Grapefruit, drugs often not a good mix

With the spate of new drugs that have come out in the past several years, it’s important for physicians to be vigilant about the interaction these drugs have with certain foods. One food item, in particular, has risen to the top of the watch list: grapefruit. The concerns aren’t new, but the medications are – and physicians are once again being reminded of the adverse effects grapefruit can have when added to the mix.

Grapefruit interacts with medications by several different mechanisms, but predominantly by inhibition of the CYP450 enzyme CYP3A4 in the small intestine, which is responsible for drug metabolism. Grapefruit contains natural chemicals called furanocoumarins, which inhibit this hepatic enzyme and lead to increased drug absorption and concentration. A small change in enzyme activity can have a significant change in absorption. After grapefruit exposure, half of the enzyme activity recovers within about 24 hours, but full recovery can take up to 72 hours, which may lead to critical health problems (1).

It only takes one grapefruit or one cup of grapefruit juice (200 ml or 7 ounces) to cause a clinically significant drug interaction (2, 3). Both whole fruit and juice may cause an interaction. Taking the medication at a different time than grapefruit is ingested usually does not prevent an interaction, which is why patients should avoid consuming grapefruit when taking certain medications. Similar interactions also may occur with limes, pomelos or Seville oranges, but few patients will consume enough of these to cause an interaction. Grapefruit remains the No. 1 citrus offender when it comes to poor interactions (3). Advise patients who take any of these interacting medications to avoid grapefruit, or suggest an alternative drug.

More than 85 of these drug interactions have been identified, including common medications such as lipid-lowering statins (complete list courtesy of Canadian Medical Association Journal). Adverse reactions include respiratory depression, rhabdomyolysis, and torsade de pointes, a type of ventricular tachycardia, which can lead to death (4).

References:

  1. Fuhr U. Drug interactions with grapefruit juice. Extent, probable mechanism and clinical relevance. Drug Saf 1998; 18:251-72.
  2. Greenblatt DJ. Update on drug interactions with grapefruit juice: an evidence-based review. Pharmacy Times 2010; 76:95-106.
  3. Bailey DG, Dresser G, Arnold JM. Grapefruit-medication interactions: forbidden fruit or avoidable consequences? CMAJ 2012;doi:10.1503/cmaj.120951 (early release subject to revision).
  4. Bressler R. Grapefruit juice and drug interactions. Exploring mechanisms of this interaction and potential toxicity for certain drugs. Geriatrics 2006; 61:12-8.