Currently Enrolling Trials
Myfembree is a combination of relugolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, estradiol, an estrogen, and norethindrone acetate, a progestin.
Myfembree is specifically indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.
Myfembree is supplied as a tablet for oral administration. Exclude pregnancy and discontinue hormonal contraceptives prior to initiating Myfembree. Take one tablet orally once daily. If a dose of Myfembree is missed, take the missed dose of 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, take Myfembree at least 6 hours before taking the P-gp inhibitor.
Mechanism of Action
Myfembree is 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, thereby reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased serum concentrations of the ovarian sex hormones estradiol and progesterone and reduced bleeding associated with uterine fibroids.
Estradiol acts by binding to nuclear receptors that are expressed in estrogen-responsive tissues. As a component of Myfembree, the addition of exogenous estradiol may reduce the increase in bone resorption and resultant bone loss that can occur due to a decrease in circulating estrogen concentrations from relugolix alone.
Progestins such as norethindrone act by binding to nuclear receptors that are expressed in progesterone responsive tissues. As a component of Myfembree, norethindrone may protect the uterus from the potential adverse endometrial effects of unopposed estrogen.
Adverse effects associated with the use of Myfembree may include, but are not limited to, the following:
- hot flush
- uterine bleeding
- decreased libido
The Myfembree drug label comes with the following Black Box Warning: Estrogen and progestin combinations, including Myfembree , increase the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events. Myfembree is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension.
Clinical Trial Results
The FDA approval of Myfembree was based on two replicate, 24-week, multinational, randomized, double-blind, placebo-controlled studies in a total of 768 premenopausal women with heavy menstrual bleeding associated with uterine fibroids. Th women were randomized 1:1:1 to receive a once daily relugolix 40 mg tablet plus an over encapsulated tablet of E2 1 mg and NETA 0.5 mg (relugolix+E2/NETA), which is equivalent to 1 tablet of Myfembree, for 24 weeks, placebo for 24 weeks, or relugolix 40 mg monotherapy for 12 weeks followed by Myfembree for 12 weeks. Treatment was initiated within the first seven days after the onset of menses. The primary endpoint was the proportion of women in the Myfembree group compared with women in the placebo group, who achieved menstrual blood loss volume of < 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment, as measured by the alkaline hematin method. In both Study L1 and Study L2, a statistically higher proportion of women treated with Myfembree achieved the primary endpoint of both an MBL volume of less than 80 mL and at least a 50% reduction from baseline in MBL volume over the last 35 days of treatment compared with placebo.