GOZELLIX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GOZELLIX (GOZELLIX).
GOZELLIX (relugolix) is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It competitively binds to GnRH receptors in the anterior pituitary gland, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby suppressing ovarian estrogen and testicular testosterone production.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2C8 and CYP2C19. |
| Excretion | Primarily renal (approx. 80%) as unchanged drug; biliary/fecal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life: 14–16 hours in healthy adults; prolonged in renal impairment (up to 30 hours in ESRD). |
| Protein binding | 85–90% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution (Vd) is 0.6–0.8 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability: 70–80% (first-pass metabolism limited). |
| Onset of Action | Oral: 2–4 hours to peak plasma concentration (Tmax). IV: immediate onset of pharmacological effect. |
| Duration of Action | Duration of therapeutic effect is 12–24 hours, with steady-state achieved after 3–5 days of twice-daily dosing. |
250 mg subcutaneously once monthly.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Not recommended in severe renal impairment (GFR <30 mL/min) due to lack of data. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate to severe hepatic impairment (Child-Pugh B or C) due to lack of data. |
| Pediatric use | Safety and efficacy not established; use not recommended. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function and consider increased sensitivity in elderly patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GOZELLIX (GOZELLIX).
| Breastfeeding | Clarithromycin is excreted into human breast milk in small amounts. The M/P ratio is approximately 0.25-0.50 based on limited data. Estimated infant dose is 1-2% of maternal weight-adjusted dose. No adverse effects in nursing infants have been reported, but caution is recommended due to potential gastrointestinal disturbance or sensitization. Consider alternative macrolides with better safety profile (e.g., azithromycin) during lactation. |
| Teratogenic Risk | Gozelix (clarithromycin) is classified as FDA Pregnancy Category C. In first trimester, human data show no consistent increased risk of major malformations, but animal studies have shown embryonic loss and cardiovascular abnormalities at doses 2-4 times the human equivalent. Second and third trimester use is associated with a possible increased risk of miscarriage and intrauterine growth restriction, though absolute risk remains low. Ototoxicity has been reported in neonates exposed in utero, particularly with high doses. Advise avoidance of use during pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to relugolix or any component of the formulation.","Concurrent use with strong P-glycoprotein (P-gp) inhibitors (e.g., verapamil, erythromycin).","Pre-existing chronic hypocalcemia.","Severe hepatic impairment (Child-Pugh Class C)."]
| Precautions | ["QT interval prolongation: Risk of Torsade de Pointes, especially in patients with congenital long QT syndrome, electrolyte abnormalities, or concomitant QT-prolonging drugs.","Hypersensitivity reactions: Urticaria, pruritus, and angioedema have been reported.","Hepatic impairment: Use with caution in moderate-to-severe hepatic impairment (Child-Pugh B or C).","Reproductive potential: May impair fertility in males and females.","Osteoporosis risk: Long-term use may lead to decreased bone mineral density."] |
Loading safety data…
| Fetal Monitoring | Monitor maternal liver function tests and renal function periodically due to potential toxicity. Fetal monitoring: ultrasound for growth restriction if used in second/third trimester. Consider auditory screening for neonates after prolonged maternal use due to risk of ototoxicity. |
| Fertility Effects | In animal studies, clarithromycin did not affect fertility at clinically relevant doses. Human data are limited; no evidence of significant adverse effects on fertility. However, as with any antibiotic, dysbiosis may transiently affect conception, but no direct impairment is documented. |