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Grapefruit and Medicines: A Possible Deadly Mix?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Sep 27, 2020.

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Love Grapefruit Juice? Drug Interactions Are Numerous

Grapefruit (Citrus paradisi) is nutritious fruit full of vitamin C, antioxidants, and a tangy-sweet flavor. However, research points to hundreds of drug interactions -- many of which may be serious -- with grapefruit.

  • Medications can interact with all forms of grapefruit - the fresh fruit, juice or even the frozen concentrate can result in problems.
  • Interactions may occur with commonly used drugs - such as those that lower cholesterol, treat high blood pressure, or even those that fight cancer.

Tip: If you drink grapefruit juice, always have your pharmacist check for drug interactions with any new prescription or over-the-counter (OTC) drug.

What Causes These Dangerous Drug Interactions with Grapefruit?

Grapefruit interactions can be dangerous because blood levels of an interacting drug may rise, potentially leading to side effects.

Drug levels rise because grapefruit compounds known as furanocoumarins can block cytochrome P450 3A4 (CYP3A4) enzymes. These enzymes, involved in the metabolism of over 50 percent of all drugs, are needed to break down drugs for elimination from the body.

Some interactions are theoretical, based on their mechanism of action, but a warning is still important. Prevention is key.

A list of types of medicines that can interact with grapefruit and grapefruit juice includes:

  • some antibiotics
  • cough or allergy medicines
  • seizure medicines
  • cholesterol-lowering agents
  • certain cancer drugs
  • pain medicine
  • medicine for high blood pressure or heart problems
  • drugs to prevent organ rejection
  • anti-anxiety medicines
  • some drugs that treat erectile dysfunction
  • certain hormone replacement therapies.

What If I Just Take My Drug At a Different Time From Grapefruit?

It seems like taking the medication and the grapefruit or juice at different times might lessen the interaction, but this is not always the case.

  • The CYP450 enzymes, found in the intestine and the liver, can stay blocked after eating or drinking grapefruit. Sometimes they can stay blocked for more than 24 hours.
  • Therefore, even certain drugs that are only given once a day cannot be separated from the "grapefruit effect".

If you need to avoid grapefruit while you are taking a certain drug, it's probably best not to consume grapefruit at all, in any form.

In some cases, your doctor may agree for you to maintain your current level of grapefruit consumption (for example, if you normally have one glass a week) but this needs to be cleared with them first.

Can I Eat Other Kinds of Citrus Fruits?

Yes, in general, most other citrus fruits are fine to eat. Exceptions are the seville orange (often used in marmalades), the pomelo (tastes like grapefruit but with a thicker rind), and limes. These fruits also contain furanocoumarins that may cause the same interactions as grapefruit.

Drinking fruit juices (for example: grapefruit, apple and orange juice) with an antihistamine called fexofenadine (Allegra) may lead to decreased blood levels of fexofenadine, meaning your antihistamine may not work as well. Take fexofenadine with water, not fruit juice. The orally-distintegrating tablet does not have to be taken with water at all, if preferred.

Technically considered a berry and not a citrus, pomegranate juice may also interact with certain medications like the breast cancer treatment Kisqali (ribociclib).

  • Patients should not consume pomegranates, pomegranate juice, grapefruit, or grapefruit juice during treatment with ribociclib unless your doctor recommends otherwise.
  • Pomegranate juice or grapefruit juice can increase your blood levels of ribociclib. Elevated blood levels of this drug can worsen side effects and lead to infections, altered blood cell counts, bleeding problems, lowered appetite, nausea, vomiting, diarrhea, stomach pain, hair loss, and fatigue, among others.

Be sure to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

How Much Grapefruit or Juice Does it Take to Cause the Interaction?

It doesn't take much.

One whole fruit or 200 milliliters (mL) of grapefruit juice (less than one cup) can block the CYP3A4 enzymes needed to break down interacting medicines. This can lead to toxic blood levels of your drug.

For example, when a common calcium channel blocker blood pressure medicine by the name of felodipine (Plendil) is taken with grapefruit juice instead of water, blood levels of the drug can more than double. This interaction can occur with other calcium channel blockers, too.

  • The manufacturers of nifedipine and nisoldipine, both calcium channel blockers used for blood pressure, also recommend avoiding grapefruit juice with these medicines.

There are many possible interactions, so be sure to tell your healthcare provider if you drink grapefruit juice and about ALL of your medicines and dietary supplements, including over-the-counter (OTC) and herbal products.

Which Drugs Commonly Cause a Grapefruit Interaction?

Examples of common grapefruit interactions include:

Not all drugs in any one class of medications have these interactions, so usually your healthcare provider can select an alternative medication.

New drugs are approved by the FDA frequently, so always have your pharmacist check for interactions with each new prescription, OTC, or herbal supplement you use.

What Kind of Side Effects Can Occur?

Side effects that may occur vary with the drug, because blood levels rise and can lead to adverse reactions specific to high levels of that particular drug.

Examples of some serious side effects include:

  • abnormal heart rhythms
  • stomach bleeding
  • muscle toxicity
  • kidney damage
  • low blood pressure
  • difficulty breathing
  • sedation
  • 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.

