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Catechol-O-methyl Transferase (COMT) Inhibitors

Another class of enzyme inhibitors, called COMT inhibitors, also prevents the metabolic breakdown of levodopa. Their main effect is to prolong the duration of action of levodopa. COMT inhibitors do not contain levodopa, and they must therefore be taken with levodopa for benefit. They may be prescribed when an inpidual experiences "wearing off," particularly when dopamine agonists are not tolerated. If dyskinesias develop after starting a COMT inhibitor, the dose of levodopa may need to be reduced. A recent study has shown that entacapone, when used as an adjunct to levodopa in parkinsonian patients without motor fluctuations, does not improve performance on standard rating scales but does improve a variety of quality-of-life measures (Olanow et al, 2004).

COMT inhibitors:

  • Entacapone(Comtan®)—200 mg tablets are usually given with each dose of levodopa
  • Tolcapone(Tasmar®)—100 mg and 200 mg tablets; generally given three times a day

Because liver toxicity has occurred in patients taking tolcapone, it is only indicated for patients whose symptoms are not adequately controlled by other medications (including entacapone). Patients taking tolcapone must have blood drawn before initiating treatment and then periodically to monitor liver function (every 2-4 weeks for the first 6 months of treatment and thereafter when clinically relevant).

Side effects for both of these medications include urine discoloration, diarrhea, vivid dreams, visual hallucinations, drowsiness, and dyskinesias.

Combined carbidopa, levodopa and entacapone

This preparation combines all 3 medications in one pill, which may be more convenient but may not be as flexible as taking the medications inpidually.

 

Doses:

Stalevo® 50: 50 mg levodopa, 12.5 mg carbidopa, and 200 mg entacapone

Stalevo® 75: 75 mg levodopa, 18.75 mg carbidopa, and 200 mg entacapone

Stalevo® 100: 100 mg levodopa, 25 mg carbidopa and 200 mg entacapone

Stalevo® 125: 125 mg levodopa, 31.25 mg carbidopa, and 200 mg entacapone

Stalevo® 150: 150 mg levodopa, 37.5 mg carbidopa, and 200 mg entacapone

Stalevo® 200: 200 mg levodopa, 50 mg carbidopa, and 200 mg entacapone

Side effects of this combined preparation are the same as for levodopa and entacapone and include: urine discoloration, diarrhea, vivid dreams, visual hallucinations, drowsiness, and dyskinesias.