Trazodone + Azoles - Drug Interactions

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).

Zalma A,von Moltke LL, Granda BW, Harmatz JS, Shader RI, Greenblatt DJ. In vitro metabolism of trazodone by CYP3A: inhibition by ketoconazole and human immunodeficiency viralprotease inhibitors. Biol Psychiatry (2000) 47, 655–61.

Desyrel (Trazodone hydrochloride). Bristol-Myers Squibb Company. US Prescribing information,January 2005.

Lewis-Hall FC. Bristol-Myers Squibb Company. Letter to healthcare professionals,April 2004.

Molipaxin (Trazodone hydrochloride). Sanofi-Aventis. UK Summary of product characteristics,July 2005.