Tolcapone

Tolcapone is a selective and reversible inhibitor of catechol- O -methyltransferase (COMT). In mammals, COMT is distributed throughout various organs.

• TASMAR is indicated as an adjunct to levodopa and carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson's disease. Because of the risk of potentially fatal, acute fulminant liver failure, TASMAR (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies.ICD-10: G20

• TASMAR tablets are contraindicated in patients with liver disease, in patients who were withdrawn from TASMAR because of evidence of TASMAR-induced hepatocellular injury or who have demonstrated hypersensitivity to the drug or its ingredients. TASMAR is also contraindicated in patients with a history of nontraumatic rhabdomyolysis or hyperpyrexia and confusion possibly related to medication (see PRECAUTIONS: Events Reported With Dopaminergic Therapy ).contraindicated

Because of the risk of potentially fatal, acute fulminant liver failure, TASMAR (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies (see INDICATIONS and DOSAGE AND ADMINISTRATION sections). BECAUSE OF THE RISK OF LIVER INJURY AND BECAUSE TASMAR WHEN IT IS EFFECTIVE PROVIDES AN OBSERVABLE SYMPTOMATIC BENEFIT, THE PATIENT WHO FAILS TO SHOW SUBSTANTIAL CLINICAL BENEFIT WITHIN 3 WEEKS OF INITIATION OF TREATMENT, SHOULD BE WITHDRAWN FROM TASMAR. TASMAR therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis ). Patients who develop evidence of hepatocellular injury while on TASMAR and are withdrawn from the drug for any reason may be at increased risk for liver injury if TASMAR is reintroduced. These patients should not ordinarily be considered for retreatment with TASMAR. Only prescribe TASMAR for patients taking concomitant carbidopa levodopa therapy. The initial dose of TASMAR is always 100 mg three times per day. The recommended daily dose of TASMAR is also 100 mg tid. In clinical trials, elevations in ALT occurred more frequently at the dose of 200 mg tid.

(see BOXED WARNING ) Because of the risk of potentially fatal, acute fulminant liver failure, TASMAR (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies (see INDICATIONS and DOSAGE AND ADMINISTRATION sections). Because of the risk of liver injury and because TASMAR, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from TASMAR. TASMAR therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. Patients with severe dyskinesia or dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis ). Patients who develop evidence of hepatocellular injury while on TASMAR and are withdrawn from the drug for any reason may be at increased risk for liver injury if TASMAR is reintroduced. Accordingly, such patients should not ordinarily be considered for retreatment. In controlled Phase 3 trials, increases to more than 3 times the upper limit of normal in ALT or AST occurred in approximately 1% of patients at 100 mg tid and 3% of patients at 200 mg tid. Females were more likely than males to have an increase in liver enzymes (approximately 5% vs 2%). Approximately one third of patients with elevated enzymes had diarrhea.

Cases of severe hepatocellular injury, including fulminant liver failure resulting in death, have been reported in postmarketing use. As of May 2005, three cases of fatal fulminant hepatic failure have been reported from more than 40,000 patient years of worldwide use. This incidence may be 10- to 100-fold higher than the background incidence in the general population. All three cases were reported within the first six months of initiation of treatment with TASMAR. Analysis of the laboratory monitoring data in over 3,400 TASMAR-treated patients participating in clinical trials indicated that increases in SGPT/ALT or SGOT/AST, when present, generally occurred within the first 6 months of treatment with TASMAR. The imprecision of the estimated increase is due to uncertainties about the base rate and the actual number of cases occurring in association with TASMAR. The incidence of idiopathic potentially fatal fulminant hepatic failure (i.e., not due to viral hepatitis or alcohol) is low. One estimate, based upon transplant registry data, is approximately 3/1,000,000 patients per year in the United States. Whether this estimate is an appropriate basis for estimating the increased risk of liver failure among TASMAR users is uncertain. TASMAR users, for example, differ in age and general health status from candidates for liver transplantation. Similarly, underreporting of cases may lead to significant underestimation of the increased risk associated with the use of TASMAR.

