Of course. Here is a comprehensive, evidence-based drug monograph for Eligard, formatted as a complete blog post.
*Introduction
Eligard (leuprolide acetate) is a long-acting injectable formulation of a gonadotropin-releasing hormone (GnRH) agonist. It is classified as an androgen deprivation therapy (ADT) and is primarily used in the management of advanced prostate cancer. By suppressing the production of testosterone, a hormone that fuels prostate cancer growth, Eligard induces a state of medical castration, effectively slowing disease progression.
Mechanism of Action
Leuprolide acetate is a synthetic analog of the naturally occurring GnRH. Its mechanism is biphasic: 1. Initial Stimulation (Flare Effect): Upon initial administration, leuprolide binds to and stimulates pituitary GnRH receptors. This causes a transient surge in the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a temporary increase in testosterone production (often seen within the first 1-2 weeks). 2. Long-Term Suppression: With continuous administration, the sustained receptor stimulation leads to downregulation and desensitization of pituitary GnRH receptors. This effectively inhibits the secretion of LH and FSH. The subsequent dramatic reduction in testicular testosterone production results in castrate levels of serum testosterone (< 50 ng/dL or < 1.7 nmol/L).
Indications
Eligard is approved for the palliative treatment of advanced prostate cancer. * Locally advanced (Stage T3-T4) carcinoma of the prostate * Metastatic (Stage D2) carcinoma of the prostate
Dosage and Administration
Eligard is administered as a subcutaneous injection only. It must be prepared by a healthcare professional immediately prior to administration. * Available Formulations: * Eligard 7.5 mg: administered every month * Eligard 22.5 mg: administered every 3 months * Eligard 30 mg: administered every 4 months * Eligard 45 mg: administered every 6 months * Administration: The injection is typically given in the upper arm, abdomen, or buttock. The site should be rotated with each injection. * Special Populations: * Renal/Hepatic Impairment: No specific dosage adjustment is recommended, but caution is advised. * Geriatric Patients: Dosing is not significantly different from that of younger adult patients.
Pharmacokinetics
* Absorption: Following subcutaneous injection, leuprolide acetate is released from the polymer matrix over the specified duration (1, 3, 4, or 6 months). The initial "flare" in testosterone levels occurs within the first few days, with castration levels achieved by the end of the second week and maintained for the duration of the dosing interval. * Distribution: The mean steady-state volume of distribution is high (~60 L), indicating extensive tissue distribution. * Metabolism: Leuprolide is metabolized by peptidase activity throughout the body. It is not significantly metabolized by cytochrome P450 enzymes. * Elimination: The mean systemic clearance is approximately 8 L/h. It is eliminated primarily by the kidneys, with less than 5% excreted as unchanged drug.
Contraindications
Eligard is contraindicated in patients with: * Known hypersensitivity to GnRH, GnRH agonist analogs, or any of the components of Eligard (including the Atrigel® delivery system). * Women who are or may become pregnant (not indicated for use in women).
Warnings and Precautions
* Tumor Flare Phenomenon: A temporary increase in serum testosterone levels during the first weeks of treatment can cause a worsening of signs and symptoms, including bone pain, spinal cord compression, and urinary obstruction. Patients with vertebral metastases or urinary tract obstruction are at particular risk. Closely monitor patients during the first few weeks of therapy. * Hyperglycemia/Diabetes: Androgen deprivation therapy can increase the risk of developing diabetes mellitus. Monitor blood glucose and manage according to current clinical practice. * Cardiovascular Disease: ADT is associated with an increased risk of myocardial infarction, sudden cardiac death, and stroke. Evaluate cardiovascular risk prior to and during therapy. * QT Prolongation: Androgen deprivation therapy may prolong the QT interval. Consider the risks and benefits in patients with congenital long QT syndrome, congestive heart failure, or those taking concomitant drugs known to prolong the QT interval. * Bone Loss: Significant bone mineral density loss can occur, increasing the risk of fractures. Assess bone health and consider bone density monitoring and prophylactic treatment. * Pituitary Apoplexy: Rare cases have been reported, often presenting as sudden headache, vomiting, visual changes, ophthalmoplegia, and altered mental status. Requires immediate medical attention.
Drug Interactions
* Drugs that Prolong the QT Interval: Concomitant use with other QT-prolonging agents (e.g., certain antiarrhythmics, antipsychotics, antibiotics) may have additive effects. Monitor accordingly. * No known pharmacokinetic interactions mediated by CYP enzymes.
Adverse Effects
Very Common (>10% incidence):* Hot flashes/sweats (most common) * Fatigue * Injection site reactions (pain, erythema, bruising) * Erectile dysfunction, decreased libido * Gynecomastia/breast tenderness
Common (1-10% incidence):* Constipation, diarrhea * Arthralgia, myalgia, osteoporosis * Headache, dizziness * Edema * Depression, emotional lability * Urinary frequency, urinary retention
Serious:* Spinal cord compression * Myocardial infarction, stroke * Prolonged QT interval * Pituitary apoplexy * Severe allergic reactions
Monitoring Parameters
* Baseline: Serum testosterone, PSA, complete blood count (CBC), metabolic panel (including glucose, renal and liver function), bone density scan (DEXA), cardiovascular risk assessment, ECG (if indicated). * Ongoing: * Testosterone: Confirm castration levels (~4 weeks after initiation and periodically thereafter). * PSA: Monitor for treatment response. * Blood Glucose/HbA1c: Annually or as clinically indicated. * Bone Mineral Density: Every 1-2 years. * Cardiovascular Health: Regular monitoring of blood pressure, lipids, and symptoms. * Renal/Hepatic Function: Periodically.
Patient Education
* Injection Schedule: Adherence to the prescribed injection schedule (monthly, every 3, 4, or 6 months) is critical for continuous testosterone suppression. * Tumor Flare: Be aware that symptoms (e.g., bone pain, difficulty urinating) may temporarily worsen during the first few weeks of treatment. Report any severe or new symptoms to your doctor immediately. * Side Effects: Hot flashes are very common but often manageable. Discuss strategies with your healthcare team. Report any chest pain, shortness of breath, signs of a stroke (e.g., weakness on one side), severe headaches, or vision changes. * Bone Health: Maintain adequate calcium and vitamin D intake. Engage in weight-bearing exercises as tolerated. Discuss the need for bone-protective medications with your doctor. * General Health: Maintain a heart-healthy diet, exercise regularly, avoid smoking, and manage weight to mitigate cardiovascular and metabolic risks associated with therapy.
References
1. Eligard® (leuprolide acetate) [Prescribing Information]. Tolmar Pharmaceuticals, Inc.; 2021. 2. Sharifi N, Gulley JL, Dahut WL. An update on androgen deprivation therapy for prostate cancer. Endocr Relat Cancer. 2010;17(4):R305-R315. 3. Shahinian VB, Kuo YF, Freeman JL, Orihuela E, Goodwin JS. Increasing use of gonadotropin-releasing hormone agonists for localized prostate cancer. Cancer. 2005;103(8):1615-1624. 4. Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006;24(27):4448-4456. 5. Michaelson MD, Cotter SE, Gargollo PC, Zietman AL, Dahl DM, Smith MR. Management of complications of prostate cancer treatment. CA Cancer J Clin. 2008;58(4):196-213. 6. The NCCN Prostate Cancer Clinical Practice Guidelines in Oncology (Version 4.2023). National Comprehensive Cancer Network.