Sertindole Carbamazepine

ANTIPSYCHOTICS CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, PRIMIDONE 1 levels of apiprazole (all), haloperidol (carbamazepine, phenobarbital), clozapine, quetiapine, sertindole (carbamazepine, phenytoin), risperidone and olanzapine (carbamazepine) Induction of metabolism Watch for poor response to these antipsychotics, and consider increasing the dose... 

Drugs can not only be substrates for a cytochrome P450 enzyme or an inhibitor of a P450 enzyme, they can also be inducers of a cytochrome P450 enzyme and thereby increase the activity of that enzyme. This was discussed in Chapter 6 for CYP450 3A4, and the induction of 3A4 activity by the anticonvulsant and mood stabilizer carbamazepine was given as an example (Fig. 6—19). Since mood stabilizers may be frequently mixed with atypical antipsychotics, it is possible that carbamazepine may be added to the regimen of a patient previously stabilized on clozapine, quetiapine, ziprasidone, or sertindole. If so, the doses of these atypical antipsychotics may need to be increased over time to compensate for the induction of 3A4 by carbamazepine. 

FIGURE 11—51. The enzyme CYP450 3A4 can be induced by the anticonvulsant and mood stabilizer carbamazepine. If this agent is stopped in a patient who is receiving an atypical antipsychotic that is a substrate for this same enzyme (i.e., clozapine, quetiapine, ziprasidone, or sertindole), the doses of these antipsychotics may need to be reduced because the autoinduction of 3A4 by carbamazepine will reverse over time once it is discontinued. 

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. 

Antidepressants mirtazapine, nefazodone, sertraline Neuroleptics thioridazine, haloperidol, clozapine, quetiapine, risperidone, sertindole, ziprasidone Mood stabilizers carbamazepine, gabapentin, lamotrigine... 

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. 

The metabolism of sertindole is markedly increased by enzyme inducers, such as phenytoin and carbamazepine, and plasma sertindole levels may be reduced by 2 to 3-fold. The manufacturers therefore say that the daily dosage of sertindole may need to be increased towards the upper end of the maximum dosage range to accommodate this interaction. ... 

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