Pimozide

As with other neuroleptics, Orap may increase the central nervous system depression produced by other CNS depressant drugs, including alcohol, hypnotics, sedatives or strong analgesics.

Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing pimozide to patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity or being subject to dehydration.

As CYP1A2 may also contribute to the metabolism of pimozide, prescribers should be aware of the theoretical potential for drug interactions with inhibitors of this enzymatic system.

Caution is advised in patients with liver disease because pimozide is metabolized in the liver.

As grapefruit juice is known to inhibit the metabolism of CYP3A4 metabolised drugs, concomitant use of grapefruit juice with pimozide should be avoided.

Concurrent use of drugs causing electrolyte imbalance is not recommended. Diuretics, in particular those causing hypokalemia, should be avoided but, if necessary, potassium-sparing diuretics are preferred.

Pimozide may impair the anti-Parkinson effect of levodopa.

As with other antipsychotic drugs, pimozide should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold (e.g. alcohol withdrawal or brain damage).

The safety of pimozide in pregnancy has not been established. Therefore, it should not be administered to women of child-bearing potential, particularly during the first trimester of pregnancy, unless, in the opinion of the physician, the expected benefits of the drug to the patient outweigh the potential risk to the foetus.

Studies in animals have shown reproductive toxicity but no teratogenic effects have been demonstrated.

Neonates exposed to antipsychotic drugs (including pimozide) during the third trimester of pregnancy are at risk of adverse effects including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

Pimozide may be excreted in breast milk. If the use of pimozide is considered essential, breast feeding should be discontinued.

Pimozide may impair alertness, especially at the start of treatment. These effects may be potentiated by alcohol. Patients should be warned of the risks of sedation and advised not to drive or operate machinery during treatment until their susceptibility is known.

The safety of pimozide was evaluated in 165 pimozide-treated subjects who participated in seven placebo-controlled trials of patients with schizophrenia, or patients with anxiety or behavioural disorders, and in 303 pimozide-treated subjects who participated in eleven active-comparator controlled clinical trials in patients with schizophrenia (10 trials, including chronic schizophrenia) or psychic fatigability (1 trial). Based on pooled safety data from these clinical trials, the most commonly reported (≥9% incidence) Adverse Drug Reactions (ADRs) were (with % incidence): Nervous System Disorders: Dizziness (11) and Somnolence (11), Extrapyramidal Disorder (9); Muscle Rigidity (9); Hyperhidrosis (13); Nocturia (12).

Including the above-mentioned ADRs, the following table (next page) displays ADRs that have been reported with the use of pimozide from either clinical-trial or post-marketing experiences. The displayed frequency categories use the following convention:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated form the available data).

In addition to the above, cardiac arrest and sudden unexplained death have been reported with the use of pimozide. These events should be considered ADRs associated with the class of medicinal products, the D2, dopamine-antagonist neuroleptics.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs (frequency unknown).