Schedule H

Oral

• Tablets: 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg (film-coated)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Schizophrenia — Adults

Parameter Details

Starting dose 1 mg twice daily

Titration Mandatory gradual escalation over minimum 4 days (see protocol below)

Usual maintenance dose 12–24 mg/day in two divided doses

Maximum dose 24 mg/day

Titration Protocol (to minimise orthostatic hypotension):

Day Morning Dose Evening Dose Total Daily Dose

1 1 mg 1 mg 2 mg

2 2 mg 2 mg 4 mg

3 4 mg 4 mg 8 mg

4 6 mg 6 mg 12 mg

5+ Adjust to maintenance — 12–24 mg

Key Clinical Notes:

• Slow titration is essential due to potent alpha-1 adrenergic blockade

• If therapy is interrupted for >3 days, re-titration from 1 mg BD is required

• ECG monitoring recommended in patients with cardiovascular risk factors

• Full therapeutic effect may take 1–2 weeks to manifest

Secondary Indications — Adults (Off-label)

Indication Dose Duration Supervision Evidence Basis

Bipolar I Disorder (Acute Mania) — OFF-LABEL Starting: 1 mg BD; Titrate to 12–24 mg/day over 4–7 days Short-term (3–4 weeks) Specialist only Limited international RCT data; not part of routine Indian psychiatry protocols

Psychosis in Parkinson's Disease NOT RECOMMENDED — — Dopamine antagonism worsens motor symptoms; quetiapine or clozapine preferred in Indian practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT RECOMMENDED below 18 years of age

• Safety and efficacy data not established in paediatric population

• No CDSCO-approved indication exists for individuals under 18 years

Secondary Indications — Paediatric Doses (Off-label)

Not applicable.

Statement: Use in children and adolescents below 18 years is not recommended. No off-label paediatric use is supported by Indian guidelines or specialist consensus.

Mild impairment (CrCl 60–89 mL/min) No dose adjustment required

Moderate impairment (CrCl 30–59 mL/min) No dose adjustment required

Severe impairment (CrCl <30 mL/min) Use with caution; limited pharmacokinetic data available

Haemodialysis Data not available; use with extreme caution

• Known hypersensitivity to iloperidone or any formulation excipient

• Congenital long QT syndrome or documented QT prolongation

• Recent acute myocardial infarction

• Uncompensated heart failure

• Concurrent use with Class IA or Class III antiarrhythmics

• Concurrent use with other drugs known to prolong QT interval significantly

• Elderly patients with dementia-related psychosis (increased mortality risk — regulatory warning)

• Patients at risk for orthostatic hypotension (dehydration, hypovolaemia, concurrent antihypertensives)

• History of cardiac arrhythmias or structural heart disease

• Pre-existing electrolyte disturbances (hypokalaemia, hypomagnesaemia)

• History of seizures or conditions lowering seizure threshold

• Patients prone to hyperprolactinaemia (monitor for galactorrhoea, amenorrhoea)

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

• Risk of aspiration pneumonia in patients with dysphagia

Parameter Details

Safety status Limited human data; animal studies suggest potential risk

Recommendation Avoid unless benefit clearly outweighs risk; use only under specialist supervision

Preferred alternatives Olanzapine, risperidone (more data in Indian obstetric psychiatry practice)

Third trimester concerns Risk of neonatal extrapyramidal symptoms and withdrawal syndrome

Monitoring Foetal growth surveillance; neonatal observation for EPS/withdrawal after delivery

Parameter Details

Compatibility Not recommended; insufficient safety data

Excretion in milk Expected to be excreted (based on pharmacology); quantitative data lacking

Preferred alternatives Risperidone (low milk transfer), olanzapine (more experience)

Infant monitoring Sedation, feeding difficulties, irritability, weight gain

Parameter Recommendation

Starting dose 1 mg twice daily

Titration Slower than standard protocol; consider extending titration to 7+ days

Special risks Higher susceptibility to orthostatic hypotension, falls, over-sedation

Dementia-related psychosis Avoid use — associated with increased mortality (regulatory warning)

Cardiac considerations Baseline ECG recommended; repeat after titration if cardiac risk factors present

Strong CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) ↑ Iloperidone plasma levels Reduce iloperidone dose by 50%

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) ↑ Iloperidone plasma levels Reduce iloperidone dose by 50%; avoid if possible

Class IA antiarrhythmics (quinidine, procainamide) Additive QT prolongation Contraindicated

