Risk Evaluation and Mitigation Strategies: A Focus on the Mycophenolic Acid Preparations

Abstract

Objective To review risks associated with mycophenolic acid (MPA) preparations and evaluate their required risk evaluation and mitigation strategies (REMS) elements. Data Sources and Extraction Articles were identified through a non–date-limited MEDLINE and EMBASE search using the terms fetal toxicity, teratogenicity, risk evaluation and mitigation strategies, REMS, MPA, mycophenolate mofetil, enteric-coated MPA, and organ transplant. Information from the Food and Drug Administration (FDA) and the manufacturers of the MPA preparations was also evaluated. Data Synthesis The MPA preparations are associated with several potential risks, including gastrointestinal disturbances and myelosuppression; however, their impact on the fetus in pregnant patients taking 1 of these agents poses the greatest risk. The FDA approved REMS programs for all MPA products, both innovator and generic preparations, in September 2012. With evidence of increased risk of miscarriage and birth defects associated with MPA use, the FDA instituted a REMS program that contains both a medication guide and elements to assure safe use (ETASU). Conclusion The medication guides for the MPA products, which were previously FDA approved, should continue to be distributed to patients who get either an initial prescription filled or a refill. The ETASU requires prescribers to complete training and obtain patient signatures on the Patient-Prescriber Acknowledgment Form. A single, national, voluntary pregnancy registry specific to this medication has been established, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA.