Post-marketing safety profile of Myfembree in approved gynecologic indications: a disproportionality analysis based...

Myfembree, a fixed-dose combination of relugolix, estradiol, and norethindrone acetate, is approved for premenopausal women with heavy menstrual bleeding associated with uterine fibroids and moderate to severe pain associated with endometriosis. Although clinical trials have demonstrated its efficacy and acceptable short-term tolerability, real-world post-marketing safety evidence focused on its approved gynecologic use remains limited. This study aimed to characterize the post-marketing safety profile of Myfembree in approved gynecologic indications using the US Food and Drug Administration Adverse Event Reporting System (FAERS). A retrospective pharmacovigilance study was conducted using FAERS reports from 2021Q2 to 2025Q4. Reports listing Myfembree as the primary suspect drug were identified, and the primary analysis was restricted to approved gynecologic indication terms, including uterine leiomyoma, heavy menstrual bleeding, and endometriosis. Disproportionality analyses were performed at the system organ class and preferred term levels using reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. Clinically relevant preferred term signals were further prioritized according to report frequency, signal stability, seriousness, and clinical plausibility. Time to onset was assessed in reports with valid treatment initiation and event dates. A total of 1423 unique reports were included. Reporting increased after approval and peaked during 2023-2024. Most reports involved female patients (87.0%), and 10.0% were classified as serious. At the system organ class level, the strongest disproportionality signal was observed for reproductive system and breast disorders. At the preferred term level, the reporting profile was dominated by bleeding- and menstruation-related events, including heavy menstrual bleeding, intermenstrual bleeding, menstruation irregular, dysmenorrhea, and polymenorrhea. Clinically relevant nongynecologic signals included hot flush, alopecia, headache, depression, mood swings, and suicidal ideation. Thromboembolic and cardiovascular signals, particularly deep vein thrombosis, pulmonary embolism, thrombosis, and blood pressure increased, were less frequent but clinically important. Among reports with evaluable dates, the median time to onset was 19 days (interquartile range 8-55), with many major bleeding and vascular events occurring within the first few weeks after treatment initiation. In real-world post-marketing reports, Myfembree was mainly associated with abnormal uterine bleeding and menstrual cycle disturbances, together with clinically important thromboembolic, vasomotor, hair-related, and neuropsychiatric signals. These findings were generally consistent with the known safety profile of the drug and provide additional evidence on adverse event patterns and onset timing in routine gynecologic practice. Continued pharmacovigilance is warranted, particularly for thromboembolic events, blood pressure-related events, mood-related symptoms, and treatment-associated bleeding abnormalities.