Pimozide (Orap) - Indications, Dose, Side effects

Pimozide (Orap) is a potent antipsychotic drug. It is more potent than chlorpromazine and even haloperidol (on a weight basis).

Indication of Pimozide:


  • Tourette disorder:

    • It is indicated for suppression of severe motor and phonic tics in patients with Tourette disorder who have failed to respond satisfactorily to standard treatment.
  • Off Label Use of Pimozide in Adults:

    • Delusional infestation (also called delusional parasitosis)

Pimozide dose in adult:

Pimozide (Orap) dose in the treatment of Tourette disorder:

  • Initial: 1 to 2 mg/day per oral in divided doses, then increase dosage as needed every other day.
  • The maximum dose is 10 mg/day or 0.2 mg/kg/day.


  • CYP2D6 genotyping/ phenotyping should be performed if therapy requires exceeding the dose of 4 mg/day; CYP2D6 poor metabolizers should be dose titrated in ≥14-day increments and should not receive doses in excess of 4 mg/day.

Pimozide (Orap) dose in the treatment of Delusional infestation (delusional parasitosis) (off-label):


  • Initial: 0.5 to 2 mg per oral once daily.
  • Increase dose based on response and tolerability in 1 mg increments every 3 to 7 days up to the usual dosage of 2 to 4 mg daily.
  • The maximum dose of 10 mg/day or 0.2 mg/kg/day.
  • Consider taper of therapy in decrements of ≥1 mg weekly after adequate relief of symptoms for 1 month, return of symptoms should be noted and considered for continued long-term treatment.

Discontinuation of therapy:

  • The manufacturer and American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend that antipsychotics should be tapered gradually to avoid withdrawal symptoms and minimize the risk of relapse.
  • The risk for withdrawal symptoms may be highest with highly anti-cholinergic or dopaminergic antipsychotics.
  • A gradual taper over 6-24 months is recommended by CPA when stopping antipsychotic therapy in patients with schizophrenia, and the APA guidelines recommend a 10% dose reduction each month.
  • Anti-parkinsonism agents should be continued for a brief period after discontinuation may prevent withdrawal symptoms.
  • When switching antipsychotics, 3 strategies have been suggested: cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), an abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose).

Pimozide dose in children:

Note: Slow titration is recommended to improve tolerability. Use the lowest effective dose. ECG monitoring is required before and especially during dosage adjustment.

Pimozide (Orap) dose in the treatment of moderate to severe Tourette disorder:


It is not recommended as a first-line due to potential cardiac toxicity, a trial of standard treatment is necessary before initiating a trial of pimozide therapy. Reliable dose-response data in patients younger than 12 years of age with Tourette disorder are lacking.

  • Children ≥2 years and Adolescents:

    • Weight-directed dosing:

      • Initial: 0.05 mg/kg/dose per oral once daily, preferably at bedtime.
      • maximum initial dose: 1 mg/dose;
      • The dose may be increased every third day if needed;
      • The maximum daily dose: 0.2 mg/kg/day not to exceed 10 mg/day.
    • Fixed dosing.

      • 0.5 to 1 mg daily;
      • The usual daily dose range: 2 to 8 mg/day.


CYP2D6 genotyping/ phenotyping should be performed if therapy requires exceeding the dose of 0.05 mg/kg/day,  CYP2D6 poor metabolizers should be dose titrated in ≥14-day increments and should not receive doses in excess of 0.05 mg/kg/day, up to 4 mg/day. This is based on a study of simulated multiple-dose pimozide exposures using pharmacokinetic parameters following a single dose in 32 healthy people; CYP2D6 poor metabolizers had higher pimozide exposure, which is a surrogate for arrhythmia risk; The study did not provide guidance for CYP2D6 intermediate or ultra-rapid metabolizers.

  • Pimozide (Orap) Dose adjustment for toxicity:

    • Children ≥2 years and Adolescents:

      • ECG changes:

        • QTc prolongation >0.47 seconds or >25% above baseline: Do not increase dose further; consider a lower dose.
      • Neutropenia:

        • Absolute neutrophil count <1,000/mm : Discontinue pimozide; monitor CBC until recovery.
      • Neuroleptic malignant syndrome:

        • Discontinue; monitor carefully if therapy is reinitiated.
      • Tardive dyskinesia signs/symptoms:

        • Consider discontinuing therapy;
        • a possible early sign of tardive dyskinesia is the fine vermicular movement of the tongue; if this appears, and the medication is stopped, tardive dyskinesia may not develop.

Pregnancy Risk Factor C

  • Studies on animal reproduction revealed negative results.
  • The newborn can experience agitation, feeding disorders, hypotonia and respiratory distress as well as somnolence and tremor.
  • These effects can be self-limiting, or may require hospitalization.
  • Antipsychotics in the last trimester are often associated with withdrawal symptoms and abnormal muscle movements in newborns.

