THERAPEUTICS

Brands

• Comtan, Stalevo

Generic?

• No

Class

• Antiparkinson agent

Commonly Prescribed for

(FDA approved in bold)

• Parkinsonism, including Parkinson’s disease (PD)

How the Drug Works

• Highly selective peripherally acting inhibitor of catechol-O-methyltransferase (COMT), an important enzyme in dopamine metabolism. Use with carbidopa-levodopa enables more levodopa to enter the brain and prevents the end-of-dose wearing-off seen in PD. Entacapone has less activity on COMT in the brain, meaning the drug is not considered centrally active

How Long Until It Works

• PD: hours to weeks

If It Works

• PD: a majority (58%) of patients taking 800 mg or more per day of levodopa will lower levodopa dose, on average by 25% of the total after starting entacapone

If It Doesn't Work

• If end-of-dose wearing-off does not improve with entacapone and levodopa, decrease the dosing interval, add a dopamine agonist or monoamine oxidase B (MAO-B) inhibitor, or consider neurosurgical options. For sudden, unpredictable wearing-off, consider apomorphine

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Entacapone is used only as an adjunctive medication in PD with levodopa

• For dyskinesias, lower dose of levodopa or add a dopamine agonist

• Younger patients with bothersome tremor: anticholinergics may help

• For severe motor fluctuations and/or dyskinesias with good “on” time, functional neurosurgery is an option

• Amantadine may help suppress dyskinesias, although benefit is often short-lived

• Depression is common in PD and may respond to low-dose SSRIs

• Cognitive impairment/dementia is common in mid-late stage PD and may improve with acetylcholinesterase inhibitors

Tests

• None required

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• COMT inhibition increases the level and duration of action of levodopa

Notable AEs

• (Entacapone alone) diarrhea (usually mild to moderate), dyspnea, weakness. May increase levodopa-related AEs such as dyskinesias, nausea, orthostatic hypotension, and hallucinations