Mixing grapefruit with medicines

Published in Medicinewise Living

Date published: About this date

Sometimes one medicine can interact badly with another in your body, and this can change how strongly the medicine works or change its side effects.

Interactions can also happen when medicines mix with certain foods or drink — and grapefruit is one example that's gained some interest in the media recently.

A review article published in the Canadian Medical Association Journal (November 2012) highlights more than 85 medicines that can interact with grapefruit, with 43 of these having potentially serious consequences.

This article outlines what this new research review says about interactions between grapefruit and medicines, some of the medicines that can cause the interaction and what you can do to avoid any harmful effects.

If you ever consume grapefruit or grapefruit juice and are taking a medicine, check whether your medicine could cause interactions.

You can check our list of high-risk medicines identified in the new review, but it's also important to check the consumer medicines information (CMI) leaflet for your medicine if available, or talk to a health professional about your particular medicine.

Grapefruit–medicine interactions: what we already know

Chemicals in grapefruit can affect how medicines work in the body

It has been known for some time that certain chemicals in grapefruit (known as furanocoumarins) can interfere with the way your body metabolises or processes many medicines in the intestine (gut) or liver before they reach your bloodstream. When this happens, more of a medicine may get into your body, making it work too strongly or causing unwanted side effects.

This happens because of their effect on 'CYP3A4' — an enzyme involved in metabolising many medicines. Medicines need to be taken orally (e.g. in the form of a tablet or liquid) to be affected by grapefruit because grapefruit mainly affects this enzyme in the gut. 

Some other citrus fruits might have a similar effect

Bitter oranges (e.g. Seville oranges) and limes may also cause interactions with medicines. Other citrus fruits such as sweet oranges and lemons don't have this same effect.

Many medicines are already known to interact with grapefruit

Several prescription, over-the-counter or complementary medicines (herbal, 'natural', vitamin and mineral) are known to interact, or potentially interact, with grapefruit. Common examples include some types of medicines for heart conditions, high blood pressure, high cholesterol, infections, epilepsy, depression, anxiety and sleep problems.

Side effects that are caused by these interactions

The exact side effects from interactions vary and depend on the medicine, but some are serious.

Serious side effects have occurred when certain medicines are taken with grapefruit, including:

  • complete heart block (resulting in a very slow heart beat)
  • torsade de pointes (rapid heartbeats that can lead to sudden death)
  • rhabdomyolysis (severe damage to skeletal muscle that can lead to kidney damage)
  • nephrotoxicity (kidney damage)
  • myelotoxicity (damage to bone marrow)
  • respiratory depression (reduced or slowed breathing).

Consuming any part or form of grapefruit can cause an interaction

The whole fruit including the juice and peel contain furanocoumarins, the chemicals that can interact with medicines. For this reason, people who take medicines that may interact with grapefruit are usually advised not to eat grapefruit or drink grapefruit juice at all. People may also be advised to avoid other related fruits that could interact with medicines.

Interactions can result from just one serve of grapefruit

Even one glass of juice or one grapefruit can have an effect on a medicine, and an interaction can occur even when the grapefruit or juice is eaten or drunk at a different time. The severity of the interaction may also depend on how often you consume grapefruit or grapefruit juice.

Medicines and merriment 

What the review says

The review raised four key points about grapefruit–medicine interactions. Information was obtained by looking at existing published reviews and case reports of interactions, in addition to product monographs and prescribing information sheets for recently marketed medicines in Canada.

The number of medicines that interact with grapefruit is rising

The introduction of new medicines over the last few years has seen an increase in the number of potential grapefruit–medicine interactions.

The review indicates that between 2008 and 2012, the number of medicines that may interact with grapefruit to cause serious side effects has risen from 17 to 43.

Certain medicines are more likely to have serious interactions with grapefruit than others

Medicines that normally reach your bloodstream in very small to moderate amounts are more likely to have significant interactions with grapefruit. This is because the effect of grapefruit can cause much larger amounts of the medicine to get into your bloodstream and cause side effects.

Affected medicines should not taken with grapefruit at any time

An interaction is possible no matter when you ingest grapefruit during treatment.

You don't need to consume large quantities of grapefruit either for problems to occur: eating a whole grapefruit or drinking 200–250 mL of juice can cause significant interactions, especially if you consume this repeatedly.

The review also suggests that another non-interacting medicine may need to be considered if you can't avoid eating grapefruit.

Older people could be more vulnerable to serious interactions

The likelihood of people experiencing grapefruit interactions with medicines can vary — and some may be more at risk than others.

