Subject sertindole

Most antipsychotic drugs have effects on the heart as a consequence of their pharmacological actions. Recently, thioridazine has been subjected to a restricted indication notice and the atypical antipsychotic sertindole had its licence withdrawn because of concerns about its potential cardiotoxicity. 

Activity at the 5HT-2 receptor is an important feature of many atypical antipsychotic drugs (e.g., risperidone, olanzapine, sertindole), but the body of knowledge on 5HT-2 ligands in anxiety is more limited (173). Nonselective 5HT-2 antagonists, such as ritanserin (112), mianserin (113), and ketanserin (114), have been shown to produce anxiolytic effects in less than half of the preclinical studies conducted (202). The clinical data for ritanserin in human subjects are likewise inconclusive (458, 459). The mixed results obtained with... 

A standardised breakfast or Maalox 45 mL had no significant effect on the AUC of a single 4-mg dose of sertindole in 16 healthy subjects, and only minor and unimportant changes occurred in maximum serum levels. No special precautions are needed if sertindole is given with Maalox, and it may be given without regard to meals. 

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... 

A single 120-mg dose of terfenadine was given to 14 healthy subjects who had taken sertindole 20 mg daily for 5 days. The pharmacokinetics of neither drug was significantly changed, nor that of the metabolite of terfenadine (carboxyterfenadine), although it was concluded that sertindole may be a modest inhibitor of the first pass metabolism of terfenadine. However, it was foimd that the combination caused an additive increase of 49 milliseconds in the QTc interval and therefore these two drugs are contraindicated by the manufacturer. ... 

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