Pregnancy: Tolcapone, when administered alone during organogenesis, was not teratogenic at doses of up to 300 mg/kg/day in rats or up to 400 mg/kg/day in rabbits (5.7 times and 15 times the recommended daily clinical dose of 600 mg, on a mg/m 2 basis, respectively). In rabbits, however, an increased rate of abortion occurred at a dose of 100 mg/kg/day (3.7 times the daily clinical dose on a mg/m 2 basis) or greater. Evidence of maternal toxicity (decreased weight gain, death) was observed at 300 mg/kg in rats and 400 mg/kg in rabbits. When tolcapone was administered to female rats during the last part of gestation and throughout lactation, decreased litter size and impaired growth and learning performance in female pups were observed at a dose of 250/150 mg/kg/day (dose reduced from 250 to 150 mg/kg/day during late gestation due to high rate of maternal mortality; equivalent to 4.8/2.9 times the clinical dose on a mg/m 2 basis). Tolcapone is always given concomitantly with levodopa/carbidopa, which is known to cause visceral and skeletal malformations in rabbits. The combination of tolcapone (100 mg/kg/day) with levodopa/carbidopa (80/20 mg/kg/day) produced an increased incidence of fetal malformations (primarily external and skeletal digit defects) compared to levodopa/carbidopa alone when pregnant rabbits were treated throughout organogenesis.

Metabolism

Effect on the Pharmacokinetics of Levodopa and its Metabolites: When tolcapone is administered together with levodopa/carbidopa, it increases the relative bioavailability (AUC) of levodopa by approximately twofold. This is due to a decrease in levodopa clearance resulting in a prolongation of the terminal elimination half-life of levodopa (from approximately 2 hours to 3.5 hours).

The highest dose of tolcapone administered to humans was 800 mg tid, with and without levodopa/carbidopa co-administration. This was in a 1-week study in elderly, healthy volunteers. The peak plasma concentrations of tolcapone at this dose were on average 30 mcg/mL (compared to 3 mcg/mL and 6 mcg/mL with 100 mg and 200 mg tolcapone, respectively). Nausea, vomiting and dizziness were observed, particularly in combination with levodopa/carbidopa. The threshold for the lethal plasma concentration for tolcapone based on animal data is >100 mcg/mL. Respiratory difficulties were observed in rats at high oral (gavage) and intravenous doses and in dogs with rapidly injected intravenous doses. Management of Overdose: Hospitalization is advised. General supportive care is indicated. Based on the physicochemical properties of the compound, hemodialysis is unlikely to be of benefit.

• Jan 29, 1998NDANDA020697Bausch
• Aug 7, 2018ANDAANDA208937Ingenus Pharms Llc

1. 1Fall298.5%
2. 2Hallucination277.9%
3. 3Dyskinesia267.6%
4. 4Death236.7%
5. 5Drug Ineffective205.8%
6. 6Pneumonia205.8%
7. 7General Physical Health Deterioration195.5%
8. 8Hyperkinesia185.2%
9. 9Dyspnoea175.0%
10. 10Akinesia164.7%
11. 11Confusional State154.4%
12. 12On And Off Phenomenon154.4%
13. 13Pathological Gambling154.4%
14. 14Tremor144.1%
15. 15Somnolence133.8%

Recent PubMed references pinned to Tolcapone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• The Seminal Role of the Proinflammatory Cytokine IL-1β and Its Signaling Cascade in Glioblastoma Pathogenesis and the Therapeutic Effect of Interleukin-1β Receptor Antagonist (IL-1RA) and Tolcapone.
  International journal of molecular sciences · 2025 · Narasimhappagari J, Liu L, Balasubramaniam M, et al.
  PMID 40725140DOI 10.3390/ijms26146893
• Effects of COMT Suppression in a Randomized Trial on the Neural Correlates of Inhibitory Processing Among People With Alcohol Use Disorder.
  Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025 · Winters DE, Schacht JP
  PMID 40517954DOI 10.1016/j.bpsc.2025.06.003
• Rescuing a Troubled Tolcapone with PEGylated PLGA Nanoparticles: Design, Characterization, and Hepatotoxicity Evaluation.
  ACS applied materials & interfaces · 2024 · Pinto M, Machado CS, Barreiro S, et al.
  PMID 38647198DOI 10.1021/acsami.4c00614
• A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans.
  CNS spectrums · 2024 · Kings E, Ioannidis K, Grant JE, et al.
  PMID 38487834DOI 10.1017/S1092852924000130
• Tolcapone in obsessive-compulsive disorder: a randomized double-blind placebo-controlled crossover trial.
  International clinical psychopharmacology · 2021 · Grant JE, Hook R, Valle S, et al.
  PMID 34310432DOI 10.1097/YIC.0000000000000368
• Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase from Entamoeba histolytica and Giardia lamblia Identifies Inhibitors of Their Trophozoite Growth Phase.
  International journal of molecular sciences · 2021 · Juárez-Saldivar A, Barbosa-Cabrera E, Lara-Ramírez EE, et al.
  PMID 34073021DOI 10.3390/ijms22115943
• Assessment of the impact of mitochondrial genotype upon drug-induced mitochondrial dysfunction in platelets derived from healthy volunteers.
  Archives of toxicology · 2021 · Ball AL, Bloch KM, Rainbow L, et al.
  PMID 33585966DOI 10.1007/s00204-021-02988-3
• Safety and efficacy of tolcapone in Parkinson's disease: systematic review.
  European journal of clinical pharmacology · 2021 · Artusi CA, Sarro L, Imbalzano G, et al.
  PMID 33415500DOI 10.1007/s00228-020-03081-x

