Tag Archives: grapefruit drug interaction

Is It Safe To Consume Grapefruit If You Take The Blood Thinner Apixiban (Eliquis)?

A patient of mine with atrial fibrillation taking the blood thinner eliquis told me that she had eaten grapefruit for two days in a row and then developed a nose bleed. She had heard of the interaction between grapefruit and certain medications and wondered if this had caused her nose bleed.

I was unaware of any eliquis/grapefruit interaction but thought this was a remarkably astute observation and question and set about to research it properly.

Among other things, I discovered that some researchers believe the grapefruit-drug interaction to be a widespread , underreported and  highly significant problem while others feel it is overblown and a rare cause of clinically important side effects.

For those, who prefer not to delves into the gory details I give you the crux of what BMS/Pfizer, the makers of apixiban (Eliquis) told me and with which I agree:

When consumed in usual dietary volumes, grapefruit juice is considered a moderate inhibitor of CYP3A4. Therefore a dose adjustment of apixaban is not expected to be required.

In other words, although not formally studied, there is no evidence that apixiban levels are increased by moderate grapefruit juice ingestion to a degree that would cause significant bleeding complications.

Although multiple sites on the internet (including the unreliable Web MD) will tell you of a potentially dangerous interaction between grapefruit and apixiban this theoretical interaction has not proven clinically significant.

Interactively Yours,

-ACP

Below is the full text of the letter BMS sent me

Bristol-Myers Squibb and/or Pfizer have not conducted any studies evaluating the concomitant use of apixaban and grapefruit juice. The decision to prescribe apixaban in patients who are concomitantly taking grapefruit juice is a clinical decision for the treating physician based on the individual’s circumstances and inaccordance with the full prescribing information for apixaban.

While in vitro data indicates grapefruit juice can inhibit both cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), clinical evidence suggests that grapefruit juice mediated interactions would be primarily due to the inhibition of CYP3A4 and the contribution of P-gp inhibition may be limited.1, 2 When consumed in usual dietary volumes, grapefruit juice is considered a moderate inhibitor of CYP3A4.1 Therefore a dose adjustment of apixaban is not expected to be required.

Apixaban is eliminated from the body through multiple pathways, with approximately 25% of the administered dose recovered as metabolites. The main metabolic pathway for apixaban is through CYP3A4/5, with minor contributions from other CYP isoenzymes. Apixaban is also a substrate of transport proteins P-gp and breast cancer resistance protein.3

  1. [1]  Hanley MJ, Cancalon P, Widmer WW,et al. The effect of grapefruit juice on drug disposition. Expert Opin Drug Metab Toxicol. 2011; 7(3):267-286.
  2. [2]  Farkas DG and Greenblatt DJ. Influence of fruit juices on drug disposition: discrepancies between in vitro and clinical studies. Expert Opin Drug Metab Toxicol. 2008;4(4):381-393.
  3. [3]  Eliquis® (apixaban) Package Insert. Bristol-Myers Squibb Company, Princeton, NJ and Pfizer Inc, New York, NY