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Comtan: A Drug in the Parkinson’s Disease Arsenal

Brand Name: Comtan
Active Ingredient: entacapone
Indication: Treatment of Parkinson’s disease in patients taking levodopa
Company Name: Novartis
Availability: Approved in October 1999

ComtanIntroduction

Levodopa has remained the standard treatment for patients with Parkinson’s disease. However, one of the major problems with this drug is “wearing off,” a situation that arises after several years of levodopa therapy when some of the drug begins to be metabolized before it has had a chance to cross the blood-brain barrier to do its work. The result: patients’ symptoms return, including disruption of motor function and impairment of the activities of daily living.

A new class of drugs called COMT inhibitors promises to help alleviate this problem, working by inactivating the enzyme that breaks down levodopa. Novartis’s Comtan (entacapone) is a new COMT inhibitor recently approved by the FDA to be administered to Parkinson’s disease patients who are taking levodopa/carbidopa. By enhancing the effects of levodopa, Comtan increases patients’ “on” time – the period during which levodopa is effectively relieving their symptoms – and decreases “off” time, the period when patients experience Parkinson’s symptoms because the drug is no longer effective. The recommended dose of Comtan is 200 mg with each levodopa dose, up to eight times daily.

How It Works

Comtan works by blocking the activity of catechol-O-methyltransferase (COMT), the enzyme that metabolizes levodopa. In doing so, Comtan increases the area under the concentration-time curve of plasma levodopa and enables more levodopa to cross the blood-brain barrier. When given in conjunction with levodopa and carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and carbidopa alone. The more sustained levodopa plasma levels result in more constant dopaminergic stimulation in the brain, leading to greater beneficial effects on the signs and symptoms of Parkinson’s disease.

Comtan: A Drug in the Parkinson’s Disease ArsenalComtan (entacapone): Clinical Study Results

The clinical benefits of Comtan were demonstrated in three clinical trials. The Nordic Multicenter Entacapone COMT Trial (NOMECOMT) examined 171 Parkinson’s disease patients who experienced wearing-off-type motor fluctuations. A six-month randomized, double-blind, placebo-controlled study was conducted. Patients took either 200 mg Comtan or placebo along with each levodopa dose (4 to 10 times daily). Patients recorded their symptoms in home diaries, recording “on” and “off” times, while examiners recorded scores according to the Unified Parkinson’s Disease Rating Scale (UPDRS). Patients’ home diaries indicated that Comtan significantly increased “on” time (9.3-10.7) and decreased “off” time (5.3-4.2). Moreover, patients taking Comtan required a lower daily levodopa dose than those on placebo: 102 mg less. Patients taking Comtan experienced a better UPDRS total score as well as better UPDRS scores for motor function and the activities of daily living (such as speaking, writing, walking, and dressing). Comtan was well-tolerated, with diarrhea being the most common nondopaminergic side effect. A second trial was conducted at 17 centers in the US and Canada by the Parkinson Study Group: the Safety and Efficacy of Entacapone Study Assessing Wearing Off (SEESAW). This double-blind, placebo-controlled trial examined 205 Parkinson’s disease patients with motor fluctuations. Patients took either 200 mg Comtan or placebo along with each levodopa dose, up to 10 times daily, and were followed for 24 weeks. As recorded in home diaries, patients who took Comtan experienced a significant increase in “on” time and a decrease in “off” time. Total UPDRS scores were also significantly improved in the patients taking Comtan, as well as UPDRS scores for motor function and activities of daily living. Total daily levodopa dose was also significantly decreased in the Comtan patients. The results of these two trials were confirmed in a third study at 32 centers in Germany and Austria, which evaluated Comtan versus placebo in 301 patients.

What the Patient Should Know

Diarrhea, nausea, abdominal pain, dyskinesia, and urine discoloration were the most common side effects reported with Comtan use. Other side effects that patients should be aware of include hallucinations, orthostatic hypotension, and effects of cognitive and motor function. Patients should therefore be advised not to stand up too quickly and to avoid driving or operating heavy machinery until they have gauged the effect of Comtan on their performance. Patient should also inform their physicians if they become pregnant or intend to breast-feed. Those who have hepatic impairment or who are taking MAO inhibitors should be treated with caution.

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