ANTIHISTAMINES AND AZOLES - OTHER ANTIHISTAMINES

Ketoconazole very markedly raised ebastine levels and markedly raised loratadine levels. In one study, this was associated with a small increase in the QT interval for both antihistamines, but there was no obvious alteration in the adverse event profile. Ketoconazole markedly raised the plasma levels of fexofenadine, and modestly raised those of desloratadine and emedastine, but these changes had no effect on the QT interval, or on adverse events. The combinations may therefore be assumed to be safe in terms of cardiac effects.
The manufacturer of ebastine advises against the use of itraconazole or ketoconazole. However, in general these changes are not expected to have a clinically relevant effect, although some caution may be warranted. Azelastine, cetirizine, levocabastine and levocetirizine do not appear to interact with ketoconazole and may therefore be suitable alternatives.
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