Comtan (entacapone) for Parkinson’s disease

What is Comtan for Parkinson’s disease?

Comtan (entacapone) for Parkinson’s disease is an oral therapy that is used as an add-on to levodopa and carbidopa for managing off episodes, the periods where levodopa wears off between doses and motor symptoms return or fluctuate.

In Parkinson’s, nerve cells that produce the chemical messenger dopamine gradually die and are lost. Because dopamine is crucial for movement and various other brain functions, this leads to both motor and nonmotor symptoms.

Levodopa is a precursor to dopamine, which the body can use to make more of the deficient messenger molecule. However, it tends to become less effective at controlling symptoms over time, resulting in off episodes. Increasing the dosage may boost its efficacy, but can also lead to side effects.

A way to increase the therapy’s effectiveness without increasing the dose is to block enzymes that alter levodopa or break it down before it reaches the brain. This strategy specifically targets DOPA decarboxylase (DDC) and catechol-O-methyltransferase (COMT). Levodopa is commonly combined with the DDC inhibitor carbidopa for this reason.

If off episodes continue to be problematic with levodopa and carbidopa, doctors may recommend adding a COMT inhibitor such as Comtan. This medication prevents the breakdown of levodopa in the body, increasing the amount that reaches the brain. Comtan’s mechanism of action is expected to help control symptoms and reduce off time.

The original developer of Comtan was Orion Pharma, but Almatica Pharma now covers its distribution in the U.S., where several Comtan generics are also available. Orion is also the original developer of Stalevo, an approved oral therapy that combines levodopa, carbidopa, and entacapone — the active ingredient in Comtan — in one pill.

Therapy snapshot

Who can take Comtan?

In the U.S., Comtan is approved as an add-on to levodopa and carbidopa to treat off episodes in people with Parkinson’s. The medication is also used as an add-on to levodopa-based regimens in the European Union, though the specific indications may vary. In Canada, the medication is available only as a generic.

The Comtan prescribing information states that it is contraindicated, or should not be used, in people with allergies to the medication or any of its ingredients.

It is also not usually recommended for people with preexisting major psychotic disorders or those who are taking a nonselective monoamine oxidase (MAO) inhibitor, a type of antidepressant. However, use of Comtan alongside MAO-B inhibitors, a type of Parkinson’s medication, is usually safe. Comtan should be used with caution in people with liver impairment.

How is Comtan administered?

Comtan is an oral medication available in 200 mg tablets. The standard recommended Comtan dosage schedule is to take one of these tablets alongside each daily dose of levodopa and carbidopa. The maximum recommended daily dose is 1,600 mg, or eight tablets.

Some people on Comtan may require a reduction in the daily levodopa dose or administration frequency to maximize treatment effectiveness and minimize side effects. Comtan can be used with both immediate- and extended-release forms of levodopa/carbidopa and can be taken with or without food.

Comtan should only be discontinued under medical supervision, because abruptly stopping the medication could cause serious side effects. When transitioning off Comtan, other Parkinson’s medications may also require adjustment.

Comtan in clinical trials

Comtan’s approvals were largely supported by three clinical trials, namely NOMECOMT, SEESAW, and CELOMEN. In each, participants took Comtan or a placebo alongside levodopa and a DDC inhibitor. Treatment was given up to 10 times per day for six months. Most participants had been experiencing motor fluctuations on their prescribed treatment regimen.

• increases in daily on time and proportional decreases in daily off time
• reductions in average daily levodopa dose
• easing of Parkinson’s symptom severity, including improvements in motor capabilities and the ability to participate in daily activities

Although the data varied somewhat by study, participants on Comtan experienced about 1-1.5 additional hours of on time per day relative to the study’s start, and a similar decrease in off time.

Comtan side effects

The most common side effects of Comtan are:

• involuntary movements that were abnormal (dyskinesia) or excessive (hyperkinesia)
• orange urine discoloration
• diarrhea
• abdominal pain
• nausea
• vomiting
• dry mouth

Dyskinesia and hyperkinesia are side effects of levodopa that Comtan may exacerbate. Adjusting the levodopa dosage can sometimes help resolve or ease these problems.

Persistent diarrhea can be a sign of drug-related microscopic colitis, a type of intestinal inflammation, but this typically resolves after discontinuing Comtan.

Several less common but potentially severe side effects are also possible, such as:

• excessive drowsiness and falling asleep during daily activities
• low blood pressure, particularly when standing up (orthostatic hypotension)
• new or worsening hallucinations and psychotic-like behavior
• impulse control challenges and compulsive behavior

These are known side effects of levodopa that Comtan may exacerbate. There are other serious complications that have been linked to levodopa, but their relationship to Comtan is not established. These include: breakdown of skeletal muscle, known as rhabdomyolysis, high fever and confusion when discontinuing treatment, and internal scarring. Some skin cancers may also occur. Doctors may recommend monitoring for signs of these conditions.

Comtan may interact with other medications, including those normally broken down by the COMT enzyme. Patients should inform their healthcare team about everything they are taking.