|Manufacturer:||Valeant Pharmaceuticals, Inc.|
|Other Info:||Before prescribing TASMAR, the physician should be thoroughly familiar with the details of this prescribing information.TASMAR SHOULD NOT BE USED BY PATIENTS UNTIL THERE HAS BEEN A COMPLETE DISCUSSION OF THE RISKS AND THE PATIENT HAS PROVIDED WRITTEN ACKNOWLEDGEMENT THAT THE RISKS HAVE BEEN EXPLAINED (SEE PATIENT ACKNOWLEDGEMENT OF RISKS SECTION).|
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the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from TASMAR.The effectiveness of TASMAR was demonstrated in randomized controlled trials in patients receiving concomitant levodopa therapy with carbidopa or another aromatic amino acid decarboxylase inhibitor who experienced end of dose wearing-off phenomena as well as in patients who did not experience such phenomena (seeCLINICAL PHARMACOLOGY: Clinical Studies).
(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the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from TASMAR.TASMAR therapy should not be initiated if the patient exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than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.
Increases to more than 8 times the upper limit of normal in liver enzymes occurred in 0.3% at 100 mg tid and 0.7% at 200 mg tid.
Elevated enzymes led to discontinuation in 0.3% and 1.7% of patients treated with 100 mg tid and 200 mg tid, respectively.
Elevations usually occurred within 6 weeks to 6 months of starting treatment.
In about half the cases with elevated liver enzymes, enzyme levels returned to baseline values within 1 to 3 months while patients continued TASMAR treatment.
When treatment was discontinued, enzymes generally declined within 2 to 3 weeks but in some cases took as long as 1 to 2 months to return to normal.Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines.
It is theoretically possible, therefore, that the combination of TASMAR and a non-selective MAO inhibitor (eg, phenelzine and tranylcypromine) would result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism.For this reason, patients should ordinarily not be treated concomitantly with TASMAR and a non-selective MAO inhibitor.Tolcapone can be taken concomitantly with a selective MAO-B inhibitor (eg, selegiline).