Adult Dosing

Treatment of Parkinson's disease

• Start 100 mg PO tid, as an adjunct to levodopa/carbidopa therapy; may cautiously increase the dose to 200 mg tid, if the anticipated incremental clinical benefit is justified
• Max: 200 mg PO tid
• If there is no improvement with 600 mg/day dose after 3 weeks of therapy (irrespective of the dose), discontinue use

• Due to the risk of potentially fatal, acute fulminant liver failure, 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

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Adjunct to levodopa and carbidopa for the treatment of idiopathic Parkinson’s disease

• Hypersensitivity to any of the ingredients of the product
• Active hepatic disease
• Two SGPT/ALT or SGOT/AST values greater than the upper limit of normal
• Tolcapone-associated hepatocellular injury
• History of non-traumatic rhabdomyolysis
• History of hyperpyrexia and confusion possibly related to medication

• Due to the risk of fatal, acute fulminant liver failure, tolcapone should 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
• Discontinue therapy if the patient fails to show substantial clinical benefit within 3 weeks of therapy initiation because of the potential risk of liver injury
• Tolcapone is contraindicated in patients exhibiting clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than ULN
• Caution is advised in patients with severe dyskinesia or dystonia
• Retreatment should not be considered in patients with a history of hepatocellular injury while using tolcapone
• Postmarketing survelliance has reported cases of severe hepatocellular injury, including fulminant liver failure resulting in death. Such cases were reported within the first six months of treatment initiation. Laboratory analysis of patients participating in clinical trials showed that increases in SGPT/ALT or SGOT/AST, when present, generally occurred within the initial 6 months of therapy
• Patients should be monitored for any emergent liver injury; patients should be advised about the need for self-monitoring for both the classical signs of liver disease (jaundice, clay colored stools) and the nonspecific ones (lethargy, fatigue, loss of appetite)
• Periodic laboratory monitoring for evidence of hepatocellular injury is advised. Early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug improves the likelihood of recovery
• Determine serum AST and ALT levels at baseline, q2-4 wks for 6 months after therapy initiation, and then periodically at intervals deemed clinically relevant. Also, liver enzymes should be monitored before increasing the dose, q2-4 wks for the next 6 months, and then periodically as clinically indicated
• Discontinue therapy if SGPT/ALT or SGOT/AST levels exceed 2 times the ULN or if clinical signs and symptoms (persistent nausea, anorexia, lethargy, fatigue, jaundice, right upper quadrant tenderness, pruritus, and dark urine) suggest the onset of hepatic dysfunction

Renal dose adjustment (Based on CrCl)

• Mild to moderate renal impairment: No dose adjustments
• Severe renal impairment: Dose adjustments not defined; use with caution

Hepatic Dose Adjustment

• Active hepatic disease or two ALT or AST values greater than the ULN: Contraindicated

See Supplemental Patient Information

• Tolcapone should 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 (due to the risk of acute fulminant liver failure) [US Black Box Warning]
• Withdraw therapy in patients who fail to show substantial clinical benefit within 3 weeks of treatment initiation (due to risk of liver injury) [US Black Box Warning]
• Contraindicated in patients exhibiting clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values greater than ULN [US Black Box Warning]
• Patients who have developed hepatocellular injury while on tolcapone and are withdrawn from the drug for any reason should not be considered for re-instituting therapy due to an increased risk of liver injury [US Black Box Warning]
• Concomitant use with non-selective MAO inhibitor is not recommended
• Patients concomitantly receiving carbidopa levodopa therapy along with tolcapone have been reported to suddenly fall asleep without prior warning signs of somnolence like drowsiness. Such episodes may have serious consequences such as automobile accidents
• Avoid abrupt withdrawal of therapy due to the risk of hyperpyrexia and confusion
• Cases of orthostatic hypotension and syncope have been reported during therapy. Patients with orthostasis at baseline are more likely to have orthostatic hypotension during therapy than those without; use cautiously in patients with orthostatic hypotension
• Therapy may cause persistent diarrhea; it is advised that all cases of persistent diarrhea should be followed up with an appropriate lab work-up
• Patients may present with hallucinations after initiation of treatment, typically within the first 2 wks. Hallucinations are often accompanied by confusion, sleep disorder and excessive dreaming; reduction in levodopa dose may reduce hallucinations
• Tolcapone may exacerbate preexisting dyskinesia by potentiating the dopaminergic side effects of levodopa
• Symptom complex resembling the neuroleptic malignant syndrome such as hyperpyrexia, muscular rigidity, and confusion have been reported in association with abrupt dose reduction or withdrawal of tolcapone
• Cases of rhabdomyolysis have been reported with tolcapone treatment
• Cases of fibrotic complications, including retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening have been reported in certain patients treated with ergot-derived dopaminergic agents
• Patients with Parkinson’s disease are at a higher risk of melanoma than the general population. Patients and healthcare providers should monitor for signs of melanoma

