cause temporary symptom exacerbation in prostate cancer patients during first weeks of therapy Cardiovascular risks: Increased risk of myocardial infarction, sudden cardiac death, and stroke Bone density loss: Significant bone mineral density reduction may occur with long-term use Diabetes and cardiovascular risk factors: May worsen glucose tolerance and cardiovascular risk profile Pituitary apoplexy: Rare cases reported, with symptoms including sudden headache, visual changes, and ophthalmoplegia Convulsions: Reported in patients with and without history of seizuresDrug Interactions
- No known clinically significant pharmacokinetic drug interactions
- Potential additive effects with other hormone therapies
- May affect metabolism of drugs metabolized by cytochrome P450 enzymes due to altered hormone levels
Adverse Effects
Common (>10%):- Hot flashes (50-80%)
- Injection site reactions
- Fatigue
- Headache
- Nausea
- Edema
- Bone pain
- Constipation
- Cardiovascular events (MI, stroke, sudden death)
- Spinal cord compression in prostate cancer patients
- QT prolongation
- Severe allergic reactions
- Seizures
- Pituitary apoplexy
- Severe bone density loss
Monitoring Parameters
- Testosterone levels (prostate cancer)
- Estradiol levels (gynecological indications)
- LH and FSH levels
- Bone mineral density (baseline and periodically)
- PSA levels (prostate cancer)
- Complete blood count, liver function tests
- Cardiovascular assessment
- Growth parameters in pediatric patients
- Signs of disease flare during initial treatment
Patient Education
- Expect initial symptom flare in first 1-2 weeks of treatment
- Report any new or worsening symptoms immediately, especially cardiovascular or neurological symptoms
- Understand that fertility will be suppressed during treatment
- Use non-hormonal contraception during and after treatment until menses resume
- Maintain adequate calcium and vitamin D intake to support bone health
- Regular follow-up appointments are essential
- Proper injection technique if self-administering
- Report injection site reactions that persist or worsen
References
1. Lupron Depot Prescribing Information. AbbVie Inc. 2023. 2. Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA. 2005;294(2):238-244. 3. Lemay A, Maheux R, Huot C, et al. Efficacy of intranasal or subcutaneous luteinizing hormone-releasing hormone agonist inhibition of ovarian function in the treatment of endometriosis. Am J Obstet Gynecol. 1988;158(2):233-236. 4. FDA Drug Safety Communication: GnRH agonists. U.S. Food and Drug Administration. 2010. 5. Smith MR, Saad F, Coleman R, et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379(9810):39-46. 6. Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009;123(4):e752-e762.