Schedule H

Oral

• Tablets (Immediate-release): 20 mg

• Tablets (Modified-release): 35 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Chronic Stable Angina Pectoris (Adjunctive Therapy)

⚠️ Not for monotherapy — Always use as add-on to conventional antianginal agents (beta-blockers, calcium channel blockers, nitrates)

Immediate-Release Formulation (20 mg tablet):

Parameter Dose

Starting dose 20 mg orally three times daily with meals

Titration Not applicable — fixed dosing regimen

Usual maintenance dose 60 mg/day in three divided doses

Maximum dose 60 mg/day

Modified-Release Formulation (35 mg MR tablet):

Parameter Dose

Starting dose 35 mg orally twice daily (morning and evening with meals)

Titration Not applicable — fixed dosing regimen

Usual maintenance dose 70 mg/day in two divided doses

Maximum dose 70 mg/day

Clinical Notes:

• Must be taken with food to improve absorption

• Does not affect heart rate or blood pressure — hemodynamically neutral

• Not effective for acute angina attacks — no rescue use

• Mechanism: Shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation, improving myocardial efficiency under ischaemic conditions

• Benefits typically seen after 2–4 weeks of regular use

• Particularly useful when beta-blockers or CCBs are contraindicated, poorly tolerated, or provide inadequate symptom control

Secondary Indications – Adults (Off-label)

Indication Dose Duration Supervision Evidence Basis

Tinnitus and Vertigo of Vascular/Ischaemic Origin (OFF-LABEL) 20 mg orally twice to three times daily OR 35 mg MR twice daily 2–3 months trial; discontinue if no benefit ENT specialist recommended Indian specialist practice; limited controlled trial data

Chorioretinal Disorders with Vascular Component (including Retinitis Pigmentosa) (OFF-LABEL) 35 mg MR orally twice daily Long-term as tolerated Specialist only (Ophthalmology) Limited evidence; used in some Indian ophthalmic protocols

Heart Failure with Reduced Ejection Fraction (HFrEF) — Adjunct (OFF-LABEL) 35 mg MR orally twice daily Long-term Specialist only (Cardiology) Some RCTs suggest improvement in exercise capacity; not standard practice; Indian Heart Failure Society does not include as routine recommendation

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable — no approved paediatric indications in India.

Secondary Indications – Paediatrics (Off-label)

Not recommended — safety and efficacy not established in patients below 18 years of age.

Age Restriction:

• Not recommended in children or adolescents under 18 years

• Off-label use is discouraged due to complete lack of paediatric pharmacokinetic and safety data

• Use only under exceptional circumstances with specialist supervision (e.g., rare paediatric vasculopathies)

Additional Notes:

• Trimetazidine is predominantly renally excreted

• Assess renal function (serum creatinine, eGFR) before initiating therapy

Note: Trimetazidine undergoes some hepatic metabolism; however, primary excretion is renal. Limited pharmacokinetic data in hepatic impairment.

• Known hypersensitivity to trimetazidine dihydrochloride or any excipients

• Parkinson's disease

• Parkinsonian symptoms (tremor, rigidity, akinesia, bradykinesia)

• Restless legs syndrome

• Other movement disorders

• Severe renal impairment (eGFR <30 mL/min/1.73 m²)

• Elderly patients (≥65 years) — significantly increased risk of movement disorders; careful neurological assessment required before and during treatment

• Moderate renal impairment (eGFR 30–59) — dose reduction may be needed

• History of extrapyramidal symptoms or falls

• Concurrent use with dopamine antagonists (may increase risk of movement disorders)

• Not to be used for acute angina treatment or as initial therapy for unstable angina/MI

• Patients should be informed to report any movement abnormalities immediately

Parameter Information

Overall Safety Safety in pregnancy not established; limited human data

Risk Unknown; no adequate controlled studies in pregnant women

Preferred Alternatives Beta-blockers (labetalol, metoprolol), calcium channel blockers (nifedipine) are better studied for angina in pregnancy

When Use May Be Justified Only if no suitable alternative and benefit clearly outweighs potential risk; requires specialist cardiology and obstetric input

Monitoring Fetal growth monitoring if used; maternal symptom assessment

Parameter Information

Compatibility Not recommended — insufficient data on excretion in human breast milk

Expected Drug Level in Milk Unknown; likely low based on physicochemical properties

Preferred Alternatives Better-studied antianginal agents (beta-blockers like metoprolol) if required

Infant Monitoring Not applicable — advised to avoid use during breastfeeding

Recommendation Avoid breastfeeding during treatment or avoid drug during breastfeeding

Parameter Recommendation

Starting dose Use lower end of dosing range; consider starting with 35 mg once daily (MR formulation) or 20 mg twice daily (IR formulation)

Titration Titrate slowly to full dose based on tolerability over 1–2 weeks

Increased Risks Extrapyramidal symptoms (tremor, rigidity, gait disturbance), falls, reversible Parkinsonism

