Relupros120 mg

Advanced Prostate Cancer (Monotherapy, Adult Men)

Relupros is an FDA-approved oral gonadotropin-releasing hormone (GnRH) receptor antagonist used as androgen deprivation therapy for the treatment of adult patients with advanced prostate cancer.

Uterine Fibroids and Endometriosis (Women, as Part of a Fixed-Dose Combination Product)

Relupros is also FDA-approved as a component of a fixed-dose combination tablet (with estradiol and norethindrone acetate) for two established indications in premenopausal women:

• Management of heavy menstrual bleeding associated with uterine fibroids.
• Management of moderate to severe pain associated with endometriosis.

Relupros is not approved as monotherapy in women; in the women's-health indications it is always combined with estradiol and norethindrone acetate to offset bone loss and protect the endometrium.

Relugolix is marketed in two distinct oral tablet formulations:

• Monotherapy tablets: each film-coated tablet contains 120 mg of Relugolix (used for prostate cancer, with a 360 mg loading dose on day one).
• Fixed-dose combination tablets: each film-coated tablet contains Relugolix 40 mg together with estradiol 1 mg and norethindrone acetate 0.5 mg (used for uterine fibroids and endometriosis in women).

Relupros is an orally active, nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist. Unlike GnRH agonists, Relupros produces rapid, reversible suppression of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and downstream sex hormones without an initial testosterone/estrogen surge ("flare").

As monotherapy, Relupros is used to suppress testosterone in men with advanced prostate cancer. As a component of a fixed-dose combination product with estradiol and norethindrone acetate, Relupros is used to suppress ovarian sex-hormone production while the added hormones provide "add-back" therapy to reduce hot flashes and limit bone loss, for treatment of uterine fibroid-related heavy menstrual bleeding and endometriosis-associated pain.

Gonadotropin-releasing hormone (GnRH) receptor antagonist; hormonal agent used in androgen-deprivation therapy (men) and hormonal suppressive therapy (women, combination product). Relupros belongs to this class.

Mechanism of Action

Relugolix competitively and reversibly binds to pituitary GnRH receptors, immediately blocking receptor activation by endogenous GnRH. This rapidly suppresses release of LH and FSH from the pituitary, which in turn reduces testosterone production in men and estrogen/progesterone production in women, without the initial hormone flare seen with GnRH agonists.

Pharmacokinetics

• Absorption: Oral bioavailability is low (~11.6% for the monotherapy dose); can be taken with or without food.
• Metabolism: Primarily via CYP3A4, with contribution from other pathways; Relugolix is also a substrate of P-glycoprotein (P-gp).
• Elimination half-life: Approximately 25 hours (combination product dose) to 61 hours (monotherapy dose) at steady state.
• Excretion: Mainly via feces, with a minor renal component.

• Tablets should be swallowed whole; they can be taken with or without food.
• Take at approximately the same time each day to maintain consistent hormone suppression.
• Do not stop or change the dose of Relupros without consulting a physician.
• For the combination product, start dosing within 7 days of the onset of a menstrual period.

• P-glycoprotein (P-gp) inhibitors (e.g., cyclosporine, erythromycin, certain antifungals): can increase Relupros plasma concentrations. Avoid concomitant use where possible; if an oral P-gp inhibitor must be used, separate dosing from Relupros by at least 6 hours.
• Combined P-gp and strong CYP3A inducers (e.g., rifampin, carbamazepine, certain anticonvulsants): can substantially reduce Relupros exposure and efficacy. For the monotherapy indication the maintenance dose may be increased to 240 mg once daily if co-administration cannot be avoided; for the combination product such inducers should generally be avoided because reduced efficacy cannot be corrected by a dose increase.
• The estrogen/progestin components of the combination product carry their own interaction profile (e.g., reduced efficacy with strong hepatic enzyme inducers, altered risk with CYP-interacting drugs); see Precautions and Warnings for thromboembolism-related interaction risk factors such as smoking.

Monotherapy in Men (Prostate Cancer)

Very common (≥10%): hot flushes, elevated blood glucose, increased triglycerides, musculoskeletal pain, anemia, fatigue, constipation, and diarrhea.

Combination Product in Women (Fibroids / Endometriosis)

Common: hot flushes/vasomotor symptoms, headache, abnormal uterine bleeding, mood changes, nausea, decreased libido, and hair thinning (alopecia).

