What You May Not Know about Grapefruit – Despite Nutritional Benefits, Important to be Aware of Possible Drug Interactions

By Mark Coggins, PharmD, CGP, FASCP

There has been a lot of discussion in the media recently regarding the nutritional benefits and drug-interaction risks associated with grapefruit.   The topic deserves increased awareness as it is estimated that 21% of families in the U.S. consume grapefruit which is an excellent source of fiber, vitamin C, antioxidants, phytochemicals, and flavonoids.

Grapefruit Effects in Parkinson’s disease and Stroke Prevention

A study conducted by researchers from Harvard University and the University of East Anglia in the UK followed 130,000 men and women over a 20-year period with 800 of the patients having developed Parkinson’s disease.  Male patients who consumed the most flavonoids had a 40% lower risk of developing Parkinson’s disease.  While this benefit was noted in males, the same link was not seen in female patients; however, other studies have found that females may lower their risk of stroke by increasing the amounts of flavonoid rich foods including grapefruit.

Grapefruit Drug-interaction Risks

Although the potential for drug-interactions involving grapefruit juice has been known for over two-decades, a report from Canadian researchers published November 26, 2012 in the Canadian Medical Association Journal has elevated the need for increased awareness of grapefruit drug-interactions with more than 85 medications now known to interact with grapefruit juice.  The report noted that the number of medications identified as interacting with grapefruit has doubled with potentially fatal interactions increasing from 17 to 43 in the past four years (2008 – 2012).

The researchers noted there are 43 medications which can cause serious side effects. In some cases even small amounts of grapefruit or grapefruit juice can have the potential to cause sudden death, acute kidney failure, respiratory failure, gastrointestinal bleeding, and other serious side effects.

Commonly used medications implicated include certain cholesterol-lowering medications, blood pressure medications, cancer treatments, and antibiotics such as erythromycin.

Examples of medications interacting with grapefruit include:

• Cholesterol lower agents such as atorvastatin (Lipitor®), lovastatin (Mevacor®), simvastatin (Zocor®)
• Blood thinning agents including apixaban (Eliquis®), clopidogel (Plavix®), and rovaroxaban (Xarelto®)
• Heart disease medications including amiodarone (Cordarone®), dronedarone (Multiq®), nifedipine, felodipine, verapamil
• Analgesics such as oxycodone (Perocet®, Oxycontin®)
• Dextromethorphan, a commonly used cough suppressant found in many over-the-counter and prescription medications (i.e. Robitussin® DM)

These potentially dangerous grapefruit drug-interactions are believed to occur as a result of chemicals known as furanocoumarins, which are also found in other citrus fruits such as limes and Seville oranges, often used in marmalade.  Furanocoumarins are believed to inhibit an enzyme that normally breaks down and inactivates about half the effects of interacting medications.  With these enzymes inhibited, medication concentrations can increase rapidly and lead to potentially toxic effects. For some medications, the effect of even one serving of grapefruit with normal doses of interacting medications can result in drug concentrations which are the equivalent of a person taking multiple doses of the medication.

Significant Increases in Drug Blood Concentrations

Studies conducted over the past decade have shown increases in the concentration of some medications taken with grapefruit to increase by as much as seven-fold.  Blood concentrations of the widely used cholesterol agent simvastatin (Zocor®) have been shown to increase by 330% when given with grapefruit. This can lead to rhabdomylosis with life-threatening muscle injury and possible kidney failure.

Because the enzymes inhibited by furanocoumarins have to be synthesized for their activity to be restored, the potential for these drug interactions can exist for 48 to 72 hours after the last exposure to grapefruit juice.  As a result, medications which interact with grapefruit can’t just be separated by a few hours to avoid the potential for these effects.

Recommendations

• Patients taking medications known to significantly interact with grapefruit should avoid grapefruit entirely.
• Patients should never stop taking medications without first consulting with their physician.
• Because all medications in the same therapeutic drug class interact with grapefruit or grapefruit juice, alternative medications may be available for those patients who do not want to stop consuming grapefruit.
• If patients consume grapefruit or grapefruit juice, it is important to make sure their physician and pharmacist are aware, especially when beginning any new prescriptions.
• Although interactions with most over the counter products and herbal remedies are believed to be safe, further research is required.  To be safe, if grapefruit is being consumed, consult with your physician or pharmacist before taking these over the counter and herbal remedies so that they can assist you in determining whether an interaction risk has been identified.

While being mindful of the current concerns for those who must avoid grapefruit because of drug interaction, it is worth noting that a hybrid grapefruit is being developed in Florida that has very low levels of furanocoumarins.  Perhaps in the future, this will provide an option for those who currently must avoid this nutritious and delicious fruit.