The forbidden fruit: How grapefruit could kill you

The video below is a new public service announcement from the US FDA on the risks of drinking grapefruit juice when taking medication.


We’ve known for over a couple of decades about the grapefruit juice interaction that affects half of all drugs to some degree, but a paper recently published in the Journal of the Canadian Medical Association (PDF) has warned that over the last four years there has been a major jump in the number of drugs that are affected by grapefruit juice to a dangerous degree. The list of drugs that are thought to be affected (PDF) includes anti-cancer drugs, anti-diabetic drugs, anti-infective drugs, anti-inflammatory agents, anti-lipemic agents, cardiovascular agents, estrogens, gastrointestinal drugs, immunosuppressants, urinary tract agents and CNS agents. The list includes painkillers that are sometimes used recreationally such as ketamine, diazepam, oxycodone and methadone. The list of potential complications is not pretty, including  kidney failure, respiratory failure and gastric bleeding. Furthermore – the list is far from extensive, these are only the ones we know about. I’ve pasted the names of some of the drugs below - but this list should not be considered extensive by any means and is no substitute for checking with your doctor or pharmacist.

Crizotinib, dasatinib, erlotinib, everolimus, lapatinib, nilotinib, pazopanib, sunitinib,vandetanib, venurafenib, artemether,  erythromycin, halofantrine, maraviroc, primaquine, quinine, primaquine,  rilpivirine, atorvastatin, lovastatin, simvastatin, amiodarone, apixaban, cilostazol, clopidogrel, dronedarone, eplerenone,  ergotamine, ticagrelor, verapamil, alfentanil – oral, buspirone, dextromethorphan, fentanyl – oral, ketamine – oral, lurasidone, oxycodone,p imozide, quetiapine, ziprasidone, cisapride, domperidone, cyclosporine, everolimus, sirolimus, tacrolimus, cyclophosphamide,  imatinib, sorafenib,  repaglinide, saxagliptin, albendazole,  praziquantel, saquinivir, budesonide – oral, colchicine,  methylprednisolone -oral, amlodipine, felodipine, losartan, manidipine,  nicardipine, felodipine, losartan, manidipine,  nicardipine, nimodipine, nisoldipine, nitrendipine, propafenone, quinidine, rivaroxaban, sibutramine,sildenafil, tadalafil, vardenafil, diazepam, fluvoxamine,  methadone, midazolam – oral,quazepam,sertraline,triazolam,estradiol,ethinylestradiol, darifenacin, fesoterodine, solifenacin,  silodosin, silodosin, etravirine, artemether, etravirine, aprepitant, carbamazepine

These drugs are cause for concern because they all have three things in common. They are all administered orally, they all aren’t very efficiently processed by the body (i.e. they have “very low to intermediate absolute bioavailability”) and crucially - they all happen to be metabolised by an enzyme called cytochrome P450 3A4 (CYP3A4) that is inhibited by grapefruit juice. If this occurs there is a risk of overdose. Once again, the list above is by no means extensive and other related citrus fruits including Seville oranges and limes also contain the same enzyme to a lesser degree. It's also worth noting that there are plenty of anecdotal reports that grapefruit juice may affect certain recreational drugs though the degree to which this may occur is extremely unclear due to the lack of experimental evidence. It seems unlikely that CYP3A4 has as much of an impact on most recreational drugs as folklore would have you believe, but it may be the case that other components of grapefruit juice could indeed have an effect, so strong caution is advised. The group most at risk of a dangerous grapefruit-drug interaction is the elderly, so if you do nothing else with this information, make sure you warn your gran!

Bailey, D., Dresser, G., & Arnold, J. (2012). Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? Canadian Medical Association Journal DOI: 10.1503/cmaj.120951

This article is not intended as medical advice, before making any changes to your medication always consult your physician.

Image credit: Shutterstock/Amero

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