Dosage & Administration
Myfembree Prescribing Information
- 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 ].
- 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 ].
Heavy Menstrual Bleeding Associated with Uterine Leiomyomas
MYFEMBREE is indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women [see Clinical Studies ].
Moderate to Severe Pain Associated with Endometriosis
MYFEMBREE is indicated for the management of moderate to severe pain associated with endometriosis in premenopausal women [see Clinical Studies ].
Limitations of Use
Use of MYFEMBREE should be limited to 24 months due to the risk of continued bone loss that may not be reversible [see Warnings and Precautions and Adverse Reactions ].
Prior to Initiation of MYFEMBREE
- Exclude pregnancy [see Contraindications ].
- Discontinue hormonal contraceptives [see Warnings and Precautions ].
Recommended Dosage
- Take one tablet of MYFEMBREE orally once daily at approximately the same time, with or without food [see Clinical Pharmacology ].
- Start MYFEMBREE as early as possible after the onset of menses but no later than seven days after menses has started [see Clinical Studies ].
- The recommended total duration of treatment with MYFEMBREE is 24 months [see Indications and Usage , Warnings and Precautions , and Adverse Reactions ].
Missed Dose
Take the missed dose of MYFEMBREE as soon as possible the same day and then resume regular dosing the next day at the usual time.
Dosage Modification for Concomitant Use with P-gp Inhibitors
Avoid concomitant use of MYFEMBREE with oral P-gp inhibitors. If concomitant use is unavoidable, take MYFEMBREE first and separate dosing by at least 6 hours [see Drug Interactions and Clinical Pharmacology ].
Tablets: Each tablet of MYFEMBREE contains a fixed-dose combination of relugolix 40 mg, estradiol (E2) 1 mg, and norethindrone acetate (NETA) 0.5 mg. The tablets are light yellow to yellow, round, film-coated, and debossed with “MVT” on one side and “415” on the other side.
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 and Warnings and Precautions ]. 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 and Clinical Pharmacology ].
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, loss, or other adverse outcomes. In the United States general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
In an embryo-fetal development study, oral administration of relugolix to pregnant rabbits during the period of organogenesis (Days 6 to 18 of gestation) resulted in abortion, total litter loss, or decreased number of live fetuses at a dose of 9 mg/kg/day (about half the human exposure at the maximum recommended human dose [MRHD] of 40 mg daily, based on AUC). No treatment related malformations were observed in surviving fetuses. No treatment related effects were observed at 3 mg/kg/day (about 0.1-fold the MRHD) or lower. The binding affinity of relugolix for rabbit GnRH receptors is unknown.
In a similar embryo-fetal development study, oral administration of relugolix to pregnant rats during the period of organogenesis (Days 6 to 17 of gestation) did not affect pregnancy status or fetal endpoints at doses up to 1000 mg/kg/day (300 times the MRHD), a dose at which maternal toxicity (decreased body weight gain and food consumption) was observed. A no observed adverse effect level (NOAEL) for maternal toxicity was 200 mg/kg/day (86 times the MRHD). In rats, the binding affinity of relugolix for GnRH receptors is more than 1000-fold lower than that in humans, and this study represents an assessment of non-pharmacological targets of relugolix during pregnancy. No treatment related malformations were observed up to 1000 mg/kg/day.
In a pre- and postnatal developmental study in pregnant and lactating rats, oral administration of relugolix to rats during late pregnancy and lactation (Day 6 of gestation to Day 20 of lactation) had no effects on pre- and postnatal development at doses up to 1000 mg/kg/day (300 times the MRHD), a dose in which maternal toxicity was observed (effects on body weight gain). A NOAEL for maternal toxicity was 100 mg/kg/day (34 times the MRHD).
Lactation
Risk Summary
Detectable amounts of estrogen and progestin have been identified in the breast milk of women receiving estrogen plus progestin therapy and can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breast-feeding is well established.
Relugolix was detected in human breast milk. In a single dose milk-only lactation study in 8 healthy adult lactating women, the mean total amount of relugolix recovered in human breast milk over the first 24 hours was 0.0031 mg and over 120 hours (5 days) was 0.0042 mg following a single, oral, maternal dose of 40 mg. The mean calculated daily infant dose was 0.0006 mg/kg/day using 0.0031mg (the amount recovered in human breast milk over the first 24 hours). The relative infant dose was 0.105% of the maternal weight-adjusted dose of 40 mg.
There are no data on the effects of relugolix or its metabolites on the breastfed child, or the effects on milk production.
The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for MYFEMBREE and any potential adverse effects on the breastfed child from MYFEMBREE or from the underlying maternal condition.
Females and Males of Reproductive Potential
Based on animal data and the mechanism of action, MYFEMBREE can cause early pregnancy loss if MYFEMBREE is administered to pregnant women [see Use in Specific Populations ].
Pregnancy Testing
MYFEMBREE may delay the ability to recognize pregnancy because it may reduce the intensity, duration, and amount of menstrual bleeding [see Warnings and Precautions ]. Exclude pregnancy before initiating treatment with MYFEMBREE. Perform pregnancy testing if pregnancy is suspected during treatment with MYFEMBREE and discontinue treatment if pregnancy is confirmed [see Contraindications and Warnings and Precautions ].
Contraception
Advise women of reproductive potential to use effective non-hormonal contraception during treatment with MYFEMBREE and for at least 1 week following discontinuation. Avoid concomitant use of hormonal contraceptives with MYFEMBREE. The use of estrogen-containing hormonal contraceptives may increase the risk of estrogen-associated adverse events and is expected to decrease the efficacy of MYFEMBREE [see Warnings and Precautions ]. The use of E2 (a component of MYFEMBREE) in patients with hepatic impairment is expected to increase the exposure to E2 and increase the risk of E2-associated adverse reactions [see Clinical Pharmacology ].
MYFEMBREE is contraindicated in women:
- With a high risk of arterial, venous thrombotic, or thromboembolic disorders [see Boxed Warning and Warnings and Precautions ]. 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 and Use in Specific Populations ].
- With known osteoporosis, because of the risk of further bone loss [see Warnings and Precautions ].
- With current or history of breast cancer or other hormone-sensitive malignancies, and with increased risk for hormone-sensitive malignancies [see Warnings and Precautions ].
- With known hepatic impairment or disease [see Warnings and Precautions ].
- 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 , Adverse Reactions ].