No

Anti-Parkinson's Agent (COMT Inhibitor)

Adjunct to levodopa and carbidopa for the treatment of signs and symptoms of idiopathic Parkinson's disease

C

Hypersensitivity to tolcapone or any component

Due to reports of fatal liver injury associated with use of this drug, the manufacturer is advising that tolcapone be reserved for use only in patients who do not have severe movement abnormalities and who do not respond to or who are not appropriate candidates for other available treatments. Use with caution in patients with pre-existing dyskinesias, hepatic impairment, or severe renal impairment. May cause orthostatic hypotension; Parkinson's disease patients appear to have an impaired capacity to respond to a postural challenge; use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Parkinson's patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and should be informed of this risk. May cause hallucinations, which may improve with reduction in levodopa therapy. Use with caution in patients with lower gastrointestinal disease or an increased risk of dehydration - tolcapone has been associated with delayed development of diarrhea (onset after 2-12 weeks).

Although not reported for tolcapone, other dopaminergic agents have been associated with a syndrome resembling neuroleptic malignant syndrome on withdrawal or significant dosage reduction after long-term use. Dopaminergic agents from the ergot class have also been associated with fibrotic complications, such as retroperitoneum, lungs, and pleura.

>10%:

Cardiovascular: Orthostatic hypotension

Central nervous system: Sleep disorder, excessive dreaming, somnolence, headache

Gastrointestinal: Nausea, diarrhea, anorexia

Neuromuscular & skeletal: Dyskinesia, dystonia, muscle cramps

1% to 10%:

Central nervous system: Hallucinations, fatigue, loss of balance, hyperkinesia

Gastrointestinal: Vomiting, constipation, xerostomia, abdominal pain, flatulence, dyspepsia

Genitourinary: Urine discoloration

Neuromuscular & skeletal: Paresthesia, stiffness

Miscellaneous: Diaphoresis (increased)

CYP3A4 and CYP2A6 enzyme substrate; COMT inhibition could slow the metabolism of methyldopa, dobutamine, apomorphine, and isoproterenol

Tolcapone is a selective and reversible inhibitor of catechol-o-methyltransferase (COMT)

Protein binding: >99.0%

Bioavailability: 65%

Half-life: 2-3 hours

Time to peak: Within 2 hours

Metabolism: Glucuronidation

Elimination: In urine and feces (40%)

Adults: Oral: Initial: 100-200 mg 3 times/day; levodopa therapy may need to be decreased upon initiation of tolcapone

Tolcapone taken with food within 1 hour before or 2 hours after the dose decreases bioavailability by 10% to 20%

Blood pressure, symptoms of Parkinson's disease, liver enzymes at baseline and then every 2 weeks for the first year of therapy, every 4 weeks for the next 6 months, then every 8 weeks thereafter. If the dose is increased to 200 mg 3 times/day, reinitiate LFT monitoring at the previous frequency. Discontinue therapy if the ALT or AST exceeds the upper limit of normal or if the clinical signs and symptoms suggest the onset of liver failure.

No information available to require special precautions

Dopaminergic therapy in Parkinson's disease (ie, treatment with levodopa) is associated with orthostatic hypotension. Tolcapone enhances levodopa bioavailability and may increase the occurrence of hypotension/syncope in the dental patient. The patient should be carefully assisted from the chair and observed for signs of orthostatic hypotension.

Take exactly as directed (may be prescribed in conjunction with levodopa/carbidopa); do not change dosage or discontinue without consulting prescriber. Therapeutic effects may take several weeks or months to achieve and you may need frequent monitoring during first weeks of therapy. Best to take 2 hours before or after a meal; however, may be taken with meals if GI upset occurs. Take at the same time each day. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). Do not use alcohol and prescription or OTC sedatives or CNS depressants without consulting prescriber. Urine or perspiration may appear darker. You may experience drowsiness, dizziness, confusion, or vision changes (use caution when driving, climbing stairs, or engaging in tasks requiring alertness until response to drug is known); orthostatic hypotension (use caution when changing position - rising to standing from sitting or lying); increased susceptibility to heat stroke, decreased perspiration (use caution in hot weather - maintain adequate fluids and reduce exercise activity); constipation (increased exercise, fluids, or dietary fruit and fiber may help); dry skin or nasal passages (consult prescriber for appropriate relief); nausea, vomiting, loss of appetite, or stomach discomfort (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report unresolved constipation or vomiting; chest pain or irregular heartbeat; difficulty breathing; acute headache or dizziness; CNS changes (hallucination, loss of memory, nervousness, etc); painful or difficult urination; abdominal pain or blood in stool; increased muscle spasticity, rigidity, or involuntary movements; skin rash; or significant worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Tablet: 100 mg, 200 mg

Kurth MC, et al, "Tolcapone Improves Motor Function and Reduces Levodopa Requirement in Patients With Parkinson's Disease Experiencing Motor Fluctuations: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial," Neurology, 1997, 48:81-7.

Sedek G, et al, "Effect of Tolcapone on Plasma Levodopa Concentrations After Coadministration With Levodopa/Carbidopa to Healthy Volunteers," Clin Neuropharmacol, 1997, 20:531-41.

Waters CH, et al, "Tolcapone in Stable Parkinson's Disease: Efficacy and Safety of Long-Term Treatment," Neurology, 1997, 49:665-71.

Watts RL, "The Role of Dopamine Agonists in Early Parkinson's Disease," Neurology, 1997, 49(Suppl 1):S34-48.