Interactions between diphenhydramine(diphenhydrAMINE) and Mellaril (thioridazine)
diphenhydrAMINE and thioridazine (Major Drug-Drug)
CONTRAINDICATED: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, all of which are substrates of the isoenzyme. Significant increases (up to severalfold) have been observed during coadministration with fluvoxamine, propranolol, and pindolol in pharmacokinetic studies. The use of thioridazine has been associated with dose-related prolongation of the QT interval, thus elevated plasma levels of the drug may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes as well as cardiac arrest and sudden death. Several cases of torsade de pointes have been reported.
MANAGEMENT: The use of thioridazine with drugs that inhibit CYP450 2D6 is considered contraindicated. Depending on the elimination half-life of these drugs, a considerable waiting period may be appropriate following their discontinuation before thioridazine is initiated. For example, the manufacturer of fluoxetine recommends that thioridazine not be administered within 5 weeks after discontinuing fluoxetine because of the drug's long half-life.
