Schedule H

Oral

Formulation Strengths Available

Tablets 4 mg, 12 mg, 16 mg

Note: Availability is limited to select psychiatric practice settings due to cardiac safety concerns and regulatory restrictions.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Schizophrenia (Adult patients only — reserve use due to QT prolongation risk)

Parameter Recommendation

Starting dose 4 mg once daily for 4–5 days

Titration Increase to 8 mg once daily for 4–5 days, then to 12 mg once daily for 4–5 days; further adjustments based on response and ECG

Usual maintenance dose 12–20 mg once daily

Maximum dose 24 mg/day

Clinical Notes:

• Slow mandatory titration required to minimise orthostatic hypotension risk

• Baseline and follow-up ECGs essential due to dose-dependent QTc prolongation

• Reserve for patients who have not responded to or cannot tolerate other antipsychotics

• Not suitable for acute psychosis management due to delayed titration schedule

• Cardiac safety profile significantly limits its use as first-line agent

Secondary Indications – Adults (Off-label)

Not applicable.

Off-label use in bipolar disorder, behavioural disturbances, or other psychiatric conditions is not recommended due to significant cardiotoxicity concerns and limited safety data.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable.

NOT RECOMMENDED in children or adolescents under 18 years. Safety and efficacy have not been established in paediatric populations.

Secondary Indications – Paediatric (Off-label)

Not applicable.

Use in patients <18 years is not supported by Indian or international data and is not advised under any circumstances.

Mild–Moderate impairment No dosage adjustment required

Severe impairment Use with caution; limited pharmacokinetic data available

Haemodialysis Not well studied; use with caution under specialist supervision

• Known hypersensitivity to sertindole or any excipients

• Congenital long QT syndrome or family history of long QT syndrome

• Baseline QTc interval >450 ms (males) or >470 ms (females)

• Concurrent use of QT-prolonging drugs (Class IA and III antiarrhythmics, certain antipsychotics, macrolides, fluoroquinolones)

• Uncorrected hypokalaemia or hypomagnesaemia

• Clinically significant bradycardia (<50 bpm)

• Recent myocardial infarction or uncompensated heart failure

• Severe hepatic impairment

• Cardiovascular disease (arrhythmias, heart failure, structural heart disease)

• History of syncope or unexplained palpitations

• Hepatic impairment (mild to moderate)

• Concurrent CYP2D6 or CYP3A4 inhibitors (may increase sertindole levels)

• Prostatic hypertrophy or risk of urinary retention

• History of paralytic ileus

• Seizure disorders or history of seizures

• Elderly patients (increased sensitivity to adverse effects)

• Risk of dose-dependent orthostatic hypotension, especially during initiation

• Avoid abrupt withdrawal to prevent rebound psychosis

• Diabetes mellitus or metabolic syndrome (monitor glucose and lipids)

Parameter Details

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

Overall safety Avoid use unless potential benefit clearly justifies fetal risk

Preferred alternatives Risperidone or olanzapine (more established safety data in pregnancy)

When may be used Only under specialist psychiatric and obstetric supervision when other options have failed

Monitoring required Fetal growth surveillance; maternal ECG monitoring; neonatal observation for extrapyramidal symptoms and poor adaptation syndrome

Parameter Details

Compatibility Not recommended; likely excreted in breast milk (levels unknown)

Preferred alternatives Olanzapine or quetiapine (lower risk in lactation)

Expected drug levels in milk Unknown; likely present

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

Recommendation Avoid breastfeeding while on sertindole if possible

Parameter Recommendation

Starting dose 4 mg once daily

Titration Very slow titration; longer intervals between dose increases (7–10 days recommended)

Usual maintenance dose Lower end of range (12 mg/day or less)

Special considerations Higher risk of QT prolongation, orthostatic hypotension, falls, and sedation

ECG monitoring Essential at baseline and with each dose change

Avoid in Patients with dementia-related psychosis (increased mortality risk with antipsychotics)

Interacting Drug/Class Effect/Risk Recommendation

Potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) Significantly increased sertindole levels → QT prolongation ⛔ Avoid combination

Potent CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) Increased sertindole levels → QT prolongation ⛔ Avoid combination or use with extreme caution; consider alternative antipsychotic

Class IA antiarrhythmics (quinidine, procainamide, disopyramide) Additive QT prolongation → torsades de pointes ⛔ CONTRAINDICATED

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

Macrolide antibiotics (erythromycin, clarithromycin) QT prolongation risk ⛔ Avoid combination

