This tablet is indicated for the treatment of heavy menstrual bleeding related to uterine leiomyomas (fibroids) in premenopausal women.

This tablet contains a combination of Relugolix, Estradiol (E2), and Norethindrone Acetate (NETA).Relugolix is a non-peptide GnRH receptor antagonist that competitively binds to pituitary GnRH receptors, reducing the release of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH). This results in lower levels of ovarian sex hormones such as estradiol and progesterone, helping to reduce excessive bleeding associated with uterine fibroids. Estradiol works by binding to nuclear receptors present in estrogen-responsive tissues. In this combination, added estradiol helps reduce bone resorption and prevents bone loss that may occur due to reduced estrogen levels caused by Relugolix alone. Norethindrone, a progestin, binds to nuclear receptors found in progesterone-responsive tissues. In this formulation, it helps protect the uterus from possible harmful endometrial effects caused by unopposed estrogen.

Exclude pregnancy and discontinue hormonal contraceptives prior to this initiation. Orally one tablet once daily. In case of missed dose, need to take as soon as possible the same day and then resume regular dosing the next day at the usual time. If concomitant use of oral P-gp inhibitors is unavoidable, need to take this tablet at least 6 hours before taking the P-gp inhibitor.

Safety and effectiveness of in pediatric patients have not been established.

With medicine: P-gp inhibitors: Co-administration of this tablet with P-gp inhibitors increases the AUC and maximum plasma concentration (Cmax) of Relugolix, which may increase the risk of adverse reactions associated with this tablet.

Combined P-gp and strong CYP3A inducers: Concomitant use with combined P-gp and strong CYP3A inducers decreases the AUC and Cmax of Relugolix, Estradiol, and/or Norethindrone, which may reduce the therapeutic effectiveness of this tablet.

With food and others: Grapefruit juice may increase the plasma concentration of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme.

• This tablet is contraindicated in patients with a high risk of arterial or venous thrombotic or thromboembolic disorders.
• It should not be used during pregnancy.
• Patients with known osteoporosis should avoid this medication.
• It is contraindicated in patients with current or previous history of breast cancer or other hormone-sensitive malignancies.
• Patients with known hepatic disease or hepatic impairment should not use this tablet.
• Undiagnosed abnormal uterine bleeding is also a contraindication.
• It should not be used in patients with known hypersensitivity to Relugolix, Estradiol, or Norethindrone Acetate.

The most common adverse reactions (incidence >3%) include hot flush, excessive sweating or night sweats, uterine bleeding, hair loss, and decreased sexual desire.

Based on animal studies and its mechanism of action, this tablet may cause early pregnancy loss. Treatment should be discontinued immediately if pregnancy occurs during therapy. There is no available data regarding the presence of Relugolix or its metabolites in human milk, its effects on the breastfed infant, or its effects on milk production. Relugolix has been detected in the milk of lactating rats, suggesting that it may also be present in human breast milk.

• Thromboembolic disorders and vascular events: Discontinue this tablet immediately if any arterial or venous thrombosis, cardiovascular event, or cerebrovascular event occurs.
• Bone loss: This tablet may reduce Bone Mineral Density (BMD), and this effect may not be fully reversible.
• Depression, mood disorders, and suicidal thoughts: Patients should seek medical attention if they develop new or worsening depression, anxiety, or other mood changes.
• Risk of early pregnancy loss: This medicine may cause early pregnancy loss. Women should use effective non-hormonal contraception during treatment.

Overdose of estrogen plus progestin may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding. Supportive treatment is recommended in case of overdose. The amount of Relugolix, Estradiol, or Norethindrone removed by hemodialysis is unknown.

Gonadotropin-releasing hormone (GnRH) antagonist

Store in a cool (below 30°C) and dry place, protected from light and moisture. Keep all medicines out of the reach of children.