Schedule H

Oral, Intramuscular (Long-Acting Injectable)

• Paliperidone extended-release tablets: 3 mg, 6 mg, 9 mg

• Paliperidone palmitate long-acting injection (LAI): 75 mg/0.75 mL, 100 mg/1 mL, 150 mg/1.5 mL prefilled syringes

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Schizophrenia — Adults

a) Oral Extended-Release Tablets:

Parameter Recommendation

Starting dose 6 mg once daily in the morning

Titration Increase by 3 mg/day at intervals of ≥5 days based on response and tolerability

Usual maintenance dose 3–12 mg once daily

Maximum dose 12 mg/day

Key Clinical Notes:

• Administer consistently with or without food

• Swallow whole; do not crush, chew, or divide tablets

• Primarily renally excreted; adjust dose if renal impairment present

b) Long-Acting Injectable (Paliperidone Palmitate — 1-Month Formulation):

Initiation Protocol:

text

Day 1 → 150 mg IM into deltoid muscle

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Day 8 (± 4 days) → 100 mg IM into deltoid muscle

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Monthly thereafter → 75–150 mg IM into deltoid or gluteal muscle

Parameter Recommendation

Starting dose 150 mg IM deltoid on Day 1

Loading dose 100 mg IM deltoid on Day 8

Usual maintenance dose 75–150 mg IM monthly

Maximum dose 150 mg/month

Key Clinical Notes:

• Deltoid injection mandatory for initiation doses to achieve therapeutic levels rapidly

• Maintenance doses may be administered in deltoid or gluteal muscle

• When switching from oral paliperidone, initiate LAI at next scheduled oral dose; overlap generally not required

1. Schizoaffective Disorder — Adults (Oral ER Tablets Only)

Parameter Recommendation

Starting dose 6 mg once daily in the morning

Titration Adjust by 3 mg/day at intervals of ≥4–7 days

Usual maintenance dose 3–12 mg once daily

Maximum dose 12 mg/day

Key Clinical Notes:

• May be used as monotherapy or as adjunct to mood stabilisers/antidepressants

• Efficacy demonstrated for both depressive and manic symptoms of schizoaffective disorder

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes Evidence Basis

Bipolar I Disorder — Maintenance (OFF-LABEL) 3–9 mg/day oral Long-term for relapse prevention Specialist only Limited RCT data; used in Indian private psychiatric practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Schizophrenia in Adolescents Aged 12–17 Years (Oral ER Tablets Only)

Body Weight Starting Dose Titration Maximum Dose

<51 kg 3 mg once daily Increase by 3 mg/day at intervals of ≥5 days 6 mg/day

≥51 kg 3 mg once daily Increase by 3 mg/day at intervals of ≥5 days 12 mg/day

Safety Monitoring Requirements:

• Weight and BMI at baseline, monthly for 3 months, then quarterly

• Fasting glucose and lipid profile at baseline, at 3 months, then annually

• Prolactin levels if symptomatic (galactorrhoea, menstrual irregularities, gynaecomastia)

• ECG for QTc if cardiac risk factors present

• Assessment for extrapyramidal symptoms at each visit

Key Clinical Notes:

• Long-acting injectable is NOT recommended for patients <18 years in India

• NOT RECOMMENDED below 12 years of age except under specialist supervision in tertiary care settings

Secondary Indications — Paediatrics (Off-label)

Not applicable. No established off-label paediatric indications documented in Indian practice.

Key Clinical Note: Paliperidone undergoes minimal hepatic metabolism; primarily excreted unchanged via kidneys.

• Known hypersensitivity to paliperidone, risperidone, or any excipient

• History of neuroleptic malignant syndrome with any antipsychotic

• Severe renal impairment (eGFR <10 mL/min) — absolute for oral; <50 mL/min for LAI

• Congenital long QT syndrome or history of torsades de pointes

• Concurrent use with drugs known to cause significant QT prolongation in patients with additional cardiac risk factors

• Pre-existing cardiovascular disease or cerebrovascular disease

• Risk factors for QT prolongation (electrolyte imbalance, bradycardia, concurrent QT-prolonging drugs)

• History of seizures or conditions lowering seizure threshold

• Parkinson's disease or Lewy body dementia (risk of severe EPS and worsening)

• Diabetes mellitus or risk factors for metabolic syndrome

• Hyperprolactinaemia or prolactin-dependent tumours

• History of orthostatic hypotension

• Elderly patients with dementia-related psychosis (increased stroke and mortality risk — avoid use)

• Patients at risk of aspiration pneumonia

• Conditions predisposing to hyperthermia (strenuous exercise, extreme heat exposure)

Parameter Recommendation

Risk category Not formally classified in India; available data suggest low teratogenic risk

When to use Only if benefit clearly outweighs risk; psychiatric specialist input essential

Preferred alternatives Olanzapine or quetiapine preferred for initiation during pregnancy in Indian obstetric-psychiatric practice

Monitoring Fetal growth monitoring; observe neonate for extrapyramidal symptoms and withdrawal signs if exposed during third trimester

Parameter Recommendation

Compatibility Compatible with breastfeeding; paliperidone excreted in breast milk at low levels

Preferred alternatives Risperidone or quetiapine (more extensive safety data available)

Expected drug levels in milk Low

Infant monitoring Observe for sedation, feeding difficulties, irritability, and inadequate weight gain

Key Clinical Note: Use lowest effective dose if continued during lactation.