Use of pimozide during breastfeeding

  • It is not known if pimozide is excreted in breast milk. 
  • The risk of serious adverse reactions in nursing infants is unknown.
  • It should be decided whether to stop nursing or discontinue using the drug.
  • This decision will depend on the importance to the mother.

Pimozide dose adjustment in renal disease:

There are no dosage adjustment provided in manufacturer’s labeling; use with caution.

Pimozide Dose adjustment in liver disease:

There are no dosage adjustment provided in manufacturer’s labeling; Use with caution.

Common Side Effects of Pimozide (Orap):

  • Central Nervous System:

    • Sedation
    • Akathisia
    • Drowsiness
    • Behavioral Changes
    • Hypertonia
  • Gastrointestinal:

    • Xerostomia
    • Constipation
  • Genitourinary:

    • Impotence
  • Neuromuscular & Skeletal:

    • Akinesia
    • Weakness
  • Ophthalmic:

    • Decreased Accommodation
    • Visual Disturbance

Rare Side Effects Of Pimozide (Orap):

  • Cardiovascular:

    • ECG Abnormality
  • Central Nervous System:

    • Depression
    • Insomnia
    • Speech Disturbance
    • Nervousness
    • Writing Difficulty
    • Headache
    • Abnormal Dreams
  • Dermatologic:

    • Skin Rash
  • Endocrine & Metabolic:

    • Increased Thirst
  • Gastrointestinal:

    • Sialorrhea
    • Diarrhea
    • Dysgeusia
    • Increased Appetite
    • Dysphagia
  • Neuromuscular & Skeletal:

    • Muscle Rigidity
    • Stooped Posture
    • Hyperkinesia
    • Myalgia
    • Torticollis
    • Tremor
  • Ophthalmic:

    • Photophobia

Frequency of side effects not defined (Some Reported For Disorders Other Than Tourette's Disorder):

  • Cardiovascular:

    • Chest Pain
    • Hypertension
    • Hypotension
    • Orthostatic Hypotension
    • Prolonged Q-T Interval On ECG
    • Syncope
    • Tachycardia
    • Ventricular Arrhythmia
  • Central Nervous System:

    • Dizziness
    • Excitement
    • Drug-Induced Extrapyramidal Reaction (Dystonia, Pseudoparkinsonism, Tardive Dyskinesia)
    • Neuroleptic Malignant Syndrome
    • Palpitations
    • Seizure
  • Dermatologic:

    • Diaphoresis
    • Skin Irritation
  • Endocrine & Metabolic:

    • Decreased Libido
    • Hyponatremia
    • Weight Changes (Gain/Loss)
  • Gastrointestinal:

    • Anorexia
    • Gastrointestinal Distress
    • Nausea
    • Vomiting
  • Genitourinary:

    • Nocturia
  • Hematologic & Oncologic:

    • Hemolytic Anemia
  • Ophthalmic:

    • Blurred Vision
    • Cataract
    • Periorbital Edema
  • Renal:

    • Polyuria

Contraindications to Pimozide (Orap):

  • Hypersensitivity to pimozide and any component of the formulation
  • Hypokalemia/hypomagnesemia
  • History of cardiac arrhythmias
  • Long QT syndrome congenital or in combination with drugs that cause long QT
  • Depression of the CNS or coma
  • Combination therapy with drugs that inhibit CYP3A4, such as itraconazole or ketoconazole, protease inhibitors (ie. atazanavir and indinavir), nelfinavir and ritonavir and sertraline), citalopram and escitalopram, and other less potent inhibitors (eg fluvoxamine and zileuton), macrolide antibiotics, eg clarithromycin and erythromycin


Manufacturer lists troleandomycin, clarithromycin and azithromycin as contraindicated macrolides. However, azithromycin doesn't inhibit CYP3A4, but can interact with pimozide based on QT prolongation.

  • Combination therapy with strong CYP2D6 inhibitors (eg paroxetine)
  • Use of medications that can cause motor or auditory tics, such as amphetamines, methylphenidate, and pemoline, concurrently with Tourette disorder medications until it is established if Tourette disorder or medications are causing the tics. Treatment for simple tics or tics not related to Tourette disorder.

Canadian labeling

  • Liver impairment
  • Renal impairment
  • Blood dyscrasias
  • Bradycardia is a significant condition
  • Congenital long QT syndrome or acquired congenital
  • Pheochromocytoma
  • Anesthesia for the spine or regional area
  • Orders that are depressing
  • Parkinson disease
  • Brain injury.

