Interaction entre Clarithromycine et Pimozide

Cisapride and pimozide ( 4.2 )

Cisapride and Pimozide Concomitant administration of clarithromycin tablets with cisapride and pimozide is contraindicated [see Drug Interactions ( 7 )] .

There have been postmarketing reports of drug interactions when clarithromycin is co‑administered with cisapride or pimozide, resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes ) most likely due to inhibition of metabolism of these drugs by clarithromycin tablets.

Colchicine (in patients with normal renal and hepatic function) Use With Caution Antipsychotics: Pimozide Contraindicated Pimozide: [See Contraindications ( 4.2 )] Quetiapine Lurasidone Quetiapine: Quetiapine is a substrate for CYP3A4, which is inhibited by clarithromycin.

Co-administration could result in increased quetiapine exposure and quetiapine related toxicities such as somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation.

Specifically, two sudden deaths have been reported when clarithromycin was added to ongoing pimozide therapy.

Because pimozide prolongs the QT interval of the electrocardiogram it is contraindicated in patients with congenital long QT syndrome, patients with a history of cardiac arrhythmias, patients taking other drugs which prolong the QT interval of the electrocardiogram or patients with known hypokalemia or hypomagnesemia (see also PRECAUTIONS - DRUG INTERACTIONS ).

Ventricular arrhythmias have been rarely associated with the use of macrolide antibiotics in patients with prolonged QT intervals, as might be produced by pimozide.

Macrolide antibiotics are inhibitors of CYP 3A4, and thus could potentially impede pimozide metabolism.

For these reasons, pimozide is contraindicated in patients receiving the macrolide antibiotics clarithromycin, erythromycin, azithromycin, dirithromycin, and troleandomycin.