If you take medicines such as cholesterol or blood-pressure drugs long term, check the leaflet for grapefruit; if listed, avoid grapefruit, pomelo, and grapefruit juice

No cost. When receiving a long-term medicine, read “Drug interactions” and “Precautions” in the leaflet. If grapefruit is listed, avoid grapefruit, pomelo, bitter oranges, limes, and their juices while taking it. If you love grapefruit, ask your doctor whether a medicine unaffected by it is an option.

A 2013 review by Canadian pharmacologists reported more than 85 drugs known or predicted to interact with grapefruit, including 43 that could cause serious adverse reactions. These include torsades de pointes, an arrhythmia that can cause sudden death; rhabdomyolysis (extensive muscle breakdown that can damage the kidneys); bone-marrow suppression; respiratory depression; gastrointestinal bleeding; and kidney injury. Grapefruit furanocoumarins bind tightly to CYP3A4, an enzyme in the cells lining the small intestine that breaks down drugs, irreversibly inactivating it. The effect subsides only after the body makes new enzyme. Before an oral medicine reaches the bloodstream, some is broken down in the small intestine and liver; this is called the first-pass effect. Inactivating the intestinal enzyme reduces this breakdown, allowing more medicine to enter the blood. One whole grapefruit or 200 mL of juice is enough to produce a clinically meaningful rise. With one serving of grapefruit, blood levels of the blood-pressure drug felodipine averaged 3 times those with water. With the same 250 mL serving of juice, individual levels ranged from 0 to 8 times those with water. For simvastatin, 200 mL of juice daily for 3 days produced total drug exposure (AUC) equal to 330% of that with water. For atorvastatin with juice, it was 180%–250%. Pravastatin, rosuvastatin, and fluvastatin were unaffected. Drinking 200 mL within 4 hours before the medicine had the strongest effect; half remained after 10 hours and a quarter after 24 hours. The review says bitter oranges, often used for marmalade, limes, and pomelos have the same effect. Sweet oranges such as navel and Valencia oranges contain no furanocoumarins and lack this effect. FDA consumer information names simvastatin, atorvastatin, and nifedipine. It says that drinking a lot of grapefruit juice can leave too much cholesterol medicine in the body, increasing liver and muscle injury risks and potentially leading to kidney failure.

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；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

Not every drug is affected, and drugs in the same class differ. Common drugs listed in the review include simvastatin, lovastatin, and atorvastatin for cholesterol, and felodipine and nifedipine for blood pressure. Others include amiodarone, ticagrelor, tacrolimus, cyclosporine, domperidone, quetiapine, and oxycodone. Clopidogrel has the opposite problem: grapefruit can make it ineffective. If the leaflet says nothing and you are unsure, ask the prescribing doctor or pharmacist. The review says people aged 45 or older buy the most grapefruit and also take the most medicines. In older people taking felodipine with grapefruit, the heart rate does not increase to compensate when blood pressure falls. Evidence is rated B because the numbers come from pharmacokinetic trials measuring blood drug levels; serious outcomes have only case reports. Benefit is rated “small”: the endpoint is blood drug concentration, and the research cannot quantify how many incidents avoidance would prevent.