Relugolix is a non-peptide small molecule, GnRH receptor antagonist. Relugolix competitively binds to pituitary GnRH receptors, thereby, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and consequently testosterone.
Absorption: Relugolix is a substrate for intestinal P-gp. The mean (CV%) absolute bioavailability of Relugolix is approximately 12%. The median (range) Tmax of Relugolix is 2.25 hours.
Effect of Food: No clinically meaningful differences in the pharmacokinetics of Relugolix were observed following consumption of a high-calorie, high-fat meal.
Distribution: Plasma protein binding of Relugolix is 68 to 71%, primarily to albumin and to a lesser extent to α1- acid glycoprotein. The mean blood-to-plasma ratio is 0.78.
Elimination: The mean effective half-life of Relugolix is 25 hours and the mean (CV %) terminal elimination half-life is 60.8 (11%) hours. The mean (CV %) total clearance of Relugolix is 29.4 (15%) L/h and the renal clearance is 8 L/h.
Metabolism: Relugolix is metabolized primarily by CYP3A and to a lesser extent by CYP2C8 in vitro.
Excretion: After oral administration of a single 80mg radiolabeled dose of Relugolix, approximately 81% of the radioactivity was recovered in feces (4.2% as unchanged) and 4.1% in urine (2.2% as unchanged).
P-gp Inhibitors: Avoid co-administration. If unavoidable, take Relugolix first, separate dosing by at least 6 hours, and monitor patients more frequently for adverse reactions. Combined P-gp and
Strong CYP3A Inducers: Avoid co-administration. If unavoidable, increase the Relupros ® dose to 240 mg once daily.
Adverse Reactions: The most common adverse reactions (≥10%) and laboratory abnormalities (≥15%) were hot flushes, glucose increased, triglycerides increased, musculoskeletal pain, haemoglobin decreased, alanine aminotransferase (ALT) increased, fatigue, aspartate aminotransferase (AST) increased, constipation, and diarrhea.
Common Side Effects: Hot flushes, Increased blood sugar levels, Increased blood fat (triglyceride) levels, Muscle and joint pain, Decreased hemoglobin levels, Increased liver enzymes, Tiredness, Constipation, Diarrhoea
Rare Side Effects: Relugolix may cause rare side effects, including Changes in the electrical activity of your heart (QT prolongation), Dizziness, Fainting, Feeling that your heart is pounding or racing (palpitations), Chest pain. Other side effects include weight gain, decreased sex drive, and erectile function problems.
The safety and efficacy of Relugolix at the recommended dose of 120 mg daily have not been established in females. Females and Males of Reproductive Potential. Based on findings in animals and mechanism of action, Relugolix may impair fertility in males of reproductive potential.
QT/QTc Interval Prolongation: Androgen deprivation therapy may prolong the QT interval.
Embryo-Fetal Toxicity: Relugolix can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception.
There is no specific experience in the management of Relugolix overdose in patients.
Gonadotropin-releasing hormone (GnRH) antagonist
Store in a cool and dry place, protect from light & moisture. Keep all medicines out of the reach of children.
