Relugolix tablet is a gonadotropin-releasing hormone (GnRH) receptor antagonist indicated for the treatment of adult patients with advanced prostate cancer.

Relugolix is a non-peptide small-molecule GnRH receptor antagonist. It competitively binds to pituitary GnRH receptors, leading to reduced secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which subsequently lowers testosterone levels.

Absorption: Relugolix is a substrate of intestinal P-glycoprotein (P-gp). Absolute bioavailability is approximately 12%, with a median Tmax of 2.25 hours.

Effect of food: No clinically significant effect on pharmacokinetics is observed with high-fat, high-calorie meals.

Distribution: Plasma protein binding is 68–71%, mainly to albumin and α1-acid glycoprotein. Blood-to-plasma ratio is 0.78.

Elimination: Mean effective half-life is 25 hours, and terminal half-life is approximately 60.8 hours. Total clearance is 29.4 L/h, and renal clearance is about 8 L/h.

Metabolism: Relugolix is mainly metabolized by CYP3A and to a lesser extent by CYP2C8.

Excretion: After a radiolabeled dose, about 81% is recovered in feces (4.2% unchanged) and 4.1% in urine (2.2% unchanged).

A loading dose of 360 mg on the first day of treatment followed by 120 mg taken once daily, at approximately the same time each day. Relugolix Tablet can be taken with or without food. Advise patients to take a missed dose of Relugolix as soon as they remember. If the dose was missed by more than 12 hours, patients should not take the missed dose and resume with the next scheduled dose. If treatment with Relugolix is interrupted for greater than 7 days, restart Relugolix with a loading dose of 360 mg on the first day, and continue with a dose of 120 mg once daily.

Pediatric Use: The safety and efficacy of Relugolix in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed between older and younger subjects.

Co-administration with P-gp inhibitors should be avoided. If unavoidable, Relugolix should be taken first, with at least a 6-hour gap between doses, and patients should be closely monitored for adverse effects.

Concomitant use of drugs that are both P-gp inhibitors and strong CYP3A inducers should be avoided. If such combination is necessary, the dose of Relupros® should be increased to 240 mg once daily under medical supervision.

Adverse reactions (≥10%) and laboratory abnormalities (≥15%) include hot flushes, increased blood glucose, increased triglycerides, musculoskeletal pain, decreased haemoglobin, elevated ALT, fatigue, elevated AST, constipation, and diarrhea.

Common side effects: Hot flushes, increased blood sugar, increased blood triglycerides, muscle and joint pain, reduced haemoglobin, raised liver enzymes, tiredness, constipation, and diarrhoea.

Rare side effects: QT interval prolongation, dizziness, fainting, palpitations, chest pain, weight gain, reduced libido, and erectile dysfunction.

Safety and efficacy of Relugolix in females have not been established at the recommended dose of 120 mg daily. Based on animal studies and its mechanism of action, Relugolix may impair fertility in males of reproductive potential.

QT/QTc prolongation may occur with androgen deprivation therapy.

Embryo-fetal toxicity has been observed; therefore, males with female partners of reproductive potential should use effective contraception during treatment.

There is no specific clinical experience in Relugolix overdose management. Treatment should be supportive and symptomatic.

Gonadotropin-releasing hormone (GnRH) antagonist

Store in a cool, dry place, protected from light and moisture. Keep all medicines out of reach of children.