NAPLEX Practice Question # 34

NAPLEX Examination.

Practice Question # 34.

COMT inhibitors NAPLEX Review

1. Tolcapone (Tasmar)

Mechanism of action

• Tolcapone is a selective and reversible inhibitor of COMT and is used as an adjunct to levodopa/carbidopa therapy.
• Tolcapone inhibits COMT both peripheral and centrally.
• COMT is the main enzyme responsible for peripheral and central metabolism of catecholamines, including levodopa. Addition of a COMT inhibitor results in the doubling of the elimination half-life of levodopa and in increased oral bioavailability of levodopa by 40% to 50%.
• Tolcapone is indicated as an adjunct therapy to carbidopa/levodopa therapy.

Administration and dosage

• Starting dose of 100 to 200 mg three times daily
• Usual daily dose of 200 mg three times daily

Precautions and monitoring

• Liver toxicity. High risk of fatal liver failure has been reported with tolcapone. Discontinue use if substantial benefi t is not seen within 3 weeks of commencement of therapy.
• Do not use in patients with liver disease or in patients who have two alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values greater than the upper limit of normal.
• Advise patient regarding self-monitoring for liver disease (i.e., clay-colored stool, jaundice, fatigue, appetite loss, or lethargy).
• Monitor AST and ALT every 2 weeks for the fi rst year, then every 4 weeks for the next 6 months and every 8 weeks thereaft er.
• MAO and COMT are two major enzyme systems involved in the metabolism of catecholamines; combination of tolcapone with a nonselective MAO inhibitor will result in inhibition of the pathway responsible for normal catecholamine metabolism.
• Tolcapone can be taken concomitantly with a selective MAO-B inhibitor, such as selegiline in recommended dose of less or equal to 10 mg/day.
• Fibrolic complications, such as retroperitoneal fi brosis, pulmonary infi ltrates or eff usion, or pleural thickening.