Which of the following drugs has a REMS program due to a high frequency of birth defects?

The drug thalidomide is associated with a Risk Evaluation and Mitigation Strategy (REMS) program due to its historical link to severe birth defects when taken during pregnancy. Initially marketed in the late 1950s and pulled from the market in the early 1960s after its teratogenic effects became evident, thalidomide can cause significant malformations in developing fetuses, including limb deformities and other serious issues.

In response to the lessons learned from thalidomide's past, regulatory agencies instituted a REMS program to control and mitigate the risks associated with its use. This program includes requirements such as patient education, prescriber qualifications, and monitoring to ensure that patients are aware of the risks and take necessary precautions, especially around pregnancy.

While isotretinoin, known under the brand name Accutane, is also associated with birth defects and has a REMS program in place, it is actually a brand name for a specific formulation of isotretinoin, and not an alternate name for thalidomide. Methotrexate is contraindicated in pregnancy and can also cause birth defects; however, it does not have a REMS program that is primarily focused on birth defects like thalidomide does. This