Schedule H

Oral

Formulation Strengths Available

Tablets 2 mg, 4 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Tourette Syndrome (Tics causing significant functional impairment)

Parameter Recommendation

Starting dose 1–2 mg once daily

Titration Increase by 2 mg at intervals of ≥3 days; adjust based on response and tolerability

Usual maintenance dose 2–8 mg/day (once daily or divided twice daily)

Maximum dose 10 mg/day

Clinical Notes:

• Baseline ECG mandatory before initiation

• Start low and titrate cautiously to minimise extrapyramidal side effects

• Use lowest effective dose for tic suppression

• More effective for vocal tics than motor tics, but both may improve

• Behavioural therapy should be considered as first-line approach before pharmacotherapy

1. Schizophrenia (when other antipsychotics unsuitable or in refractory cases)

Parameter Recommendation

Starting dose 2–4 mg/day in 1–2 divided doses

Titration Increase by 2 mg at intervals of ≥1 week based on tolerability and clinical response

Usual maintenance dose 4–8 mg/day

Maximum dose 20 mg/day (specialist only; ECG mandatory at doses above 10 mg/day)

Clinical Notes:

• Considered second-line due to significant QT prolongation risk

• Baseline and repeat ECG monitoring required at each dose escalation

• Consider only when other antipsychotics have failed and cardiac monitoring is feasible

Secondary Indications – Adults (Off-label)

Indication Dose Duration Notes

Delusional Disorder (OFF-LABEL) 2–8 mg/day Based on clinical response; often long-term Specialist only; supported by case series and Indian specialist practice

Monosymptomatic Hypochondriacal Psychosis (OFF-LABEL) 2–8 mg/day Long-term based on response Specialist only; limited evidence from case reports

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Tourette Syndrome (Age ≥12 years)

Parameter Recommendation

Starting dose 1 mg once daily

Titration Increase by 1 mg every 3–4 days based on response and tolerability

Usual maintenance dose 2–6 mg/day

Maximum dose 0.2 mg/kg/day OR 10 mg/day (whichever is lower)

Safety Monitoring:

• Baseline ECG mandatory before therapy initiation

• Repeat ECG after each dose escalation

• Monitor for extrapyramidal side effects, sedation, and weight changes

• Regular assessment of tic severity and functional impairment

Secondary Indications – Paediatric (Off-label)

Not applicable.

Age Restriction Statement: Not recommended in children <12 years except in rare circumstances under direct supervision of a paediatric neurologist or child psychiatrist with appropriate cardiac monitoring.

Mild–Moderate impairment No specific dose adjustment required

Severe impairment Use with caution; monitor closely for CNS side effects

Haemodialysis Limited data; use with caution under specialist supervision

• Known hypersensitivity to pimozide or any excipients

• Congenital long QT syndrome or known QT prolongation

• History of cardiac arrhythmias (especially ventricular) or recent myocardial infarction

• Concurrent use with potent CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir)

• Concurrent use with other QT-prolonging drugs (amiodarone, quinidine, sotalol, procainamide)

• Concurrent use with SSRIs (fluoxetine, sertraline, paroxetine)

• Severe CNS depression or comatose states

• Parkinson's disease

• Phaeochromocytoma

• History of cardiovascular disease

• Electrolyte disturbances (hypokalemia, hypomagnesemia) — correct before initiation

• History of seizure disorders

• Hepatic impairment (mild to moderate)

• Risk of extrapyramidal symptoms, especially in children and elderly

• Patients at risk for aspiration pneumonia

• Concurrent use with other CNS depressants

• Baseline and periodic ECG monitoring is mandatory

• Risk of tardive dyskinesia with prolonged use

Parameter Details

Risk category No formal India-specific category; limited human data; animal studies suggest risk

Overall safety Avoid unless no safer alternatives exist for severe Tourette syndrome or psychosis

Preferred alternatives Haloperidol or risperidone may be preferred with more established safety data

When may be used Only if potential benefit clearly justifies fetal risk; requires specialist psychiatric and obstetric input

Monitoring required Maternal ECG monitoring; fetal growth surveillance; neonatal observation for extrapyramidal symptoms and withdrawal signs

Parameter Details

Compatibility Not recommended; unknown infant risk

Drug levels in milk Likely present; human data limited

Preferred alternatives Haloperidol preferred if antipsychotic required during breastfeeding

Monitoring in infant Observe for sedation, poor feeding, irritability, developmental milestones

Parameter Recommendation

Starting dose 1 mg once daily

Titration Slow titration; increase by 1 mg every 5–7 days

Usual maintenance dose 2–4 mg/day (lower than adult doses)

Special considerations Higher risk of extrapyramidal symptoms, anticholinergic effects, orthostatic hypotension, falls

QT monitoring Especially critical; baseline and follow-up ECG mandatory

Avoid in Elderly with pre-existing arrhythmias, Parkinsonism, dementia-related psychosis (increased mortality risk)

Potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) Increased pimozide levels → QT prolongation, torsades de pointes ⛔ CONTRAINDICATED

SSRIs (fluoxetine, paroxetine, sertraline) CYP2D6 inhibition → increased pimozide levels → QT prolongation ⛔ CONTRAINDICATED

Fluvoxamine Strong CYP1A2 inhibition → increased pimozide exposure ⛔ CONTRAINDICATED

Macrolide antibiotics (erythromycin, azithromycin) Additive QT prolongation ⛔ Avoid concurrent use

Class IA/III antiarrhythmics (amiodarone, quinidine, sotalol, procainamide) Additive QT prolongation → torsades de pointes ⛔ CONTRAINDICATED

Fluoroquinolones (ciprofloxacin, levofloxacin) Additive QT prolongation ⛔ Avoid concurrent use

Tricyclic antidepressants Additive QT prolongation and anticholinergic effects ⛔ Avoid combination

Interacting Drug/Class Effect/Risk Recommendation

Carbamazepine CYP3A4 induction → reduced pimozide levels Monitor efficacy; may need dose adjustment

Phenytoin CYP3A4 induction → reduced pimozide levels Monitor efficacy

Rifampicin CYP3A4 induction → significantly reduced pimozide levels Monitor for loss of efficacy; may need dose increase

Valproate May increase sedation and EPS risk Monitor closely

Anticholinergic agents Additive anticholinergic effects (constipation, urinary retention, confusion) Use with caution

Alcohol and CNS depressants Additive sedation Advise avoidance; use caution

Grapefruit juice CYP3A4 inhibition → increased pimozide levels Advise avoidance

• Extrapyramidal symptoms (akathisia, dystonia, Parkinsonism)

• Sedation/somnolence

• Insomnia

• Dry mouth

• Constipation

• Blurred vision

• Dizziness

• Mild QT interval prolongation

• Restlessness

Adverse Effect Clinical Action

Torsades de pointes / Ventricular arrhythmias Dose-dependent; immediate discontinuation; cardiology referral; hospitalisation

Sudden cardiac death Rare but documented; emphasises need for ECG monitoring

Neuroleptic Malignant Syndrome Immediate discontinuation; supportive care; ICU admission

Severe extrapyramidal symptoms / Tardive dyskinesia Dose reduction or discontinuation; consider alternative agent

Hyperprolactinaemia May cause amenorrhoea, galactorrhoea, gynaecomastia; reassess need for therapy

Seizures Especially in predisposed patients; discontinue if new-onset seizures occur

Phase Parameters to Monitor

Baseline ECG (QTc interval); serum electrolytes (K⁺, Mg²⁺); hepatic and renal function; psychiatric evaluation; weight

After initiation/dose change Repeat ECG after each dose increase; monitor for EPS, sedation, and clinical response

Long-term ECG every 3–6 months if on chronic therapy; periodic monitoring of prolactin-related symptoms; weight; fasting glucose; lipid profile

QTc Thresholds:

• Avoid initiation if baseline QTc >450 ms (males) or >470 ms (females)

• Discontinue if QTc increases by >60 ms from baseline or exceeds 500 ms

Brand Name Manufacturer

Orap Janssen

Pimozide Intas

Note: Availability may be limited in some regions; generic versions available under the name "Pimozide" from various manufacturers.

• NLEM status: Not included in NLEM

• NPPA price control: Not under price control

• Government supply: Not routinely stocked in all government facilities; may require special procurement

1. ECG is non-negotiable: Always obtain baseline ECG and repeat after each dose escalation. QT prolongation risk is dose-dependent and potentially fatal.

1. Second-line for schizophrenia: Reserve for cases where other antipsychotics have failed and cardiac monitoring is feasible. First-generation alternatives (haloperidol) or second-generation antipsychotics are preferred first-line.

1. Tourette syndrome approach: Consider behavioural therapy (habit reversal training, CBIT) before pharmacotherapy. Use lowest effective dose for tic suppression.

1. Avoid polypharmacy with QT-prolonging agents: Common co-prescriptions (macrolides, fluoroquinolones, certain antidepressants) can cause dangerous drug interactions.

1. Elderly and paediatric populations: Use lower starting doses, slower titration, and vigilant monitoring for EPS and cardiac effects.

1. Correct electrolytes first: Ensure serum potassium and magnesium are within normal limits before initiating therapy to reduce arrhythmia risk.

pimozide; antipsychotic; first-generation; Tourette syndrome; tics; schizophrenia; QT prolongation; ECG monitoring; extrapyramidal symptoms; paediatric-specialist; Schedule H

RxIndia v1.0 — 17 May 2025

• CDSCO approved product information

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine

• AIIMS Adult and Paediatric Psychiatry Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• IAP Advisory on Tourette Syndrome (clinical practice reference)