Dosing and uses of Orap (pimozide)
Adult dosage forms and strengths
tablets
- 1mg
- 2mg
Tourette Disorder
Initial 1-2 mg PO qDay ; increase every other day; not to exceed 10 mg/day
Maintenance: <0.2 mg/kg/day or 10 mg/day, choose lowest dose
Pediatric dosage forms and strengths
tablets
- 1mg
- 2mg
Tourette Disorder
< 2 years
- Safety & efficacy not established
2-12 years
- Initial: 0.05 mg/kg/day PO qHS
- Can be increased q3Days to 0.2 mg/kg/day PO qHS
- Maintenance dose: 2-4 mg/day; not to exceed 10 mg/day
>12 years
- Initial 1-2 mg PO qDay ; increase every other day; not to exceed 10 mg/day
- Maintenance: <0.2 mg/kg/day or 10 mg/day, choose lowest dose
Orap (pimozide) adverse (side) effects
>10%
Akinesia (40%)
Drowsiness (35%)
EPS (10-15%)
Sedation (70%)
Speech disorder (10-15%)
Visual disturbance (20%)
Dry mouth (25%)
Constipation (20%)
Impotence (10-15%)
1-10%
Appetite increase
Thirst increase
Dizziness
Drug-induced tardive dystonia
Nervousness
Photosensitivity
Taste change
Orthostatic hypotension
Diminished sweating
Nasal congestion
Diarrhea
Urinary retention
Retinitis pigmentosa
Frequency not defined
Ineffective thermoregulation
Heatstroke or hypothermia (rare)
Neuroleptic malignant syndrome (rare)
Seizure (rare)
Prolonged QT intervaL
Torsades de pointes
Obstipation (rare)
Paralytic ileus (rare)
Agranulocytosis (rare)
Disorder of hematopoietic structure (rare)
Leukopenia (rare)
Thrombocytopenia (rare)
Cholestatic jaundice syndrome (rare)
Drug-induced lupus erythematosus, systemic (rare)
Priapism (rare)
Death
Warnings
Black box warnings
Patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials. The deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature.
This drug is not approved for the treatment of patients with dementia-related psychosis.
Contraindications
Documented hypersensitivity
CNS depression (including coma), neuroleptic malignant syndrome (NMS), poorly controlled seizure disorder
Use as first-line treatment
Tics not associated with Tourette's
Prolongs QT interval: concurrent QT-prolonging drugs or congenital long QT patients
Concomitant CYP3A4 or CYP2D6 inhibitors
Cautions
FDA Warning regarding off-label use for dementia in elderly
Avoid grapefruit juice
Risk of EPS & NMs
Leukopenia/neutropenia and agranulocytosis reported; possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia
If history of clinically significant low WBC or drug-induced leukopenia/neutropenia, monitor complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of a clinically significant decline <1000/mm³ in WBC in absence of other causative factors and continue monitoring WBC until recovery
Pregnancy and lactation
Pregnancy category: C
Neonates exposed to antipsychotic drugs during the 3rd trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery
These complications vary in severity; in some cases, symptoms have been self-limited, while in other cases neonates have required intensive care unit support and prolonged hospitalization
Lactation: unknown, avoid
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Orap (pimozide)
Mechanism of action
Phenylbutylpiperadine; potent centrally acting dopamine D2 receptor antagonist
Absorption
Bioavailability: 40-50%
Peak plasma time: 6-8 hr
Peak plasma concentration: 4-19 ng/mL (dose dependent)
Metabolism
Metabolism: Hepatic P450 enzyme CYP3A4 and CYP2D6
Metabolites: Inactive
Elimination
Half-life elimination: 55 hr
Excretion: Urine
Dialyzable: Unknown
Pharmacogenetics
Poor CYP2D6 metabolizers exhibit higher pimozide concentrations than extensive CYP2D6 metabolizers
Approximately 7-10% of Caucasians and 3-8% of African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PMs)
Serum concentrations observed in poor metabolizers are similar to those seen with strong CYP2D6 inhibitors (eg, paroxetine)
Time to achieve steady state pimozide concentrations is expected to be longer (approximately 2 weeks) in poor metabolizers because of the prolonged half-life
Alternative dosing strategies are recommended in patients who are genetically poor CYP2D6 metabolizers
Genetic testing laboratories
- Genotyping tests for CYP2D6 variants are commercially available through the following companies
- Applied Biosystems (https://www.appliedbiosystems.com/)
- GenPath Diagnostics (https://www.genpathdiagnostics.com/)
