Myfembree now available for use in women with endometriosis, uterine fibroids

A new prescription drug, Myfembree (relugolix 40 mg, estradiol 1 mg and norethindrone acetate 0.5 mg tablet), is now available in Canada. It is being supplied by Pfizer Canada, in partnership with Sumitomo Pharma Canada.1,2 Myfembree is indicated in premenopausal women for the management of heavy menstrual bleeding associated with uterine fibroids and for the management of moderate to severe pain associated with endometriosis.1Myfembree is a three-drug fixed-dose combination product. It contains relugolix, a gonadotropin releasing hormone (GnRH) receptor antagonist. Relugolix binds to GnRH receptors in the anterior pituitary gland, leading to a reduction in the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This limits the production of estrogen and progesterone, which reduces bleeding associated with uterine fibroids and pain associated with endometriosis. The estradiol component may help alleviate symptoms, such as vasomotor symptoms and bone mineral density loss, which can occur due to a decrease in circulating estrogen concentrations from relugolix alone.Norethindrone acetate is a synthetic progestin; it acts as a progesterone receptor agonist, which reduces estrogen-induced endometrial hyperplasia.1The recommended dosage of Myfembree is one tablet once daily, starting as early as possible after the onset of menses, but no later than five days after menses has started. If the product is started later in the menstrual cycle, irregular and/or heavy bleeding may initially occur. Instruct patients to take Myfembree at about the same time each day, with or without food.1 Pregnancy must be ruled out and hormonal contraceptives should be discontinued prior to starting Myfembree. Women should be advised to use effective nonhormonal contraception during treatment and for one week following discontinuation.1 The most common adverse effects of Myfembree are vasomotor symptoms, decreased libido, abnormal uterine bleeding and alopecia. More serious potential adverse effects include thromboembolic disorders and vascular events, bone loss, suicidal ideation and mood disorders (including depression), hepatic impairment, transaminase elevations, gallbladder disorders, elevated blood pressure, changes in menstrual bleeding pattern (including metrorrhagia), uterine fibroid prolapse or expulsion, elevated lipid and glucose levels, and hypersensitivity reactions. The duration of Myfembree use should be limited to 24 months due to the risk of continued bone loss, which may not be reversible.1Myfembree is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events. It is also contraindicated in women with current or a history of hormone-sensitive malignancies (e.g., breast cancer, endometrial cancer).1In terms of drug interactions, avoid Myfembree use with oral P-gp inhibitors (e.g., erythromycin), as such combinations may increase relugolix concentrations and the risk of adverse reactions. If concomitant use is unavoidable, take Myfembree first, separate dosing by at least six hours, and monitor patients for adverse reactions. Also avoid use with combined P-gp and strong CYP3A inducers (e.g., rifampin), as they may reduce concentrations of relugolix, estradiol and/or norethindrone, which may decrease the therapeutic effects of Myfembree.1 Medical Letter consultants point out that heavy menstrual bleeding occurs in up to 20%–30% of premenopausal women and is commonly caused by uterine fibroids. Heavy menstrual bleeding is typically treated with a combination contraceptive (oral, patch or vaginal ring) or a levonorgestrel-releasing intrauterine device (e.g., Mirena), but these drugs do not reduce the size of uterine fibroids. Oral and injectable progestin-only contraceptives, oral tranexamic acid and oral nonsteroidal anti-inflammatory drugs are also used, but they are less effective. Injectable formulations of GnRH agonists are effective, but they can cause long-term gonadal suppression and hypoestrogenic adverse effects.3Medical Letter consultants concluded that Myfembree can reduce menstrual blood loss in premenopausal women with uterine fibroids, with convenient once-daily dosing. However, despite the inclusion of estradiol and norethindrone acetate to lessen the hypoestrogenic effects of relugolix, reductions in bone mineral density have occurred, and may be irreversible. Therefore, treatment should be limited to 24 months. How Myfembree compares to other pharmacologic and surgical options for management of heavy menstrual bleeding due to fibroids remains to be determined.3A November 2022 review published in the journal Drugs noted that in the two phase 3 LIBERTY trials, Myfembree substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroid-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment for up to two years did not induce clinically meaningful bone loss in the majority of women. The authors concluded that Myfembree is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids.4Women with symptomatic uterine fibroids have also experienced substantial improvements in health-related quality of life with Myfembree treatment, including improvements in emotional well-being, physical and social activities, and sexual function. Substantial reductions in overall symptom burden and distress have also been reported.5The 24-week SPIRIT 1 and 2 trials showed that Myfembree significantly improved endometriosis-associated pain compared to placebo and was well tolerated. The investigators concluded that this oral therapy has the potential to address the unmet clinical need for long-term medical treatment for endometriosis, reducing the need for opioid use or repeated surgical treatment.6 The two-year SPIRIT open label extension study demonstrated that treatment with Myfembree for up to two years improved menstrual and nonmenstrual pain, dyspareunia and function in women with endometriosis. After an initial decline (< 1%), the mean bone mineral density remained stable during the two-year study period.7 References1. Pfizer Canada. Myfembree (relugolix, estradiol and norethindrone acetate tablets) product monograph. Kirkland, QC; October 13, 2023. (accessed February 9, 2024).2. Sumitomo Pharma America. Sumitomo Pharma and Pfizer Canada announce availability of Myfembree in Canada. January 31, 2024. (accessed February 9, 2024).3. Anon. Myfembree for fibroid-associated heavy menstrual bleeding. Med Lett Drugs Ther 2021; August 9. 4. Syed YY. Relugolix/estradiol/norethisterone (norethindrone) acetate: a review in symptomatic uterine fibroids. Drugs 2022;82:1549-56. (accessed February 9, 2024).5. Stewart EA, Lukes AS, Venturella R, et al. Quality of life with relugolix combination therapy for uterine fibroids: LIBERTY randomized trials. Am J Obstet Gynecol 2023;228(3):320.e1-320.e11. (accessed February 9, 2024).6. Giudice LC, As-Sanie S, Ferreira JCA, et al. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet 2022;399:2267-79. (accessed February 9, 2024).7. Becker CM, Johnson NP, As-Sanie S, et al. Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study. Hum Reprod 2024 Jan 18:dead263. (accessed February 9, 2024).

Myfembree now available for use in women with endometriosis, uterine fibroids

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