It is advised to avoid taking fexofenadine with fruit juices. But does this apply to all fruit juices or only grapefruit juice? And what about tomato juice – are tomatoes not also fruit?  And why the warning only about the juice – what happens if you eat the fruit instead of drinking the juice? 

Grapefruit and Drug Metabolism – A Closer Look at CYP Interactions: Many of us might have come across warnings about the potential interaction between grapefruit juice and certain medications. Let’s delve deeper into the science behind this. Grapefruits, along with other specific citrus fruits like pomelos and Seville oranges (often termed as bitter oranges or sour oranges), are rich in polyphenols, notably furanocoumarins. These compounds play a crucial role in inhibiting various cytochrome P450 enzymes, including CYP3A4, CYP1A2, CYP2C9, and CYP2D6.

Why does this matter? The inhibition of the CYP3A4 enzyme, in particular, impedes its ability to effectively metabolize certain drugs. As a result, there can be an unintended increase in the drug levels within the bloodstream, amplifying the risk of side effects or even toxicities. It’s noteworthy that CYP3A4 is pivotal for the metabolism of a wide range of medications. Consequently, grapefruit’s interaction can potentially affect the efficacy and safety of medications such as statins (targeting high cholesterol), calcium channel blockers (for managing hypertension), calcineurin inhibitors (used in immunosuppression), and benzodiazepines (prescribed for anxiety and insomnia).

Fruit and Fexofenadine – Reduced Absorption:  Contrary to the increased plasma concentration of drugs seen following inhibition of CYP enzymes, fruit juices decrease intestinal absorption of the second-generation H1 antihistamine, fexofenadine. The mechanism behind this interaction involves intestinal transporters, specifically organic anion-transporting polypeptides (OATPs).


Numerous drugs are transported by OATPs, but fexofenadine is particularly vulnerable to inhibition of OATPs as it is transported by OATP1B1, OATP1A2, OATP1B3 and OATP2B1. OATPs are inhibited by various flavonoids and other bioactive compounds found in a number of fruits, herbs and beverages. While there are many potential drug-food interactions, only grapefruit, oranges and apples have been consistently shown to have clinically relevant effects.

Intestinal Transporter Inhibitory Food Bioactive Compound
OATP1A2 grapefruit juice compounds, orange juice compounds, apple juice compounds, naringin, hesperidin, apigenin, kaempferol, quercetin
OATP1B1 naringenin, naringin, quercetin, daidzein, genistein, glycyrrhizin, caffeine
OATP1B3 apigenin, kaempferol, quercetin, naringenin, naringin, rutin, daidzein, genistein, glycyrrhizin, caffeine
OATP2B1 grapefruit juice compounds, apple juice compounds, orange juice compounds, apigenin, kaempferol, quercetin, naringenin, naringin, rutin, daidzein, genistein, glycyrrhizin, caffeine
Food Bioactive Compound Potential Dietary Sources
grapefruit juice compounds grapefruit
orange juice compounds oranges
apple juice compounds apples
naringin rosemary, grapefruit, pomelo, oranges
naringenin Mexican oregano, grapefruit, oranges, celery seeds, tomatoes (lower levels)
hesperidin peppermint, blood orange, orange, tangerine, lemon, lime, grapefruit
apigenin marjoram, Italian oregano, common sage
kaempferol capers, cumin, cloves, caraway, tomatoes (low levels)
quercetin black elderberry, Mexican oregano, capers, cloves, shallots, onions
rutin buckwheat, asparagus, unpeeled apples, figs, black tea, green tea, elderflower tea
daidzein cheonggukang soy paste, soy tempe, fermented soy tofu, miso soy paste, soy yoghurt, soy tofu, soy milk
genistein soy tempe, fermented soy tofu, miso soy paste, cheonggukang soy paste, soy yoghurt, soy milk, soy tofu
glycyrrhizin licorice
caffeine coffee, beverages supplemented with caffeine, chocolate

Whole Fruit, Not Just Fruit Juices: Often, cautions about mixing medications with fruit specifically mention fruit juices. This focus on juices is largely due to the concentration of fruit polyphenols they contain. For instance, a small glass of grapefruit juice can pack as many polyphenols as an entire grapefruit. However, it’s crucial to recognize that consuming the whole fruit can similarly influence drug interactions, just as its juice can. So, when considering medications and dietary choices, it’s essential to factor in both whole fruits and their juices.

Sources and suggested reading:

Briguglio M, Hrelia S, Malaguti M, Serpe L, Canaparo R, Dell’Osso B, Galentino R, De Michele S, Dina CZ, Porta M, Banfi G. Food Bioactive Compounds and Their Interference in Drug Pharmacokinetic/Pharmacodynamic Profiles. Pharmaceutics. 2018 Dec 14;10(4):277. doi: 10.3390/pharmaceutics10040277.

Chen M, Zhou SY, Fabriaga E, Zhang PH, Zhou Q. Food-drug interactions precipitated by fruit juices other than grapefruit juice: An update review. J Food Drug Anal. 2018 Apr;26(2S):S61-S71. doi: 10.1016/j.jfda.2018.01.009.

Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705. doi: 10.1111/j.1476-5381.2009.00430.x.

Paśko P, Rodacki T, Domagała-Rodacka R, Palimonka K, Marcinkowska M, Owczarek D. Second generation H1 – antihistamines interaction with food and alcohol-A systematic review. Biomed Pharmacother. 2017 Sep;93:27-39. doi: 10.1016/j.biopha.2017.06.008.