Drug Interactions with Grapefruit Juice

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Aug 30, 2019.

Which drugs interact? | Why does grapefruit juice interact with drugs? | Possible side effects | Timing | Which other juices interact? | Common drugs that interact with grapefruit juice | Other resources

Which drugs interact with grapefruit juice?

While grapefruit is a nutritious fruit, many patients are concerned about the potential for drug interactions with grapefruit juice. Maybe you've receive a medication prescription container with an affixed warning label that recommends you avoid grapefruit or grapefruit juice while taking the medication. Grapefruit juice interactions can even occur with over-the-counter (OTC) drugs. But why is this so important?

Interactions with grapefruit can occur with common and important medications - such as those that lower cholesterol, treat high blood pressure, or even those that fight cancer.

Grapefruit juice affects how drugs are changed (metabolized) in the body for eventual elimination and can alter the amount of drug in your blood. This can lead to enhanced side effects or lower drug effectiveness.

New drugs are approved frequently, so it is wise to research your drug interactions with grapefruit juice drug with the Drugs Interaction Checker. Check with your pharmacist or doctor to confirm any interactions you may find.

Examples of common medications that interact with grapefruit juice include certain statin cholesterol drugs such as atorvastatin (Lipitor), lovastatin, simvastatin (Zocor), felodipine (Plendil) and other calcium channel blockers, clarithromycin (Biaxin), and loratadine (Claritin). Some immunosuppressants have been reported to cause kidney damage, and certain pain medications when mixed with grapefruit juice may be linked with depressed breathing.

Why does grapefruit interact with drugs?

Drugs or toxins are usually broken down (metabolized) so that they can be eliminated from the body. Grapefruit or grapefruit juice can alter enzymes in the body and affect how drugs are changed in the body before they are eliminated.

Grapefruit juice decreases the activity of the cytochrome P450 3A4 (CYP3A4) enzymes that are responsible for breaking down many drugs and toxins.

Grapefruit contains compounds known as furanocoumarins that block the CYP3A4 enzymes. When grapefruit juice is consumed, the enzyme’s ability to break down the drug for elimination is decreased.

Blood levels of the drug may rise, resulting in a risk for new or worsened side effects.

One whole fruit or 200 milliliters of grapefruit juice (a bit less than one cup) can block the CYP3A4 enzymes and lead to toxic blood levels of the drug.

Not all drugs in any one drug class usually have a grapefruit interaction, so usually your doctor can select an alternative medication.

If you drink grapefruit juice, always have your pharmacist run a drug interaction check with your medications to rule out an interaction before you combine them.

What side effects are possible?

Side effects can vary based on the interacting drug and possible side effects.

Side effects can range from abnormal heart rhythms, stomach bleeding, muscle pain, muscle breakdown, kidney damage, low blood pressure, difficulty breathing, sedation, and dizziness.

Other reactions may occur -- it depends on the drug and the levels of the drug in the blood.

If you have been warned about a possible drug interaction with grapefruit, ask your healthcare provider to describe the possible side effect and learn how to recognize it.

Can I take my medicine at a different time from grapefruit juice to prevent the interaction?

Taking medications at a different time from when grapefruit juice is consumed will not prevent the interaction. The effects of grapefruit juice on certain medications can last for over 24 hours. So, even if you take a medicine that is given only once per day, grapefruit and grapefruit juice should still be avoided for the entire treatment period.

In some cases, you may be able to drink smaller quantities of grapefruit juice, so you should follow the directions on the patient information leaflet for each individual drug or ask your healthcare provider.

What other types of juice interact with drugs?

Other kinds of fruit juice besides grapefruit juice may rarely interfere with medications. For most medications, orange juice, apple juice, or grape juice can be consumed instead of grapefruit juice without any concern for an interaction. However, orange or apple juice can cause an interaction with fexofenadine (Allegra) and aliskerin (Tekturna).

You should use caution when eating anything made with the seville orange (often used in marmalades), the pomelo (a citrus fruit with a similar flavor to grapefruit but less tart), and limes. These fruits also contain furanocoumarins and may cause the same interactions as grapefruit. Studies with these fruits are not as frequent, so their risk level is not fully known.

Pomegranate juice (from a berry) is a delicious fruit that is full of antioxidants and vitamin C. However, this "superfood" has an interaction with the breast cancer treatment ribociclib (Kisqali), as noted in product labeling. The manufacturer recommends that patients avoid pomegranate or grapefruit and their juices while taking Kisqali. These juices can increase the blood levels of ribociclib, leading to enhanced side effects such as infections, changes in blood cell counts, reduced appetite, nausea and vomiting, diarrhea, hair loss (alopecia), and fatigue.

Increasingly, more drugs are being shown to interact with other juices. Aliskiren (brand name: Tekturna) is a renin inhibitor medication used to treat high blood pressure. Research has shown that drinking orange, apple, or grapefruit juices regularly or within a short period before or after a dose of aliskiren can interfere with the absorption of the medication. Blood levels of the drug may decrease, and its blood-pressuring lowering effect may be compromised. You should avoid drinking orange, apple, or grapefruit juice during treatment with aliskiren, unless your doctor advises otherwise.

