Behind the headlines: Does grapefruit interact with Xarelto (rivaroxaban)?
The claim: In a recent newspaper article (ref 1), it was stated that “grapefruit eaten in ordinary amounts can interact harmfully with some common prescription drugs”. Among the drugs listed is the oral anticoagulant Xarelto® (rivaroxaban).
Xarelto was approved by the FDA on November 2, 2012 for the treatment and prevention of deep vein thrombosis and pulmonary embolism. The FDA-approved prescribing information makes no mention of a grapefruit/Xarelto interaction. As Xarelto is a newly approved drug in which both patients and healthcare professionals are learning about its use, I wondered if the newspaper article was true: Does grapefruit interact with Xarelto?
The answer: Yes, grapefruit may interact with the metabolism of Xarelto, which may, in theory, lead to increased risk of bleeding.
The research facts: The source for the newspaper article is a peer-reviewed article which appeared online in November 2012 in the Canadian Medical Association Journal, reviewing drug interactions with grapefruit (ref 2). In the journal article, 85 drugs were listed as having “potential interactions” with grapefruit, of which Xarelto is one of them. An intermediate risk for GI bleeding is listed as being associated with a Xarelto/grapefruit interaction. The publication is a review article, not an original study that produced scientific data.
According to the authors (Ref 2) drugs that interact with grapefruit have the following characteristics;they are 1. administered orally, 2. have very low to intermediate absolute bioavailability and 3. are metabolized by the cytochrome P450 3A4 enzyme (CYP3A4). The inclusion of Xarelto among the list of drugs interacting with grapefruit appears to be based upon these criteria and not because there have been clinical studies or specific case reports or of adverse interactions published.
In a survey of the research literature, I found no other journal articles referencing a Xarelto-grapefruit interaction.
The FDA’s Center for Drug Evaluation and Research, Office of Clinical Pharmacology Review in a review of Xarelto in 2009 stated that “Grapefruit juice may also increase plasma concentrations of XARELTO and should be avoided.” However, there was no other data provided to add clarity to this advice. There is no mention of grapefruit in any of the FDA approved prescribing information on Xarelto released in November, 2012.
The practical implication: Be aware of the possible interaction of Xarelto and grapefruit, but don’t be overly alarmed about consuming a small or moderate amount on occasion or regularly. It is probably advisable to keep grapefruit intake to a moderate amount, although the exact amount of grapefruit to be considered ‘moderate’ or ‘excessive’ is unclear. Some clinicians I spoke with advise no more than 1 glass of grapefruit juice per day as a suggested threshold of ‘moderate grapefruit consumption’, however this appears to be based more on opinion and general guidance rather than scientific data. If a person has a high risk of bleeding, it may be wise to avoid all grapefruit as precaution. As with all things, it is best to speak directly with your healthcare professionals who will know all your potential risk factors for increased bleeding.
“Drugs, grapefruit clash”, News and Observer, page 5B, 12-17-2012
David G. Bailey, George Dresser, and J. Malcolm O. Arnold Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? CMAJ cmaj.120951; published ahead of print November 26, 2012,