The solubility of pimozide in water is less than 0.01 mg/mL; it is slightly soluble in most organic solvents.
Each white Pimozide tablet contains either 1 mg or 2 mg of pimozide and the following inactive ingredients: calcium stearate, microcrystalline cellulose, lactose anhydrous and corn starch.
CLINICAL PHARMACOLOGY
Pharmacodynamic Actions
Pimozide tablets, USP is an orally active antipsychotic drug product which shares with other antipsychotics the ability to blockade dopaminergic receptors on neurons in the central nervous system. Although its exact mode of action has not been established, the ability of pimozide to suppress motor and phonic tics in Tourette’s Disorder is thought to be a function of its dopaminergic blocking activity. However, receptor blockade is often accompanied by a series of secondary alterations in central dopamine metabolism and function which may contribute to both pimozide’s therapeutic and untoward effects. In addition, pimozide tablets, USP in common with other antipsychotic drugs, has various effects on other central nervous system receptor systems which are not fully characterized.
Metabolism and Pharmacokinetics
More than 50% of a dose of pimozide is absorbed after oral administration. Based on the pharmacokinetic and metabolic profile, pimozide appears to undergo significant first pass metabolism. Peak serum levels occur generally six to eight hours (range 4 to 12 hours) after dosing.
Pimozide is extensively metabolized, primarily by N-dealkylation in the liver. This metabolism is catalyzed mainly by the cytochrome P450 3A4 (CYP 3A4) enzymatic system and to a lesser extent, by cytochrome P450 1A2 (CYP 1A2) and cytochrome P450 2D6 (CYP 2D6). Two major metabolites have been identified, 1-(4-piperidyl)-2-benzimidazolinone and 4,4-bis(4-fluorophenyl) butyric acid. The antipsychotic activity of these metabolites is undetermined. The major route of elimination of pimozide and its metabolites is through the kidney.
The mean serum elimination half-life of pimozide in schizophrenic patients was approximately 55 hours. There was a 13-fold interindividual difference in the area under the serum pimozide level-time curve and an equivalent degree of variation in peak serum levels among patients studied. The significance of this is unclear since there are few correlations between plasma levels and clinical findings.
Effects of food and disease upon the absorption, distribution, metabolism and elimination of pimozide are not known. Effects of concomitant medication and genetic variations on pimozide metabolism are described in the CONTRAINDICATIONS and PRECAUTIONS sections.
INDICATIONS & USAGE
Pimozide Tablets, USP is indicated for the suppression of motor and phonic tics in patients with Tourette’s Disorder who have failed to respond satisfactorily to standard treatment. Pimozide Tablets, USP is not intended as a treatment of first choice nor is it intended for the treatment of tics that are merely annoying or cosmetically troublesome. Pimozide Tablets, USP should be reserved for use in Tourette’s Disorder patients whose development and/or daily life function is severely compromised by the presence of motor and phonic tics.
Evidence supporting approval of Pimozide Tablets, USP for use in Tourette’s Disorder was obtained in two controlled clinical investigations which enrolled patients between the ages of 8 and 53 years. Most subjects in the two trials were 12 or older.
DOSAGE & ADMINISTRATION
General
The suppression of tics by Pimozide Tablets, USP requires a slow and gradual introduction of the drug. The patient’s dose should be carefully adjusted to a point where the suppression of tics and the relief afforded is balanced against the untoward side effects of the drug.
