Introduction
Relugolix is an orally administered gonadotropin-releasing hormone (GnRH) receptor antagonist approved by the FDA for the management of advanced prostate cancer. It represents a significant advancement in hormonal therapy for prostate cancer, offering a rapid suppression of testosterone with a favorable administration profile compared to traditional GnRH agonists.
Mechanism of Action
Relugolix competitively binds to pituitary GnRH receptors, thereby rapidly inhibiting the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This action results in swift suppression of testicular testosterone production without the initial testosterone surge ("flare phenomenon") associated with GnRH agonists. Within days of initiation, relugolix achieves medical castration levels (testosterone <50 ng/dL).
Indications
- Advanced prostate cancer in adults
- Specifically approved for patients with advanced hormone-sensitive prostate cancer
Dosage and Administration
Standard dosing: 360 mg loading dose on day 1, followed by 120 mg once daily Administration: Oral administration with or without food Special populations:- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution in severe impairment
- Elderly: No dosage adjustment required
Pharmacokinetics
Absorption: Rapidly absorbed with peak concentrations achieved within 2-4 hours Distribution: Extensive tissue distribution with approximately 68-71% plasma protein binding Metabolism: Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8 Elimination: Half-life of approximately 25 hours; primarily excreted in feces (70%) and urine (22%)Contraindications
- Hypersensitivity to relugolix or any component of the formulation
- Pregnancy (category X)
- Concomitant use with strong CYP3A inducers (rifampin, carbamazepine, St. John's wort)
Warnings and Precautions
- QT interval prolongation: Monitor electrolytes and ECG in patients with congenital long QT syndrome, congestive heart failure, or those taking other QT-prolonging drugs
- Embryo-fetal toxicity: May cause fetal harm; women of reproductive potential should use effective contraception
- Cardiovascular events: Increased risk of myocardial infarction, stroke, and cardiovascular death observed in clinical trials
- Laboratory monitoring: Regular assessment of testosterone, PSA, and hematologic parameters recommended
Drug Interactions
Strong CYP3A inducers: Contraindicated (significantly decrease relugolix exposure) Strong CYP3A inhibitors: Avoid concomitant use (increase relugolix exposure) P-gp inhibitors: Use with caution (may increase relugolix concentrations) QT-prolonging drugs: Increased risk of torsades de pointesAdverse Effects
Common (≥10%): Hot flashes, increased glucose, increased triglycerides, musculoskeletal pain, decreased hemoglobin Serious: Myocardial infarction, stroke, prolonged QT interval, neutropenia Other notable effects: Increased weight, fatigue, constipation, diarrheaMonitoring Parameters
- Testosterone levels: At 4 weeks and periodically thereafter
- PSA levels: Regularly during treatment
- Complete blood count: Baseline and periodically
- Liver function tests: Baseline and as clinically indicated
- ECG: In patients with cardiac risk factors
- Lipid profile: Baseline and periodically
- Blood glucose: Baseline and periodically
Patient Education
- Take medication at approximately the same time each day
- Do not stop treatment without consulting your healthcare provider
- Report any chest pain, shortness of breath, or neurological symptoms immediately
- Be aware of potential hot flashes and discuss management strategies
- Inform all healthcare providers about relugolix use before starting new medications
- Use effective contraception if partner is of reproductive potential
- Regular follow-up appointments are essential for monitoring treatment response and safety
References
1. FDA prescribing information: Relugolix (Orgovyx) 2. Shore ND, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020;382(23):2187-2196 3. Smith MR, et al. Phase III HERO study of relugolix in men with advanced prostate cancer. J Clin Oncol. 2020;38(15_suppl):5602 4. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2021 5. US National Library of Medicine. DailyMed - Relugolix tablet. 2021