If you take a medicine long term, such as a cholesterol or blood pressure drug, check the leaflet for grapefruit; if it is mentioned, don't eat grapefruit or pomelo and don't drink grapefruit juice

Cost

Free. When you get a medicine you will take long term, look at the "drug interactions" and "precautions" sections of the leaflet. If grapefruit is mentioned, don't eat grapefruit, pomelo, sour orange or lime, or drink their juice, while you are on the medicine. If you love grapefruit, ask your doctor whether you can switch to a medicine that isn't affected.

What you get

A 2013 review by Canadian pharmacology researchers says that more than 85 drugs are known or expected to interact with grapefruit. Of these, 43 may cause serious adverse effects. The serious effects include torsades de pointes, a heart rhythm disorder that can cause sudden death. They also include rhabdomyolysis (massive muscle breakdown, which can damage the kidneys), bone marrow suppression, respiratory depression, gastrointestinal bleeding and kidney injury. The furanocoumarins in grapefruit permanently disable an enzyme in the small intestine that breaks down drugs (CYP3A4). Less of the drug is broken down in the gut, so more of it reaches the blood. A whole grapefruit or 200 mL of juice is enough to raise the level of the drug in the blood to a clinically meaningful degree. When the blood pressure drug felodipine was taken with grapefruit juice, the drug in the blood averaged 3 times the level seen when it was taken with water. With the same 250 mL serving of juice, the effect ranged from 0 to 8 times in different people. When the cholesterol drug simvastatin was taken with 200 mL of juice a day for 3 days, the total amount of drug in the blood (AUC) was 330% of that with water. For atorvastatin with juice it was 180% to 250%. Pravastatin, rosuvastatin and fluvastatin are not affected. Drinking 200 mL of juice within 4 hours before taking the drug has the largest effect. After 10 hours half of the effect remains, and after 24 hours a quarter. The review says that sour orange (often used for marmalade), lime and pomelo have the same effect. Sweet oranges such as navel and Valencia oranges contain no furanocoumarins and do not have this effect. The U.S. FDA's consumer article names simvastatin, atorvastatin and nifedipine. It says that when a lot of grapefruit juice is drunk, cholesterol drugs stay in the body too long, which raises the risk of liver and muscle damage and can lead to kidney failure.

Notes

Not all drugs are affected, and even within the same class they differ. Among the common drugs the review lists are the cholesterol drugs simvastatin, lovastatin and atorvastatin, and the blood pressure drugs felodipine and nifedipine. Also on the list are amiodarone, ticagrelor, tacrolimus, cyclosporine, domperidone, quetiapine, oxycodone and others. Clopidogrel works the other way: with grapefruit it won't work. If the leaflet doesn't say and you aren't sure, ask the doctor who prescribed the drug or a pharmacist. The review says that people over 45 buy the most grapefruit and also take the most drugs. When an older person takes felodipine and eats grapefruit, the heart rate does not speed up to compensate when blood pressure falls. Graded B because the numbers come from pharmacokinetic trials that measured blood levels, and the serious consequences rest only on case reports. The size of the benefit is set at "small": the endpoint is blood level, and the studies can't say how many incidents would be avoided.

Evidence grade

B : Supported by research but without a precise number, or based on small or single studies.

Sources

1. Bailey DG, Dresser G, Arnold JMO (2013). Grapefruit–medication interactions: forbidden fruit or avoidable consequences? CMAJ, 185(4):309-316. https://doi.org/10.1503/cmaj.120951
2. U.S. Food and Drug Administration (2021). Grapefruit Juice and Some Drugs Don't Mix. https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix

Translated from the Chinese original. Original book, section 34, tip 13. This section is about health and medicines. It is general information, not a substitute for a doctor’s diagnosis or prescription. Content may be out of date and rules differ by place. When you actually deal with an agency, a doctor or a court, follow what local officials, doctors and lawyers tell you. Disclaimer