Grapefruit and Prescription Drugs: A Growing Dangerous Combination

Pharmacists have known of the potential dangerous interaction grapefruit and grapefruit juice have with certain prescription drugs for at least 20 years. However, a new Canadian study published in the Canadian Medical Association Journal finds the number of commonly used prescription drugs with this possible dangerous interaction with grapefruit is on the rise. The potential side effects are escalating as well, according to researchers, including death.

Each year, researchers say, more than six new drugs which hit the market also land on the “Grapefruit Interacting Drugs” list, bringing the total identified to more than 85 drugs. Though some side effects are mild, others include acute kidney failure, respiratory failure, gastric bleeding, and sudden death. When researchers first discovered this connection, they found ill effects were due to the fruit causing certain prescription drugs to concentrate in the patient’s bloodstream.

Hillcrest Medical Center pharmacist, Manish Patel, explains how this works, “Grapefruit juice is a potent inhibitor of the intestinal cytochrome P-450 3A4 system (specifically: CYP3A4 - mediated drug metabolism) which is responsible for the first-pass metabolism of many medications.  This interaction can lead to increases in bioavailability and corresponding increases in serum drug levels.  In many cases, the increased serum drug levels can produce some readily observable symptoms.”

Whether eaten or consumed as a drink, citrus including grapefruit, limes, pomelos, and some oranges contain an active ingredient which interacts with the digestive enzyme, CYP3A4. This enzyme’s job is to protect the body from harmful toxins, which means it typically dilutes the effectiveness of medication by about 50 percent. Physicians take this into account when prescribing medication to their patients.

However, citrus like grapefruit can interrupt this normal process, thus increasing the strength of the medication dramatically. Taken with the wrong medications, grapefruit can triple or quadruple the dosage the patient thinks they are receiving once it is in their system.

Examples of possible interactions include:

(1)  Excessive sedation: benzodiazepines.  
(2) Increased risk of rhabdomyolyis: HMG-CoA reductase inhibitors (statins)-- there are some exceptions.
(3)  Symptomatic hypotension: dihydropyridine calcium antagonists (some exceptions exist).  
(4) QT interval prolongation: astemizole, cisapride, pimozide,  terfenadine.  

These interactions do not necessarily result when consuming grapefruit or grapefruit juices at the same time as taking the medication. “It is important to remember, one glass of grapefruit juice could elicit the maximum blocking effect, and the effect may persist for longer than 24 hours,” says Patel. “Since the effects can last for such a prolonged period of time, grapefruit juice does not have to be taken at the same time as the medication in order for the interaction to occur. Since waiting 24 hours between having grapefruit juice and taking -- sometimes daily -- medications, many people are advised not to drink grapefruit juice at all while taking certain drugs.”

To view the complete Grapefruit Interacting Drugs list, click here.

If you have questions about your medications and possible interaction with grapefruit, Patel says to keep the communication lines open, “Always talk to your doctor or pharmacist when starting a new medication or when consuming grapefruit juice with a medication, even if you have been on it for years.”