Grapefruit–drug interactions
[1] Affected drugs typically have an auxiliary label saying "Do not take with grapefruit" on the container, and the interaction is elaborated upon in the package insert.
[7] Although a prospective cohort study of middle-aged women indicated that some flavonoid-rich foods are associated with a reduction in all-cause mortality, frequent grapefruit consumption was associated with a small increase in all-cause mortality, possibly because of the clinically significant drug interactions of the non-flavonoid components.
[8] The effect of grapefruit juice with regard to drug absorption was originally discovered in 1989 by a group led by pharmacologist David Bailey.
[9] The effect was first discovered accidentally in 1989, when a test of drug interactions with alcohol used grapefruit juice to hide the taste of the ethanol.
[15][17] The effects are caused by furanocoumarins (and, to a lesser extent, flavonoids) which are compounds produced by many plants including but not limited to grapefruit.
[11] There are three ways to test if a fruit interacts with drugs: The first approach involves risk to trial volunteers.
Depending on growing and processing conditions, concentrations of the interacting polyphenol compounds can vary dramatically.
Many citrus cultivars are hybrids of a small number of ancestral species, which have now been fully genetically sequenced.
[33][34] Many traditional citrus groups, such as true sweet oranges and lemons, seem to be bud sports, mutant descendants of a single hybrid ancestor.
Even if it is known, it is not possible to be certain that a cultivar will not interact with drugs on the basis of taxonomy, as it is not known which ancestors lack the capacity to make the problematic polyphenol compounds.
Pomelo (the Asian fruit that was crossed with an orange to produce grapefruit) contains high amounts of furanocoumarin derivatives.
[11] Tests on some tangelos (hybrids of mandarins/tangerines and pomelo or grapefruit) have not shown significant amounts of furanocoumarin; these studies were also conducted on eight fruit all picked at one time from one tree.
[38] Other less-common citrus species also referred to as lemons or limes are genetically distinct from the more common varieties, with different proportions of pomelo ancestry.
[42] This interference can decrease the absorption of a variety of commonly used medications, including beta blockers like atenolol, antibiotics like ciprofloxacin, and antihistamines like montelukast.
From 2008 to 2012, the number of drugs known to potentially interact with grapefruit, with risk of harmful or even dangerous effects (gastrointestinal bleeding, nephrotoxicity), increased from 17 to 43.
Drugs that interact usually share three common features: they are taken orally, normally only a small amount enters systemic blood circulation, and they are metabolized by CYP3A4.
Examples of such known CYP3A4 inhibitors include cisapride (Propulsid),[46] erythromycin, itraconazole (Sporanox), ketoconazole (Nizoral), and mibefradil (Posicor).
