Is Zetia (Ezetimibe) Safe During Pregnancy?
Ezetimibe should be avoided during pregnancy and nursing, as all lipid-lowering drugs are not recommended in pregnant women or those who may become pregnant. 1
Guideline Recommendations
The 2022 BMJ and American College of Cardiology guidelines explicitly state that all lipid-lowering drugs, including ezetimibe, should be avoided during pregnancy and nursing. 1 Instead, lifestyle interventions should be considered during pregnancy and nursing as general management for dyslipidemia. 1
FDA Labeling and Safety Data
The FDA drug label for ezetimibe provides critical information about pregnancy use: 2
- There are insufficient data on ezetimibe use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. 2
- Ezetimibe should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 2
- Animal reproduction studies showed no adverse developmental effects in rats and rabbits at doses up to 10 and 150 times human exposure, respectively, though increased skeletal findings were observed at high doses. 2
- Fetal exposure to ezetimibe was confirmed in animal studies, with placental transfer documented. 2
Clinical Context and Risk-Benefit Considerations
The American College of Cardiology provides nuanced guidance for specific high-risk scenarios: 1
- Women on lipid-lowering drugs for primary prevention should discontinue therapy (except bile acid sequestrants if needed) at least 1 month and preferably 3 months before attempted conception, or immediately if already pregnant. 1
- For very high-risk patients with established ASCVD, multiple risk factors, or homozygous familial hypercholesterolemia (HoFH), individual discussions with healthcare professionals are advised to consider ongoing therapeutic needs during pregnancy. 1
- There are no adequate and well-controlled studies of ezetimibe in pregnant women. 1
Breastfeeding Considerations
Ezetimibe should not be used in nursing mothers unless the potential benefit justifies the potential risk to the infant. 2
- There is no information about the presence of ezetimibe in human milk. 2
- Animal studies show ezetimibe is present in rat milk, suggesting it will likely be present in human milk. 2
- Lipid-lowering therapy may be resumed after completion of breastfeeding. 1
Alternative Management During Pregnancy
Bile acid sequestrants are the only lipid-lowering agents approved for use during pregnancy if treatment is absolutely necessary. 1, 3 However, pregnant patients managed with bile acid sequestrants should be monitored for vitamin K deficiency. 1
Intensive lifestyle modifications and dietary interventions (such as Mediterranean diet) should be the primary management strategy during pregnancy. 1 Referral to a lipid specialist and registered dietitian is strongly recommended for high-risk pregnant patients. 1
Key Clinical Pitfalls to Avoid
- Do not continue ezetimibe in women planning pregnancy without careful risk-benefit assessment and discussion. 1
- Do not assume ezetimibe is safe simply because animal studies showed no major teratogenic effects—human data are insufficient. 2
- Do not overlook the need for preconception counseling in women of childbearing age taking lipid-lowering therapy. 1
- Remember that physiologic elevation of lipids during pregnancy is normal and does not necessarily require pharmacologic intervention. 1, 3