COMT Inhibitors

COMT inhibitors prolong the effectiveness of a dose of levodopa by preventing its breakdown. Two agents are approved in the United States, entacapone (Comtan®) and tolcapone (Tasmar®). Both have been shown to decrease the duration of "off" time (the period of time when PD symptoms are present) in patients with significant off time. Tolcapone is more effective than entacapone, reducing off time in clinical trials by 2-3 hours, versus 1 to 2 hours for entacapone. Both treatments usually allow reduction of levodopa dose, in the range of 20% to 25%.

Entacapone is dosed at 200 mg with each levodopa dose. Diarrhea is the most common side effect, which may require stopping treatment, but it occurs in severe form in only about 5% of patients.

Tolcapone is dosed at 100 or 200 mg, three times per day. Side effects include diarrhea, which may eliminate this as a treatment option in up to 15% of patients. Four cases of severe liver disease (acute fulminant hepatic necrosis), with three deaths, were reported in 1998, and led the FDA to issue a "black box" warning on tolcapone. This warning recommends that physicians only prescribe tolcapone for patients whose symptoms cannot be adequately controlled without it. Frequent liver function monitoring is required for patients commencing therapy. This requires a blood test every 2-4 weeks for the first 6 months, to be sure that certain critical liver function values are not rising. After that, blood tests are recommended at intervals deemed clinically relevant. Treatment should be discontinued if the ALT/AST levels rise above twice the upper limit of normal.

A combination of levodopa, carbidopa, and entacapone in a single tablet (Stalevo®) is also available, with a similar side effect profile to the agents used alone.

	MAO-B Inhibitors