Schedule H

Oral

Formulation Strengths Available

Tablets 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Schizophrenia (Adults)

Parameter Recommendation

Starting dose 1 mg once daily (Days 1–4)

Titration Increase to 2 mg once daily (Days 5–7), then to target dose

Usual maintenance dose 2–4 mg once daily

Maximum dose 4 mg/day

Clinical Notes:

• May be administered with or without food

• Dose reduction required with concomitant strong CYP3A4 inhibitors or CYP2D6 inhibitors (reduce by 50%)

• Dose increase may be needed with strong CYP3A4 inducers (up to double the usual dose)

• Slower titration recommended in elderly or patients with significant comorbidities

• Allow at least 1 week at each dose before further titration

Secondary Indications – Adults (Off-label):

Indication Dose Duration Notes

Adjunctive therapy in Major Depressive Disorder (MDD) Starting: 0.5 mg once daily; Titration: Increase to 1 mg/day after Week 1; Usual: 1–2 mg/day; Maximum: 3 mg/day Assess response by 6–8 weeks OFF-LABEL in India; US FDA-approved; Specialist psychiatrist only; Evidence: POLARIS, Thase et al. RCTs

Irritability associated with Autism Spectrum Disorder 0.5–2 mg once daily; titrate slowly Long-term OFF-LABEL; Specialist only (psychiatrist/neurodevelopmental); Limited direct evidence; extrapolated from aripiprazole/risperidone data

Agitation in Alzheimer's dementia 0.5–2 mg once daily Short-term use only OFF-LABEL; US FDA-approved 2023; Not approved in India; Use with extreme caution due to mortality risk in dementia; Specialist only

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

NOT APPROVED for paediatric use in India. No approved paediatric indications.

Secondary Indications – Paediatrics (Off-label):

Indication Age Dose Notes

Schizophrenia (adolescent) ≥13 years Starting: 0.5–1 mg once daily; Titration: Increase by 0.5–1 mg/week; Maintenance: 2–4 mg/day; Maximum: 4 mg/day OFF-LABEL; Specialist child/adolescent psychiatrist only; Limited evidence

Safety Monitoring for Paediatric Use:

• Monitor for extrapyramidal symptoms (EPS), akathisia

• Regular weight and BMI monitoring (metabolic effects)

• Fasting glucose and lipid profile at baseline and periodically

• Monitor for sedation and impact on academic performance

• Assess for suicidality, especially during early treatment

• Prolactin levels if clinically indicated

Age Restrictions:

• Not recommended in children <13 years except in clinical trial settings under specialist supervision

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) Starting dose: 0.5 mg once daily; Maximum: 2 mg/day

ESRD / Haemodialysis Use with caution; limited data; start at 0.5 mg/day; titrate slowly; not expected to be removed by dialysis

• Known hypersensitivity to brexpiprazole or any excipient

• History of neuroleptic malignant syndrome (NMS) with any antipsychotic agent

• Elderly patients with dementia-related psychosis — increased risk of cerebrovascular events and mortality (boxed warning equivalent)

• History of seizures or conditions lowering seizure threshold

• Cardiovascular disease — risk of orthostatic hypotension, particularly during initial titration

• Diabetes mellitus or risk factors for diabetes — may worsen glycaemic control

• Obesity or metabolic syndrome — monitor for weight gain

• Suicidal ideation — particularly when used for depression; close monitoring in early weeks

• History of leukopenia/neutropenia — may exacerbate

• Parkinson's disease or Lewy body dementia — may worsen motor symptoms

• Risk of akathisia — especially in first few weeks

• Patients with swallowing difficulties — risk of aspiration with antipsychotic-induced dysphagia

• Concurrent use with strong CYP3A4 inducers — may reduce efficacy; dose adjustment needed

• CYP2D6 poor metabolisers — may have higher drug exposure

Parameter Recommendation

Overall safety Limited human data; animal studies show some developmental toxicity at high doses

Risk category Caution advised (no formal Indian category; US FDA removed letter categories)

When may be used Only if potential benefit justifies risk; specialist psychiatrist supervision essential

Preferred alternatives Haloperidol (most data in pregnancy), olanzapine, or quetiapine (based on Indian obstetric psychiatry practice)

Maternal monitoring Glucose tolerance, weight, extrapyramidal symptoms

Fetal/neonatal monitoring Third trimester exposure: monitor neonate for EPS, sedation, respiratory distress, feeding difficulties (extrapyramidal and/or withdrawal symptoms reported with antipsychotics)

Parameter Recommendation

Compatibility Not recommended; insufficient human data

Milk excretion Unknown; likely excreted based on drug properties

Preferred alternatives Olanzapine, quetiapine, or risperidone (more lactation data available)

Infant monitoring If breastfeeding unavoidable: monitor for sedation, poor feeding, irritability, developmental milestones

Parameter Recommendation

Starting dose 0.5–1 mg once daily

Titration Slower than younger adults; increase at weekly intervals

Maximum dose 4 mg/day (same as adults, but often lower doses sufficient)

Key risks Orthostatic hypotension (falls risk), sedation, confusion, cognitive impairment

Special warning NOT approved for dementia-related behavioural symptoms — increased risk of stroke and mortality in this population

Monitoring Renal and hepatic function; falls assessment; cognitive status; metabolic parameters

Interacting Drug/Class Mechanism Effect & Recommendation

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) Decreased metabolism of brexpiprazole Increased plasma levels → Reduce brexpiprazole dose by 50%

Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) Decreased metabolism of brexpiprazole Increased plasma levels → Reduce brexpiprazole dose by 50%

