Contraindications to Myfembree
Myfembree (relugolix/estradiol/norethindrone acetate) is contraindicated in patients with known or suspected pregnancy, current or history of breast cancer, active or recent arterial thromboembolic disease (stroke or MI), active or history of venous thromboembolism (DVT/PE), undiagnosed abnormal uterine bleeding, known hepatic impairment or disease, and known severe hypersensitivity to any component of the product.
Absolute Contraindications
Based on the FDA drug label information and established guidelines for combination hormonal therapies, the following are absolute contraindications:
Pregnancy and Reproductive Considerations
- Known or suspected pregnancy 1
- Myfembree can cause fetal harm and should not be used during pregnancy 2
- Males with female partners of reproductive potential must use effective contraception 2
Cardiovascular and Thromboembolic Conditions
Active or recent (within past year) arterial thromboembolic disease, including:
Active deep vein thrombosis or pulmonary embolism 1
History of venous thromboembolism (DVT or PE) 1
These contraindications align with established guidelines for estrogen-progestin combination therapies, which consistently identify thromboembolic disease as a major contraindication 4, 5, 6.
Malignancies
- Known, suspected, or history of breast cancer 1
- Carcinoma of the endometrium 3
- Known or suspected estrogen-sensitive malignancies 4
The estrogen component in Myfembree makes it inappropriate for patients with hormone-sensitive cancers, consistent with broader menopausal hormone therapy guidelines 4.
Hepatic Conditions
- Impaired liver function or active liver disease 1
- Hepatic adenomas or carcinomas 3
- Cholestatic jaundice of pregnancy or jaundice with previous hormonal contraceptive use 3
Bleeding Disorders
- Undiagnosed abnormal vaginal or genital bleeding 1
This requires evaluation before initiating therapy to rule out malignancy or other serious pathology 4.
Hypersensitivity
- Known severe hypersensitivity to relugolix or any product components 2
- Hypersensitivity reactions including angioedema have been reported; the drug should be withheld for symptoms and discontinued for severe reactions 2
Additional High-Risk Conditions Requiring Caution
While not absolute contraindications per the FDA label, the following conditions warrant extreme caution based on combination hormonal therapy guidelines:
Cardiovascular Risk Factors
- Uncontrolled or severe hypertension (systolic ≥160 mmHg or diastolic ≥100 mmHg) 3
- Migraine headaches with focal neurologic symptoms 3
- Valvular heart disease with complications 3
Metabolic Conditions
- Diabetes with vascular involvement 3
Surgical Considerations
- Surgery with prolonged immobilization 3
- Consider discontinuing before elective surgery and resuming when ambulation is normal 6
Clinical Context
The contraindications for Myfembree reflect the combined risks of its three components: relugolix (GnRH antagonist), estradiol, and norethindrone acetate. The estrogen-progestin add-back therapy, while designed to mitigate hypoestrogenic effects and preserve bone mineral density 7, 8, introduces the same thromboembolic and malignancy risks associated with other combination hormonal therapies 4, 5.
Important caveat: The relugolix component alone has minimal contraindications (only severe hypersensitivity) 2, but the addition of estradiol and norethindrone acetate substantially expands the contraindication profile to match that of other estrogen-progestin combinations 4, 3.