Sertindole Diltiazem

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

CALCIUM CHANNEL BLOCKERS SERTINDOLE Plasma concentrations of sertindole are t by diltiazem and verapamil Diltiazem and verapamil inhibit CYP3A4-mediated metabolism of sertindole Avoid co-administration raised sertindole concentrations are associated with an t risk of prolonged Q-T interval and therefore ventricular arrhythmias, particularly torsades de pointes... 

The manufacturers of sertindole contraindicate the concurrent use of cimetidine, diltiazem, erythromycin, itraconazole, ketoco-nazole, terfenadine and verapamil because of an increased risk of cardiac arrhythmias. Carbamazepine and phenytoin reduce plasma sertindole levels whereas fluoxetine and paroxetine increase them. No clinically relevant interactions occur with alprazolam, antacids, food or tobacco smoking. 

Studies in patients found that diltiazem, nifedipine or verapamil resulted in a 20% reduction in the sertindole elearanee, attributed to inhibition of CYP3A metabolism. The manufaeturers contraindieate concurrent use (diltiazem and verapamil are specifically named) as raised sertindole levels may prolong the QT interval. ... 

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