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the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from TASMAR.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PATIENTS WHO DEVELOP EVIDENCE OF HEPATOCELLULAR INJURY WHILE ON TASMAR AND ARE WITHDRAWN FROM THE DRUG FOR ANY REASON MAY BE AT INCREASED RISK FOR LIVER INJURY IF TASMAR IS REINTRODUCED.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.
Cases of severe hepatocellular injury, including fulminant liver failure resulting in death, have been reported in postmarketing use. As of May 2005, 3 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. Underreporting of cases may lead to significant underestimation of the increased risk associated with the use of TASMAR. All 3 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.
A prescriber who elects to use TASMAR in face of the increased risk of liver injury is strongly advised to monitor patients for evidence of emergent liver injury. Patients should be advised of the need for self-monitoring for both the classical signs of liver disease (eg, clay colored stools, jaundice) and the nonspecific ones (eg, fatigue, loss of appetite, lethargy).
Although a program of periodic laboratory monitoring for evidence of hepatocellular injury is recommended, it is not clear that periodic monitoring of liver enzymes will prevent the occurrence of fulminant liver failure. However, it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Accordingly, the following liver monitoring program is recommended.
Before starting treatment with TASMAR, the physician should conduct appropriate tests to exclude the presence of liver disease. In patients determined to be appropriate candidates for treatment with TASMAR, serum glutamic-pyruvic transaminase (SGPT/ALT) and serum glutamic-oxaloacetic transaminase (SGOT/AST) levels should be determined at baseline and periodically (i.e. every 2 to 4 weeks) for the first 6 months of therapy. After the first six months, periodic monitoring is recommended at intervals deemed clinically relevant. Although more frequent monitoring increases the chances of early detection, the precise schedule for monitoring is a matter of clinical judgement. If the dose is increased to 200 mg tid (see DOSAGE AND ADMINISTRATION section), liver enzyme monitoring should take place before increasing the dose and then be conducted every 2 to 4 weeks for the following 6 months of therapy. After six months, periodic monitoring is recommended at intervals deemed clinically relevant.
TASMAR should be discontinued if SGPT/ALT or SGOT/AST levels exceed 2 times the upper limit of normal or if clinical signs and symptoms suggest the onset of hepatic dysfunction (persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, and right upper quadrant tenderness).
TASMARÂ® is available as tablets containing 100 mg or 200 mg tolcapone.
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. 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.
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Published Studies Related to Tasmar (Tolcapone)
Replacing a dopamine agonist by the COMT-inhibitor tolcapone as an adjunct to L-dopa in the treatment of Parkinson's disease: a randomized, multicenter, open-label, parallel-group study. [2010.05]
OBJECTIVE: This study investigated the feasibility, safety, and potential benefit in motor symptom control when switching from a dopamine agonist to tolcapone as an adjunctive therapy in patients with Parkinson's disease with a fluctuating response to levodopa (l-dopa). We determined the efficacy of 2 replacement strategies... CONCLUSIONS: Tolcapone, in principle, seems to be an alternative adjunct for patients, who fail to receive sufficient benefit from a dopamine agonist, for example, in case they do not tolerate an increase in dose or have unacceptable side effects. The switch from a dopamine agonist to tolcapone can be done safely within a few days.
Tolcapone effects on gating, working memory, and mood interact with the synonymous catechol-O-methyltransferase rs4818c/g polymorphism. [2009.12.01]
BACKGROUND: The functional catechol-O-methyltransferase (COMT) valine158methionine (val158met) polymorphism determines prepulse inhibition (PPI) levels and working memory performance and the effects of tolcapone on these functions. Here, we explored the effects of the synonymous COMT rs4818 C/G polymorphism and tolcapone on PPI and working memory... CONCLUSIONS: Catechol-O-methyltransferase haplotype analyses are essential in future research. Prepulse inhibition and working memory may both relate to PFC DA levels according to an inverted U-shaped curve function. Tolcapone could be potentially useful in the treatment of conditions with deficient sensorimotor gating and working memory such as schizophrenia and prodromal states but only in a genotype-specific manner.
Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism. [2008.12]
Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working memory of subjects homozygous for the Val (low PFC DA) and the Met (high PFC DA) alleles of the COMT Val158Met polymorphism...
