Schedule H

Oral

• Tablet 200 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ Parkinson's Disease — Adjunct to Levodopa/Carbidopa

For patients experiencing end-of-dose motor fluctuations ("wearing-off" phenomenon)

Parameter Details

Starting dose 200 mg orally with each dose of levodopa/carbidopa

Titration No dose titration of entacapone required; reduce levodopa dose by 10–30% if dyskinesias develop

Usual maintenance dose 200 mg with each levodopa/carbidopa dose (typically 3–6 times daily)

Maximum dose 1600 mg/day (8 doses of 200 mg)

Key Clinical Notes:

• ⚠️ No antiparkinsonian effect when used alone — must always be co-administered with levodopa/carbidopa

• Administer simultaneously with each levodopa/carbidopa dose

• Primary mechanism: Inhibits peripheral COMT, reducing levodopa metabolism and prolonging its therapeutic effect

• Preferred first-line COMT inhibitor over tolcapone due to superior hepatic safety profile

Secondary Indications — Adults (Off-label)

Not applicable — no established off-label uses documented in Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable

Secondary Indications (Off-label)

Not applicable

Age Restriction Statement:

• Not approved or recommended for use below 18 years of age

• Safety and efficacy not established in paediatric population

• Use in children or adolescents should be avoided except in controlled clinical trial settings under specialist supervision

• Severe hepatic impairment

• Known hypersensitivity to entacapone or any excipient

• History of neuroleptic malignant syndrome (NMS)

• History of non-traumatic rhabdomyolysis

• Concurrent use of non-selective MAO inhibitors (e.g., phenelzine, tranylcypromine)

• Concurrent use of MAO-A and MAO-B inhibitors together (e.g., moclobemide + selegiline combination)

• Pheochromocytoma

• Pre-existing dyskinesias (may worsen; often requires levodopa dose reduction)

• Patients at risk of neuroleptic malignant syndrome or rhabdomyolysis during intercurrent illness or dose changes

• History of impulse control disorders (gambling, hypersexuality, binge eating, compulsive shopping)

• Orthostatic hypotension (especially in patients on antihypertensives)

• Elderly patients with cognitive impairment or hallucinations

• History of severe diarrhoeal illness

• Concurrent use with dopamine agonists

Aspect Details

Risk classification Not formally classified in India; animal studies show reproductive toxicity

Human data Limited/insufficient

When to use Only if benefit clearly outweighs risk; specialist supervision mandatory

Preferred alternative Levodopa/carbidopa alone (used with caution in pregnancy)

Monitoring Serial fetal growth scans, maternal blood pressure

Aspect Details

Compatibility Not recommended

Excretion in milk Unknown; data lacking in humans

Preferred alternative Levodopa/carbidopa alone (used with caution)

Infant monitoring Feeding difficulty, hypotonia, lethargy, poor weight gain

• Starting dose: 200 mg with each levodopa/carbidopa dose (same as younger adults)

• Titration: Proceed cautiously; closely monitor for dopaminergic adverse effects

• Extra risks:

• Hallucinations and confusion (higher incidence)

• Orthostatic hypotension and falls

• Cognitive disturbances

• Dyskinesias (consider reducing levodopa dose by 10–30% at initiation)

• Regular neuropsychiatric assessment recommended

Drug/Class Mechanism/Effect Recommendation

Non-selective MAO inhibitors (phenelzine, tranylcypromine) Catecholamine accumulation → hypertensive crisis Contraindicated

MAO-A + MAO-B inhibitor combination Synergistic catecholamine effects Contraindicated

Warfarin Protein displacement → increased INR and bleeding risk Monitor INR closely; adjust warfarin dose accordingly

Levodopa/carbidopa Enhanced dopaminergic effect → dyskinesias Reduce levodopa dose by 10–30% if dyskinesias occur

Other dopamine agonists (bromocriptine, pramipexole, ropinirole) Additive dopaminergic effects → dyskinesias, impulse control disorders Use with caution; monitor closely

Drug/Class Mechanism/Effect Recommendation

Antihypertensives (especially alpha-blockers) Additive hypotensive effect Monitor blood pressure regularly

Iron salts/supplements Chelation reduces entacapone absorption Separate dosing by at least 2 hours

Rifampicin and other enzyme inducers May reduce entacapone plasma levels Monitor for reduced efficacy

Tricyclic antidepressants Additive CNS effects Monitor for sedation and neurological symptoms

CNS depressants (benzodiazepines, opioids) Additive sedative effects Monitor for excessive sedation

Catecholamine-metabolized drugs (adrenaline, noradrenaline, dopamine, dobutamine, isoprenaline) COMT inhibition enhances effect Use with caution; dose adjustment may be needed

• Diarrhoea (may appear weeks after initiation; can be severe)

• Dyskinesia

• Nausea

• Urine discolouration (reddish-brown) — benign, reassure patient

• Dizziness

• Orthostatic hypotension

• Hallucinations (especially in elderly)

• Abdominal pain

• Dry mouth

• Fatigue

• Neuroleptic malignant syndrome (NMS) — especially with abrupt withdrawal or dose reduction; requires immediate discontinuation and hospitalisation

• Rhabdomyolysis — monitor CK levels; assess for muscle pain, weakness, dark urine

• Severe diarrhoea with dehydration and electrolyte imbalance (hypokalaemia)

• Impulse control disorders (pathological gambling, hypersexuality, compulsive eating/shopping)

• Severe hallucinations and psychosis (especially in advanced Parkinson's disease or elderly)

• Hepatotoxicity (rare, but monitor LFTs)

Phase Parameters

Baseline LFTs (ALT, AST), blood pressure, mental status examination, motor function assessment

After initiation/dose change Dyskinesia severity, diarrhoea, orthostatic blood pressure, neuropsychiatric status (within 2–4 weeks)

Long-term (chronic use) Periodic LFTs, blood pressure monitoring, INR (if on warfarin), neuropsychiatric assessment for impulse control disorders and hallucinations

Clinical Vigilance:

• Assess for NMS signs during dose adjustments or intercurrent illness

• Monitor for new-onset impulse control behaviours throughout treatment

• Comtan (Novartis)

• Entacom (Sun Pharma)

• Entecap (Intas)

• Entazin (Zydus)

• Entadep (Alkem)

• Ecapone (Macleods)

• Syncapone (Torrent) — FDC with levodopa/carbidopa

Note: Fixed-dose combinations (FDCs) with levodopa/carbidopa are also available under various brand names.

• Tablet 200 mg: ₹12–26 per tablet (brand-dependent)

• Not included in NLEM 2022

• Not NPPA price-controlled

• Availability in government supply may vary by state

1. Always co-prescribe with levodopa/carbidopa — entacapone has no antiparkinsonian effect as monotherapy

1. First-line COMT inhibitor in India due to favourable hepatic safety compared to tolcapone

1. Anticipate dyskinesias at initiation — proactively reduce levodopa dose by 10–30% if they occur

1. Reddish-brown urine discolouration is harmless — counsel patients in advance to prevent alarm

1. Delayed-onset diarrhoea may appear weeks after starting therapy — evaluate promptly and consider discontinuation if persistent or severe

1. Screen for impulse control disorders regularly — counsel patients and caregivers about behavioural changes (gambling, hypersexuality, compulsive spending)

Entacapone; Parkinson's disease; COMT inhibitor; levodopa adjunct; motor fluctuations; wearing-off; dyskinesia; impulse control disorder; neurology

RxIndia v1.0 — 11 Apr 2025

• CDSCO product information

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Neurology Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• NLEM 2022 (entacapone not listed — confirmed)