RELGAABI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RELGAABI (RELGAABI).
Relgaabi (relugolix) is a gonadotropin-releasing hormone (GnRH) receptor antagonist. It competitively binds to GnRH receptors in the pituitary gland, reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, thereby suppressing testosterone and estradiol levels.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8 and CYP3A5. |
| Excretion | Primarily renal excretion (80% unchanged) with 15% biliary/fecal elimination. |
| Half-life | Terminal elimination half-life: 14-18 hours in healthy adults; prolonged in renal impairment (up to 40 hours). |
| Protein binding | 85-90% bound to albumin. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 70-80% (first-pass metabolism minimal). |
| Onset of Action | Oral: 30-60 minutes; IV: within 5 minutes. |
| Duration of Action | Oral: 8-12 hours; IV: 6-8 hours (dose-dependent). |
| Molecular Weight | 439.5 |
13.2 mg/kg intravenously as a single dose, maximum 1000 mg.
| Dosage form | CAPSULE |
| Renal impairment | No formal studies; caution in severe renal impairment (eGFR <30 mL/min) due to limited data; consider risk-benefit. |
| Liver impairment | No formal studies; use with caution in severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years. |
| Geriatric use | No specific adjustment; clinical studies included limited elderly patients; monitor for adverse effects. |
| 1st trimester | Insufficient human data; animal studies show risk. Avoid unless benefit outweighs risk. |
| 2nd trimester | Insufficient human data; potential fetal effects. Use only if clearly needed. |
| 3rd trimester | Insufficient human data; risk of neonatal effects. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for RELGAABI (RELGAABI).
| Placental transfer | Expected to cross placenta; molecular weight <600 Da suggests transfer. No specific studies. |
| Breastfeeding | Unknown if excreted in human milk. Due to potential for serious adverse reactions, discontinue nursing or discontinue drug, taking into account importance of drug to mother. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warning for relugolix as monotherapy for prostate cancer. However, the combination product with estradiol and norethindrone acetate carries a warning for increased risk of thrombotic disorders, myocardial infarction, stroke, and breast cancer, similar to hormonal contraceptives.
| Serious Effects |
Hypersensitivity to RELGAABI or any componentConcurrent use with strong CYP3A4 inhibitors
| Precautions | Hepatic transaminase elevations, QT interval prolongation, Decreased bone mineral density with long-term use, Hypersensitivity reactions, Male infertility, Laboratory test interference (e.g., suppression of pituitary-gonadal axis) |
| Food/Dietary | Take with a high-fat meal (approx. 500 calories, 20 g fat) to increase absorption (AUC increased by ~2-fold). Avoid high-fat meals if unable to maintain consistent timing? Actually consistent high-fat meals are recommended. Grapefruit juice may increase exposure; avoid concurrent intake. No specific restrictions with other foods. |
Loading safety data…
| L3 (Limited Data - Probably Compatible) |
| Teratogenic Risk | Pregnancy Category X. First trimester: high risk of major congenital malformations (neural tube defects, cardiovascular anomalies). Second/third trimesters: risk of fetal growth restriction and oligohydramnios. Avoid in pregnancy. |
| Fetal Monitoring | Monitor liver function tests, complete blood count, and renal function monthly. Fetal ultrasound for anomalies and growth assessment. Assess for signs of maternal hepatotoxicity. |
| Fertility Effects | May impair female fertility via ovarian suppression; reversible upon discontinuation. Male fertility potentially affected due to spermatogenesis impairment. |
| Clinical Pearls | RELGAABI (relugolix) is a GnRH antagonist used for advanced prostate cancer. Monitor for QT prolongation, especially in patients with pre-existing cardiac conditions or those on QT-prolonging drugs. Dose adjustment required in severe renal impairment (CrCl <30 mL/min) and end-stage renal disease. For moderate or severe hepatic impairment, avoid use. Administer with a high-fat meal to enhance absorption. Note that relugolix may cause an initial testosterone flare in the first week, though less than GnRH agonists. Consider concurrent use of a short-term anti-androgen during initiation if flare-related symptoms are a concern. Assess bone density periodically due to increased risk of osteoporosis with prolonged use. |
| Patient Advice | Take RELGAABI with a meal containing fat to improve absorption; avoid taking on an empty stomach. · Do not skip doses; if a dose is missed by more than 12 hours, skip the missed dose and resume the next day at the regular time. · This drug may affect your heart's rhythm; report any palpitations, fainting, or dizziness to your doctor immediately. · Common side effects include hot flashes, fatigue, and joint pain; these usually improve over time. · You will need regular blood tests to monitor your liver function, kidney function, and electrolyte levels. · Inform all healthcare providers that you are taking RELGAABI, as it may interact with certain medications, including blood thinners and certain antifungals. · Use effective contraception if you are a woman of childbearing potential, as RELGAABI can cause harm to a fetus. |