Entacapone, sold under the brand name Comtan among others, is a medication used to treat Parkinson’s disease. It is not a standalone therapy but functions as an “add-on” treatment, taken with the medications levodopa and carbidopa. Its purpose is to address the “wearing-off” phenomenon that many people with Parkinson’s experience, where symptoms return between scheduled doses of their primary medication. Entacapone helps levodopa, the main therapeutic agent, function more consistently and for longer periods within the body.
Mechanism of Action
Entacapone’s function is tied to levodopa’s role in Parkinson’s therapy. Levodopa is a precursor to dopamine, a neurotransmitter deficient in the brains of individuals with Parkinson’s disease. When administered, levodopa travels through the bloodstream, crosses the blood-brain barrier, and is converted into dopamine to alleviate motor symptoms.
A challenge in this process is the enzyme catechol-O-methyltransferase (COMT). This enzyme is widely distributed in peripheral tissues, such as the liver and kidneys. It metabolizes or breaks down levodopa before it can reach the brain, reducing the amount available for conversion into dopamine.
Entacapone is a COMT inhibitor that selectively and reversibly blocks the enzyme’s action in tissues outside the brain. By inhibiting COMT, entacapone prevents the premature breakdown of levodopa, allowing for higher and more sustained levels in the bloodstream. This increases the quantity of levodopa that can pass through the blood-brain barrier, resulting in more constant dopaminergic stimulation and a greater reduction in Parkinson’s symptoms.
This action extends the therapeutic window of each levodopa dose, helping to smooth out fluctuations in motor function. It allows for a more stable and continuous supply of dopamine in the brain. This can reduce the periods of immobility and stiffness known as “off” time.
Proper Administration and Dosage
Entacapone must be taken with each prescribed dose of levodopa/carbidopa. This ensures its COMT-inhibiting effect is active while levodopa is in the bloodstream, maximizing its availability to the brain.
The standard dose is a 200 mg tablet taken with every levodopa/carbidopa dose, up to a maximum of eight times per day for a total of 1600 mg. The medication can be taken with or without food, as this does not impact its function. However, patients are advised that high-fat, high-calorie meals may delay levodopa’s absorption.
If a dose is missed, skip it entirely. Wait until the next scheduled levodopa/carbidopa dose and take the regular entacapone tablet at that time. Do not take two doses at once to make up for a missed one, as this can increase the risk of side effects.
Potential Side Effects
Common Side Effects
Common side effects are often linked to increased levodopa levels. The most frequently reported is dyskinesia, an increase in involuntary movements, which occurs because higher dopamine activity can overstimulate motor pathways. Other common effects include nausea, stomach pain, diarrhea, and dry mouth.
A harmless side effect is the discoloration of urine to a brownish-orange color. This change is a normal result of the body processing the medication and is not a sign of a health problem. Patients are forewarned about this effect to prevent alarm.
Serious Side Effects
Less frequent side effects require prompt medical attention. Hallucinations and significant confusion can occur, particularly in older individuals. Severe or persistent diarrhea is also a concern, as it can begin months after starting the medication and may lead to dehydration if not addressed.
A rare but serious condition is rhabdomyolysis, the breakdown of muscle tissue. Symptoms include unexplained muscle pain, weakness, fever, and dark-colored urine, distinct from the harmless brownish-orange discoloration. Another very rare reaction is neuroleptic malignant syndrome (NMS), which can manifest with high fever, severe muscle stiffness, and confusion.
Important Drug and Health Interactions
Pre-existing health conditions can influence the use of entacapone. Individuals with a history of liver disease may require caution, as the drug is processed by the liver and impairment can double its concentration in the body.
Entacapone should not be taken with non-selective monoamine oxidase (MAO) inhibitors, such as phenelzine. Both COMT and MAO are enzymes that metabolize catecholamines, and inhibiting both simultaneously can lead to dangerous increases in heart rate and blood pressure. Caution is also advised with other drugs metabolized by COMT, like dobutamine or isoproterenol.
Other substances can affect entacapone’s absorption. Taking iron supplements at the same time can interfere with the body’s ability to absorb the medication because they can bind in the gastrointestinal tract. To avoid this, space the administration of entacapone and iron supplements by at least two to three hours.