Can citrus juices interfere with drug metabolism?

I heard that citrus juices can interfere with drug metabolism. What should we tell patients about this potential interaction?

Certain citrus fruits, including grapefruit, Seville orange, and bitter orange, may inhibit enzymes in the liver that are responsible for drug metabolism. This can result in an accumulation of the drug building up in the body over time. The cytochrome P-450 (CYP) enzyme 3A4 is the most affected; however, CYP1A2, 2C19, and other enzymes are affected to a lesser extent. Enzyme inhibition occurs within 4 hours of ingesting the fruit and can last for 3 to 7 days. Therefore, simply separating consumption of citrus fruits and medications by a few hours does not avoid this interaction.

When advising patients about citrus fruit consumption, their chemotherapy and other medications should be reviewed with a pharmacist to detect potential drug interactions. Patients regularly taking drugs predominantly metabolized by CYP3A4 (also known as 3A4 substrates) are best advised to avoid consuming citrus fruits. Patients who consume citrus fruits with these medications are likely to accumulate higher concentrations of the drug, leading to more adverse effects or toxicity. Examples of this include sedation with benzodiazepines (eg, alprazolam [Alprazolam Intensol, Niravam, Xanax, generics]) or myalgias with HMG-CoA reductase inhibitors (eg, simvastatin [Zocor, generics]). Patients taking 3A4 substrates occasionally may have lower risk for toxicity because there is less chance of accumulation with intermittent dosing (eg, ondansetron [Zofran, Zuplenz, generics] prior to chemotherapy every 3 weeks). That being said, avoidance of citrus juices when taking the substrate is the best practice in case repeat dosing is required (eg, delayed or breakthrough nausea requiring repeat doses of ondansetron). ONA

Lisa Thompson is assistant professor, Department of Clinical Pharmacy, University of Colorado Denver School of Pharmacy, Aurora, Colorado.

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