ORGOVYX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORGOVYX (ORGOVYX).
Gonadotropin-releasing hormone (GnRH) receptor antagonist; competitively blocks GnRH receptors in the anterior pituitary, rapidly reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, leading to suppression of testosterone production.
| Metabolism | Primarily hydrolyzed by esterases, with minimal involvement of cytochrome P450 (CYP) enzymes. |
| Excretion | Primarily hepatic metabolism; approximately 21% of dose recovered as unchanged drug in urine, with ~80% recovered as metabolites in feces over 7 days. |
| Half-life | Terminal elimination half-life is approximately 28.6 hours (range 22–36 hours) in patients; supports once-daily dosing with steady state achieved by day 7. |
| Protein binding | Approximately 97–99% bound primarily to alpha-1-acid glycoprotein and to a lesser extent serum albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) ~508 L (~6.4 L/kg for a 79 kg individual) indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Absolute oral bioavailability is ~22% (under fasting conditions); co-administration with high-fat meal increases Cmax by ~2-fold and AUC by ~1.7-fold, with relative bioavailability ~60% vs fasting. |
| Onset of Action | Following oral administration, maximal androgen suppression (testosterone <50 ng/dL) is achieved within 4 weeks, with significant serum testosterone reduction observed by day 15. |
| Duration of Action | Androgen suppression persists for the duration of once-daily dosing; upon discontinuation, testosterone levels return to baseline within ~2–3 months. |
120 mg orally three times daily (total daily dose 360 mg). Administer with a low-fat meal (<30% fat) to reduce gastrointestinal adverse effects.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >=30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) or ESRD due to lack of data. |
| Liver impairment | No dose adjustment for Child-Pugh A or B. Not recommended in Child-Pugh C due to potential increased exposure. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment. Monitor for increased incidence of hot flushes, fatigue, and diarrhea in patients >=65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORGOVYX (ORGOVYX).
| Breastfeeding | It is unknown if relugolix is excreted in human breast milk. In animal studies, relugolix and its metabolites were present in milk. M/P ratio is not available. Because of the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for 1 month after the last dose. |
| Teratogenic Risk | ORGOVYX (relugolix) is contraindicated in pregnancy. Based on animal studies and its mechanism of action (GnRH receptor antagonist), it can cause fetal harm. First trimester: High risk of miscarriage and congenital anomalies. Second and third trimesters: Risk of fetal gonadotropin suppression and developmental abnormalities. Effective contraception must be used during treatment and for 1 month after discontinuation. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to relugolix or any component of the formulation.","Use in women who are or may become pregnant."]
| Precautions | ["QT/QTc interval prolongation risk; avoid use in patients with congenital long QT syndrome, electrolyte abnormalities, or concurrent use of Class IA/III antiarrhythmics.","Hypersensitivity reactions including urticaria, pruritus, and angioedema.","Embryo-fetal toxicity in females of reproductive potential."] |
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| Fetal Monitoring | If inadvertent exposure occurs during pregnancy, immediate obstetrical consultation is indicated. Monitor pregnancy viability and fetal development with ultrasound. Assess for potential fetal growth restriction and congenital anomalies. For women of childbearing potential, pregnancy testing is recommended prior to initiation of therapy, monthly during treatment, and 1 month after discontinuation. |
| Fertility Effects | ORGOVYX suppresses pituitary-ovarian axis leading to anovulation and reduced fertility. This effect is expected to be reversible upon discontinuation, but the time to return of fertility is variable and may take several months. Women planning pregnancy should discontinue ORGOVYX and allow for return of menses. |