Ketoconazole or itraconazole may inhibit metabolism of trazodone
Clinical evidence,mechanism, importance and management
An in vitro study demonstrated that ketoconazole inhibited metabolism of trazodone to its principal metabolite, meta-chlorophenylpiperazine (See reference number 1). Trazodone is a substrate for cytochrome P450 isoenzyme CYP3A4 and inhibitors of this enzyme such as ketoconazole or itraconazole may inhibit its metabolism, leading to substantial increases in trazodone plasma concentrations with potential for adverse effects (See reference number 2-4). The FDA in US and manufacturers of trazodone recommend that a lower dose of trazodone should be considered if it is given with a potent CYP3A4 inhibitor such as ketoconazole or itraconazole (See reference number 2-4). However, UK manufacturer also suggests that combination should be avoided where possible (See reference number 4).
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