Macrolides Fexofenadine

Concomitant use of macrolide antibiotics or imidazole antifungal agents may lead to serious ventricular arrhythmias. Fexofenadine ... 

Many Hj antihistamines are metabolized by CYPs. Thus, inhibitors of CYP activity such as macrolide antibiotics (e.g., erythromycin) or imidazole antifungals (e.g.,ketoconazole) can increase Hj antihistamine levels, leading to toxicity. Some newer antihistamines, such as cetirizine, fexofenadine, levocabastine, and acrivastine, are not subject to these drug interactions. 

There is a case of torsade de pointes possibly due to spiramycin with the sedating antihistamine mequitazine. The situation with erythromycin and loratadine is unclear as one study found that the combination caused a very slight increase in QT interval. Both azithromycin and erythromycin raise fexofenadine levels, but this had no effect on the QT interval, or on adverse events. Azelastine, cetirizine, desloratadine, and intranasal levocabastine seem to be free of clinically relevant interactions with macrolides. 

Fexofenadine levels are raised by both azithromycin and erythromycin but because this does not result in adverse cardiac effects concurrent use is considered safe. Azelastine, cetirizine (and therefore probably its isomer levocetirizine) desloratadine and levocabastine seem to be free from clinically significant pharmacokinetic interactions, and have no cardiac effects, and so may therefore provide suitable alternatives if a non-sedating antihistamine is needed in a patient taking macrolides. 

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