Schedule H

Oral, Intramuscular (short-acting acetate and long-acting depot decanoate)

Formulation Strength

Tablets (Dihydrochloride) 10 mg, 25 mg

IM Injection — Acetate (short-acting) 50 mg/mL

IM Depot Injection — Decanoate (long-acting) 200 mg/mL (in oil base)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Schizophrenia and Other Psychotic Disorders — Oral Therapy

(Zuclopenthixol dihydrochloride tablets)

Parameter Recommendation

Starting dose 10–20 mg/day in 2–3 divided doses

Titration Increase gradually over several days based on clinical response and tolerability

Usual maintenance dose 20–50 mg/day in divided doses

Maximum dose 75 mg/day (specialist supervision required)

Clinical Notes:

• Often reserved for patients intolerant or inadequately responsive to other typical antipsychotics

• Once stabilised, may consider conversion to depot formulation for maintenance

1. Acute Psychotic Agitation — IM Acetate (Short-acting)

(For rapid tranquillisation in acutely disturbed psychotic patients)

Parameter Recommendation

Starting dose 50–150 mg deep IM as single injection

Titration May repeat after 2–3 days if clinically required

Usual maintenance dose Not applicable (acute use only)

Maximum dose 400 mg total over course of treatment (typically 1–3 injections over 1 week)

Clinical Notes:

• Onset of action: 2–4 hours; duration of effect: 2–3 days

• Not for maintenance therapy — transition to oral or depot formulation once acute episode controlled

• Administer deep IM in gluteal muscle only

• Monitor vital signs post-injection

1. Schizophrenia — Maintenance Therapy with IM Depot (Decanoate)

(Long-acting formulation for chronic schizophrenia)

Parameter Recommendation

Starting dose 200 mg IM; may increase to 200–400 mg for first injection based on prior oral tolerability

Titration Adjust dose and interval based on clinical response over subsequent injections

Usual maintenance dose 200–400 mg IM every 2–4 weeks

Maximum dose 600 mg per single injection; average weekly dose should not exceed 200 mg

Clinical Notes:

• Initiate depot only after establishing tolerability with oral zuclopenthixol

• Administer deep IM into gluteal muscle; rotate injection sites

• Test dose with oral formulation recommended before first depot injection

• Steady-state achieved after approximately 3 months of regular injections

Secondary Indications — Adults Only (Off-label, if any)

Indication Dose Duration Notes Evidence

Acute mania in bipolar disorder IM acetate 50–100 mg once OR short oral course (20–40 mg/day) Short-term only (days to 1–2 weeks) OFF-LABEL; Specialist only Limited RCT evidence; used in Indian tertiary psychiatry practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable.

Zuclopenthixol is NOT routinely recommended in children and adolescents.

• Safety and efficacy data limited in patients <18 years

• Use only under paediatric psychiatrist supervision in exceptional circumstances

• Minimum age generally considered: ≥15 years in severe, treatment-refractory cases

Secondary Indications — Paediatric Doses (Off-label, if any)

Indication Dose Duration Notes Evidence

Severe conduct disorder with aggression (≥15 years) Starting: 2–5 mg/day orally; Titration: Gradual; Maximum: 0.5 mg/kg/day Short-term; reassess frequently OFF-LABEL; Specialist only (paediatric psychiatrist) Limited case series; off-label use in tertiary centres only

Safety Statement:

• Not recommended below 15 years except under specialist supervision in exceptional circumstances

• Monitor closely for extrapyramidal symptoms, sedation, metabolic effects

• Depot formulations not recommended in paediatric population

Mild to moderate impairment No specific dose adjustment required

Severe impairment (eGFR <30) Use with caution; start at lower end of dose range; monitor for excessive sedation and EPS

Haemodialysis Limited data; not significantly dialyzed; use with caution

• Known hypersensitivity to zuclopenthixol or other thioxanthene derivatives

• CNS depression or comatose states

• Parkinson's disease or other extrapyramidal disorders

• Phaeochromocytoma

• Severe cardiovascular disease (recent myocardial infarction, decompensated heart failure, significant conduction abnormalities)