Atenolol, a beta blocker agent also used to treat high blood pressure and angina (chest pain) may have an interaction with orange juice, but the health implications are not really known. Orange juice may block the absorption and lead to lower levels of atenolol in the blood. Patients should avoid consuming large amounts of orange juice to prevent fluctuations in atenolol blood drug levels.

Does Allegra interact with orange juice?

This is one of the most well-known orange juice drug interactions and one of the first ones identified. But it's interaction is a bit different. Fexofenadine (Allegra), a popular non-drowsy antihistamine available over-the-counter (OTC) can interact not only with grapefruit juice, but also with apple and orange juice. However, in the case of fexofenadine, blood levels of the drug go down and the effectiveness of the antihistamine may be reduced. This interaction occurs by a different mechanism than CYP450 3A4, but nonetheless, it is recommended that fexofenadine be taken with water, and not fruit juice.

Talk to your healthcare provider

Health care providers should be informed of which medications patients are taking, including any prescription and OTC drugs, herbal supplements and vitamins. Update your pharmacist any time you start or even stop taking a medication. It is important to check for potential drug interactions

Warnings labels on prescription bottles should be followed. If an interaction is found to occur, it may be possible that an alternative medication can be prescribed and the interaction can be avoided.

Common drugs that interact with grapefruit

Examples of some of the most common grapefruit or grapefruit juice drug interactions that can occur include:

Other resources

There are numerous other drug interactions with grapefruit and grapefruit juice; this is not a complete list. Other juices, like apple and orange, are now also being found to interact with some medications. How should you proceed?

Additional grapefruit juice drug interactions, and interactions with other juices, can be researched in the Drug Interaction Checker. You can also check your Patient Medication Guide that accompanies your prescription, and your pharmacist may include a label on your bottle warning you of an interaction.

Always be sure to consult with your doctor or pharmacist to understand the significance of any drug interaction, and follow prescription recommendations to help avoid toxic drug levels and unpleasant side effects.

You might also consider joining the Drugs.com Grapefruit Support group. Here you can chat about this topic at more length, review the latest questions and keep up to date with recent news about grapefruit juice interactions.

See Also

Sources Chen M, Zhou SY, Fabriaga E, et al. Food-drug interactions precipitated by fruit juices other than grapefruit juice: An update review. J Food Drug Anal. 2018 Apr;26(2S):S61-S71. doi: 10.1016/j.jfda.2018.01.009. Epub 2018 Feb 15. Product Information. Ibrance (palbociclib). Pfizer U.S. Pharmaceuticals Group, New York, NY. Accessed October 6, 2019. FDA. FDA Consumer Health Articles. Grapefruit Juice and Some Drugs Don't Mix. Accessed August 31, 2019 at https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix Bailey DG, Malcolm J, Arnold O, et al. Grapefruit juice-drug interactions. Br J Clin Pharmacol 1998;46:101-110. Accessed August 31, 2019 at https://doi.org/10.1046/j.1365-2125.1998.00764.x Jetter A1, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther. 2002 Jan;71(1):21-9. Horn J, Hansten P. Fruit Juice Interactions. Pharmacy Times. Published Online Dec 1, 2005. Accessed August 31, 2019 at https://www.pharmacytimes.com/publications/issue/2005/2005-12/2005-12-5042 Mayo Clinic. Consumer Health. I like to drink grapefruit juice but hear that it can interfere with some prescription medications. Is that true? Accessed March 30, 2019 at http://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/food-and-nutrition/faq-20057918 Bailey DG, Dresser G, Arnold M, et al. Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? CMAJ. 2012. Accessed March 30, 2019. Hansten PD, Horn JR. The Top 100 Drug Interactions. A Guide to Patient Management. H&H Publications. Freeland, WA. Accessed August 31, 2019.

Shimomura S, Wanwimolruk S, Chen J. Drug Interactions with Grapefruit Juice: An Evidenced-Based Overview. Pharmacy Times. Accessed March 30, 2019 at http://www.direct-ms.org/wp-content/uploads/2018/01/Grapefruit-juice-drug-reactions.pdf Srinivas NR. Is pomegranate juice a potential perpetrator of clinical drug-drug interactions? Review of the in vitro, preclinical and clinical evidence. Eur J Drug Metab Pharmacokinet. 2013 Dec;38(4):223-9. Accessed August 31, 2019 at https://www.ncbi.nlm.nih.gov/pubmed/23673492 Komperda KE. Potential interaction between pomegranate juice and warfarin. Pharmacotherapy. 2009 Aug;29(8):1002-6. Accessed March 30, 2019 at https://www.ncbi.nlm.nih.gov/pubmed/19637955 Hidaka M, Okumura M, Fujita K, et al. Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metab Dispos. 2005 May;33(5):644-8. Accessed March 30, 2019 at http://dmd.aspetjournals.org/content/33/5/644#sec-4 Kim H, Yoon YJ, Shon JH, et al. Inhibitory effects of fruit juices on CYP3A activity. Drug Metab Dispos. 2006 Apr;34(4):521-3. Accessed March 30, 2019 at http://dmd.aspetjournals.org/content/34/4/521#T2

Further information

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