From the Guidelines
Entacapone is a catechol-O-methyltransferase (COMT) inhibitor used to treat Parkinson's disease, primarily by extending the duration of symptom relief from levodopa therapy and reducing "wearing-off" periods. As a COMT inhibitor, entacapone works by blocking the enzyme that breaks down levodopa in the body, allowing more levodopa to reach the brain where it can be converted to dopamine 1. This mechanism of action helps in managing the symptoms of Parkinson's disease more effectively, especially in patients who experience motor fluctuations despite optimized levodopa therapy. Key points about entacapone include:
- It is typically prescribed alongside levodopa and carbidopa
- The standard dosage is 200 mg taken with each levodopa/carbidopa dose, up to a maximum of 8 times daily (1,600 mg)
- Common side effects include diarrhea, urine discoloration, nausea, abdominal pain, and increased dyskinesia
- Entacapone does not provide benefit when taken alone and must be used with levodopa to be effective
- It is particularly helpful for patients experiencing motor fluctuations despite optimized levodopa therapy, as evidenced by its role in reducing the elevation of homocysteine levels associated with levodopa treatment 1. Overall, entacapone plays a significant role in the management of Parkinson's disease, especially in conjunction with levodopa therapy, and its use can contribute to improved symptom control and potentially slower disease progression 1.
From the FDA Drug Label
Entacapone is an inhibitor of catechol-O-methyltransferase (COMT), used in the treatment of Parkinson's disease as an adjunct to levodopa and carbidopa therapy. The chemical name of entacapone is (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide Its empirical formula is C 14H 15N 3O 5
Entacapone is a COMT inhibitor used in the treatment of Parkinson's disease as an adjunct to levodopa and carbidopa therapy 2.
- It works by inhibiting the COMT enzyme, which is involved in the breakdown of levodopa.
- The mechanism of action of entacapone is believed to be through its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa 2.
- Entacapone increases the area under the curve (AUC) of levodopa by approximately 35% and prolongs the elimination half-life of levodopa from 1.3 hours to 2.4 hours 2.
From the Research
Definition and Mechanism of Action
- Entacapone is a selective inhibitor of catechol-O-methyltransferase (COMT), an enzyme involved in the metabolism of catecholamines and catechol compounds 3, 4, 5.
- It works by inhibiting the activity of COMT in the peripheral nervous system, thereby prolonging the action of levodopa and reducing fluctuations in response 3, 4, 5.
Pharmacokinetics and Pharmacodynamics
- Entacapone is rapidly absorbed, with a time to maximum concentration of approximately 1 hour, and has a plasma elimination half-life of 0.4 to 0.7 hour in the beta phase and 2.4 hours in the gamma phase 3.
- It is 98% protein bound and is almost completely metabolized before excretion, with 0.1%-0.2% of the dose unchanged in urine 3.
- Entacapone inhibits erythrocyte-soluble COMT activity in a dose-dependent fashion, with 48% inhibition after a 400-mg dose and 82% inhibition after an 800-mg dose 3.
Clinical Efficacy and Safety
- Entacapone has been shown to be effective in increasing "on" time and decreasing "off" time in patients with Parkinson's disease who experience motor fluctuations 3, 4, 5, 6, 7.
- It is generally well tolerated, with most adverse effects attributed to levodopa-related dopaminergic effects, including dyskinesias and nausea 3, 4, 5, 6, 7.
- The recommended dosage of entacapone is 200 mg administered orally with each dose of levodopa/carbidopa, up to 8 doses per day 3, 4, 5.