Interactions : אינטראקציות

4.5      Interactions with other medicinal products and other forms of interaction
Increases in the QT interval related to sertindole treatment may be exacerbated by the co-administration of other drugs known to significantly increase the QT interval. Co-administration of such drugs is therefore contraindicated (see section 4.3). Such an interaction may occur e.g.
between quinidine and sertindole. In addition to the effects on QT interval prolongation (see section 4.3), CYP2D6 is markedly inhibited by quinidine.

Sertindole is extensively metabolised by the CYP2D6 and CYP3A isozymes of the cytochrome P450 system. CYP2D6 is polymorphic in the population and both isozymes can be inhibited by a variety of psychotropic and other drugs (see section 4.4).

CYP2D6
The plasma concentration of sertindole is increased by a factor of 2 - 3 in patients concurrently taking fluoxetine or paroxetine (both potent CYP2D6 inhibitors), sertindole should therefore only be used concomitantly with these or other CYP2D6 inhibitors with extreme caution. A lower maintenance dose of sertindole may be needed and careful ECG monitoring should be undertaken before and after any dose adjustment of these drugs (see section 4.4).

CYP3A
Minor increases (<25%) in sertindole plasma concentrations have been noted for macrolide antibiotics (e.g. erythromycin, a CYP3A inhibitor) and calcium channel antagonists (diltiazem, verapamil). However, the consequences could be greater in CYP2D6 poor metabolisers (since elimination of sertindole by both CYP2D6 and CYP3A would be affected). Therefore, because it is not possible to routinely identify patients who are poor metabolisers of CYP2D6, the concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels (see section 4.3).

The metabolism of sertindole may be significantly enhanced by agents known to induce CYP isozymes, notably rifampicin, carbamazepine, phenytoin and phenobarbital, which can decrease the plasma concentrations of sertindole by a factor of 2 to 3. Reduced antipsychotic efficacy in patients receiving these drugs or other inducing agents may require the dose of sertindole to be adjusted to the upper dosage range.