Schedule H

Oral

⚠️ Limited/Unverified Availability in India

• Tablets: 70 mg (as hydrochloride) — reported internationally

• CDSCO approval status: Not confirmed in official database

• Prescribers should verify local availability before initiating therapy

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Major Depressive Disorder (MDD)

Parameter Recommendation

Starting dose 70 mg once daily (preferably at bedtime) or 70 mg twice daily

Titration Increase by 70 mg every 5–7 days based on response and tolerability

Usual maintenance dose 140–210 mg/day in 1–2 divided doses

Maximum dose 210 mg/day (up to 280 mg/day under specialist care in refractory cases)

Clinical notes:

• Less sedating than amitriptyline — can be given during daytime if needed

• Therapeutic response typically observed within 2–4 weeks

• Gradual tapering recommended when discontinuing

• Prodrug — converted to desipramine (active metabolite) in vivo

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

1. Anxiety Disorders with Depressive Features — OFF-LABEL

• Dose: Start 70 mg/day; titrate to 140–210 mg/day

• Duration: Minimum 6–8 weeks trial

• Specialist only

• Evidence: Limited studies; extrapolated from TCA class effects

1. Chronic Pain Syndromes (with comorbid depression) — OFF-LABEL

• Dose: 70–140 mg/day

• Duration: Long-term as per clinical response

• Specialist only

• Evidence: Based on TCA class efficacy in neuropathic pain; limited direct data for lofepramine

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable — Lofepramine is not approved for paediatric use.

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

Not recommended — Insufficient safety and efficacy data in children and adolescents.

Age restriction: Not recommended below 18 years except under exceptional specialist supervision.

Moderate impairment (eGFR 30–59) Use with caution; start at lower dose

Severe impairment (eGFR <30) Avoid or use with extreme caution; active metabolite (desipramine) may accumulate

Dialysis Limited data; not significantly dialysable

• Hypersensitivity to lofepramine, desipramine, or other TCAs

• Recent myocardial infarction (within 3 months)

• Arrhythmias, particularly heart block

• Concomitant use with MAO inhibitors or within 14 days of MAOI discontinuation

• Severe hepatic impairment

• Acute porphyria

• Manic phase of bipolar disorder

• History of epilepsy or lowered seizure threshold

• Cardiovascular disease (monitor ECG)

• Urinary retention or prostatic hypertrophy

• Narrow-angle glaucoma

• Hyperthyroidism or patients on thyroid medication

• Elderly patients (increased sensitivity)

• History of bipolar disorder (risk of manic switch)

• Diabetes mellitus (may affect glycaemic control)

• Concurrent CNS depressants

• Suicidal ideation (especially early in treatment)

• Avoid abrupt discontinuation

Parameter Recommendation

Risk category Limited data; use only if benefit outweighs risk

Preferred alternatives Sertraline generally preferred in Indian obstetric practice

When may be used Severe refractory depression under psychiatric supervision

Monitoring Neonatal withdrawal symptoms and sedation if used in third trimester

Parameter Recommendation

Compatibility Not recommended; lofepramine and metabolite desipramine pass into breast milk

Preferred alternatives Sertraline or nortriptyline (better safety data)

Levels in milk Low to moderate

Infant monitoring Sedation, poor feeding, irritability, weight gain

• Starting dose: 35–70 mg/day

• Titration: Slow — increase every 1–2 weeks

• Maximum dose: Generally limit to 140 mg/day

• Extra risks:

• Orthostatic hypotension and falls

• Cognitive impairment

• Cardiac conduction abnormalities

• Urinary retention

• Note: Lofepramine has better tolerability profile than older TCAs in elderly, but caution still required

Interacting Drug Effect/Risk Management

MAO inhibitors Serotonin syndrome, hypertensive crisis Contraindicated; 14-day washout required

SSRIs (fluoxetine, paroxetine) CYP2D6 inhibition increases desipramine levels Avoid or reduce lofepramine dose; monitor toxicity

Class 1C antiarrhythmics Additive cardiac conduction effects Avoid combination

QT-prolonging drugs Risk of torsades de pointes Avoid combination

Sympathomimetics Exaggerated cardiovascular effects Use with extreme caution

Alcohol Enhanced CNS depression Counsel avoidance

Interacting Drug Effect/Risk Management

Carbamazepine Enzyme induction reduces lofepramine levels Monitor efficacy; may need dose adjustment

Phenytoin Enzyme induction reduces levels Monitor clinical response

Rifampicin Reduced efficacy Consider alternative or increase dose

Cimetidine Inhibits metabolism; increased TCA levels Monitor for adverse effects

Oral contraceptives May increase TCA levels Monitor for toxicity

Antihypertensives (clonidine, guanethidine) Reduced antihypertensive effect Avoid combination if possible

Anticholinergics Additive anticholinergic effects Minimise combined use

• Dry mouth

• Constipation

• Nausea

• Dizziness

• Headache

• Tremor

• Sweating

• Insomnia or drowsiness

• Weight changes

Note: Lofepramine generally causes fewer anticholinergic and sedative effects compared to amitriptyline.

• Cardiac arrhythmias and conduction disturbances

• Seizures

• Hepatotoxicity (rare; monitor LFTs if symptoms arise)

• Mania or hypomania induction

• Suicidal ideation (especially in younger adults)

• Agranulocytosis (rare)

• Hyponatraemia/SIADH

• Serotonin syndrome (with interacting drugs)

Phase Parameters

Baseline ECG (especially if cardiac risk factors), LFTs, renal function, blood pressure, suicide risk assessment

After initiation Mood and suicidality weekly for first 4 weeks; blood pressure; tolerability assessment

Long-term Periodic ECG if dose >140 mg/day; LFTs if hepatic symptoms; weight; mood monitoring

⚠️ Limited/Unverified Availability

• Specific brand names in India: NOT CONFIRMED

• International brands: Gamanil® (UK), Lomont® (UK)

• Prescribers should verify current availability with local distributors or specialty pharmacies

• Not applicable — pricing data not available due to unverified market presence

• If imported: likely to be expensive compared to locally available TCAs

• Not listed in NLEM 2022

• Not under DPCO price control

• Lofepramine is a prodrug metabolised to desipramine — onset of action may be slightly delayed

• Better cardiac safety profile compared to older TCAs (amitriptyline, imipramine) — lower risk of fatal overdose

• Less anticholinergic burden than amitriptyline — may be better tolerated in some patients

• If unavailable in India, consider nortriptyline as an alternative with relatively better tolerability among available TCAs

• SSRIs remain first-line antidepressants per Indian Psychiatric Society guidelines

• Due to limited availability, ensure reliable supply before initiating long-term therapy

lofepramine; tricyclic antidepressant; TCA; depression; desipramine prodrug; limited availability India; psychiatry; better cardiac safety

RxIndia v0.3 — 13 Jan 2025

• CDSCO database — availability not confirmed

• Indian Pharmacopoeia / National Formulary of India — NOT listed

• NLEM 2022 — NOT listed

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

• Standard international TCA monographs (for pharmacological data)

• Note: Clinical information adapted from international sources due to limited Indian-specific data