Tolcapone
- Atc Codes:N04BX01
- CAS Codes:134308-13-7
- PHARMGKB ID:134308-13-7
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Genes that may be involved
- Drug Interactions
- Nutrition/Nutraceutical Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
Europe
Austria: Tasmar; Belgium: Tasmar; Bulgaria: Tasmar; Czech Republic: Tasmar; Denmark: Tasmar; Estonia: Tasmar; France: Tasmar; Germany: Tasmar; Greece: Tasmar; Hungary: Tasmar; Ireland: Tasmar; Italy: Tasmar; Latvia: Tasmar; Lithuania: Tasmar; Luxembourg: Tasmar; Malta: Tasmar; Netherlands: Tasmar; Poland: Tasmar; Portugal: Tasmar; Romania: Tasmar; Slovakia: Tasmar; Slovenia: Tasmar; Spain: Tasmar; Sweden: Tasmar; UK: Tasmar.
North America
USA: Tasmar.
Latin America
Argentina: Tasmar; Brazil: Tasmar; Mexico: Tasmar.
Drug combinations
Chemistry
Tolcapone: C~14~H~11~NO~5~. Mw: 273.24. (1) Methanone, (3,4-dihydroxy-5-nitrophenyl)(4-methylphenyl)-; (2) 3,4-Dihydroxy-4′-methyl-5-nitrobenzophenone. CAS-134308-13-7 (1993).
Pharmacologic Category
Antiparkinsonian Agents; Catechol-O-Methyltransferase (COMT) Inhibitors. (ATC-Code: N04BX01).
Mechanism of action
A selective and reversible inhibitor of catechol-O-methyltransferase (COMT). In presence of a decarboxylase inhibitor (e.g. carbidopa), COMT is the major degradation pathway for levodopa. Inhibition of COMT leads to more sustained plasma levels of levodopa and enhanced central dopaminergic activity.
Therapeutic use
Adjunct to levodopa and carbidopa for treatment of signs and symptoms of idiopathic Parkinson’s disease in motor fluctuations not responsive to other therapies.
Pregnancy and lactiation implications
May be teratogenic; based on animal studies. There are no adequate, well-controlled studies in pregnant women. Use only if benefit outweighs risk. Excretion in breast milk unknown (not recommended in nursing women).
Unlabeled use
Contraindications
Hypersensitivity to tolcapone or any component of the formulation. History of liver disease or tolcapone-induced hepatocellular injury. Nontraumatic rhabdomyolysis or hyperpyrexia and confusion.
Warnings and precautions
Tolcapone, in conjunction with other drug therapy which alters brain biogenic amine concentrations (e.g. MAOIs, SSRIs), associated with syndrome resembling neuroleptic malignant syndrome (hyperpyrexia and confusion) on abrupt withdrawal or dosage reduction (concomitant use of tolcapone and nonselective MAOIs should be avoided). Dopaminergic agents used for Parkinson’s disease or restless legs syndrome associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Risk for melanoma development increased in Parkinson’s disease patients. May cause hallucinations, which may improve with reduction in levodopa therapy. Associated with delayed development of diarrhea (use with caution in lower GI disease or increased risk of dehydration). Fatal liver injury associated with use (use should be reserved for patients experiencing inadequate symptom control or who are not appropriate candidates for other available treatments). Severe rhabdomyolysis reported with use. May cause orthostatic hypotension and syncope. Use with caution in risk of hypotension (such as patients receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Dopaminergic agents from ergot class associated with fibrotic complications, such as retroperitoneal fibrosis, pulmonary infiltrates or effusion and pleural thickening (unknown whether non-ergot, pro-dopaminergic agents such as tolcapone confer this risk). Concomitant use of tolcapone and nonselective MAOIs should be avoided (selegiline is a selective MAO type B inhibitor (when given orally at ≤10 mg/day) and can be taken with tolcapone). Use with caution in pre-existing dyskinesias (exacerbation of pre-existing dyskinesia reported). Levodopa dosage reduction may be required, particularly in patients with levodopa dosages >600 mg daily or with moderate-to-severe dyskinesia prior to initiation. Use with caution in hepatic impairment, and in severe renal impairment.