Itraconazole Antihistamines

Non-sedating antihistamines (e.g. loratidine, e.g. Clarityn cetirizine, e.g. Benadryl, Piriteze, Zirtek clemastine), which can cause dangerous arrhythmias with antifungal agents (itraconazole, ketoconazole), antibiotics (erythromycin, clarithromycin) and drugs used to counteract acidity... 

It seems likely that combining itraconazole with astemi-zole (59) and terfenadine (60,61) will lead to increased effects of these antihistamines (62). 

In vitro studies have shown that ketoconazole inhibits the metabolism of astemizole. Ketoconazole, and to a lesser extent itraconazole and miconazole, also appear to reduce the metabolism of terfenadine by inhibition of the cytochrome P450 isoenzyme CYP3A. " High serum levels of astemizole and terfenadine (but not its metabolites) block cardiac potassium channels leading to prolongation of the QT interval, which may precipitate the development of torsade de pointes arrhythmia (see Table 15.2 , (p.583)). The risk of cardiac arrhythmias with other non-sedating antihistamines appears to be non-existent or very much lower (see Table 15.2 , (p.583)), so any pharmacokinetic interactions do not result in clinically relevant cardiac toxicity. In fact, studies have shown that desloratadine at nine times the recommended dose, fexofenadine in overdose, and mizolastine at four times the recommended dose do not affect the QT interval. However, some questions remain about loratadine and ebastine. Additionally, some studies have reported that ketoconazole alone is associated with a small increase in QT interval, and at least one case of torsade de pointes has been reported for ketoconazole alone. Therefore the cardiac effects of ketoconazole may be additive with those of the antihistamines, and this may be important for ebastine and loratadine. 

Shon JH, Yeo CW, Liu KH, Lee SS, Cha U, Shin JG. Itraconazole and rifampin alter significantly the disposition and antihistamine effect of ebastine and its metabolites in healthy participants. J Clin Pharmacol 2010 50(2) 195-204. 

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