Category: antihistamines

Which fruit to avoid with fexofenadine?

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).

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Do levocetirizine and cetirizine really cause drowsiness?

I have looked at the package insert for XyzalⓇ (levocetirizine) and see no mention of drowsiness. Isn’t it that second and third generation antihistamines do not cause drowsiness or only cause drowsiness on overdose?

Levocetirizine is the levorotatory (“left-handed”) enantiomer of the second generation antihistamine cetirizine, which is a racemic mixture. Levocetirizine is sometimes referred to as a third generation antihistamine because it is a derivative of a second generation agent.

First generation antihistamines enter the brain and cause drowsiness by antihistamine actions at H1 receptors. Second generation antihistamines enter the brain less than first generation antihistamines and so cause less drowsiness. However, among the second generation antihistamines, not all are equal. Some, including cetirizine, still cause some degree of drowsiness.

Even for levocetirizine, the drowsiness is significant enough at normal clinical doses that a special precaution when driving, having high-risk work, or operating machinery is included in the product insert (see image below).  The term used for drowsiness in the package insert is somnolence.

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