Aprepitant inhibits the metabolism of midazolam and doubles the levels of oral midazolam after 5 days of concurrent use. A few days after aprepitant treatment is stopped a transient slight reduction in midazolam plasma levels may occur. Other benzodiazepines metabolised by CYP3A4 (alprazolam, triazolam) would be expected to interact similarly. Aprepitant appears to have less effect on intravenous midazolam. Fosaprepitant, a prodrug of aprepitant, would be expected to interact similarly.
Aprepitant may be expected to increase the drowsiness and length of sedation and amnesia in patients given midazolam (and possibly alprazolam or triazolam). Consider reducing the midazolam dose and monitor the outcome of concurrent use carefully.
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