Combined strong CYP3A4 + CYP2D6 inhibitors Dual pathway inhibition Markedly increased levels → Reduce brexpiprazole dose to 25% of usual dose

Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, phenobarbital) Increased metabolism of brexpiprazole Reduced efficacy → Consider doubling brexpiprazole dose over 1–2 weeks; reduce back when inducer stopped

Dopamine agonists (levodopa, pramipexole, ropinirole) Pharmacodynamic antagonism Reduced efficacy of dopamine agonists → Avoid combination; if essential, monitor for worsening Parkinson's symptoms

Interacting Drug/Class Effect & Recommendation

Antihypertensives (all classes) Additive hypotensive effect, especially orthostatic → monitor BP during titration

CNS depressants (benzodiazepines, opioids, alcohol, antihistamines) Additive sedation → use cautiously; advise patient

SSRIs/SNRIs (beyond CYP2D6 effect) Potential additive serotonergic effects; monitor for serotonin syndrome; some SSRIs are CYP2D6 inhibitors (see major interactions)

Moderate CYP3A4 inhibitors (erythromycin, diltiazem, verapamil, grapefruit juice) May modestly increase brexpiprazole levels → monitor for adverse effects

Anticholinergic drugs Additive anticholinergic burden → monitor for confusion, constipation, urinary retention, especially in elderly

QT-prolonging drugs (fluoroquinolones, ondansetron, some antipsychotics) Brexpiprazole has minimal QT effect, but caution with multiple QT-prolonging agents → ECG if clinically indicated

• Akathisia (restlessness) — most common, especially early in treatment

• Weight gain

• Headache

• Somnolence or insomnia

• Dizziness

• Constipation

• Nasopharyngitis

• Fatigue

• Increased appetite

• Anxiety or restlessness

• Tremor

Adverse Effect Clinical Action

Neuroleptic malignant syndrome (NMS) Hyperthermia, rigidity, altered consciousness, autonomic instability → Immediate discontinuation; ICU care

Tardive dyskinesia Involuntary movements, especially orofacial → consider dose reduction or switch; may be irreversible

Seizures Rare; dose-dependent → discontinue if seizures occur

Suicidal ideation/behaviour Especially in depression, adolescents → close monitoring; consider discontinuation

Severe hyperglycaemia / diabetic ketoacidosis Rare → monitor glucose; discontinue if DKA

Leukopenia / neutropenia / agranulocytosis Rare → discontinue if ANC <1000/mm³; monitor for infection

Cerebrovascular events (in elderly with dementia) Increased stroke risk → avoid use in dementia-related psychosis

Dysphagia / aspiration pneumonia Risk in elderly or those with swallowing difficulties → monitor

Pathological gambling / impulse control disorders Rare; reported with dopamine modulators → monitor and counsel

Week 2–4 Akathisia and EPS assessment; suicidality monitoring (especially in depression); weight

Month 3 Weight, BMI; fasting glucose; lipid profile; blood pressure; EPS/tardive dyskinesia screening

Every 3–6 months (long-term) Weight/BMI; fasting glucose and lipids annually (or more frequent if abnormal); EPS/tardive dyskinesia assessment; mental state; renal/hepatic function if comorbidities

As clinically indicated Prolactin (if symptoms of hyperprolactinaemia); ECG (if QT concerns); CBC (if infection or prior haematological abnormality)

Rexulti Lundbeck/Otsuka (imported) 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg

Bexpra Sun Pharma 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg

Brexitol Intas 0.5 mg, 1 mg, 2 mg, 4 mg

Brexia Torrent 1 mg, 2 mg, 4 mg

Note: Brand availability may vary by region. Generic formulations from multiple manufacturers are available.

Strength Approximate Price per Tablet

0.5 mg ₹20–₹40

• Not included in NLEM 2022

• Not under NPPA price control

• Primarily available in private retail; limited government supply

• Long half-life (91 hours) allows once-daily dosing and provides stability in plasma levels, improving compliance and reducing withdrawal symptoms if doses are occasionally missed

• Akathisia is the most troublesome early side effect — counsel patients; may require dose reduction, slower titration, or short-term use of propranolol or benzodiazepine

• Lower metabolic risk profile compared to olanzapine and clozapine, but still requires metabolic monitoring; may be preferred in patients with pre-existing metabolic concerns

• CYP interaction awareness is critical — always check for CYP3A4 and CYP2D6 inhibitors/inducers; dose adjustments are well-defined and should be applied

• Not a substitute for antidepressant monotherapy — in MDD, brexpiprazole is only effective as adjunctive therapy (off-label in India); do not use alone for depression

• Useful switch option from aripiprazole in patients experiencing activation, insomnia, or akathisia — brexpiprazole has lower intrinsic activity at D2 receptors

• No depot formulation available — oral adherence must be ensured; consider alternatives if compliance is a concern

brexpiprazole; schizophrenia; atypical antipsychotic; serotonin-dopamine modulator; adjunct depression; MDD augmentation; CYP3A4 substrate; CYP2D6 substrate; akathisia; metabolic monitoring; NLEM-excluded; psychiatry

RxIndia v1.0 — 21 May 2025

• CDSCO approved product information

• National Formulary of India (NFI)

• Indian Psychiatric Society clinical practice recommendations

• AIIMS Psychiatry Department treatment protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th Edition

• Harrison's Principles of Internal Medicine, 21st Edition

• Thase ME et al. Efficacy of brexpiprazole as adjunctive therapy in MDD (POLARIS trials) — for off-label indication only

• US FDA prescribing information (Rexulti) — supportive reference for off-label uses