• Congenital or acquired QT prolongation syndromes

• Concurrent use with drugs known to cause significant QT prolongation

• Blood dyscrasias

• History of seizures or epilepsy — lowers seizure threshold

• Elderly patients — increased susceptibility to adverse effects

• Hepatic impairment

• Cardiovascular disease (stable)

• Hyperprolactinaemia or prolactin-dependent tumours

• History of breast carcinoma

• Narrow-angle glaucoma

• Prostatic hypertrophy or urinary retention

• Diabetes mellitus — may worsen glycaemic control

• Hypokalaemia or hypomagnesaemia — increased risk of arrhythmias

• Risk of venous thromboembolism

• Hot weather or conditions predisposing to hyperthermia

• Dose conversion required when switching between oral and depot formulations

Parameter Recommendation

Risk category Generally avoid unless clearly indicated; limited human data

Preferred alternatives Haloperidol (short-term, more safety data); risperidone (with experience)

When to use Only if potential benefit clearly justifies risk; use lowest effective dose; avoid in first trimester if possible

Monitoring Fetal growth (serial ultrasound); observe neonate for extrapyramidal symptoms, sedation, and withdrawal symptoms if exposed in third trimester

Parameter Recommendation

Compatibility Not recommended during breastfeeding

Preferred alternatives Risperidone or haloperidol (better studied; lower milk excretion)

Drug levels in milk Not well characterised; likely moderate

Infant monitoring Sedation, poor feeding, abnormal movements, irritability

Parameter Recommendation

Starting dose (oral) 2–5 mg/day; increase very gradually

Starting dose (depot) 100–200 mg IM every 3–4 weeks

Titration Very slow; monitor response over weeks before dose adjustment

Special risks Orthostatic hypotension (falls risk), excessive sedation, bradycardia, confusion, cognitive impairment, increased susceptibility to EPS and tardive dyskinesia

Precautions Avoid in dementia-associated psychosis — increased risk of stroke and mortality; ensure adequate hydration

Interacting Drug/Class Effect Mechanism Management

QT-prolonging drugs (quinolones, macrolides, amiodarone, haloperidol, ondansetron) Additive QT prolongation; risk of torsades de pointes Pharmacodynamic interaction Avoid combination; if essential, monitor ECG

CNS depressants (opioids, benzodiazepines, alcohol) Profound sedation; respiratory depression Additive CNS depression Avoid or use with extreme caution; reduce doses

Levodopa and dopamine agonists Antagonism of antiparkinsonian effect Dopamine receptor blockade Avoid combination — worsening of Parkinson's symptoms

CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion) Increased zuclopenthixol levels; toxicity risk Inhibition of metabolism Monitor closely; consider dose reduction

Antihypertensives Enhanced hypotensive effect Additive pharmacodynamic effect Monitor blood pressure; adjust antihypertensive dose if needed

Metoclopramide, prochlorperazine Increased risk of extrapyramidal symptoms Additive dopamine blockade Avoid combination

Interacting Drug/Class Effect Management

Carbamazepine Reduced zuclopenthixol levels CYP enzyme induction — may need to increase antipsychotic dose; monitor efficacy

Rifampicin Reduced zuclopenthixol efficacy CYP induction — consider alternative antipsychotic

Valproate Additive CNS depression; possible increased levels Monitor for sedation

Lithium Increased risk of neurotoxicity (confusion, tremor, EPS) Use with caution; monitor for neurotoxic symptoms

Anticholinergic drugs (trihexyphenidyl, antihistamines) Additive anticholinergic effects Monitor for constipation, urinary retention, confusion, dry mouth

Antidiabetic agents (metformin, sulfonylureas, insulin) Worsening glycaemic control Monitor blood glucose; adjust antidiabetic therapy as needed

Phenytoin, phenobarbital Reduced zuclopenthixol levels CYP induction — monitor clinical response

• Extrapyramidal symptoms (tremor, rigidity, bradykinesia, akathisia)

