Usage
Leuprolide is prescribed for various conditions, including:
- Prostate Cancer: Palliative treatment of advanced prostate cancer.
- Endometriosis: Management of endometriosis symptoms.
- Uterine Fibroids: Preoperative treatment to reduce fibroid size and bleeding.
- Central Precocious Puberty (CPP): Treatment of early onset puberty in children.
- Breast Cancer (in premenopausal women): Adjuvant treatment for hormone receptor-positive breast cancer.
- Prostate Cancer: As part of androgen deprivation therapy (ADT).
Pharmacological Classification: Gonadotropin-releasing hormone (GnRH) agonist.
Mechanism of Action: Leuprolide initially stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). However, continuous administration leads to downregulation of GnRH receptors, ultimately suppressing the release of LH and FSH. This results in decreased estrogen production in women and decreased testosterone production in men.
Alternate Names
Leuprolide acetate
Brand Names: Lupron, Lupron Depot, Lupron Depot-Ped, Eligard, Camcevi, Fensolvi, Viadur.
How It Works
Pharmacodynamics: Leuprolide acts as a GnRH agonist, initially stimulating and subsequently suppressing the release of gonadotropins (LH and FSH) from the pituitary gland. This leads to a decrease in sex hormones (estrogen in women and testosterone in men).
Pharmacokinetics:
- Absorption: Variable depending on the formulation and route of administration. Depot formulations provide sustained release.
- Metabolism: Primarily hepatic and renal enzymatic degradation.
- Elimination: Excreted mainly through the kidneys, with a small amount in feces. The terminal half-life is approximately 3 hours for immediate-release formulations and longer for depot formulations.
Mode of Action: Leuprolide binds to GnRH receptors in the pituitary gland. Initially, this binding stimulates LH and FSH release. However, continuous exposure leads to receptor desensitization and downregulation, ultimately suppressing gonadotropin secretion.
Receptor Binding: GnRH receptor agonist.
Elimination Pathways: Renal and hepatic.
Dosage
Standard Dosage
Adults:
- Prostate Cancer: 7.5 mg IM monthly, 22.5 mg IM every 3 months, 30 mg IM every 4 months, or 45 mg IM every 6 months. Subcutaneous formulations are also available with similar dosing regimens.
- Endometriosis: 3.75 mg IM monthly or 11.25 mg IM every 3 months.
- Uterine Fibroids: 3.75 mg IM monthly for up to 3 months preoperatively.
Children (CPP):
- Dosage is based on body weight and should be individualized.
- Various IM and subcutaneous formulations are available with different dosing regimens.
- Monitoring of hormone levels is essential for dosage adjustment.
Special Cases:
- Elderly Patients: No specific dosage adjustments are typically required.
- Patients with Renal Impairment: Caution is advised. Dose adjustment may be needed in severe renal impairment.
- Patients with Hepatic Dysfunction: Dose adjustment may be needed in severe hepatic impairment.
- Patients with Comorbid Conditions: Consider individual patient factors, especially cardiovascular disease, diabetes, osteoporosis, seizures, and QT prolongation.
Clinical Use Cases
Leuprolide is not typically used in the context of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. It is primarily used for chronic conditions like prostate cancer, endometriosis, uterine fibroids, and central precocious puberty.
Dosage Adjustments
Dose adjustments should be considered based on patient response, tolerability, and comorbidities like renal or hepatic dysfunction.
Side Effects
Common Side Effects:
Hot flashes, injection site reactions, fatigue, headache, nausea, decreased libido, erectile dysfunction, gynecomastia in men, vaginal dryness in women, mood changes.
Rare but Serious Side Effects:
Pituitary apoplexy, QT prolongation, seizures, allergic reactions (including anaphylaxis), osteoporosis/bone fractures with prolonged use.
Long-Term Effects:
Osteoporosis, increased risk of cardiovascular events (in men with prostate cancer).
Adverse Drug Reactions (ADR):
Anaphylaxis, pituitary apoplexy, QT prolongation, seizures.
Contraindications
- Hypersensitivity to leuprolide or other GnRH agonists.
- Pregnancy and breastfeeding.
- Undiagnosed vaginal bleeding.
Drug Interactions
Leuprolide can interact with various medications, including drugs that prolong the QT interval, such as certain antiarrhythmics and some antibiotics. It’s important to review a comprehensive drug interaction list before prescribing. Interactions with alcohol, smoking and other lifestyle factors are not prominently described in the information available.
Pregnancy and Breastfeeding
Pregnancy Safety Category: X (contraindicated). Leuprolide can cause fetal harm. A negative pregnancy test should be confirmed before initiating treatment in women of reproductive potential. Effective non-hormonal contraception is required during treatment.
Breastfeeding: Leuprolide is contraindicated during breastfeeding. It’s unknown if it passes into breast milk.
Drug Profile Summary
- Mechanism of Action: GnRH agonist, suppresses gonadotropin release, leading to decreased sex hormone production.
- Side Effects: Hot flashes, injection site reactions, fatigue, decreased libido, erectile dysfunction, osteoporosis.
- Contraindications: Hypersensitivity, pregnancy, breastfeeding, undiagnosed vaginal bleeding.
- Drug Interactions: Drugs that prolong QT interval.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Varies depending on indication and formulation.
- Monitoring Parameters: Sex hormone levels, PSA levels (in prostate cancer), bone mineral density with long-term use.
Popular Combinations
Leuprolide is sometimes used in combination with an anti-androgen (like bicalutamide) in the treatment of prostate cancer. Add-back therapy (estrogen/progestin) may be used with leuprolide in women to mitigate side effects like hot flashes and bone loss. Norethindrone acetate can be used to improve anaemia in women with uterine fibroids before fibroid surgery.
Precautions
- Monitor for disease flare during initial treatment.
- Monitor bone mineral density in long-term use.
- Assess for cardiovascular risk factors in men receiving treatment for prostate cancer.
- Ensure appropriate contraception in women of reproductive potential.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Leuprolide?
A: Dosage varies depending on the indication, patient age, and formulation. Consult the detailed dosage section above for specifics.
Q2: How does Leuprolide work in prostate cancer?
A: It reduces testosterone levels, which can slow the growth of prostate cancer.
Q3: What are the common side effects of Leuprolide in women?
A: Hot flashes, vaginal dryness, decreased libido, mood changes.
Q4: Can Leuprolide be used during pregnancy?
A: No, it’s contraindicated during pregnancy as it can harm the fetus.
Q5: What are the long-term risks of Leuprolide treatment?
A: Osteoporosis and increased risk of cardiovascular events (in men with prostate cancer).
Q6: How is CPP treated with Leuprolide?
A: Dosage is individualized based on the child’s weight and response.
Q7: How long does it take for Leuprolide to start working?
A: Effects can be seen within a few weeks, but maximal suppression of sex hormones may take several months.
Q8: What should patients be monitored for during Leuprolide treatment?
A: Sex hormone levels, disease flare (initially), bone mineral density (long-term), and potential drug interactions.
Q9: What are the contraindications for the use of Leuprolide?
A: Hypersensitivity to the drug, pregnancy, breastfeeding, undiagnosed vaginal bleeding.
Q10: Can Leuprolide be used for other cancers than prostate cancer?
A: Yes. Leuprolide can be used for the treatment of premenopausal breast cancer.
