Itraconazole Ebastine

Ketoconazole increases mizolastine levels, which resulted in some QT prolongation in one study, therefore all azoles are contraindicated. The manufacturers of ebastine advise caution with ketoconazole and itraconazole as ketoconazole raises ebastine levels. The manufacturers of acrivastine advise caution with azoles due to a lack of data. 

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. 

The use of azole antifungals with mizolastine is also contraindicated, and the manufacturer of ebastine advises against the concurrent use of ketoconazole and itraconazole. Because there are no data on acrivastine with ketoconazole, the manufacturer advises caution. ... 

Ebastine In a 3-way crossover sequential study with 2-week washouts, 10 healthy participants took itraconazole for 6 days, rifampicin for 10 days, or neither, followed by oral 20 mg ebastine [155]. Itraconazole reduced the oral clearance of ebastine to 10% and increased the AUC of its active metabolite, carebastine, threefold. Rifampicin reduced the AUC of carebastine to 15%, markedly reduced the oral availability of ebastine, and significantly reduced histamine-induced skin reactions. 

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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