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Harvard Commentaries
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School

Man to Man Man to Man

Caution -- Grapefruit and Medication

March 21, 2014

By Harvey B. Simon M.D.

Harvard Medical School

Today's pharmacies depend on computers to track your medicines, check for drug interactions, and warn you about drinking alcohol when taking certain medicines. They also tell you whether you should take your pills with meals or on an empty stomach.

But there's another important issue to consider: the interaction between certain foods and medications.

Take grapefruit and grapefruit juice. They provide enough vitamin C, potassium, dietary fiber and other nutrients to earn the American Heart Association's "heart-check" mark.

Grapefruit juice is also tasty, which is why 21% of all households in the United States buy grapefruit juice and 14% of all American men drink it regularly. That's the good news. The bad news is that grapefruit juice can interact with dozens of medications, sometimes with dangerous results.

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The Chemical Culprit

Doctors are not sure which of the hundreds of chemicals in grapefruit are responsible for changing the way your body handles certain drugs. The leading candidate is furanocoumarin. It is also found in Seville (sour) oranges and tangelos; although these fruits have not been studied in detail, the guidelines for grapefruit should apply to them as well.

Furanocoumarin doesn't interact directly with your pills. Instead, it binds to an enzyme in your intestinal tract known as CYP3A4, which normally reduces the absorption of certain medicines. When grapefruit juice blocks the enzyme, it's easier for the medication to pass from your gut to your bloodstream. Blood levels will rise faster and higher than normal. In some cases, the abnormally high levels can be dangerous.

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Which Medicines Are Affected?

Grapefruit juice can boost the effect of many drugs to varying degrees.


Big effect

Little or no effect

Type of drug (use)
Generic name (brand name)
Generic name (brand name)
Calcium channel blockers (high blood pressure, angina)
Felodipine (Plendil); Nifedipine (Procardia, Adalat)
Verapamil (Calan, Isoptin); Diltiazem (Cardizem); Amlodipine (Norvasc)
Statins (cholesterol)
Atorvastatin (Lipitor); Simvastatin (Zocor); Lovastatin (Mevacor)
Fluvastatin (Lescol); Pravastatin (Pravachol); Rosuvastatin (Crestor); Pitavastatin (Livalo)
Immunosuppressants (transplants)
Cyclosporine (Sandimmune)
Benzodiazepines (anxiety, insomnia)
Diazapam (Valium); Triazolam (Halcion) ; Midazolam (Versed)
Flurezapam (Dalmane); Clonazepam (Klonapin)
Other neurological and psychiatric drugs (anxiety, insomnia)
Buspirone (Buspar); Sertraline (Zoloft); Carbamazepine (Tegretol)
Haloperidol (Haldol); Trazodone (Deseryl); Zolpidem (Ambien)

It doesn't take much grapefruit juice to boost the levels of drugs that are susceptible. A single glass can produce a 47% reduction of the intestinal enzyme that regulates absorption. And because this effect of the juice wears off slowly, a third of its impact is still evident after 24 hours.

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How To Avoid Problems

If you take one of the affected medicines:

  • Switch to orange juice.
  • If you are really hooked on grapefruit juice, though, you can ask your doctor whether you can switch to a related drug that's less vulnerable to the boosting effect.
  • Avoid taking your pills and your juice simultaneously; the more time between the two, the better. And the smaller your glass of juice, the better.
  • If you are on a low or moderate dose of the medicine, you can probably get away with an occasional glass of grapefruit juice. But if you are on a high dose, it could be dangerous. This is especially true in the case of calcium channel blockers, which can lower your blood pressure or slow your heart rate excessively.

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Drugs for Erectile Dysfunction

Grapefruit juice may boost blood levels of drugs for erectile dysfunction (ED). These include sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra). This could be a good thing for some men who haven't responded well to the usual doses. But the combination could also trigger headaches, flushing, or even dangerously low blood pressure. All three pills are metabolized by the CYP3A4 enzyme, which might make them susceptible to grapefruit juice.

Additional research will clarify the grapefruit juice-medication connection. While awaiting juicy new results, though, men should remember that the interaction is fact, not pulp fiction.

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Harvey B. Simon, M.D., is an Associate Professor of Medicine at Harvard Medical School and a member of the Health Sciences Technology Faculty at Massachusetts Institute of Technology. He is the founding editor of the Harvard Men's Health Watch newsletter and author of six consumer health books, including The Harvard Medical School Guide to Men's Health (Simon and Schuster, 2002) and The No Sweat Exercise Plan, Lose Weight, Get Healthy and Live Longer (McGraw-Hill, 2006). Dr. Simon practices at the Massachusetts General Hospital; he received the London Prize for Excellence in Teaching from Harvard and MIT.

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