Safety and tolerability of adjunctive tolcapone treatment in patients with early Parkinson's disease. [2007.09]
OBJECTIVE: The safety and tolerability of adjunctive tolcapone initiated simultaneously with levodopa was evaluated with a focus on increases in liver transaminase and hepatotoxicity... CONCLUSIONS: Tolcapone seemed to be safe and was generally well tolerated as an adjunctive treatment in patients starting treatment with carbidopa/levodopa for symptomatic PD. Mild increases in transaminase levels--< 3 times the ULN--occurred commonly in both placebo and tolcapone treated patients, whereas potentially serious increases of up to > or = 3 times the ULN were infrequent.
18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson's disease. [2002.03.01]
Tolcapone is a potent, selective, and reversible inhibitor of cathecol-O-methyl-transferase (COMT)... These findings are compatible with clinical doses of tolcapone having a significant blocking effect on peripheral and central COMT but not DDC activity in PD.
Clinical Trials Related to Tasmar (Tolcapone)
Tolcapone Treatment of Pathological Gambling [Completed]
Role of the Catechol-O-methyltransferase (COMT) in the Physiological Regulation of Vigilance [Completed]
In this study, pharmacologic effects of COMT inhibition during sleep deprivation in healthy
subjects in dependence of their Val158Met genotype of COMT are studied. Potential effects
are identified by measurement of vigilance and cognitive performance as well as EEG
measurements during wake and sleep.
- Trial with medicinal product
Pilot Study of Tolcapone in Smokers [Completed]
The goals of this within-subject pilot study are: (1) assess the feasibility and safety of
administering the Catechol-O-Methyl-Transferase (COMT) inhibitor, tolcapone, to smokers, and
(2) explore whether tolcapone may reduce abstinence-induced cognitive and affective symptoms
that promote relapse. A secondary exploratory goal is to assess whether these effects may
be more pronounced in smokers who carry a high risk COMT genotype for smoking relapse: COMT
Effects of Tolcapone on Frontotemporal Dementia [Recruiting]
This study will test the effects of a medication called tolcapone on cognitive, behavioral,
and language problems seen in patients with frontotemporal dementia (FTD). Tolcapone
increases the amount of dopamine, a brain chemical that may be lowered in FTD. The study
will see if tolcapone can improve thinking, behavior, and language in people with FTD and
will look at the effects of the drug on brain activity.
Patients with FTD who are between 40 and 85 years of age may be eligible for this study.
Participants will be seen as outpatients at the Columbia University Medical Center
approximately one a week for 4 weeks. They take tolcapone or a placebo (a look-alike pill
with no active ingredient) during study week 1. During study week 3, those who took placebo
during week 1 now take tolcapone for 1 week and those who took tolcapone now take placebo.
In addition, patients undergo the following tests and procedures:
- Neurological tests to evaluate attention, problem-solving and memory. These tests are
repeated several times during the course of the study.
- Test to look for a gene that affects the amount of dopamine in the brain, using blood
samples collected in a previous study.
- Blood draws four times during the study.
- Functional MRI (fMRI) to learn about changes in brain regions that are involved in
performing tasks. For fMRI, the patient lies on a table that can slide in and out of
the scanner, a narrow metal cylinder surrounded by a magnetic field. The procedure
takes about 60 minutes and is performed four times over the course of the . FMRI
involves taking pictures of the brain during MRI while the subject performs a task so
that changes in the brain that occur during these tasks can be studied.
Treatment for Nicotine Addiction in Women [Not yet recruiting]
The purpose of this study is to use a medication tolcapone and or placebo to test if the
symptoms of nicotine withdrawal lessens , and or changes in smoking urges, and mental
reasoning in female smokers over a 72 hour period.
Reports of Suspected Tasmar (Tolcapone) Side Effects
Pathological Gambling (4),
Generalised Oedema (2),
Impulse-Control Disorder (2),
Pleural Effusion (2),
Congestive Cardiomyopathy (2),
Atrial Fibrillation (2),
Abnormal Behaviour (2),
Cardiac Failure (2), more >>
Page last updated: 2015-08-28