Introduction
Orgovyx (relugolix) is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist approved by the FDA in December 2020 for the treatment of advanced prostate cancer. It represents a significant advancement in androgen deprivation therapy (ADT) as the first oral hormone therapy for this indication, offering patients an alternative to injectable GnRH agonists.
Mechanism of Action
Relugolix competitively binds to pituitary GnRH receptors, rapidly suppressing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This immediate suppression results in rapid reduction of testicular androgen production without the initial testosterone surge ("flare phenomenon") associated with GnRH agonists. Within days of initiation, relugolix achieves medical castration (testosterone levels < 50 ng/dL).
Indications
- Treatment of advanced prostate cancer in adults
- Approved for both metastatic and non-metastatic disease
- Used as continuous androgen deprivation therapy
Dosage and Administration
Standard dosing: 360 mg loading dose on day 1, followed by 120 mg once daily Administration: Oral tablet, taken 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 in approximately 2 hours Distribution: Extensive tissue distribution with a volume of distribution of ~40 L Metabolism: Primarily metabolized by CYP3A4 and CYP2C8 Elimination: Half-life of approximately 25 hours; primarily excreted in feces (90%) with minimal renal excretion Protein binding: >90% to plasma proteinsContraindications
- Hypersensitivity to relugolix or any component of the formulation
- Pregnancy (based on mechanism of action)
- Women who are or may become pregnant
Warnings and Precautions
QT prolongation: May prolong QT interval; assess benefits and risks in patients with congenital long QT syndrome, congestive heart failure, or electrolyte abnormalities Embryo-fetal toxicity: Can cause fetal harm; males with female partners of reproductive potential should use effective contraception during treatment and for 2 weeks after final dose Ischemic heart disease: Increased risk of myocardial infarction and other ischemic events observed in clinical trials Hyperglycemia/diabetes: May increase blood glucose levels and worsen diabetes CV effects: Monitor for hypertension and other cardiovascular eventsDrug Interactions
Strong CYP3A4 inducers: Avoid concomitant use (e.g., rifampin, carbamazepine, St. John's wort) Strong CYP3A4 inhibitors: May increase relugolix exposure; consider benefits and risks P-gp inhibitors: May increase relugolix absorption Drugs that prolong QT interval: Use with caution when co-administered with other QT-prolonging agentsAdverse Effects
Most common (>10%):- Hot flashes (54%)
- Increased glucose (44%)
- Increased triglycerides (30%)
- Musculoskeletal pain (30%)
- Decreased hemoglobin (28%)
- Constipation (12%)
- Diarrhea (12%)
- Fatigue (12%)
- QT prolongation
- Ischemic cardiovascular events
- Severe hyperglycemia
- Elevated liver enzymes
- Anemia
Monitoring Parameters
Baseline:- Testosterone levels
- ECG (especially in patients at risk for QT prolongation)
- Complete blood count
- Liver function tests
- Lipid profile
- Blood glucose/HbA1c
- Electrolytes (especially potassium, magnesium, calcium)
- Testosterone levels at 4 weeks and periodically thereafter
- ECG as clinically indicated
- Blood pressure monitoring
- Regular assessment of cardiovascular status
- Monitoring for signs/symptoms of diabetes
- Periodic liver function tests and lipid panels
Patient Education
- Take medication at approximately the same time each day
- Do not crush or chew tablets; swallow whole
- Report any chest pain, palpitations, or shortness of breath immediately
- Be aware of potential hot flashes and management strategies
- Maintain regular follow-up appointments for monitoring
- Inform all healthcare providers about Orgovyx use
- Use effective contraception if partner is of reproductive potential
- Report any new or worsening symptoms promptly
- Do not stop medication without consulting healthcare provider
References
1. FDA Prescribing Information: Orgovyx (relugolix) 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. ClinicalTrials.gov: HERO Study (NCT03085095) 4. Smith MR, et al. Cardiovascular Safety of Relugolix Versus Leuprolide in Patients with Advanced Prostate Cancer: The HERO Study. J Clin Oncol. 2021;39(15_suppl):5002 5. US National Library of Medicine: Relugolix Drug Monograph 6. NCCN Guidelines: Prostate Cancer Version 4.2021 7. European Association of Urology Guidelines: Prostate Cancer 2021