The 10 most recently updated of 28 ClinicalTrials.gov registrations naming Tolcapone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Clinical Trial of Tolcapone in Obsessive Compulsive Disorder
  Active not recruiting · Phase 2 · Interventional · 49 enrolled · University of Chicago
  NCT05624528updated 2026-06-10
• COMT Inhibition Among Individuals With Comorbid AUD/ADHD
  Completed · Phase 2 · Interventional · 23 enrolled · University of Colorado, Denver
  NCT03904498updated 2026-05-04
• Microbiome Derived Metabolism and Pharmacokinetics
  Completed · Phase 1 · Interventional · 17 enrolled · Rutgers, The State University of New Jersey
  NCT05065671updated 2026-04-29
• Remediation of Impaired Self-Regulation in Patients With Mild TBI
  Completed · Early phase 1 · Interventional · 55 enrolled · VA Office of Research and Development
  NCT02260570updated 2025-09-22
• Gait Analysis in Neurological Disease
  Recruiting · Observational · 120 enrolled · Beth Israel Deaconess Medical Center
  NCT02994719updated 2025-06-08
• Effects of Tolcapone on Frontotemporal Dementia
  Completed · Phase 2 · Interventional · 28 enrolled · Columbia University
  NCT00604591updated 2024-08-28
• Trial of Tolcapone With Oxaliplatin for Neuroblastoma
  Terminated · Phase 1 · Interventional · 5 enrolled · Giselle Sholler
  NCT02630043updated 2024-08-06
• Dopaminergic Mechanisms Underlying Human Social Behavior
  Completed · Early phase 1 · Interventional · 70 enrolled · University of California, Berkeley
  NCT04205994updated 2024-05-16
• Evaluation of Tolcapone as a Cognitive Enhancer in Schizophrenia
  Unknown · Phase 2 · Interventional · 20 enrolled · Clinica Universidad de Navarra, Universidad de Navarra
  NCT06387771updated 2024-04-29
• Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control
  Completed · Phase 2 · Interventional · 90 enrolled · Medical University of South Carolina
  NCT02949934updated 2023-06-09

Frequently asked questions

How does Tolcapone work?

Tolcapone is a selective and reversible inhibitor of catechol- O -methyltransferase (COMT). In mammals, COMT is distributed throughout various organs.

What is Tolcapone used for?

According to FDA labeling, Tolcapone carries indications including: TASMAR is indicated as an adjunct to levodopa and carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson's disease. Because of the risk of potentially fatal, acute fulminant liver failure, TASMAR (tolcapone) should ordinarily be used in patients with Parkinson's disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tolcapone?

Tolcapone is classified as Other dopaminergic agents, Catechol-O-Methyltransferase Inhibitor, Catechol O-Methyltransferase Inhibitors, Increased Central Nervous System Dopamine Activity.

What are the brand names for Tolcapone?

Tolcapone is marketed under brand names including Tasmar.

What are the contraindications for Tolcapone?

Tolcapone labeling lists contraindications including: TASMAR tablets are contraindicated in patients with liver disease, in patients who were withdrawn from TASMAR because of evidence of TASMAR-induced hepatocellular injury or who have demonstrated hypersensitivity to the drug or its ingredients. TASMAR is also contraindicated in patients with a history of nontraumatic rhabdomyolysis or hyperpyrexia and confusion possibly related to medication (see PRECAUTIONS: Events Reported With Dopaminergic Therapy ).. Always consult the full prescribing information and a clinician.