FDA Announces Availability of Two Final Guidances, Clinical and In Vitro Drug Interaction Studies -- Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions

FDA Announces Availability of Two Final Guidances, Clinical and In Vitro Drug Interaction Studies -- Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions

On January 23, 2020, the U.S. Food and Drug Administration (FDA) announced the availability of two drug-drug interaction (DDI) final guidances for industry titled “Clinical Drug Interaction Studies -- Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions” and “In Vitro Drug Interaction Studies -- Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions”. These final guidances define a systematic, risk-based approach to the assessment of DDIs and are intended to help sponsors of investigational new drug applications and applicants of new drug applications evaluate DDIs during drug development, determine essential information to communicate in labeling, and mitigate risk. 

Patients frequently use more than one medication at a time. Unanticipated, unrecognized, or mismanaged DDIs are an important cause of morbidity and mortality associated with prescription drug use and have occasionally caused the withdrawal of approved drugs from the market. The clinical DDI guidance describes clinical studies to evaluate the DDI potential of an investigational drug, including: (1) the timing and design of the clinical studies; (2) the interpretation of the study results; and (3) the options for managing DDIs in patients. Specifically, this guidance provides considerations for evaluating Cytochrome P450 (CYP) enzyme- or transporter-mediated pharmacokinetic interactions. The in vitro DDI guidance focuses on in vitro experimental approaches to evaluate the interaction potential between investigational drugs with CYP enzymes and transporters as well as how in vitro results can inform future clinical DDI studies.

The “Clinical Drug Interaction Studies -- Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions” guidance is available at https://go.usa.gov/xdgu7 and the “In Vitro Drug Interaction Studies --Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions” guidance is available at https://go.usa.gov/xdgup. Please refer to these guidances for more details.

The FDA website for Drug Development and Drug Interactions supplements these guidances and provides illustrative listings of in vitro and clinical substrates, inhibitors, or inducers of CYP enzymes or transporters. These lists are periodically updated based on newly available information. The most recent update was in December 2019.  Please refer to the following website for more information: https://go.usa.gov/xdgut. Additional information on how the FDA evaluates the risk of DDIs can be found in a CDER Conversation with Dr. Issam Zineh, Director of the Office of Clinical Pharmacology, available at https://go.usa.gov/xngZV.