Schedule H

Oral

• Tablets: 25 mg, 50 mg, 100 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Major Depressive Disorder (Moderate to Severe)

Parameter Recommendation

Starting dose 50 mg twice daily (or 25 mg twice daily in elderly/sensitive patients)

Titration Increase by 25–50 mg every 3–4 days based on tolerance and response

Usual maintenance dose 200–300 mg/day in 2–3 divided doses

Maximum dose 400 mg/day (outpatients); 600 mg/day (hospitalised patients under supervision)

Clinical Notes:

For doses exceeding 300 mg/day, administer in divided doses with larger portion at bedtime

Onset of therapeutic effect typically 1–2 weeks; full benefit may take 4–6 weeks

Faster onset compared to many other TCAs due to dopamine receptor activity

Consider ECG monitoring when doses exceed 300 mg/day

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

Parameter Recommendation

Starting dose 50 mg twice daily

Titration Increase by 50 mg every 3–4 days

Usual maintenance dose 200–400 mg/day in divided doses

Maximum dose 400 mg/day

Evidence basis: Historical use; amoxapine has mild antipsychotic activity via dopamine receptor blockade

Atypical antipsychotics generally preferred in current practice

Parameter Recommendation

Starting dose 25 mg at bedtime

Titration Increase by 25 mg weekly as tolerated

Usual maintenance dose 25–75 mg/day at bedtime

Maximum dose 100 mg/day

Evidence basis: Weak; occasional use in resource-limited settings when other agents unavailable

Other TCAs (amitriptyline, nortriptyline) preferred for neuropathic pain

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

NOT ROUTINELY RECOMMENDED in patients <18 years

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

Minimum age: 12 years (under strict psychiatric specialist supervision)

Parameter Recommendation

Starting dose 1 mg/kg/day in 2–3 divided doses

Titration Increase cautiously based on response and tolerability

Usual maintenance dose 100–200 mg/day

Maximum dose 200 mg/day (up to 300 mg/day in hospitalised adolescents)

Safety Monitoring:

• Baseline ECG mandatory

• Blood pressure monitoring at each visit

• Weight monitoring monthly

• Close surveillance for suicidal ideation (especially first 4 weeks)

• Monitor for extrapyramidal symptoms

Important: Avoid in children <12 years unless under exceptional circumstances with specialist supervision. Higher risk of seizures and cardiotoxicity in paediatric population.

Mild to moderate impairment No specific adjustment; initiate at lower end of dose range

• Known hypersensitivity to amoxapine or other tricyclic antidepressants

• Recent myocardial infarction (within 4 weeks)

• History of seizure disorder

• Concurrent use of MAO inhibitors or within 14 days of discontinuing MAOIs

• Narrow-angle glaucoma

• Severe urinary retention

• Acute recovery phase following myocardial infarction

• Cardiovascular disease — risk of conduction delays and arrhythmias

• Elderly patients — increased fall risk, anticholinergic burden, cognitive impairment

• History of suicidal ideation — monitor closely, especially in early treatment weeks

• Lowered seizure threshold — particularly at higher doses

• Diabetes mellitus — may alter glycaemic control

• Prostatic hypertrophy — urinary retention risk

• Hepatic dysfunction — drug extensively metabolised hepatically

• Avoid abrupt withdrawal — taper gradually to prevent discontinuation symptoms

• Bipolar disorder — risk of precipitating mania

Aspect Information

Overall safety Limited human data; animal studies show fetal toxicity at high doses; generally avoided

Recommendation Use only if benefit clearly outweighs risk; specialist psychiatric supervision mandatory

Preferred alternatives Sertraline, fluoxetine (SSRIs) preferred in Indian obstetric psychiatry practice

Monitoring Fetal growth surveillance; neonatal observation for CNS depression and withdrawal symptoms if used near term

Aspect Information

Compatibility Not recommended during breastfeeding

Excretion in milk Amoxapine and active metabolites excreted in breast milk; levels potentially significant

Preferred alternatives Sertraline preferred in lactating mothers in Indian settings

Infant monitoring If unavoidable: monitor infant for sedation, hypotonia, poor feeding, seizures

• Starting dose: 25 mg once or twice daily

• Titration: Increase very slowly in increments of 10–25 mg at weekly intervals

• Usual maintenance: Lowest effective dose; typically lower than adult doses

• Additional risks:

• Increased susceptibility to falls

• Confusion and cognitive impairment

• Pronounced anticholinergic effects

• Orthostatic hypotension

• Cardiac conduction abnormalities

• Monitoring: ECG at baseline and periodically; renal and hepatic function; regular cognitive assessment