Class III antiarrhythmics (amiodarone, sotalol) Additive QT prolongation Contraindicated

Other QT-prolonging drugs (haloperidol, chloroquine, ondansetron, moxifloxacin) Additive QT prolongation Avoid combination; if essential, frequent ECG monitoring

Interacting Drug/Class Mechanism Clinical Action

Carbamazepine (CYP3A4 inducer) ↓ Iloperidone levels May require dose increase; monitor efficacy

Phenytoin (CYP3A4 inducer) ↓ Iloperidone levels Monitor for reduced antipsychotic effect

Valproate Additive CNS depression Monitor for excessive sedation

SSRIs (sertraline, escitalopram) Mild CYP2D6 inhibition; additive CNS effects Monitor for EPS, sedation

Antihypertensives Additive hypotensive effect Monitor blood pressure; adjust doses accordingly

Diuretics (thiazides, furosemide) ↑ Orthostatic hypotension risk via volume depletion Ensure adequate hydration; monitor electrolytes

Benzodiazepines Additive sedation Use lowest effective doses of both

• Dizziness

• Orthostatic hypotension

• Somnolence/sedation

• Dry mouth

• Weight gain

• Nasal congestion

• Tachycardia

• Fatigue

Adverse Effect Action Required

QT prolongation / Torsades de pointes Discontinue immediately if QTc >500 ms or increase >60 ms from baseline

Neuroleptic Malignant Syndrome (NMS) Medical emergency — immediate discontinuation and supportive care

Tardive dyskinesia May be irreversible; consider dose reduction or discontinuation

Seizures Caution in predisposed patients; discontinue if new-onset seizures

Priapism Medical emergency — immediate urological intervention required

Severe orthostatic hypotension May cause syncope, falls; re-titrate if therapy resumed after interruption

Metabolic syndrome Long-term monitoring for diabetes, dyslipidaemia

Timepoint Parameters

Baseline ECG (QTc interval), serum electrolytes (K⁺, Mg²⁺), fasting glucose, lipid profile, weight, BMI, blood pressure, CBC, LFTs

During titration Blood pressure (sitting and standing), heart rate, symptoms of orthostatic hypotension

After titration complete ECG (especially if cardiac risk factors or on other QT-prolonging drugs)

Every 3 months (first year) Weight, blood pressure, fasting glucose

Every 6 months (ongoing) Fasting glucose, lipid profile, weight, blood pressure

As clinically indicated Prolactin levels (if symptoms of hyperprolactinaemia), ECG (long-term or high-risk patients), movement disorder assessment (tardive dyskinesia screening)

• Fanapt® (Vanda/imported)

• Ilopex® (Abbott)

• Ilozap®

• Ilopra®

• Ilorid®

• Various other generic manufacturers

Note: Brand availability may vary by region and procurement channel.

Strength Approximate Price per Tablet

2 mg ₹6–10

4 mg ₹8–12

6 mg ₹10–15

10 mg ₹12–18

12 mg ₹15–20

• Not included in NLEM; not under NPPA price control

• Government supply availability limited

1. Mandatory slow titration: Always initiate with 1 mg BD and titrate over minimum 4 days to prevent severe orthostatic hypotension — do not skip titration steps.

1. Re-titration rule: If therapy is interrupted for more than 3 days, restart from 1 mg BD and re-titrate upward.

1. Lower EPS profile: Iloperidone has lower extrapyramidal side effect risk compared to risperidone; consider for patients with prior EPS sensitivity.

1. Not for acute agitation: Lacks rapid onset; not suitable for management of acute psychotic agitation requiring immediate control.

1. QT vigilance: Always screen for QT-prolonging co-medications and electrolyte abnormalities before initiation; ECG monitoring is essential in at-risk patients.

1. CYP2D6 poor metabolisers: Patients who are known CYP2D6 poor metabolisers may have elevated drug levels — consider dose reduction.

iloperidone; schizophrenia; atypical antipsychotic; second-generation antipsychotic; QT-prolongation; EPS-low; renal-safe; pregnancy-caution; psychiatry; Schedule H

RxIndia v1.1 — 22 Jan 2025

• CDSCO approved product information

• Indian Psychiatric Society expert consensus

• AIIMS Psychiatry treatment protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• NLEM 2022 (confirmed iloperidone not listed)

• Selected international product monographs (off-label indications marked accordingly)