Schedule H

Oral

• Tablet 100 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ Adjunctive Treatment of Parkinson's Disease

For patients with motor fluctuations ("wearing-off") not adequately controlled by levodopa/carbidopa with or without other dopaminergic agents

Parameter Details

Starting dose 100 mg orally three times daily (administered with each levodopa/carbidopa dose)

Titration Increase to 200 mg TID only if substantial clinical benefit observed and LFTs remain within normal limits

Usual maintenance dose 100 mg TID

Maximum dose 200 mg TID (600 mg/day)

Key Clinical Notes:

• ⚠️ Must be co-administered with levodopa/carbidopa — no antiparkinsonian effect as monotherapy

• ⚠️ Reserve for patients failing or intolerant to entacapone due to higher hepatotoxicity risk

• Discontinue if no meaningful clinical benefit observed within 3 weeks

• Consider reducing levodopa dose by 10–30% if dyskinesias develop or worsen

Secondary Indications — Adults (Off-label)

Not applicable — no routinely 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 recommended for use below 18 years of age

• Safety and efficacy not established in paediatric population

• Not supported by Indian guidelines

• Consider only within clinical trial settings under specialist supervision

⚠️ Fatal hepatotoxicity reported — do not initiate if baseline transaminases exceed 2× ULN. Stringent LFT monitoring is mandatory throughout treatment.

• Active liver disease or baseline transaminases >2× ULN

• History of tolcapone-induced hepatotoxicity

• Moderate to severe hepatic impairment

• Hypersensitivity to tolcapone or any excipient

• Patients unable or unwilling to comply with mandatory liver function monitoring

• Pheochromocytoma (COMT inhibition elevates catecholamine levels — hypertensive crisis risk)

• Concurrent use with non-selective MAO inhibitors

• History of any hepatic impairment (even currently mild)

• Previous rhabdomyolysis or unexplained myopathy

• Pre-existing psychiatric disorders (hallucinations, psychosis, impulse control disorders)

• Orthostatic hypotension (may worsen with levodopa combination)

• Pre-existing dyskinesias (may require levodopa dose reduction)

• Elderly with polypharmacy

• History of diarrhoeal illness

Aspect Details

Risk classification Not formally classified in India; fetal toxicity observed in animal studies

Human data Insufficient

When to use Only if benefit clearly outweighs risk and levodopa therapy is essential

Preferred alternative Entacapone (if COMT inhibition necessary during pregnancy)

Monitoring Fetal movements, maternal blood pressure

Aspect Details

Compatibility Not recommended

Excretion in milk Unknown

Preferred alternative Entacapone if COMT inhibition required

Infant monitoring Feeding difficulties, sedation, lethargy

• Starting dose: 100 mg TID (same as younger adults)

• Titration: Proceed cautiously; increase only with confirmed clinical benefit and normal LFTs

• Specific risks: Orthostatic hypotension, cognitive disturbances, falls, confusion

• Monitoring: Closer hepatic monitoring advisable due to polypharmacy; regular postural blood pressure assessment

• Hepatotoxicity risk is not age-dependent but vigilance is essential

Drug/Class Mechanism/Effect Recommendation

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

Levodopa/carbidopa Enhanced dopaminergic effect → dyskinesias Reduce levodopa dose by 10–30% as clinically needed

Warfarin Metabolic interference → elevated INR Monitor INR closely; adjust warfarin dose accordingly

Hepatotoxic drugs (isoniazid, methotrexate, valproate) Additive hepatic injury risk Avoid combination or intensify LFT monitoring

Drug/Class Mechanism/Effect Recommendation

MAO-B inhibitors (selegiline, rasagiline) Additive dopaminergic effects Use with caution; monitor for serotonin syndrome

SSRIs, SNRIs Enhanced serotonergic/dopaminergic activity Monitor for neurotoxicity

Tricyclic antidepressants Additive dopaminergic effects Monitor neurological status

CYP2C9 substrates (phenytoin, tolbutamide) Potential metabolic competition Monitor drug levels where feasible

Antihypertensives Additive hypotensive effect Monitor blood pressure regularly

Iron supplements May reduce absorption Separate administration by 2 hours

• Diarrhoea (>10%; may be dose-limiting)

• Dyskinesia

• Nausea

• Sleep disturbances (vivid dreams, insomnia)

• Dizziness

• Orthostatic hypotension

• Dry mouth

• Abdominal pain

• Urine discolouration (bright yellow — benign)

• Hepatotoxicity — including fulminant hepatic failure (potentially fatal; requires immediate discontinuation)

• Rhabdomyolysis — discontinue if unexplained muscle pain, tenderness, or weakness occurs

• Neuroleptic malignant-like syndrome — on abrupt withdrawal

• Severe hallucinations, psychosis

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

• Severe diarrhoea with dehydration (may require hospitalisation)

Parameter Schedule

Baseline ALT, AST, total bilirubin (mandatory before initiation)

First 6 months LFTs every 2 weeks

6–12 months LFTs every 4 weeks

Beyond 12 months Periodic LFTs as clinically indicated

Clinical Monitoring:

• Signs of liver injury: fatigue, anorexia, jaundice, dark urine, right upper quadrant tenderness

• Levodopa dosing: reduce if dyskinesias emerge

• Blood pressure: assess for orthostatic hypotension

• Psychiatric status: impulse control behaviours, hallucinations

⚠️ Discontinue immediately if ALT/AST exceeds 3× ULN or clinical hepatotoxicity signs appear.

• Tasmar (imported; limited availability)

• No major domestic Indian brand currently marketed

• May require sourcing through neurology specialty centres or special import channels

• Limited availability; pricing varies

• Approximate: ₹200–₹300 per 100 mg tablet (imported)

• Not included in NLEM

• Not NPPA price-controlled

• May require special sourcing arrangements

1. Never use as monotherapy — tolcapone has no antiparkinsonian effect without levodopa/carbidopa

1. Entacapone is preferred first-line COMT inhibitor in India due to tolcapone's hepatotoxicity risk

1. Reserve tolcapone for patients with "wearing-off" symptoms uncontrolled by entacapone

1. 3-week rule: if no clinical improvement within 3 weeks, discontinue tolcapone

1. LFT compliance is essential — do not prescribe if patient cannot adhere to monitoring schedule

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

1. Gradual withdrawal recommended to avoid neuroleptic malignant-like syndrome

Tolcapone; Parkinson's disease; COMT inhibitor; levodopa adjunct; hepatotoxicity; motor fluctuations; wearing-off; impulse control disorder; specialist use; neurology

RxIndia v1.0 — 03 May 2025

• CDSCO

• Indian Pharmacopoeia

• AIIMS Neurology Protocols

• API Textbook of Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Manufacturer prescribing information (adapted to Indian context)