Does Zetia (ezetimibe) use during pregnancy increase the risk of fetal deformities?

Ezetimibe (Zetia) Should Be Avoided During Pregnancy Due to Insufficient Safety Data

Ezetimibe (Zetia) should be avoided during pregnancy unless the potential benefit justifies the potential risk to the fetus, as there are insufficient data on its use in pregnant women to evaluate for drug-associated risk of fetal deformities. 1

Evidence on Ezetimibe in Pregnancy

FDA Labeling and Safety Data

• The FDA label clearly states 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 1
• Animal reproduction studies showed no adverse developmental effects in pregnant rats and rabbits at doses up to 10 and 150 times the human exposure, respectively 1
• However, animal data cannot fully predict human outcomes, and human safety data remain limited

Clinical Guidelines

• Multiple clinical guidelines consistently recommend avoiding ezetimibe during pregnancy:
  • The American College of Cardiology (ACC) explicitly states that ezetimibe should be used during pregnancy only if the potential benefit justifies the risk to the fetus 2
  • Clinical practice guidelines recommend that all lipid-lowering drugs, including ezetimibe, should be avoided during pregnancy and nursing or in women who may become pregnant 2

Management Recommendations for Lipid-Lowering in Pregnancy

Pre-Conception Planning

• Women who are currently on lipid-lowering drugs for primary prevention of cardiovascular disease should be advised to discontinue pharmacologic therapy:
  • At least 1 month and preferably 3 months before attempted conception, or
  • Immediately if the patient is already pregnant 2

Alternative Approaches During Pregnancy

• Lifestyle interventions should be considered during pregnancy as general management for dyslipidemia 2
• Bile acid sequestrants are the only lipid-lowering agents approved for use during pregnancy 3
  • If bile acid sequestrants are used, patients should be monitored for vitamin K deficiency 2

Special Considerations

• For patients with established clinical atherosclerotic cardiovascular disease (ASCVD) who are at very high risk, including those with multiple risk factors or homozygous familial hypercholesterolemia:
  • Consultation with a lipid specialist is strongly recommended 2
  • Individual risk-benefit assessment may be necessary in these high-risk cases 2

Important Caveats and Monitoring

Monitoring During Pregnancy

• If a woman becomes pregnant while taking ezetimibe, the medication should be discontinued unless the benefits of therapy outweigh the potential risks to the fetus 1
• Pregnant patients who discontinue lipid-lowering therapy should be monitored for significant elevations in LDL-C and triglycerides during pregnancy (recognizing that a progressive rise in both LDL-C and triglycerides is physiologic during pregnancy) 2

Post-Pregnancy Considerations

• Lipid-lowering therapy may be resumed after completion of breastfeeding 2
• There is no information about the presence of ezetimibe in human milk or its effects on the breastfed infant 1

Conclusion

Based on the available evidence, ezetimibe should be avoided during pregnancy due to insufficient safety data regarding fetal deformities. The risk-benefit profile does not support routine use during pregnancy except in cases where the potential maternal benefit clearly outweighs the unknown fetal risks. Alternative approaches such as lifestyle modifications or bile acid sequestrants should be considered for managing dyslipidemia during pregnancy.