Sertindole Erythromycin

Erythromycin (especially intravenous use), halofantrine, some quinolones Amisulpride, haloperidol, sertindole, thioridazine, pimozide Cisapride... 

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. 

The most common mechanism of dysrhythmias at the molecular level is by inhibition of the potassium channels known as IK, which are encoded by the human ether-a-go-go-related gene (HERG). The antidysrhythmic drugs that affect these channels include almokalant, amiodar-one, azimilide, bretylium, dofetilide, ibutilide, sematilide, D-sotalol, and tedisamil (all drugs with Class III actions) and bepridil, disopyramide, prenylamine, procainamide, propafenone, quinidine, and terodiline (all drugs with Qass I actions). Other drugs that affect these channels but are not used to treat cardiac dysrhythmias include astemizole and terfenadine (antihistamines), cisapride, erythromycin, haloperidol, sertindole, and thioridazine. 

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. 

A single 4-mg dose of sertindole was given to 10 healthy subjects before and after a course of erythromycin 250 mg every 6 hours for 10 days. The mean maximum serum levels were increased by 15%, probably because erythromycin inhibits the cytochrome P450 isoenzyme CYP3A4, but this was not considered to be clinically significant. The incidence of adverse events also rose (diarrhoea, abdominal pain, dizziness) but no ECG changes were seen. Nevertheless the manufacturers contraindicate erythromycin because raised sertindole levels may prolong the QT interval. Also... 

Granneman GR, Wozniak P, Ereshefsky L, Silber C, Mack R, Effect of erythromycin on the pharmacokinetics of sertindole (M94-145). Poster presentation at the American College of Neuropsychopharmacology Annual Meeting, San Juan, Puerto Rico, December 1996,... 

Wong SL, Cao G, Mack RJ, Granneman GR. The effect of erythromycin on the CYP3A component of sertindole clearance in healthy voiuntQQrs. J Clin Pharmacol (1997) 37,1056-61. 

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