Estradiol / norethindrone / relugolix Pregnancy and Breastfeeding Warnings

Brand names: Myfembree

Medically reviewed by Drugs.com. Last updated on Jun 15, 2023.

Estradiol / norethindrone / relugolix Pregnancy Warnings

Use is contraindicated during pregnancy.

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned

Risk summary: Based on its mechanism of action and findings from animal studies, this drug may cause early pregnancy loss; limited human data on use of this drug in pregnant women are insufficient to inform a drug-related risk of adverse maternal or fetal outcomes.

Comments:
-A pregnancy exposure registry is available.
-Exclude pregnancy prior to initiation of therapy and discontinue treatment if pregnancy occurs.
-Inadvertent exposure to estrogens or progestins (progestogens) in early pregnancy has demonstrated minimal or no increased risk of harmful effects in children born following exposure.
-Avoid use of this drug in combination with hormonal contraceptives; estrogen-containing hormonal contraceptives may increase the risk of estrogen-associated side effects and is expected to decrease the efficacy of this drug.
-This drug may delay the ability to recognize pregnancy as it may reduce the intensity, duration, and amount of menstrual bleeding.
-Contraceptive properties: According to some authorities, this drug inhibits ovulation and provides adequate contraception at the recommended dose. Other authorities advise that patients of childbearing potential use nonhormonal contraception during therapy and for 1 week after the last dose.
-When considered to provide adequate contraception, patients of childbearing potential should use nonhormonal contraception for 1 month after starting therapy with this drug and for 7 days after two or more missed consecutive doses; concomitant use of hormonal contraceptives is contraindicated.
-Advise patients that ovulation will return rapidly after stopping treatment; appropriate contraceptive methods should be reviewed before discontinuing therapy and alternative contraception should be started immediately after this drug is stopped.

Animal studies with estrogens and progestins have failed to reveal evidence of teratogenicity; epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) after exposure to estrogens and progestins before conception or during early pregnancy. Animal studies with relugolix have revealed evidence of fetolethality. Oral administration of relugolix to pregnant rabbits during organogenesis resulted in abortion, total litter loss, or decreased number of live fetuses at exposures about half the human exposure at the maximum recommended human dose (MRHD), based on AUC; no treatment related malformations were seen in surviving fetuses and no treatment related effects were seen at exposures about 0.1-fold the MRHD or lower. Oral administration of relugolix to pregnant rats during organogenesis did not affect pregnancy status or fetal endpoints at exposures 300 times the MRHD, but maternal toxicity (decreased body weight gain and food intake) was observed. There are no controlled data in human pregnancy.

To monitor the outcomes of pregnant women exposed to this combination drug, a pregnancy registry has been established. In the US, pregnant women and health care providers are encouraged to call 1-855-428-0707.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

See references

Estradiol / norethindrone / relugolix Breastfeeding Warnings

Breastfeeding is not recommended.
-According to some authorities: Breastfeeding is contraindicated during use of this drug and for 2 weeks after the last dose.

Excreted into human milk: Yes (estrogen, progestin); Unknown (relugolix)
Excreted into animal milk: Yes

Comments:
-The developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
-The effects in the nursing infant are unknown; any potential adverse effects in the breastfed child due to this drug or the mother's underlying condition should be considered.
-Detectable amounts of estrogen and progestin have been found in the breast milk of women receiving estrogen plus progestin and can reduce milk production in breastfeeding women; while this reduction can occur at any time, it is less likely to occur once breastfeeding is well established.

RELUGOLIX: In animal studies, this drug was present in post-partum animal milk at concentrations 10 times higher than the plasma two hours after experimental dose. When a drug is present in animal milk, it is likely present in human milk.

ESTRADIOL:
Limited information on the use of estradiol during breastfeeding indicates administration route and dosage form affect the amount transferred into breast milk (e.g., vaginal administration results in measurable amounts in milk, but transdermal patches do not). There are no data on the use of oral estradiol hemihydrate in breastfeeding patients. Across multiple studies, transdermal estradiol doses between 50 to 200 mcg did not increase estradiol in breastfed infants or cause any adverse effects. However, delayed and reduced weight gain may have been caused by this drug in some documented cases.

NORETHINDRONE (NORETHISTERONE):
Fair quality evidence indicates that norethindrone does not adversely affect the composition of milk, the growth and development the infant, or the milk supply. Peak levels of norethindrone occurred within 1-3 hours of dose. In one study, infant serum levels reached 0.8% of peak maternal serum levels drawn at 2 to 2.5 hours after dosing.

See references

Further information

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