General Information

Comtan (entacapone) is an inhibitor of catechol-O-methyltransferase (COMT).

Comtan is specifically indicated as an adjunct to levodopa / carbidopa to treat patients with idiopathic Parkinson’s Disease who experience the signs and symptoms of end-of-dose “wearing-off”.

Comtan is supplied as tablets for oral administration. The recommended dose of Comtan is one 200 mg tablet administered concomitantly with each levodopa/carbidopa dose to a maximum of 8 times daily (200 mg x 8 = 1600 mg per day). Clinical experience with daily doses above 1600 mg is limited.

Mechanism of Action

Entacapone inhibits COMT and alters the plasma pharmokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease. The higher levodopa levels also lead to increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa.

Side Effects

The most commonly reported side-effects were dyskinesia, nausea, diarrhea, abdominal pain and urine discoloration. A very small percentage of participants in the trials also experienced hallucinations. Dopaminergic side effects like dyskinesia often improved after adjustment of the levodopa dosage.

Clinical Trial Results

The effects of Comtan were tested on nearly 700 patients in worldwide, multi-center trials. Compared to a placebo, patients with Parkinson's who took Comtan demonstrated improved motor performance and had significantly increased amounts of "on" time each day. Several important Phase III studies indicated that the benefits were salient for patients who showed deteriorating response to levodopa/carbidopa, particularly in important activities of daily living such as speaking, handwriting, walking and dressing.