Orap (Pimozide): Comprehensive Overview

Orap, the brand name for pimozide, is a potent antipsychotic medication primarily prescribed for managing severe motor and vocal tics associated with Tourette’s syndrome. Its efficacy in reducing the frequency and intensity of tics has made it a valuable treatment option for patients unresponsive to other therapies.

Chemical Composition and Properties

• Chemical Name: 1-[1-[4,4-bis(4-fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazole-2-one
• Molecular Formula: C28H29F2N3O
• Molecular Weight: 461.55 g/mol
• Physical Appearance: White, odorless crystalline powder
• Solubility: Slightly soluble in water; soluble in organic solvents

Pharmacodynamics and Mechanism of Action

Pimozide functions by selectively blocking dopamine receptors, particularly the D2 subtype, in the central nervous system. This antagonistic action modulates neurotransmitter activity, leading to a reduction in the hyperactivity associated with tics in Tourette’s syndrome.

Pharmacokinetics

• Absorption: Pimozide is well-absorbed orally, with peak plasma concentrations typically reached within 6 to 8 hours post-administration.
• Distribution: The drug exhibits extensive distribution throughout body tissues and has a high affinity for plasma proteins.
• Metabolism: Pimozide is metabolized primarily in the liver via the cytochrome P450 system, notably CYP3A4 and CYP2D6 enzymes.
• Elimination Half-Life: The elimination half-life ranges from 55 to 65 hours, indicating prolonged action.
• Excretion: Excreted mainly through feces, with a smaller proportion eliminated via urine.

Indications

Orap 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.

Dosage Forms and Strengths

Orap is available in tablet form with the following strengths:

Strength (mg)	Imprint Code	Color	Shape	NDC Code
1	ORAP 1	White	Round	57844-151
2	ORAP 2	White	Round	57844-152

Dosage and Administration

• Adults:
  • Initial Dose: 1 to 2 mg per day, administered in divided doses.
  • Maintenance Dose: The dosage may be increased every other day based on therapeutic response and tolerance, not exceeding a maximum of 10 mg per day.
• Pediatric Patients (12 years and older):
  • Initial Dose: 0.05 mg/kg per day, with gradual increases every third day as needed.
  • Maximum Dose: Should not exceed 0.2 mg/kg per day or 10 mg per day, whichever is less.

Special Populations

• Hepatic Impairment: Caution is advised; dose adjustments may be necessary due to reduced metabolism.
• Renal Impairment: Use with caution; monitor for signs of toxicity.

Contraindications

• Known hypersensitivity to pimozide or any of its components.
• Patients with congenital long QT syndrome or a history of cardiac arrhythmias.
• Concomitant use with medications that prolong the QT interval or inhibit CYP3A4 enzymes.

Warnings and Precautions

• QT Prolongation: Pimozide has been associated with QT interval prolongation, leading to serious heart rhythm disturbances. Regular ECG monitoring is recommended.
• Tardive Dyskinesia: Long-term use may lead to tardive dyskinesia, a potentially irreversible condition characterized by involuntary movements.
• Neuroleptic Malignant Syndrome: A rare but life-threatening condition; monitor for symptoms such as high fever, muscle rigidity, and altered mental status.

Adverse Reactions

Common adverse reactions include:

• Drowsiness
• Dry mouth
• Constipation
• Blurred vision
• Dizziness

Serious adverse reactions may include:

• Cardiovascular Effects: QT prolongation, ventricular arrhythmias, and sudden death.
• Extrapyramidal Symptoms: Including tremors, rigidity, and bradykinesia.
• Hematologic Effects: Leukopenia, neutropenia, and agranulocytosis.

Drug Interactions

• CYP3A4 and CYP2D6 Inhibitors: Concomitant use can increase pimozide levels, enhancing the risk of adverse effects.
• QT-Prolonging Agents: Avoid co-administration with other drugs known to prolong the QT interval.
• CNS Depressants: Concurrent use may potentiate sedative effects; use with caution.

Monitoring Parameters

• Regular ECGs to monitor heart rhythm.
• Serum electrolyte levels, particularly potassium and magnesium.
• Complete blood counts to detect potential hematologic adverse effects.

Orap is prescribed to help reduce and control motor tics (uncontrolled movements) and vocal tics (uncontrolled sounds), which are common in Tourette syndrome. It works by decreasing the excessive activity of dopamine in the brain, thereby managing these symptoms.

US Brand Name:
Orap

Generic Name:
Pimozide

Other Brand Name:
Orap

Packaging:
100 tablets

Manufacturer:
Johnson & Johnson

Form:
Tablet

Strength:
2 mg