Parameter Recommendation

Starting dose 3 mg once daily (oral)

Titration Slower titration recommended; increase at intervals of ≥7 days

Special risks Increased susceptibility to orthostatic hypotension, falls, sedation, EPS, and anticholinergic-like effects

Important caution AVOID in elderly patients with dementia-related psychosis due to significantly increased risk of cerebrovascular events and mortality

Strong CYP3A4 inducers (carbamazepine, rifampicin, phenytoin) Increased paliperidone clearance Reduced antipsychotic efficacy Avoid combination or increase paliperidone dose with close monitoring

Class IA antiarrhythmics (quinidine, procainamide) Additive QT prolongation Risk of torsades de pointes Avoid concurrent use

Class III antiarrhythmics (amiodarone, sotalol) Additive QT prolongation Risk of torsades de pointes Avoid concurrent use

Other QT-prolonging agents (haloperidol, erythromycin, fluoroquinolones, methadone, ondansetron) Additive QT prolongation Increased arrhythmia risk Avoid if possible; ECG monitoring if unavoidable

Dopamine agonists (levodopa, pramipexole, ropinirole) Pharmacological antagonism Reduced efficacy of both agents Avoid in Parkinson's disease patients

Interacting Drug/Class Clinical Effect Recommendation

Valproate May slightly increase paliperidone exposure Monitor for increased adverse effects

Antihypertensives (all classes) Additive hypotensive effect Monitor blood pressure; dose adjustment may be needed

Diuretics (thiazides, loop diuretics) Electrolyte disturbances may enhance QT prolongation risk Monitor electrolytes periodically

Clozapine Additive sedation, metabolic effects, and hypotension Use with caution; enhanced monitoring required

Alcohol and CNS depressants (benzodiazepines, opioids) Additive sedation and respiratory depression Counsel patients; use lowest effective doses

Lithium Potential for neurotoxicity at high doses Monitor lithium levels and neurological status

• Somnolence and sedation

• Extrapyramidal symptoms (dystonia, akathisia, parkinsonism — dose-related)

• Weight gain

• Headache

• Dizziness

• Hyperprolactinaemia (may be asymptomatic or cause galactorrhoea, amenorrhoea, gynaecomastia)

• Akathisia

• Tachycardia

• Increased salivation

• Orthostatic hypotension

• Constipation

• Nasopharyngitis

Adverse Effect Clinical Action

Neuroleptic Malignant Syndrome (hyperthermia, rigidity, autonomic instability, altered consciousness) Discontinue immediately; supportive care; may require ICU management

QT prolongation / Torsades de pointes Discontinue; correct electrolytes; cardiology consultation

Tardive dyskinesia Consider dose reduction or discontinuation; may be irreversible

Severe extrapyramidal symptoms Dose reduction; anticholinergic agents may be used

Cerebrovascular events (especially in elderly with dementia) Avoid use in this population

Seizures Discontinue; evaluate for underlying causes

Angioedema and hypersensitivity reactions Discontinue immediately; manage anaphylaxis if present

Venous thromboembolism Clinical vigilance in high-risk patients

At initiation and dose changes Extrapyramidal symptoms; sedation level; orthostatic blood pressure; heart rate

Monthly (first 3 months) Weight, BMI

Quarterly (ongoing) Weight, BMI; assessment for movement disorders; clinical response

Every 6–12 months Fasting glucose; lipid profile; prolactin (or earlier if symptomatic); ECG (if on other QT-prolonging drugs)

As clinically indicated CBC; liver function tests; ECG

• Invega (Janssen)

• Palido (Sun Pharma)

• Palip XR (Intas)

• Paliris (Micro Labs)

• Palipe (Torrent)

• Invega Sustenna — Paliperidone Palmitate LAI (Janssen)

Note: Oral paliperidone included under NLEM 2022 for schizophrenia. Prices vary across states and procurement channels.

• Ideal choice when once-daily dosing and minimal hepatic metabolism are desired (useful in hepatic impairment or polypharmacy with hepatically metabolised drugs)

• Consider switching from risperidone to paliperidone if patient experiences dose-limiting EPS while maintaining adequate D2 receptor blockade

• The LAI formulation's loading dose strategy (150 mg Day 1 + 100 mg Day 8) rapidly achieves therapeutic concentrations without prolonged oral supplementation

• Prolactin elevation is more pronounced with paliperidone compared to many other atypicals; monitor for menstrual disturbances, sexual dysfunction, and gynaecomastia

• QT prolongation risk is dose-dependent; perform baseline ECG in patients with cardiac risk factors before initiating therapy

• Do NOT administer oral and injectable formulations concurrently

• Ghost tablet (empty shell) in stool is normal with ER formulation; counsel patients to prevent unnecessary concern

paliperidone; atypical antipsychotic; schizophrenia; schizoaffective disorder; long-acting injectable; LAI; prolactin elevation; QT prolongation; NLEM India; renal-safe antipsychotic; second-generation antipsychotic

RxIndia v1.0 — 10 Jun 2025

• CDSCO approved product information

• Indian National Formulary (NFI)

• National List of Essential Medicines (NLEM) 2022

• AIIMS Drug Formulary

• API Textbook of Medicine, 11th Edition

• Product Inserts: Invega, Invega Sustenna (Janssen India)

• ICMR Guidelines for management of psychosis in adults

• Indian Psychiatric Society clinical practice recommendations

• Goodman & Gilman's The Pharmacological Basis of Therapeutics