Additional Precautions Assess baseline neurological status (gait, tremor, rigidity) before initiation; regular neurological review every 6 months; assess renal function before and during therapy; discontinue immediately if movement disorders develop

Interacting Drug Mechanism Effect Management

Dopamine Antagonists (metoclopramide, prochlorperazine, haloperidol, risperidone) Additive dopamine blockade Increased risk of extrapyramidal symptoms and Parkinsonism Avoid combination, especially in elderly; if essential, monitor closely for movement disorders

Levodopa / Dopamine Agonists Pharmacodynamic antagonism at dopaminergic pathways Potential worsening of Parkinsonian symptoms; reduced efficacy of dopaminergic therapy Contraindicated in patients with Parkinson's disease or on antiparkinsonian drugs

Interacting Drug Effect Management

Beta-blockers, Calcium Channel Blockers, Nitrates Additive antianginal effect; theoretical synergy Generally beneficial combination; intended use; monitor for symptomatic hypotension if adding nitrates

Antihypertensives (ACE inhibitors, ARBs, diuretics) Potential additive hypotensive effects (though trimetazidine is haemodynamically neutral) Monitor blood pressure; unlikely to be clinically significant

Opioid Analgesics Additive sedation in elderly Use with caution in elderly; monitor for excessive sedation

CNS-active Drugs (antipsychotics, antidepressants with extrapyramidal potential) Additive risk of tremor or extrapyramidal symptoms Monitor neurological status

Note: Trimetazidine has no significant CYP450-mediated interactions; drug interaction profile is relatively limited.

• Gastrointestinal disturbance (nausea, vomiting, dyspepsia, abdominal pain)

• Dizziness

• Headache

• Asthenia, fatigue

• Rash, pruritus

• Somnolence

Adverse Effect Clinical Action

Extrapyramidal Symptoms (tremor, rigidity, bradykinesia, gait instability) — dose-dependent and more common in elderly Discontinue immediately; symptoms usually reversible within 4 months of stopping; refer to neurology if symptoms persist

Reversible Parkinsonism Discontinue immediately; most cases resolve after stopping drug; neurology consultation recommended

Severe Hypersensitivity Reactions (angioedema, anaphylaxis — rare) Discontinue permanently; emergency management

Thrombocytopenia (very rare) Monitor platelet count; discontinue if significant; haematology referral

Agranulocytosis (very rare) Discontinue immediately; haematology referral; supportive care

Fixed Drug Eruption (rare) Discontinue; dermatology consultation

After initiation (4–8 weeks) Symptom response (angina frequency, exercise tolerance); neurological status (any new tremor, gait difficulty, stiffness); tolerability assessment

Long-term (every 6–12 months) Neurological examination (especially in elderly — screen for extrapyramidal symptoms); renal function (annually or sooner if elderly or CKD); reassess need for continued therapy

If movement disorders develop Discontinue immediately; reassess; neurology referral if symptoms persist beyond 4 months

Modified-Release (35 mg):

• Vastarel MR™ (Serdia/Servier)

• Flavedon MR™ (Serdia)

• Trimetazidine MR™ (Various)

• Carvidon MR™ (Sun Pharma)

• Trimet MR™

Immediate-Release (20 mg):

• Trimetazidine™ (Generic — various manufacturers)

• Trimet™

• Carvidon™

Note: Modified-release 35 mg formulation is more commonly prescribed due to twice-daily dosing convenience. Fixed-dose combinations are not commonly available.

Regulatory: Not listed under NLEM 2022; not under NPPA price control; prices vary by brand and region

1. Adjunctive therapy only — Trimetazidine is never first-line or monotherapy for angina; always add to beta-blockers, CCBs, or nitrates when these provide inadequate symptom control or are limited by adverse effects

1. Haemodynamically neutral — Does not affect heart rate or blood pressure; particularly useful in patients with hypotension or bradycardia where beta-blockers or CCBs are problematic

1. Parkinsonism screening is essential — Always screen for pre-existing movement disorders before starting; contraindicated in Parkinson's disease; risk is dose-dependent and highest in elderly

1. Elderly require special attention — Start at lower doses; monitor neurological status regularly; discontinue immediately if tremor, gait disturbance, or rigidity develops — symptoms are usually reversible

1. Renal function determines eligibility — Avoid in severe renal impairment (eGFR <30); reduce dose in moderate impairment; check eGFR before and during therapy

1. No acute benefit — Does not relieve acute angina attacks; patients must continue to use short-acting nitrates (GTN sublingual) for breakthrough symptoms

angina; metabolic-antianginal; adjunctive-therapy; Parkinsonism-risk; extrapyramidal-caution; elderly-caution; renal-adjustment; haemodynamically-neutral; Schedule-H; not-NLEM

RxIndia v1.0 — 10 May 2025

• CDSCO Product Information

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine

• AIIMS Pharmacology Guidelines

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• European Medicines Agency (EMA) Safety Review on Trimetazidine (2012) — for Parkinsonism risk data

• Indian cardiology specialist practice consensus

• Trimetazidine Product Inserts — Indian manufacturers