Effects of Grapefruit or its Juice on Bioavailability of Medications

This page is intended to help you avoid having trouble that grapefruit or its juice can cause with medicines you take. My last spot check of Medscape / Medline / NIH for more information about this was in September 2014. If you just want my lists of affected drugs, scroll down past the Introduction. I try to keep this page reasonably current, but you should regard it as a primer on the subject, not the definitive textbook!

Introduction

Grapefruit juice inhibits cytochrome P-450 3A4 (CYP4503A4) isoenzyme and P-glycoprotein (P-gp) transporters in the intestines and liver. That can change how fast you absorb medicine and how readily your body can use the medicine (which is called bioavailability). The effect lasts as much as 24 hours after you eat grapefruit or drink the juice.

Repeated consumption of grapefruit or its juice while you are taking particular drugs on a regular schedule can cause the drugs to build up too much in your blood, which can be harmful to you. There are other particular drugs that become significantly less effective if you consume grapefruit juice. For that matter, grapefruit can interact similarly with a few supplements and at least one food.

In some instances grapefruit causes pharmacokinetic or pharmacodynamic changes (translation: modifies how the drug behaves). This can happen separately from any effect on bioavailability.

Although grapefruit is best known for having these effects, other fruits and fruit juices are proving to have such effects too.

I am not a pharmacist or doctor. I only have a non-professional level of access to medical literature and training, so I do not know what some of these substances are used for. What matters is whether you are taking any of these and need to know this–just as I once needed to know because my breakfast grapefruit juice was canceling out most of a prescription I was taking. It’s no joking matter. I didn’t have to be so ill. Some people have died from the interactions between grapefruit juice and medicines or supplements. The FDA’s website includes a summary report about adverse incidents with supplements–I was stunned to see that a supplement containing both grapefruit and licorice (a deadly combination) has been sold in the USA and some deaths have been reported in association with it.

If you are taking a drug or supplement that is not mentioned here and want to consume a fruit or juice, the best way to find out whether that will set up an adverse interaction is to ask your pharmacist. The pharmacist has access to better information (and more detailed information, and the training to understand subtleties) than I do.

Note: Some of the drugs mentioned in this page have been taken off the market in one or more countries. They are still listed here in case you are in a country where they are still sold.

Medicines that are Stronger with Grapefruit

Most of these are medicines for which grapefruit increases bioavailability. These are medications that linger more than they should and build up in your body if you consume grapefruit within 24 hours of taking the drug. These are mostly drugs that normally have low oral bioavailability (meaning, you don’t absorb them efficiently after taking them) because a substance called CYP3A4 mediates presystemic metabolism of the drug. CYP3A4 is an enzyme in intestinal cells that oxidizes part of the dose of some drugs before they get into the bloodstream.

Grapefruit (and pomegranate, in case you need to know) interferes with oxidation via CYP3A4 so that more of the drug gets into the bloodstream. The substances responsible for this in grapefruit are naringenin and bergamottin. In some instances, to cause trouble you would have to repeatedly consume grapefruit while taking the drug. In other instances, grapefruit can affect a single dose of the medication enough to cause problems.

Alpha Blockers

  • terazosin (Hytrin), a selective alpha 1 antagonist used to treat high blood pressure and, in men, symptomatic benign prostatic hyperplasia (BPH)

Antiarrhythmics

  • digoxin

Antihistamines

  • astemizole (Hismanal), non-sedating antihistamine
  • terfenadine (Seldane), non-sedating antihistamine (no longer sold in USA)
  • alprazolam (Xanax)
  • buspirone (Buspar), by a factor of 4.3

Beta-adrenergic Blockers

  • talinolol

Calcineurin Inhibitors

  • Tacrolimus

Calcium Channel Blockers (Treating Hypertension)

  • amlodipine (Norvasc), calcium channel blocker, two-fold or more effect
  • benzothiazepine
  • felodipine (Plendil), increases bioavailability 200%, interaction causes hypotension
  • losartan potassium, time until drug appearance in serum increases and mean retention time increases
  • nifedipine (Adalat, Procardia), lengthens time to maximum concentration, but does not change maximum concentration level
  • nisoldipine (Sular), increases bioavailability 57%
  • nitrendipine (Baypress)
  • pranidipine, by ratios of 1.5 to 1.75 (significantly increases heart rate)
  • verapamil (Calan, Calan SR, Covera, Isoptin, Isoptin SR, Verelan, Verelan PM, generics), increases bioavailability by 36%, both grapefruit and the drug inhibit P-glycoprotein