Cautions: Use cautiously in

• Severe renal impairment
• Severe dystonia

Supplemental Patient Information

• Educate patients of the clinical signs and symptoms that suggest the onset of hepatic injury, such as persistent nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus, and right upper quadrant tenderness. Advise patients to seek medical attention if symptoms of hepatic failure occur
• Inform patients about the need to have regular blood tests to monitor liver enzymes
• Caution patients against rising rapidly after sitting or lying down, particularly if they have been doing so for long duration, and during treatment initiation
• Advise patients to refrain from driving, operating machinery, or performing any hazardous task until they have gained sufficient experience on the medication to gauge whether or not it significantly affects their mental and/or motor performance
• Instruct patients to promptly inform their physician if they experience new or increased gambling urges, increased sexual urges, or other intense urges while receiving this drug

Pregnancy: Category C

Breast feeding: Safety unknown. It is not known whether tolcapone is excreted in human milk; but as many drugs are excreted in human milk, manufacturer advises caution while administering to nursing women.

• CNS: Worsening dyskinesia, sleep disorder, excessive dreaming, somnolence, confusion, dizziness, compulsive behavior, headache, hallucinations
• GI: Nausea, anorexia, severe diarrhea, vomiting, constipation, xerostomia, abdominal pain
• HEPA: Hepatocellular injury, fulminant liver failure, hepatotoxicity
• CVS: Orthostatic hypotension, syncope
• RESP: URTI, pleural effusion
• GU: UTI, urine discoloration, hematuria
• DERM: Increased sweating
• MUSC: Muscle cramps, rhabdomyolysis, dystonia
• MISC: Fatigue, neuroleptic malignant syndrome, multiple organ failure, falling

• Anti-Parkinson agent; precise mechanism of action unknown; inhibits catechol-O-methyltransferase (COMT) and alters the plasma pharmacokinetics of levodopa
• Completely metabolized in the liver through glucuronidation; CYP450: 3A4 and 2A6
• Excretion: Urine 60% (0.5% unchanged) and feces 40%
• Half-life: 2-3 hrs

US Trade Name(s)

• Tasmar

US Availability

Tasmar

• TABS: 100 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• Tasmar

UK Availability

Tasmar

• TABS: 100 mg

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Neurologic

Antiparkinson Agents

Catechol O Methyltransferase (COMT) Inhibitors

Pricing data from www.DrugStore.com in U.S.A.

• Tasmar 200 MG TABS [Bottle] (VALEANT)
  90 mg = $660.01
  270 mg = $1959.97
• Tasmar 100 MG TABS [Bottle] (VALEANT)
  90 mg = $980.02
  270 mg = $2879.98

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

Drug Name: Tasmar 100 MG Oral Tablet

Ingredient(s): Tolcapone

Imprint: TASMAR;100;V

Color(s): Brown

Shape: Hexagon (6 sides)

Size (mm): 10.00

Score: 1

Inactive Ingredient(s): lactose monohydrate / microcrystalline cellulose / dibasic calcium phosphate anhydrous / povidone k-30 / sodium starch glycolate / talc / magnesium stearate / hydroxypropyl methycellulose / titanium dioxide / ethylcellulose / triacetin / sodium lauryl sulfate / yellow iron oxide / red iron oxide

Drug Label Author:
Valeant Pharmaceuticals, Inc.

DEA Schedule:
Non-Scheduled

Drug Name: Tasmar 200 MG Oral Tablet

Ingredient(s): Tolcapone

Imprint: TASMAR;200;V

Color(s): Brown

Shape: Hexagon (6 sides)

Size (mm): 13.00

Score: 1

Inactive Ingredient(s): lactose monohydrate / microcrystalline cellulose / dibasic calcium phosphate anhydrous / povidone k-30 / sodium starch glycolate / talc / magnesium stearate / hydroxypropyl methycellulose / titanium dioxide / ethylcellulose / triacetin / sodium lauryl sulfate / red iron oxide

Drug Label Author:
Valeant Pharmaceuticals, Inc.

DEA Schedule:
Non-Scheduled