tolcapone


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tolcapone

 [tōl´kah-pōn″]
an agent used as an adjunct to levodopa and carbidopa in treatment of Parkinson's disease.

tolcapone

Tasmar

Pharmacologic class: Catecholamine inhibitor

Therapeutic class: Antiparkinsonian

Pregnancy risk category C

FDA Box Warning

Before prescribing or administering drug, make sure you're thoroughly familiar with prescribing information.

Don't administer until prescriber has discussed risks with patient and patient has provided written acknowledgment that risks have been explained.

Due to risk of hepatocellular injury (including potentially fatal, acute fulminant liver failure), drug ordinarily should be used in patients with Parkinson's disease who are receiving L-dopa/carbidopa, experiencing symptom fluctuations, and not responding satisfactorily to or not appropriate candidates for other adjunctive therapies. Withdraw therapy if patient doesn't show substantial benefit within 3 weeks of starting drug.

Don't initiate therapy if patient has clinical evidence of hepatic disease. Don't restart therapy if patient developed hepatocellular injury while receiving drug and was withdrawn from therapy for any reason.

Before and during therapy, obtain appropriate tests to exclude liver disease. Discontinue drug if alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceed two times the upper limit of normal or if clinical signs and symptoms suggest onset of hepatic dysfunction.

Action

Unknown. When given with levodopacarbidopa, thought to reversibly inhibit catechol O-methyltransferase, leading to increased levodopa bioavailability and stimulation in brain.

Availability

Tablets: 100 mg, 200 mg

Indications and dosages

Adjunct to levodopa-carbidopa in idiopathic Parkinson's disease

Adults: Initially, 100 mg P.O. t.i.d. given with levodopa-carbidopa. If beneficial, may increase dosage to 200 mg P.O. t.i.d.; maximum dosage is 600 mg daily. If response inadequate after 3 weeks, stop therapy.

Contraindications

• Hypersensitivity to drug
• Nontraumatic rhabdomyolysis
• Drug-related hyperpyrexia or confusion
• Hepatic disease, alanine aminotransferase or aspartate aminotransferase elevation
• History of tolcapone-induced hepatocellular injury

Precautions

Use cautiously in:
• renal or cardiac disease, hypertension, asthma
• concurrent use of nonselective MAO inhibitor (such as phenelzine, tranylcypromine)
• pregnant or breastfeeding patients.

Administration

Before giving first dose, obtain patient's written informed consent for drug therapy.
• Check liver function tests before starting drug.

Don't stop drug abruptly, because this may cause a syndrome similar to neuroleptic malignant syndrome.
• Know that levodopa-carbidopa dosage may be decreased to minimize dyskinesia.

Adverse reactions

CNS: dizziness, asthenia, headache, fatigue, hypokinesia, mental deficiency, agitation, tremor, hyperactivity, paresthesia, irritability, syncope, depression, speech disorder, confusion, sleep disorder, excessive dreaming, hallucinations, drowsiness, hypertonia, imbalance, falling, hyperkinesias, dystonia, dyskinesia

CV: hypotension, chest discomfort or pain, orthostatic hypotension, palpitations

EENT: tinnitus, sinus congestion, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, abdominal pain, flatulence, dry mouth, anorexia

GU: hematuria, urinary tract infection (UTI), urinary incontinence, urine discoloration, urinary disorder, erectile dysfunction

Hepatic: jaundice, severe hepatocellular injury (including fulminant hepatic failure, death)

Musculoskeletal: neck pain, arthritis, muscle cramps, stiffness, rhabdomyolysis

Respiratory: upper respiratory infection, dyspnea, bronchitis

Skin: rash, dermal bleeding, diaphoresis

Other: fever, influenza

Interactions

Drug-drug. Desipramine: increased risk of adverse tolcapone reactions

Nonselective MAO inhibitors (such as phenelzine, tranylcypromine): inhibition of principal pathways of tolcapone metabolism

Warfarin: increased warfarin blood level

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase: increased levels

Patient monitoring

• Monitor parkinsonian symptoms during first 3 weeks of therapy. Report improvement (or lack thereof) to help determine if therapy should continue.
• Assess neurologic status closely.

