FDA Draft Guidance 2012: Drug Interaction Studies- Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations

This guidance provides recommendations for sponsors of new drug applications (NDAs) and biologics license applications (BLAs) for therapeutic biologics regulated by CDER regarding in vitro and in vivo studies of drug metabolism, drug transport, and drug-drug or drug-therapeutic protein interactions. Drug interactions can result when one drug alters the pharmacokinetics of another drug or its metabolites. Drug interactions also can reflect the additive nature of the pharmacodynamic effect of either drug when taken with the other drug. The main focus of this guidance is pharmacokinetic drug interactions. This guidance reflects the Agency’s view that the pharmacokinetic interactions between an investigational new drug and other drugs should be defined during drug development, as part of an adequate assessment of the drug’s safety and effectiveness. It is important to understand the nature and magnitude of drug-drug interactions (DDI) for several reasons. Concomitant medications, dietary supplements, and some foods, such as grapefruit juice, may alter metabolism and/or drug transport abruptly in individuals who previously had been receiving and tolerating a particular dose of a drug. Such an abrupt alteration in metabolism or transport can change the known safety and efficacy of a drug.