entacapona

Entacapona, commonly referred to as entacapone, is a selective peripheral catechol-O-methyltransferase (COMT) inhibitor used in the treatment of Parkinson's disease. It is sold under brand names such as Comtan and is administered as an adjunct to levodopa-containing therapy to reduce motor fluctuations, particularly the wearing-off effect that can occur with long-term levodopa use. It is not used alone.

Mechanism of action

Entacapone inhibits COMT in peripheral tissues, which decreases the peripheral conversion of levodopa to 3-O-methyldopa. By raising and prolonging the amount of levodopa available to the brain, it helps maintain more consistent dopaminergic stimulation. The drug has limited ability to cross the blood-brain barrier, so its primary action is peripheral rather than central.

Clinical use

Entacapone is indicated for patients with Parkinson's disease who experience motor fluctuations while taking levodopa. It is typically prescribed in combination with levodopa-carbidopa or levodopa alone and is not a substitute for levodopa.

Administration and dosing

The usual dose is 200 mg taken with each dose of levodopa-containing medication. The typical maximum daily dose is 1600 mg. It can be taken with or without food, but iron-containing preparations should be separated from entacapone by about two hours, as iron can reduce entacapone absorption.

Pharmacokinetics

Entacapone is administered orally and is rapidly absorbed. It has a short elimination half-life and is primarily metabolized in the liver to glucuronide conjugates, with excretion in urine and feces.

Adverse effects and safety

Common adverse effects include diarrhea, nausea, dry mouth, abdominal pain, dyskinesias, and orthostatic hypotension. Urine discoloration and rare skin reactions may occur. Serious liver injury is uncommon but has been reported; entacapone is generally considered to have a lower hepatotoxicity risk than some other COMT inhibitors. Contraindications include known hypersensitivity to entacapone. Caution is advised in patients with significant hepatic impairment. Like other dopaminergic therapies, entacapone can increase levodopa–related adverse effects, including dyskinesias.