The history, regulatory journey and Fortrea’s revival of Rifampin in DDI studies

Drug-drug interaction (DDI) studies are a cornerstone of modern clinical pharmacology, ensuring that new therapies and existing medications are safe and effective when administered alongside each other. Among the tools available to researchers, rifampin has long stood out as the preferred agent for inducing the cytochrome CYP3A enzyme, a pathway responsible for metabolizing approximately 30% of all small molecule drugs. However, recent years have seen rifampin’s role in DDI studies decline due to safety concerns related to levels of impurities1, resulting in a search for suitable alternatives. This article traces the history of rifampin in DDI research, the FDA’s evolving response to nitrosamine impurities, the limitations of alternative inducers and Fortrea’s innovative solution in collaboration with Emery Pharma.