Co-administration increases AUC and Cmax of relugolix, may increase risk of adverse reactions. Avoid use; if unavoidable, separate dosing by at least 6 hours and monitor.
Source: NLP:relugolix, estradiol hemihydrate, and norethindrone acetate
Relugolix, Estradiol Hemihydrate, And Norethindrone Acetate Interactions
Brand names: Myfembree
Gonadotropin Releasing Hormone Receptor Antagonist · Gonadotropin Releasing Hormone Receptor Antagonists · Cytochrome P450 3A Inducers · Cytochrome P450 2B6 Inducers · Breast Cancer Resistance Protein Inhibitors · P-Glycoprotein Inhibitors
Route: Oral
FDA Black Box Warning
WARNING: THROMBOEMBOLIC DISORDERS AND VASCULAR EVENTS Estrogen and progestin combinations, including MYFEMBREE, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism (PE), deep vein thrombosis (DVT), stroke and myocardial infarction (MI), especially in women at increased risk for these events [see Warnings and Precautions ( 5.1 )]. 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 [see Contraindications ( 4 )]. WARNING: THROMBOEMBOLIC DISORDERS AND VASCULAR EVENTS See full prescribing information for complete boxed warning Estrogen and progestin combinations, including MYFEMBREE, increase the risk of thrombotic or thromboembolic disorders, especially in women at increased risk for these events. ( 5.1 ) 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. ( 4 )
Contraindications
4 CONTRAINDICATIONS MYFEMBREE is contraindicated in women: With a high risk of arterial, venous thrombotic, or thromboembolic disorders [see Boxed Warning and Warnings and Precautions ( 5.1 )] . Examples include women over 35 years of age who smoke and women who are known to have: current or history of deep vein thrombosis or pulmonary embolism vascular disease (e.g., cerebrovascular disease, coronary artery disease, peripheral vascular disease) thrombogenic valvular or thrombogenic rhythm diseases of the heart (e.g., subacute bacterial endocarditis with valvular disease, or atrial fibrillation) inherited or acquired hypercoagulopathies uncontrolled hypertension headaches with focal neurological symptoms or migraine headaches with aura if over 35 years of age Who are pregnant. Exposure to MYFEMBREE early in pregnancy may increase the risk of early pregnancy loss [see Warnings and Precautions ( 5.9 ) and Use in Specific Populations ( 8.1 )] . With known osteoporosis, because of the risk of further bone loss [see Warnings and Precautions ( 5.2 )]. With current or history of breast cancer or other hormone-sensitive malignancies, and with increased risk for hormone-sensitive malignancies [see Warnings and Precautions ( 5.3 )] . With known hepatic impairment or disease [see Warnings and Precautions ( 5.5 )] . With undiagnosed abnormal uterine bleeding. With known anaphylactic reaction, angioedema, or hypersensitivity to MYFEMBREE or any of its components. Anaphylactoid reactions, urticaria, and angioedema have been reported [see Warnings and Precautions ( 5.14 ), Adverse Reactions ( 6.2 )]. High risk of arterial, venous thrombotic, or thromboembolic disorder. ( 4 ) Pregnancy. ( 4 ) Known osteoporosis. ( 4 ) Current or history of breast cancer or other hormone-sensitive malignancies. ( 4 ) Known hepatic impairment or disease. ( 4 ) Undiagnosed abnormal uterine bleeding. ( 4 ) Known hypersensitivity to components of MYFEMBREE. ( 4 )
Pregnancy & Breastfeeding
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to MYFEMBREE during pregnancy. Pregnant females exposed to MYFEMBREE and healthcare providers are encouraged to call the MYFEMBREE Pregnancy Exposure Registry at 1-855-428-0707. Risk Summary MYFEMBREE is contraindicated in pregnancy [see Contraindications ( 4 ) and Warnings and Precautions ( 5.9 )]. Based on findings from animal studies and its mechanism of action, MYFEMBREE may cause early pregnancy loss. Discontinue MYFEMBREE if pregnancy occurs during treatment [see Warnings and Precautions ( 5.9 ) and Clinical Pharmacology ( 12.1 )] . The limited human data with the use of MYFEMBREE in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes [see Data ]. In animal reproduction studies, oral administration of relugolix in pregnant rabbits during organogenesis resulted in spontaneous abortion and total litter loss at relugolix exposures about half those at the maximum recommended human dose (MRHD) of 40 mg. In both rabbits and rats, no fetal malformations were present at any dose level tested which were associated with relugolix exposures about half and approximately 300 times exposures in women at the MRHD, respectively [see Data ]. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to estrogens and progestins before conception or during early pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. There are insufficient data to conclude whether the presence of uterine fibroids or endometriosis reduces the likelihood of achieving pregnancy or increases the risk of adverse pregnancy outcomes. All pregnancies have a background risk of birth defect, l
2 interactions on record
Decreases AUC and Cmax of relugolix, estradiol, and/or norethindrone, may decrease therapeutic effects of MYFEMBREE. Avoid use.
Source: NLP:relugolix, estradiol hemihydrate, and norethindrone acetate