Monitor liver function tests. Watch closely for signs and symptoms of hepatic impairment.
• Closely monitor temperature. Stay alert for fever and other indications of infection (particularly upper respiratory infection, influenza, and UTI).

Patient teaching

• Tell patient to take drug with first levodopa-carbidopa dose of day.

2Advise patient to immediately report signs or symptoms of liver problems (persistent nausea, fatigue, appetite loss, dark urine, itching, tenderness on right side of abdomen, and yellowing of skin or eyes).
• Instruct patient to promptly report signs and symptoms of infection.

Advise female patient to immediately report suspected pregnancy. Caution her not to breastfeed.
• Tell patient drug may cause involuntary movements, hallucinations, light-headedness, and other significant reactions. Urge him to use safety measures as needed.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Advise patient to move slowly when sitting up or standing, to avoid dizziness from sudden blood pressure decrease.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

tolcapone

/tol·ca·pone/ (tōl´kah-pōn″) an antidyskinetic used as an adjunct to levodopa and carbidopa in the treatment of Parkinson's disease.

tolcapone

an antiparkinsonian agent.
indication It is used in the treatment of parkinsonism.
contraindication Known hypersensitivity to this drug prohibits its use.
adverse effects Life-threatening effects include hemolytic anemia, leukopenia, and agranulocytosis. Other adverse reactions include dystonia, dyskinesia, dreaming, psychosis, hallucinations, dizziness, chest pain, hypotension, cataract, eye inflammation, diarrhea, constipation, urinary tract infection, urine discoloration, uterine tumor, micturition disorder, sweating, and alopecia. Common side effects include fatigue, headache, confusion, orthostatic hypotension, nausea, vomiting, anorexia, and abdominal distress.

tolcapone

Tasmar® Neurology A COMT inhibitor used with levodopa/carbidopa to treat Parkinson's disease Adverse effects Liver toxicity
References in periodicals archive ?
Persons who used levodopa, entacapone, tolcapone, ropinirole, pramipexole, apomorphine, bromocriptine, or selegiline were directly contacted by phone and invited to be examined by a neurologist unless a) they reported taking small doses of dopamine agonists for restless leg syndrome, b) treatment was discontinued after [less than or equal to] 1 month, or c) there was a documented history of drug-induced parkinsonism.
In the study, published online today (March 19) in the journal Current Biology, participants on two separate visits received a pill containing either a placebo or tolcapone, a drug that prolongs the effects of dopamine, a brain chemical associated with reward and motivation in the prefrontal cortex.
COMT inhibitors: Entacapone is a peripherally acting COMT inhibitor, while tolcapone is able to cross the blood-brain barrier and acts both peripherally and in the CNS.
In a double-blinded, placebo-controlled study, 23 adult research participants were given either tolcapone, a medication approved by the Food and Drug Administration (FDA) that inhibits a dopamine-degrading enzyme, or a placebo.
For example, the COMT inhibitor, tolcapone (Tasmar[R]), has been withdrawn from use in several countries (excluding the US) because it can increase liver problems by as much as 100%.
Also, hepalotoxicity is associated with tolcapone (but not entacapone), and patients taking tolcapone must give informed consent and take twice-monthly hepatic function tests for 6 months.
11) Tolcapone, a clinically approved COMT inhibitor for the treatment of PD, assists in managing problematic symptoms through maintenance of dopamine levels.
For motor fluctuations, the panel recommended that entacapone and rasagiline be offered, while pergolide, pramipexole, ropinirole, and tolcapone may be considered to reduce "off time" in PD.
The co-promotion deal will also give both companies an increased profile within the field of neurology, a goal that Valeant has already taken great steps towards with its recent acquisition of the COMT inhibitor tolcapone (Tasmar(R)), which has received widespread support from movement disorders specialists and will be relaunched in the UK early next year.
Effect of tolcapone, a catechol-O-methyl-transferase inhibitor, on striatal dopaminergic transmission during blockade of dopamine uptake.
Tolcapone (Tasmar) is the first COMT inhibitor to be available and works both peripherally and centrally to allow a greater half-life of levodopa and dopamine.
The study 'Tolcapone (CAS 134308-13-7) Market Research Report 2011' presents an overview of the Tolcapone market globally and regionally by contemplating and analyzing its parameters.