• Drowsiness/sedation

• Fatigue

• Dry mouth

• Blurred vision

• Weight gain

• Orthostatic hypotension

• Tachycardia

• Hypersalivation

• Constipation

• Dizziness

• Hyperprolactinaemia (galactorrhoea, amenorrhoea, sexual dysfunction)

Adverse Effect Action Required

Neuroleptic Malignant Syndrome (hyperthermia, rigidity, autonomic instability, altered consciousness) Discontinue immediately; emergency hospitalisation; supportive care

Tardive dyskinesia May be irreversible; discontinue if clinically feasible; switch to atypical antipsychotic

Severe acute dystonia Administer anticholinergic (procyclidine/promethazine IM); reduce dose

QT prolongation / Torsades de pointes Discontinue; ECG monitoring; correct electrolytes

Seizures Dose-dependent risk; discontinue or reduce dose; neurological evaluation

Hepatotoxicity Discontinue; monitor LFTs; specialist evaluation

Agranulocytosis (rare) Discontinue; urgent haematological evaluation

Venous thromboembolism (DVT/PE) Clinical assessment; appropriate treatment

Phase Parameters

Baseline ECG (QTc interval); LFTs; renal function; CBC; fasting glucose; fasting lipid profile; weight; BMI; blood pressure; prolactin (if symptoms); pregnancy test in women of childbearing age

After initiation / dose change Vital signs and sedation level (first few days, especially with IM acetate); EPS assessment within 1–2 weeks; blood pressure monitoring for orthostatic hypotension

Long-term Weight and BMI every 3 months; fasting glucose and lipids every 6 months; ECG annually (or more frequently if risk factors); LFTs annually; monitor for tardive dyskinesia (AIMS scale) every 6 months; prolactin if symptoms emerge

Brand Name Manufacturer Formulations

Clopixol Lundbeck Tablets 10 mg, 25 mg; Injection (Acetate) 50 mg/mL; Depot (Decanoate) 200 mg/mL

Cloxipol Sun Pharma Tablets 10 mg, 25 mg

Zuclop Intas Tablets 10 mg, 25 mg

Note: Depot and acetate injections may have limited availability; confirm with local suppliers

Notes:

• Not included in NLEM 2022

• Not under NPPA price control

• Available in both public (tertiary psychiatric centres) and private sectors

1. IM Acetate for acute control only: Use zuclopenthixol acetate for rapid tranquillisation (onset 2–4 hours, duration 2–3 days); never use for maintenance therapy — always transition to oral or depot

1. Establish oral tolerability before depot: Always confirm patient tolerates oral zuclopenthixol before initiating depot injections to avoid prolonged adverse effects from a long-acting formulation

1. EPS is dose-dependent: Extrapyramidal symptoms are common — start at lower doses and titrate slowly; consider prophylactic anticholinergic (trihexyphenidyl) in patients at high risk

1. Depot injection technique: Must be administered deep IM into gluteal muscle only — not deltoid; rotate injection sites; aspirate before injection to avoid intravascular administration

1. Tardive dyskinesia surveillance: Risk increases with cumulative dose and duration — use lowest effective dose; conduct AIMS assessment every 6 months; risk highest in elderly

1. Smoking affects metabolism minimally: Unlike some antipsychotics, zuclopenthixol levels are not significantly affected by smoking status

zuclopenthixol; antipsychotic; typical antipsychotic; thioxanthene; schizophrenia; depot injection; acute agitation; rapid tranquillisation; extrapyramidal symptoms; tardive dyskinesia; QT prolongation; elderly caution; Schedule H; psychiatry

RxIndia v1.0 — 10 Jun 2025

• CDSCO (Central Drugs Standard Control Organisation)

• Indian Pharmacopoeia / National Formulary of India (IP/NFI)

• NLEM 2022 (for exclusion note)

• API Textbook of Medicine

• AIIMS Psychiatry Formulary and Prescribing Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian Psychiatric Society Treatment Guidelines

• Product Inserts: Clopixol (Lundbeck)

• RCT/Meta-analysis (for bipolar mania — off-label use)