Important labelling changes have been made for all dosage forms of thioridazine hydrochloride (Mellaril®) by the manufacturer.

A boxed warning has been added to prominently advise clinicians that thioridazine has been shown to prolong the QTc interval in a dose-related manner and drugs with this potential have been associated with torsade de pointes-type arrhythmias and sudden death. Mesoridazine is the major active metabolite of thioridazine and appears to have the capacity to prolong the QTc interval.

Thioridazine hydrochloride is now indicated only for schizophrenic patients who fail to show an acceptable response to adequate courses of treatment with other antipsychotic drugs. It is contraindicated with certain other drugs, including fluvoxamine, propranolol, pindalol, any drug that inhibits P450 2D6 isozyme, e.g. fluoxetine and paroxetine, and agents known to prolong the QTc interval such as disopyramide, procainamide and quinidine. Thioridazine hydrochloride is also contraindicated in patients know to have reduced levels of the P450 2D6 isozyme as well as in patients with congenital long QT syndrome or a history of cardiac arrhythmias.

Before being considered for treatment, patients should have a baseline electrocardiogram (ECG) performed and serum potassium levels measured. Periodic ECGs and serum potassium levels may be useful. Thioridazine should be discontinued in patients who are found to have a QTc interval over 500 m/sec.

Patients currently being treated with thioridazine hydrochloride should be fully informed of this information. Switching to a different antipsychotic agent should be considered and continuation of thioridazine hydrochloride treatment should be based on a careful assessment of the potential benefits and risks.

Reference: Letter from Novartis, USA, dated 7 July 2000 and letter from Novartis Pharmaceuticals Canada Inc., Canada, dated, 31 July 2000.