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Author: Admin | 2025-04-28
Plasma concentrations if taken with grapefruit juice.23-24 The antiarrhythmic drugs amiodarone (Cordarone) and dronedarone (Multaq) are affected by grapefruit juice, as are other cardiovascular drugs, including cilostazol (Pletal) and ranolazine (Ranexa).25 Anticonvulsants [carbamazepine (Tegretol)], antipsychotics [pimozide (Orap)], human immunodeficiency virus medications [indinavir (Crixivan), saquinavir (Invirase)], and cancer medications [nilotinib (Tasigna), pazopanib (Votrient)] all interact with grapefruit juice. 26Reduced Drug ActivityThe antihistamine medication fexofenadine (Allegra) was the first medication discovered to exhibit reduced bioavailability when combined with grapefruit juice. The mechanism relies on OATP inhibition by naringin. Other common medications that exhibit this interaction include beta-blocking medications (eg, talinolol, acebutolol, and celiprolol) and levothyroxine.11 If taken with grapefruit juice, the therapeutic effect of these medications will be diminished. Prodrugs that are activated by CYP3A4 metabolism may also demonstrate reduced activity when taken with grapefruit juice. The antiplatelet agent clopidogrel (Plavix) is a good example. When 14 healthy volunteers drank grapefruit juice for 3 days and then took clopidogrel, plasma concentrations of clopidogrel’s active metabolite only reached 13% of that in the control group.27 The reduced concentration was accompanied by a marked decrease in the platelet-inhibitory effect of the drug. Other drugs that rely on CYP3A4 for activation include losartan (Cozaar), codeine, and tamoxifen. Studies have not directly assessed the interaction, but grapefruit juice could, theoretically, reduce the efficacy of these drugs.6Practical ImplicationsCase reports confirm that grapefruit juice-drug interactions can create clinically relevant and serious side effects.15 As CYP3A4 inhibition increases drug bioavailability, toxicity becomes a real concern. Drugs that are most likely to reach toxic levels are those that undergo extensive metabolism by CYP3A4 in the small intestine. Reports of adverse events from grapefruit juice interaction include hypotension with cardiovascular agents, sedation with anxiolytic agents, nephrotoxicity with immunosuppressant agents, and respiratory depression with pain medications.15Even a single intake of 1 glass (250mL) of grapefruit juice produces a meaningful and lasting inhibition of CYP3A4 and a clinically significant nutrient-drug interaction.28 In fact, when subjects continued to drink grapefruit juice for 14 days, they experienced no further effect beyond the effect of a single glass. In addition, the compounds responsible for the nutrient-drug interaction (ie, bergamottin and naringin) are also present in sufficient quantities in whole grapefruit to produce a clinical effect.29 Any recommendation to avoid grapefruit juice intake should, therefore, also include a recommendation to avoid the whole fruit. The duration of grapefruit juice’s effect on drug metabolism varies among studies. Because its primary mechanism of effect involves irreversible CYP3A4 enzyme inhibition, the effect of drinking a single glass of grapefruit juice can last for more than 3 days.30 However, in a study evaluating the interaction between grapefruit juice and simvastatin, the effect became negligible after just 24 hours.31 For interactions that involve OATP inhibition, the duration of effect is much shorter.32 In the studies that showed grapefruit juice mitigated the therapeutic effect of fexofenadine, the duration of effect was between 2 and 4 hours.11It might be proposed that regular and consistent intake of grapefruit juice could decrease the drug dosage required
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