Grapefruit-medication interactions: forbidden fruit or avoidable consequences?

action between grapefruit and certain medications more than 20 years ago. Currently, more than 85 drugs, most of which are available in Canada, are known or predicted to interact with grapefruit. This interaction en hances systemic drug concentration through impaired drug metabolism. Many of the drugs that interact with grapefruit are highly prescribed and are essential for the treatment of important or common medical conditions. Recently, however, a disturbing trend has been seen. Between 2008 and 2012, the number of medications with the potential to interact with grapefruit and cause serious ad verse effects (i.e., torsade de pointes, rhabdomyolysis, myelotoxicity, respiratory depression, gastrointestinal bleeding, nephrotoxicity) has increased from 17 to 43, representing an average rate of increase exceeding 6 drugs per year. This increase is a result of the introduction of new chemical entities and formulations. This review identifies the key scientific concepts and clinical implications of grapefruit– drug interactions relevant to medical practice. We focus on grapefruit because it is the most widely examined, but other citrus fruits may have similar consequences. It was recently found that grapefruit and certain other citrus juices act by an additional mechanism to cause diminished systemic concentration of certain drugs by in hibiting drug transporters. However, we will focus on the most well-known and well-studied interaction: that of interference in the activity of the cytochrome P450 3A4 (CYP3A4) enzyme. A summary of the evidence used in this review, which comes mainly from randomized controlled trials, is found in Box 1.