Schedule H

Oral

• Tablets: 25 mg, 50 mg, 100 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Schizophrenia (Acute and Chronic)

Parameter Recommendation

Starting dose 25 mg once or twice daily, administered after food

Titration Increase by 25–50 mg increments every 3–4 days based on clinical response and tolerability

Usual maintenance dose 150–300 mg/day in 2–3 divided doses

Maximum dose 300 mg/day (up to 350 mg/day only in specialist-monitored inpatient settings)

Clinical Notes:

• Sedative and anticholinergic effects are prominent during early initiation — commence at lower dose in vulnerable patients

• Therapeutic response may take up to 2 weeks to become apparent

• Administer with food to improve tolerability

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

Indication Dose Duration Notes Evidence Basis

Bipolar disorder (acute mania) — OFF-LABEL 100–300 mg/day in divided doses Short-term as per symptomatic control Specialist only; usually second-line after standard mood stabilisers or other atypical antipsychotics Korean and Japanese studies; not standard in Indian psychiatric practice

PAEDIATRIC DOSING (Specialist Only)

Age Restriction: Not recommended below 18 years due to lack of safety and efficacy data.

Age Group Recommendation

Below 13 years Contraindicated — no data available

13–17 years May be considered only by specialist child psychiatrist under close monitoring; no established dosing — use lowest effective adult dose with extreme caution

Safety Monitoring (if used in adolescents 13–17 years):

• Baseline and periodic ECG monitoring

• Regular weight, metabolic parameters, and extrapyramidal symptom assessment

• Close supervision for behavioural changes

Secondary Indications — Paediatrics (Off-label, if any)

Not applicable — no established or recommended off-label paediatric indications.

Severe impairment (eGFR <30) Use with caution; limited data available — consider 25–50% dose reduction and slower titration

Haemodialysis No data available — avoid use or seek specialist nephrology/psychiatry input

Peritoneal dialysis No data available

• Known hypersensitivity to zotepine or any formulation component

• Acute angle-closure glaucoma

• History of bone marrow suppression or agranulocytosis

• Comatose states or significant CNS depression (alcohol, opioids, sedatives)

• Recent myocardial infarction (within 3 months)

• Severe cardiac arrhythmias or uncontrolled heart failure

• Concurrent use with drugs known to cause significant QT prolongation

• Seizure disorders or history of seizures — zotepine lowers seizure threshold (dose-related risk)

• Urinary retention or prostatic hypertrophy — anticholinergic effects may exacerbate symptoms

• Cardiovascular disease — risk of QT prolongation and arrhythmias

• Elderly patients — heightened risk of orthostatic hypotension, falls, and confusion

• Hepatic dysfunction — drug may accumulate; monitor LFTs

• Diabetes mellitus or metabolic risk factors — may alter glucose metabolism and lipid profile

• Parkinson's disease — may worsen motor symptoms

• History of ileus or severe constipation — anticholinergic effects may precipitate paralytic ileus

Parameter Details

Risk category No formal category in India; limited human data available

Safety concern Second/third trimester exposure associated with neonatal extrapyramidal symptoms, withdrawal syndrome, and respiratory difficulties

Preferred alternatives Olanzapine, haloperidol (if antipsychotic essential during pregnancy)

When to use Only when benefit clearly outweighs risk; requires specialist psychiatric supervision

Monitoring required Fetal growth surveillance, assessment of fetal tone and movements; postnatal monitoring for respiratory distress, feeding difficulties, abnormal muscle tone in neonate

Parameter Details

Compatibility Not recommended during breastfeeding

Drug levels in milk Excreted in breast milk (animal data); human data limited

Preferred alternatives Olanzapine or risperidone — use with infant monitoring

Infant monitoring Sedation, poor feeding, inadequate weight gain, irritability, extrapyramidal symptoms

Parameter Recommendation

Starting dose 12.5–25 mg once daily at night

Titration Slower titration — increase every 5–7 days based on tolerability

Extra risks Postural hypotension and falls; anticholinergic effects (confusion, urinary retention, constipation); extrapyramidal symptoms; cognitive impairment

Monitoring Orthostatic blood pressure at each visit; cognitive function assessment; regular review for falls risk

Interacting Drug/Class Mechanism/Effect Management

CNS depressants (alcohol, opioids, benzodiazepines) Additive sedation and respiratory depression Avoid combination; if essential, use lowest doses with monitoring