Fluoroquinolones (moxifloxacin, levofloxacin) QT prolongation risk ⛔ Avoid combination

Diuretics causing hypokalaemia (furosemide, thiazides) Increased QT prolongation risk via electrolyte disturbance Correct electrolytes before initiating; monitor K⁺ and Mg²⁺ closely

Other antipsychotics with QT effects (haloperidol, ziprasidone) Additive QT prolongation ⛔ Avoid combination

Interacting Drug/Class Effect/Risk Recommendation

Carbamazepine CYP3A4 induction → reduced sertindole levels Avoid if possible; monitor efficacy if used

Phenytoin CYP induction → reduced sertindole levels Avoid if possible; monitor efficacy

Rifampicin Strong CYP3A4 induction → significantly reduced sertindole levels Avoid combination

Alcohol Additive CNS depression Counsel patient; avoid concurrent use

Benzodiazepines and other sedatives Additive CNS depression Use with caution; monitor sedation

Antihypertensives Additive hypotension (especially during initiation) Monitor blood pressure; start sertindole cautiously

Metformin No direct interaction but metabolic monitoring advised Monitor glucose levels periodically

• QTc prolongation (dose-dependent)

• Orthostatic hypotension (especially during titration)

• Dizziness

• Weight gain

• Dry mouth

• Nasal congestion

• Ejaculatory dysfunction / decreased libido

• Peripheral oedema

• Sedation

• Constipation

Adverse Effect Clinical Action

Torsades de pointes / Ventricular arrhythmias Immediately discontinue; cardiology referral; hospitalisation

Sudden cardiac death Rare but documented in post-marketing surveillance

Neuroleptic Malignant Syndrome Immediate discontinuation; supportive care; ICU admission if severe

Seizures Discontinue if new-onset; evaluate underlying cause

Agranulocytosis (rare) Monitor for infection signs; check CBC; discontinue if confirmed

Severe orthostatic hypotension with syncope Reduce dose or discontinue; evaluate for contributing factors

Phase Parameters to Monitor

Baseline ECG (QTc interval); serum electrolytes (K⁺, Mg²⁺); liver function tests; fasting glucose and lipid profile; blood pressure; weight

During titration ECG after each dose increase; blood pressure (orthostatic); clinical response and tolerability

After reaching maintenance ECG within 1–2 weeks of final dose stabilisation

Long-term ECG every 3 months; weight and metabolic parameters (glucose, lipids) every 6 months; periodic assessment of mental status and treatment necessity

QTc Thresholds:

• Do not initiate if baseline QTc >450 ms (males) or >470 ms (females)

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

Brand Name Manufacturer Notes

Sertima Intas Pharmaceuticals Limited availability

Note: Limited commercial availability in India due to regulatory restrictions and cardiac safety concerns. Usually procured via specialised psychiatric hospital settings. Import-based options may be available in select centres.

• NLEM status: Not included in NLEM

• NPPA price control: Not under price control

• Government supply: Not routinely available in government facilities

1. Mandatory ECG monitoring: Always obtain baseline ECG and serum electrolytes before initiating sertindole. Repeat ECG after each dose increase and periodically during maintenance.

1. Last-resort antipsychotic: Reserve sertindole for patients who have failed or are intolerant to other antipsychotics. Not suitable as first-line agent due to cardiac risk profile.

1. Slow titration is non-negotiable: The 4-5 day interval between dose increases cannot be shortened. Rushing titration significantly increases orthostatic hypotension and cardiac risks.

1. QTc threshold for discontinuation: If QTc exceeds 500 ms at any point, immediately discontinue sertindole and do not rechallenge.

1. Not for acute settings: Due to mandatory slow titration, sertindole is unsuitable for management of acute psychosis or agitation. Use other antipsychotics for rapid stabilisation.

1. Avoid in elderly with dementia: Increased mortality risk with antipsychotics in dementia-related psychosis — avoid sertindole in this population.

sertindole; atypical antipsychotic; schizophrenia; QT prolongation; ECG monitoring; cardiac risk; specialist-only; CYP2D6; CYP3A4; Schedule H

RxIndia v1.0 — 04 May 2025

• CDSCO approved product information

• Indian Pharmacopoeia / National Formulary of India

• Indian Psychiatric Society Clinical Practice Guidelines

• AIIMS Psychiatry Protocols

• API Textbook of Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• ICMR Guidelines (antipsychotic safety recommendations)