Drug reference

Tolcapone

COMT Inhibitor · Antiparkinsonian

COMT InhibitorAntiparkinsonian

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Toxicity in animal studies. Use only if potential benefit outweighs risk.

FDA category + note

Top interactionssee all 12 →

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Mechanism

Tolcapone prevents the peripheral breakdown of levodopa by inhibiting catechol-O-methyltransferase (COMT). This action increases the bioavailability of levodopa, allowing a greater amount to reach the brain where it can be converted to dopamine.

Indications

Adjunct to co-beneldopa or co-careldopa in Parkinson’s disease with ‘end-of-dose’ motor fluctuations if another inhibitor of peripheral catechol-O-methyltransferase is inappropriate (under expert supervision)Parkinson's disease (adjunct to L-DOPA)Adjunctive PD therapy given with each dose of levodopa, for "wearing-off"Used as an adjuvant to levodopa-carbidopa for advanced and fluctuating Parkinson's disease (reserved for those not responding to entacapone in some regions due to safety concerns)

Dosing

Adult: 100 mg 3 times a day, continuing beyond 3 weeks only if substantial improvement, leave 6 hours between each dose.
Renal adjustment: Caution if eGFR less than 30 mL/minute/1.73 m2.
Hepatic adjustment: Avoid in severe hepatic impairment. Consider dose reduction in moderate hepatic impairment.
Max dose: 200 mg per dose (max 600 mg daily)

Pharmacokinetics

Duration

relatively long duration of action

Contraindications

Phaeochromocytoma
Previous history of hyperthermia
Previous history of neuroleptic malignant syndrome
Previous history of rhabdomyolysis
Severe dyskinesia
Severe hepatic impairment
Re-introduction after discontinuation due to abnormal liver function tests or symptoms of liver disorder
Acute fatal hepatitis (in some regions)
Rhabdomyolysis (in some regions)

Side effects

Common

Appetite decreasedChest painConfusionConstipationDiarrhoeaDizzinessDrowsinessDry mouthGastrointestinal discomfortHallucinationHeadacheHyperhidrosisInfluenza like illnessMovement disordersNauseaPostural hypotensionSleep disordersSyncopeUpper respiratory tract infectionUrine discolourationVomitingorthostatic hypotensionvivid dreamshallucinationsyellow-orange discolouration of urinedyskinesia

Serious