Carbamazepine CYP enzyme induction — reduces zotepine plasma levels Avoid combination or increase zotepine dose with therapeutic monitoring

QT-prolonging drugs (amiodarone, sotalol, fluoroquinolones, ondansetron, haloperidol) Additive QT prolongation — risk of torsades de pointes Contraindicated — do not co-prescribe

Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion) Inhibits zotepine metabolism — increased plasma levels Reduce zotepine dose; monitor for adverse effects

Interacting Drug/Class Effect Management

Antihypertensives (ACE inhibitors, beta-blockers, calcium channel blockers) Additive hypotensive effect Monitor blood pressure during titration; adjust antihypertensive dose if required

Anticholinergic agents (trihexyphenidyl, oxybutynin, antihistamines) Additive anticholinergic burden — constipation, urinary retention, cognitive impairment Use with caution; monitor bowel and bladder function

Valproate Additive CNS depression; potential pharmacokinetic interaction Monitor for excessive sedation; adjust doses as needed

Oral antidiabetic agents and insulin Zotepine may impair glycaemic control Monitor blood glucose more frequently; adjust diabetes therapy if needed

Levodopa and dopamine agonists Pharmacological antagonism Avoid in Parkinson's disease; may reduce efficacy of antiparkinsonian therapy

• Sedation and drowsiness

• Dizziness

• Dry mouth

• Constipation

• Weight gain

• Postural hypotension

• Tachycardia

• Mild extrapyramidal symptoms (less frequent than typical antipsychotics)

• Hyperprolactinaemia (less common than risperidone)

Adverse Effect Clinical Notes

Neuroleptic Malignant Syndrome (NMS) Fever, rigidity, altered consciousness, autonomic instability — requires immediate discontinuation and hospitalisation

Agranulocytosis Rare but serious; monitor CBC if unexplained fever, sore throat, or infection

Torsades de Pointes Risk increased with QT-prolonging co-medications or electrolyte imbalance

Seizures Dose-related risk; more likely at doses >300 mg/day

Hepatotoxicity Rare; monitor LFTs if unexplained nausea, jaundice, or abdominal pain

Venous thromboembolism Rare; be vigilant for DVT/PE symptoms

Phase Parameters to Monitor

Baseline CBC, LFTs, renal function, fasting glucose, lipid profile, weight/BMI, blood pressure (including orthostatic), ECG (especially if cardiac history or risk factors)

After initiation/dose change Sedation, extrapyramidal symptoms, orthostatic blood pressure, heart rate; repeat ECG if dose exceeds 200 mg/day or if cardiac symptoms emerge

Long-term (every 3–6 months) Weight, BMI, fasting glucose, lipid profile, LFTs; CBC if clinical concern; monitor for tardive dyskinesia; assess treatment adherence and therapeutic response

• Zotis® (Micro Labs)

• Zotran® (Intas Pharmaceuticals)

• Zoticare® (Unicure Remedies)

• Other generic formulations available

Strength Approximate Price per Tablet

Note: Not included in NLEM; not under NPPA price control. Prices may vary by brand and region.

• More sedating than most other atypical antipsychotics — can be advantageous in highly agitated or sleep-disturbed psychotic patients, but start with low doses

• Anticholinergic burden is significant — avoid or use extreme caution in elderly patients with dementia, urinary retention, or constipation

• Not a first-line agent in India — typically reserved for patients intolerant to risperidone, olanzapine, or aripiprazole

• Obtain baseline ECG in patients with cardiac history, electrolyte abnormalities, or on concomitant QT-prolonging medications before initiation

• Gradual dose tapering is recommended when discontinuing to prevent rebound psychotic symptoms or cholinergic rebound

• Less metabolic adverse effect profile compared to clozapine and olanzapine, but still requires metabolic monitoring

zotepine; schizophrenia; atypical antipsychotic; dibenzothiazepine; anticholinergic; sedation; dopamine-serotonin antagonist; weight gain; QT prolongation risk; psychiatry

RxIndia v1.1 — 10 Jan 2025

• CDSCO Product Database

• Indian Drug Review

• AIIMS Psychopharmacology Consensus Guidelines

• API Textbook of Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Postgraduate Psychiatry Modules (NIMHANS)

• Select international monographs for off-label data (Korea, Japan) — used only for off-label indication