Pimozide is a conventional antipsychotic used largely in the therapy of Tourette syndrome. Pimozide therapy has not been associated with serum aminotransferase elevations nor with cases of clinically apparent acute liver injury.
Pimozide (pim' oh zide) is a diphenylbutylpiperidine derivative that differs structurally from the phenothiazines and appears to act by blocking dopamine type 2 (D2) receptors. Pimozide has other central and peripheral effects including anticholinergeric and alpha adrenergic blockade. Pimozide is indicated for the therapy of severe motor and verbal tics in patients with Tourette syndrome. It has also been used in therapy of schizophrenia. Pimozide was approved for use in the United States in 1984. As therapy of schizophrenia, pimozide has been replaced in large part by the atypical antipsychotics, which have fewer extrapyramidal side effects. Pimozide continues to be used in patients with Tourette syndrome. Pimozide is available as tablets of 1 and 2 mg in generic forms and under the brand name Orap. Typical doses are 1 to 2 mg daily in divided doses, increasing to a maximum of 10 mg daily. Pimozide can prolong the QT interval and, in rare instances, has caused sudden death for which reason the dose should be carefully chosen and drug levels monitored. Common side effects include drowsiness, dizziness, headache, blurred vision, dry mouth, and constipation.
Liver test abnormalities have not been reported to occur in of patients on pimozide, but the degree and duration of monitoring done in initial studies were not clear. Instances of clinically apparent acute liver injury have not been reported due to pimozide, and thus must be exceedingly rare if they occur.
Mechanism of Injury
Pimozide is extensively metabolized by the liver partially via the cytochrome P450 system (predominantly CYP 2D6) and levels can be seriously elevated in patients who concurrently receive CYP 2D6 inhibitors, particularly in persons who are poor metabolizers of CYP 2D6 substrates. The lack of hepatotoxicity may relate in part to the low dosage used (less than 10 mg daily).
REPRESENTATIVE TRADE NAMES
Pimozide – Generic, Orap®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 16 January 2014
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