Warnings and precautions

  • Modified cardiac conduction

    • Pimozide may cause dangerous arrhythmias, by altering the cardiac conduction.
    • Patients with congenital QT intervals (caused by drugs) are not advised to take it.
    • High doses (1 mg/kg), can cause sudden death. Therefore, regular ECG monitoring during therapy is essential.
    • Before starting therapy, it is important to correct any electrolyte imbalances (hypokalemia or hypermagnesemia).
  • Anticholinergic effects

    • Pimozide is a potent cholinergic blockade with a high level of potency. It may cause constipation, xerostomia and blurred vision.
    • Patients with reduced gastrointestinal motility, paralytic and ileus, urinary retentions, BPH, xerostomia, and visual impairments should not use it.
  • Blood dyscrasias

    • Pimozide may cause leukopenia and neutropenia. A rapid assessment is needed if you have low WBC, or have had drug-induced leukopenia/neutropenia.
    • If the absolute neutrophil count is 1,000/mm, therapy should be stopped
  • Depression in the CNS:

    • CNS depression may occur when there are impaired mental or physical abilities. 
    • CNS depression can lead to impaired physical or mental abilities.
    • Patients should be cautious about driving and operating machinery.
  • Aspiration/Esophageal dysmotility/Esophageal dysmotility

    • Antipsychotic use has been linked to esophageal dysmotility (esophageal aspiration)
    • Risk factors include Alzheimer's Disease, age >75 Years.
  • Extrapyramidal symptoms

    • Extrapyramidal symptoms such as pseudo-parkinsonism and acute dystonic reactions may be present, along with tardive dyskinesia and akathisia.
      • Dystonia is more common in males who are younger, take higher doses of antipsychotics and use conventional ones.
      • The risk of tardive dyskinesia is not limited to females.
      • With tardive dyskinesia symptoms or signs, therapy should be stopped immediately.
  • Hyperprolactinemia

    • Increased prolactin levels are a common side effect of antipsychotics.
  • Neuroleptic malignant Syndrome (NMS).

    • A neuroleptic malignant condition that presents with altered mental state changes, fever, muscle rigidity and autonomic instability, elevated CPK, myoglobinuria and acute renal failure is warranted to be stopped.
  • Temperature regulation

    • It should not be used for heat exposure, dehydration, strenuous exercise, or concomitant anticholinergic medication.
  • Cardiovascular disease

    • Patients with severe cardiovascular disease should be cautious.
  • Dementia

    • Seniors with dementia-related psychosis may die from heart failure or infection in the wild.
    • Patients with Parkinson disease or Lewy body dementia should not use it.
    • The APA recommends that elderly patients suffering from dementia-related psychosis should be given second-generation antipsychotics, as they are more likely to experience side effects.
    • Pimozide has not been approved to treat dementia-related psychosis.
  • Hepatic impairment

    • Patients with hepatic impairment should be cautious.
  • Renal impairment

    • Patients with impaired renal function should be cautious.
  • Seizure disorder

    • Patients with seizure history should not be exposed to alcohol, brain injury, or concurrent treatment with medication that may lower their seizure threshold.

Monitoring parameters:

  • Vital signs
  • CYP2D6 genotyping and phenotyping
  • CBC
  • Tests of liver function
  • Electrolytes in serum
  • Fasting blood glucose
  • Profil de lipid
  • ECG monitoring
  • Weighing, height, BMI and waist circumference
  • Mental health
  • Annual changes in menstruation, libido and development of galactorrhea (yearly)
  • Monitoring for abnormal involuntary movements and parkinsonian signs at baseline.
  • Monitor weekly until dose stabilization is achieved for at least two weeks after it's introduction, and for at most 2 weeks following any significant dose increases.
  • Tightening of the teeth (every 6 to 12 months; high-risk patients, every 3 months).
  • Visual changes, ocular examinations (yearly for patients over 40 years old; annually for younger patients).

How to administer Pimozide (Orap)?

It should be given orally without regard to meals preferably at bedtime.

Mechanism of action of Pimozide (Orap):

  • Pimozide is a diphenylbutylperidine antipsychotic. 
  • It is a centrally-acting antagonist of dopamine receptors and has neuroleptic properties.

The onset of action:

  • Within 1 week Maximum effect: 4 to 6 weeks

Duration of action:

  • Variable


  • ≥50%

Protein binding:

  • 99%


  • Hepatic via N-dealkylation primarily by CYP3A4, but with contributions by CYP1A2 and CYP2D6; significant first-pass effect

Half-life elimination:

  • Children 6 to 13 years (n=4): Mean ± SD: 66 ± 49 hours
  • Adults 23 to 39 years (n=7): Mean ± SD: 111 ± 57 hours.

Time to peak serum concentration:

  • 6 to 8 hours
  • Range: 4 to 12 hours


  • Urine

International Brands of Pimozide:

  • Orap
  • PMS-Pimozide
  • Fopo
  • Mozep
  • Orap
  • Orap
  • Orap
  • Orap Forte
  • Orap Forte
  • Pimodac
  • Pirium
  • Pizide
  • Topimo

Pimozide Brands in Pakistan:

No Brands Available in Pakistan.