Orap (Pimozide)

Pimozide is used in the management of disorders involving dopaminergic overactivity, particularly movement and psychotic disorders.

• Tourette syndrome: reduces the frequency and severity of motor and vocal tics.
• Chronic schizophrenia: helps control persistent psychotic symptoms when other agents are insufficient.
• Other refractory psychotic disorders: may be employed to manage symptoms unresponsive to standard antipsychotics.
• Schizoaffective disorder: assists in stabilizing mood and psychotic features.

• Pimozide exerts its therapeutic effect primarily by antagonizing dopamine D2 receptors in the central nervous system, thereby diminishing dopaminergic neurotransmission. It also exhibits antagonistic activity at serotonin 5‑HT2, alpha‑adrenergic, and calcium channel sites, which contributes to its antipsychotic and anti‑tremor properties. These actions result in a reduction of abnormal motor output and stabilization of mood.

Pimozide may cause a range of adverse reactions, varying from mild to severe.

Common Side Effects

• Sedation: feeling of drowsiness or reduced alertness.
• Extrapyramidal symptoms: muscle stiffness, tremor, or restlessness.
• Weight gain: increase in body weight over time.
• Dry mouth: reduced salivation leading to oral discomfort.
• Constipation: slowed gastrointestinal motility causing difficulty passing stool.
• Blurred vision: temporary visual disturbances.

Serious or Rare Side Effects

• Neuroleptic malignant syndrome: life‑threatening reaction with fever, rigidity, and autonomic instability.
• Tardive dyskinesia: irreversible involuntary movements, especially of the face and tongue.
• QT prolongation: cardiac rhythm disturbance that can lead to arrhythmia.
• Agranulocytosis: severe reduction in white blood cells increasing infection risk.
• Severe hypotension: marked drop in blood pressure causing dizziness or fainting.
• Seizures: rare occurrence of convulsive episodes.

When prescribing pimozide, several precautions should be observed to ensure patient safety.

• Cardiac monitoring: obtain baseline ECG and periodically assess QT interval due to risk of prolongation.
• Hepatic impairment: adjust dose or avoid use in patients with severe liver dysfunction.
• Elderly patients: monitor closely for increased sensitivity to extrapyramidal effects.
• Pregnancy and lactation: use only if potential benefit justifies potential risk to fetus or infant.
• Drug interactions: avoid concomitant strong CYP3A4 inhibitors that may raise pimozide plasma levels.
• Store at room temperature: keep in the original container, protect from moisture and light.

Pimozide interacts with several medicines, requiring attention to avoid adverse outcomes.

Major Interactions (Avoid)

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): can markedly increase pimozide concentrations and risk of QT prolongation.
• Other QT‑prolonging agents (e.g., haloperidol, quinidine, sotalol): additive risk of serious cardiac arrhythmias.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may reduce pimozide effectiveness by lowering plasma levels.

Moderate Interactions (Monitor Closely)

• CNS depressants (e.g., benzodiazepines, opioids): may enhance sedation and respiratory depression.
• Anticholinergic drugs (e.g., benztropine, atropine): increase anticholinergic burden and may worsen dry mouth or constipation.
• Lithium: may heighten risk of extrapyramidal symptoms when combined.