Who is Most at Risk for Grapefruit Interactions?

  • Grapefruit juice is primarily consumed by an older crowd - kids tend to shy away from it's slightly sour taste.
  • Plus, older patients may be at a greater risk of interactions because they are more likely to drink grapefruit juice and take several different medications.

This is why having a drug interaction review with each new medicine - and even if you stop a medicine - is so important.

You can also join the Drugs.com Grapefruit Support group to discuss this topic at more length and keep up to date with the latest news.

Which Drugs are Most Dangerous to Take with Grapefruit Juice?

Each person is unique and the severity of an interaction can very from person to person.

  • Some cancer drugs, antibiotics, or heart medications may lead to an abnormal heart rhythm when combined with grapefruit.
  • Muscle and kidney damage can be a serious side effect with statins used for lowering cholesterol.
  • Some immunosuppressants used after organ transplants have been reported to cause kidney damage.
  • Certain pain medications may be linked with depressed breathing when taken with grapefruit.

There are too many posible drug interactions to list, so be proactive and ask your healthcare provider and research yourself, too.

Movantik and Grapefruit Juice Don't Mix

AstraZeneca’s Movantik (naloxegol) is used for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain.

Movantik is an oral, opioid receptor antagonist. It counteracts the effect of opioid agonists (painkillers) that can slow the intestines and frequently lead to constipation.

  • In studies, 1,352 participants received 12.5 milligrams (mg) or 25 mg of Movantik or a placebo (sugar pill) once daily for 12 weeks.
  • Results showed that 41% to 44% of participants experienced an increase in bowel movements per week, compared to 29% of participants receiving placebo.

However, Movantik has an interaction with grapefruit, too, and you should not consume grapefruit or grapefruit juice during treatment with Movantik, because blood levels of the drug can be significantly increased.

You may be more likely to have side effects and withdrawal symptoms such as sweating, tearing, runny nose, chills, diarrhea, abdominal pain, anxiety, insomnia, irritability, restlessness, and yawning.

Addyi and Grapefruit Juice

Addyi (flibanserin) is approved to treat hypoactive sexual desire disorder (low sex drive) in premenopausal women; however, it can cause severe low blood pressure and fainting when used together with alcohol (close in time). You should wait at least two hours after consuming one or two standard alcoholic drinks before taking Addyi at bedtime OR you should skip your Addyi dose if you have consumed three or more alcoholic drinks that evening.

But Addyi also has an important drug interaction with grapefruit and grapefruit juice, too.

Do not drink grapefruit juice with Addyi.

  • Grapefruit juice can significantly increase the blood levels of Addyi. Avoid the consumption of grapefruit and grapefruit juice during treatment.
  • Certain compounds in grapefruit appear to increase the levels of Addyi by blocking its CYP450 3A4 metabolism (breakdown). This effect can vary widely based on the amount, concentration, or type of grapefruit you consume.
  • Talk to your doctor or pharmacist if you have any questions or concerns. Be sure your healthcare provider knows about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Are There Drug Interactions With Pomegranate?

Pomegranate juice is full of antioxidants and vitamin C, like many other juices, and is now considered a "superfood".

  • Some people drink pomegranate for its health effects on the heart, to help prevent cancer, lower blood pressure, or for prostate health in men.
  • However, more research is needed to determine if pomegranate is beneficial in the long run for our health.

Like grapefruit, pomegranate may have an effect on how drugs are metabolized (broken down and removed from the body) due to blocking of certain CYP enzymes - like CYP3A4 and 2C9.

  • As mentioned, the manufacturer of Kisqali, a breast cancer treatment approved in March 2017, states it has specific drug-food interactions with both pomegranate and grapefruit juice.
  • It is recommended that patients avoid pomegranate or grapefruit and their juices while taking Kisqali as the combination may increase the amount of Kisqali in the blood, possibly causing worsened side effects.

Theoretically, drugs that may have interactions with grapefruit juice may have interactions with pomegranate juice as they affect similar enzymes. Warfarin, some blood pressure or cholesterol medications, carbamazepine, or other drugs that are broken down by CYP3A4 or 2C9 may also have interactions with pomegranate juice.

Be sure to tell your doctor and pharmacist if you regularly drink pomegranate juice, too.

How to Best Avoid Dangerous Grapefruit Interactions?

Grapefruit is a healthy and delicious snack and juice, but it is best to avoid grapefruit and its juice if drug interactions are possible. Plus, there are hundreds of grapefruit interactions, and new ones are discovered often, including newly FDA-approved medications.

If you discover that you are at risk for an interaction with a drug you currently take, call your healthcare provider to determine the best course of action.

  • It may be that the interaction is minor and no course of action is needed.
  • Alternatively, you may need to avoid grapefruit altogether or your healthcare provider may need to prescribe an alternate drug.
  • It's always easier to prevent a drug interaction and its effects, instead of dealing with it after the fact, so be sure to check for possible interactions before any new drug, herbal or OTC is started.

Finished: Grapefruit and Medicines - A Possible Deadly Mix?

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Sources

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Further information

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