People over the age of 45 years appear to be most vulnerable as they are the main buyers of grapefruit and are more likely to receive prescriptions for medicines. People over the age of 70 years may be at particularly high risk of experiencing harmful effects from an interaction.

Which medicines can interact?

The review provided a risk ranking for 89 medicines that have, or could result in, interactions with grapefruit. The authors ranked medicines by assessing:

  • How much more of the medicine is absorbed into the body than usual, because of grapefruit.
  • How serious the side effects are that result from this increased amount of medicine.

The table below provides a list of medicines that were assessed as high risk. According to the review, people taking these medicines should avoid grapefruit and other potentially interacting citrus fruits (such as Seville oranges and limes) during treatment, or be prescribed an alternative medicine instead. Only medicines currently marketed in Australia have been included in the list.

Medicines with a higher risk of serious interactions with grapefruit 

Medicine category Active ingredients*
(oral forms only)
Possible harmful effects
Anti-cancer medicinesDasatinib, Erlotinib, Everolimus, Lapatinib, Nilotinib, Pazopanib, Sunitinib Rapid heartbeats that can lead to sudden death; damage to bone marrow; and/or kidney damage
Antibiotic medicinesErythromycin Rapid heartbeats that can lead to sudden death
Antimalarial medicinesPrimaquine Damage to bone marrow

Quinine (Quinbisul, Quinate) Rapid heartbeats that can lead to sudden death
Antiviral medicinesMaraviroc Low blood pressure, fainting

Rilpivirine Rapid heartbeats that can lead to sudden death
Cholesterol and lipid medicinesAtorvastatin (atorvastatin with amlodipine), simvastatin Damage to skeletal muscle that can lead to kidney damage
Medicines for heart conditions or high blood pressureAmiodarone Rapid heartbeats that can lead to sudden death

Eplerenone High potassium levels in blood, serious heart arrhythmias

Verapamil Complete heart block
Anti-clotting medicinesApixaban, cilostazol Gastrointestinal bleeding

Clopidogrel (see also clopidogrel with aspirin) Loss of effectiveness

Ticagrelor Gastrointestinal or kidney bleeding
Anxiety medicinesBuspirone Dizziness, drowsiness
Cough and cold medicinesDextromethorphan Hallucinations, drowsiness
Opioid pain relievers Fentanyl (lozenge), oxycodone (Endone, OxyContin, OxyNorm) Reduced or slowed breathing
Medicines for psychotic conditionsQuetiapine Dizziness, drowsiness

Ziprasidone Rapid heartbeats that can lead to sudden death
Nausea and vomiting medicinesDomperidone Rapid heartbeats that can lead to sudden death
Immune-system-modifying medicinesCyclosporin, everolimus, sirolimus, tacrolimus Damage to bone marrow and/or kidney damage

*Active ingredients can be available under different brand names. Look up your active ingredient on our Medicine Finder page to find a list of brand names.

Other medicines that may interact

The review also assessed a number of medicines as having an 'intermediate' risk of a harmful interaction with grapefruit. Some examples of medicines in this category include:

What if my medicine is not in the list?

The list of interacting medicines identified in the review is not a complete list of medicines that could interact with grapefruit. Grapefruit might cause interactions with other medicines, including non-prescription and complementary medicines, not just those you get on prescription.

The more medicines you take, the more likely you may come across an interaction.

Note also that the information provided by the review is intended as a guide only for doctors prescribing these medicines, particularly for older people. Get individualised advice about what you need to do with your medicines from your doctor or pharmacist.

If you are in doubt about whether your medicine could interact with grapefruit or other related citrus fruits, avoid consuming these fruits until you can check with your health professional.

What you can do to avoid harmful interactions

  • Find out whether any of your medicines interact with grapefruit juice by talking to your doctor or pharmacist, or read the 'Taking other medicines' section of the consumer medicine information (CMI) leaflet. You can download the CMI for your medicine from the NPS Medicine Finder or ask your pharmacist or doctor to print it out for you.
  • Get advice from your doctor or pharmacist if you're taking a medicine that may interact and you want grapefruit in your diet. Your doctor or pharmacist can discuss your risk of an interaction with you and suggest an alternative treatment if appropriate.
  • Call the NPS Medicines Line on 1300 MEDICINE (1300 633 424) to get information about interactions with your prescription, over-the-counter and complementary medicines (herbal, 'natural', vitamins and minerals) from a pharmacist.
  • Call the Adverse Medicines Events (AME) Line on 1300 134 237 if you suspect that your medicine is causing a problem and you're worried about using it. AME line provides consumers with an avenue for reporting and discussing adverse experiences with medicines.
  • Read more about understanding interactions.