Drug/Class Mechanism Clinical Action

MAO inhibitors (phenelzine, tranylcypromine, selegiline) Risk of hypertensive crisis, serotonin syndrome Contraindicated — 14-day washout required

SSRIs (fluoxetine, paroxetine) Serotonin syndrome risk; CYP2D6 inhibition increases amoxapine levels Avoid combination

QT-prolonging drugs (haloperidol, amiodarone, moxifloxacin) Additive cardiotoxicity Avoid or ECG monitoring essential

Anticholinergic drugs (antihistamines, atropine, oxybutynin) Additive anticholinergic toxicity Avoid or minimise concurrent use

CNS depressants (alcohol, benzodiazepines, opioids) Additive sedation, respiratory depression Avoid combination or use with extreme caution

Drug/Class Interaction Clinical Action

Antihypertensives (alpha-blockers, diuretics) Potentiation of hypotensive effect Monitor blood pressure closely

Oral antidiabetics, insulin Altered glycaemic control Monitor blood glucose frequently

Phenytoin, carbamazepine CYP induction may lower amoxapine levels Monitor therapeutic response; may need dose adjustment

Cimetidine CYP inhibition may increase amoxapine levels Monitor for toxicity

Warfarin Potential alteration in anticoagulant effect Monitor INR

Rifampicin CYP induction reduces amoxapine efficacy Monitor response; may need higher doses

• Drowsiness, sedation

• Dry mouth

• Constipation

• Dizziness

• Orthostatic hypotension

• Weight gain

• Blurred vision

• Urinary hesitancy

• Tachycardia

• Tremor

Adverse Effect Clinical Action

Seizures (dose-related) Immediate discontinuation; hospitalisation if status epilepticus

Cardiac arrhythmias, QT prolongation Discontinue; cardiology consultation; ECG monitoring

Extrapyramidal symptoms (tardive dyskinesia, akathisia) Reduce dose or discontinue; particularly with prolonged high-dose use

Neuroleptic malignant syndrome (rare) Immediate discontinuation; hospitalisation required

Suicidal ideation (especially early treatment) Urgent psychiatric evaluation; consider discontinuation

Hepatotoxicity (rare) Monitor LFTs; discontinue if significant elevation

Agranulocytosis (rare) Check CBC; discontinue and haematology referral

Serotonin syndrome Discontinue; supportive care

Phase Parameters Frequency

Baseline ECG (mandatory if age >40 years or cardiac risk), LFT, renal function, blood pressure, weight, suicide risk assessment Before initiation

During titration Blood pressure, mental status, suicidal ideation monitoring, ECG (if high doses) Weekly for first 4 weeks

Long-term Weight, ECG (if doses >300 mg/day), LFT (if clinical suspicion), electrolytes (if on diuretics), depression severity assessment Every 3–6 months

Brand Name Manufacturer

Demolox Intas Pharmaceuticals

Asendin Lederle (historical)

Note: Limited availability; mostly private sector; not typically available in government supply

• Not included in NLEM — not under NPPA price control

• Private purchase only; limited government availability

1. Unique among TCAs — Amoxapine possesses mild antipsychotic activity due to dopamine D2 receptor blockade, making it potentially useful in depression with psychotic features.

1. Faster onset of action — Therapeutic effects may be observed within 7–10 days, earlier than most other TCAs; consider in patients needing quicker response.

1. EPS risk from metabolite — The active metabolite 7-hydroxyamoxapine has dopamine-blocking properties; monitor for extrapyramidal symptoms, especially in long-term or high-dose use.

1. Lower anticholinergic burden — Compared to amitriptyline, amoxapine has relatively less anticholinergic activity, though still significant in elderly.

1. Overdose is potentially fatal — High cardiotoxicity and seizure risk in overdose; dispense limited quantities to patients with suicidal risk; consider safer alternatives (SSRIs) in high-risk patients.

1. ECG monitoring essential — Obtain baseline ECG in all patients >40 years or with cardiac risk factors; repeat if doses exceed 300 mg/day.

Amoxapine; antidepressant; TCA; tricyclic; major depressive disorder; psychiatric-specialist; seizure-risk; QT-prolongation; elderly-caution; pregnancy-avoid; EPS-risk

RxIndia v1.0 — 28 May 2025

• CDSCO (formulations and Schedule H listing)

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Indian Psychiatric Society Clinical Practice Guidelines

• AIIMS Psychiatry formulary guidance