Less common but serious: thromboembolic events, uterine fibroid prolapse/expulsion, significant mood disturbance including depression.

Pregnancy

Men (monotherapy): Relupros can be present in semen; male patients with a pregnant partner or a partner of reproductive potential should use effective contraception during treatment and for 2 weeks after the last dose, because of potential fetal harm.

Women (combination product): Relupros combination therapy is contraindicated in pregnancy; based on its mechanism of action it can cause early pregnancy loss. Pregnancy should be excluded before starting treatment, and a non-hormonal contraceptive method should be used during treatment and for at least one week after stopping. Amenorrhea caused by treatment may delay recognition of pregnancy.

Lactation

Limited data suggest Relupros and, for the combination product, its hormonal components are present in breast milk and may reduce milk production. Relupros should be used during breastfeeding only if clearly needed, weighing the benefit to the mother against any potential risk to the breastfed infant; consult a physician.

• QT prolongation: Androgen deprivation with Relupros monotherapy may prolong the QT/QTc interval. Use with caution and consider periodic ECG and electrolyte monitoring in patients with congenital long QT syndrome, heart failure, electrolyte abnormalities, or concurrent use of other QT-prolonging drugs.
• Cardiovascular risk: Androgen-deprivation therapy, including Relupros monotherapy, has been associated with increased cardiovascular risk; monitor cardiovascular status closely in men with pre-existing cardiovascular disease.
• Bone mineral density loss: Both the monotherapy and combination-product uses of Relupros can reduce bone mineral density with prolonged treatment, which may not be fully reversible. Follow product-specific monitoring guidance and limit combination-product use to 24 months.
• Thromboembolism (combination product): The estrogen/progestin components increase the risk of venous and arterial thromboembolic events; see Contraindications for absolute exclusions and use caution with other thromboembolic risk factors (e.g., smoking, obesity, immobilization).
• Mood changes (combination product): New or worsening depression and, rarely, suicidal ideation have been reported; monitor mood and advise patients to seek prompt medical attention for new psychiatric symptoms.
• Hepatic monitoring: Liver enzyme elevations have been reported; the combination product is contraindicated in hepatic impairment or active liver disease (see Contraindications).
• Hypersensitivity: Angioedema and other serious hypersensitivity reactions have been reported with Relupros monotherapy; discontinue promptly if a severe reaction occurs.
• Dosing, formulation, and the overall safety profile differ meaningfully between the monotherapy (prostate cancer, men) and combination-product (fibroids/endometriosis, women) uses of Relupros; always consider the specific product and indication being treated.

Reported effects of Relupros overdose (chiefly with the combination product) include nausea, vomiting, breast tenderness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding. There is no specific antidote for Relupros overdose. If overdose is suspected, seek immediate medical attention or contact a poison control center; treatment is supportive and symptomatic, guided by a physician.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

• Renal impairment: No dose adjustment of Relupros monotherapy is required in mild to severe renal impairment; renal-impairment data for the combination product are limited, and it should be used with caution.
• Hepatic impairment: No dose adjustment of Relupros monotherapy is required in mild to moderate hepatic impairment (not studied in severe impairment). The combination product is contraindicated in hepatic impairment or active liver disease.
• Elderly: No overall differences in safety or effectiveness have been observed based on age for the monotherapy indication; use with usual caution given the higher likelihood of comorbidities.
• Pediatric patients: Safety and efficacy of Relupros, in either formulation, have not been established in pediatric patients; Relupros is not indicated for pediatric use.

For advanced prostate cancer, Relupros monotherapy is generally continued for as long as clinically indicated, as directed by the treating physician. For uterine fibroids and endometriosis, the Relupros combination product should be limited to a maximum of 24 continuous months, due to the risk of bone mineral density loss that may not be fully reversible with longer use.

GnRH receptor antagonists (oral, nonpeptide); in its combination formulation, classified together with estrogen-progestin hormonal therapy. Relugolix is the antagonist component in both formulations.

Relugolix reversibly blocks pituitary GnRH receptors, rapidly suppressing LH and FSH release and, consequently, testosterone (in men) or estrogen/progesterone (in women) production, without the initial hormonal flare associated with GnRH agonists.

Safety and efficacy of Relupros, in both the monotherapy and combination-product formulations, have not been established in pediatric patients. Relupros is not approved or recommended for use in children or adolescents.