Immunosuppressants

  • tacrolimus (Prograf)

Protease Inhibitors, some but not all

  • saquinavir (Invirase), 50% to 200% increase

Statins (Cholesterol Reduction)

  • atorvastatin (Lipitor)
  • lovastatin (Altocor)
  • pitavastatin
  • simvastatin (Zocor)

Other Types

  • bortezomib, a proteasome inhibitor used to treat multiple myeloma
  • carbamazepine (Tegretol), tested in epilepsy patients
  • cisapride (Propulsid)
  • colchicine (Colcrys)
  • cyclosporine, by 35% to 55%
  • diazepam (Valium)
  • dihydroergotamine, known as DHE, given intravenously for migraines that resist standard treatments, grapefruit may be consumable with caution
  • estradiol, 17beta form, can increase the risk of breast cancer in women taking estrogen
  • flutamide (Eulexin)
  • midazolam (Versed)
  • triazolam (Halcion)

Medicines that are Weaker with Grapefruit

The technical way to say this is medicines for which grapefruit decreases bioavailability. These medications are partially blocked by grapefruit. (Enzyme CYP3A4 is not the only thing grapefruit can interact with.) The partial blockage weakens the effect of these drugs, so they can’t do as much good for you as they should.

Antihistamines

  • fexofenadine hydrocholoride (Allegra), by 67%, a non-sedating antihistamine (even more inhibited by orange juice at 72% or apple juice at 77%)

Other Medicines

  • indinavir (Crixivan), a protease inhibitor, by 26%
  • itraconazole

Other Adverse Interactions

In this section, if the medical literature I found (usually studies published in Medscape) specifies the nature of the interaction, I describe it. Not all of these interactions involve drugs.

  • fluoxetine (Prozac): The interaction is serious serotonin syndrome, from excessive buildup of serotonin in the brain.
  • licorice: Deglycerated licorice (DGL) is often taken to ease gastritis. When combined with grapefruit, the result is severe dehydration, which in turn causes potassium deficiency. Depleted potassium can become a medical emergency and can even be fatal.
  • red yeast rice: This is often used to reduce lipid levels. The nature of the adverse interaction with grapefruit was not specified.
  • sirolimus (Rapamune): This prevents post-transplant rejection of transplanted kidneys. The nature of the adverse interaction was not specified; however, the study said apple juice also should be avoided with this drug.

Tested and Showed No Significant Interaction

angiotensin II receptor antagonists (except some effect occurs with losartan potassium)
dihydropyridine
diltiazem (except plasma half-life increases)
quinine
(Pravachol)
warfarin, low-intensity therapy tested

Books about Drug Interactions

The Essential Herb-Drug-Vitamin Interaction Guide: The Safe Way to Use Medications and Supplements Together

Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1e

The Natural Pharmacist : Drug-Herb-Vitamin Interactions Bible

A-Z Guide to Drug-Herb-Vitamin Interactions Revised and Expanded 2nd Edition: Improve Your Health and Avoid Side Effects When Using Common Medications and Natural Supplements Together

Drug Interaction Facts 2014: The Authority on Drug Interactions

Information Sources

This page contains a summary of what I found on this subject in reputable sources, mostly in Medscape and Medline. I also looked at USA FDA lists and notices published by the USA NIH. Unlike many interactions between foods and drugs, this one escaped notice until 1996. Tests are constantly being done to identify more affected drugs and dietary supplements.

  • Medscape and the related Medline are reference websites heavily used by medical professionals to look up the latest studies about health and medicine. Medscape is the primary resource I use for this lens.
  • USA Food and Drug Administration (FDA) compiles and publishes information from reports of adverse interactions and side effects for medications and health supplements. Because the exact location of such data in their website can move, I am pointing you to the main FDA web page. You can find the interaction and side effect data from here.
  • US National Institutes of Health (NIH) is part of the USA Department of Health and Human Services. NIH is the USA’s medical research agency.

Thank You for Visiting

If you know of more grapefruit interactions (or proven non-interactions), please point me to the citation. Even within Medscape, my primary source, a study can easily escape my notice. This page is intended to help people avoid getting into trouble the way I did when my grapefruit juice at breakfast blocked 2/3 of the effect of a drug I needed. People using drugs to manage cholesterol or for post-transplant anti-rejection are particularly vulnerable. Let’s all help them stay safe.