Comtess (Entacapone): Uses, Dosage & Side Effects
A COMT inhibitor that extends and stabilizes levodopa action in Parkinson's disease
Comtess (entacapone) is a COMT inhibitor (catechol-O-methyltransferase inhibitor) used as an adjunct to levodopa therapy in the treatment of Parkinson's disease. It works by blocking the enzyme that breaks down levodopa in peripheral tissues, thereby increasing the amount of levodopa that reaches the brain and extending its duration of action. Comtess is always taken together with each dose of levodopa/carbidopa or levodopa/benserazide and has no anti-parkinsonian effect on its own. By reducing motor fluctuations and increasing daily “on-time,” entacapone helps patients with Parkinson's disease maintain more stable symptom control throughout the day.
Quick Facts: Comtess
Key Takeaways
- Comtess (entacapone) is a COMT inhibitor that must always be taken together with levodopa — it has no therapeutic effect on Parkinson's symptoms when used alone.
- Each 200 mg tablet is taken simultaneously with every dose of levodopa/decarboxylase inhibitor, up to a maximum of 10 tablets (2,000 mg) per day.
- Entacapone extends levodopa’s half-life from approximately 1.3 to 2.4 hours, increasing daily “on-time” by approximately 1–2 hours and reducing motor fluctuations.
- The most common side effects are dyskinesias, nausea, and harmless reddish-brown urine discoloration; your doctor may need to reduce the levodopa dose when starting entacapone.
- Never stop Comtess abruptly, as sudden withdrawal (particularly with concurrent reduction of other antiparkinsonian drugs) can trigger neuroleptic malignant syndrome (NMS), a potentially life-threatening condition.
What Is Comtess and What Is It Used For?
Comtess contains the active substance entacapone, a selective and reversible inhibitor of the enzyme catechol-O-methyltransferase (COMT). This enzyme is one of the principal pathways for the peripheral metabolism of levodopa, the most effective medication for treating the motor symptoms of Parkinson's disease. When a patient takes levodopa orally, a significant proportion is broken down by COMT into an inactive metabolite called 3-O-methyldopa (3-OMD) before it can cross the blood-brain barrier and be converted into dopamine. By inhibiting COMT, entacapone prevents this breakdown, allowing more levodopa to reach the brain and providing a more sustained therapeutic effect.
Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopamine-producing neurons in the substantia nigra pars compacta of the brain. The resulting dopamine deficiency leads to the cardinal motor symptoms of the disease: resting tremor, muscular rigidity, bradykinesia (slowness of movement), and postural instability. Levodopa remains the gold-standard treatment for these symptoms, as it crosses the blood-brain barrier and is converted to dopamine. However, as the disease progresses, many patients develop motor fluctuations — periods when the medication wears off before the next dose is due, leading to a return of parkinsonian symptoms (known as “end-of-dose deterioration” or “wearing-off”).
Entacapone was developed specifically to address these motor fluctuations. When co-administered with levodopa and a decarboxylase inhibitor (either carbidopa or benserazide), entacapone increases the area under the plasma concentration-time curve (AUC) of levodopa by approximately 35–40% and extends its elimination half-life from approximately 1.3 hours to 2.4 hours. In clinical trials, this translated to an average increase in daily “on-time” (the period when Parkinson's symptoms are well controlled) of approximately 1–2 hours, with a corresponding reduction in “off-time” (the period when symptoms return).
It is critical to understand that entacapone has no anti-parkinsonian effect of its own. It works exclusively by enhancing the pharmacokinetics of levodopa. Without concurrent levodopa therapy, entacapone provides no clinical benefit. For this reason, each Comtess tablet must be taken at the same time as a dose of levodopa. Entacapone acts only in the peripheral tissues and does not cross the blood-brain barrier to any clinically significant extent, meaning it does not directly affect central dopamine metabolism.
Entacapone was first approved by the European Medicines Agency (EMA) in 1998 and subsequently by the United States Food and Drug Administration (FDA) in 1999. It is also available in a fixed-dose combination with levodopa and carbidopa under the brand name Stalevo. The World Health Organization recognizes COMT inhibitors as an important adjunct therapy in the management of Parkinson's disease, and entacapone is recommended in international guidelines including those from the National Institute for Health and Care Excellence (NICE) and the Movement Disorder Society (MDS) for the management of wearing-off motor fluctuations.
What Should You Know Before Taking Comtess?
Contraindications
There are specific clinical situations in which Comtess must not be used. Understanding these contraindications is essential for preventing serious and potentially life-threatening adverse events. You should not take Comtess if any of the following apply:
- Hypersensitivity: Known allergy to entacapone or any excipient in the formulation, including soy lecithin. Patients allergic to peanuts or soy must not use Comtess, as the film coating contains soy lecithin.
- Pheochromocytoma: A rare tumor of the adrenal gland that produces excessive catecholamines. Entacapone, by inhibiting catecholamine metabolism, can increase the risk of a severe hypertensive crisis in these patients.
- Liver disease: Hepatic impairment of any severity is a contraindication, as entacapone is primarily metabolized by the liver and impaired hepatic function could lead to dangerously elevated drug levels.
- Concurrent use of certain antidepressants: Some antidepressants that inhibit catecholamine reuptake or metabolism may interact dangerously with entacapone. Consult your doctor or pharmacist to determine whether your specific antidepressant is safe to use with Comtess.
- History of neuroleptic malignant syndrome (NMS): Patients with a prior episode of NMS should not receive entacapone, as the condition may recur.
- History of non-traumatic rhabdomyolysis: Patients who have previously experienced rhabdomyolysis (severe muscle breakdown) not caused by injury should avoid entacapone.
Seek immediate medical attention if you experience severe muscle rigidity, high fever, tremors, agitation, confusion, rapid heartbeat, or altered consciousness. These may be symptoms of NMS, a potentially life-threatening condition that can occur when Comtess or other antiparkinsonian medications are suddenly stopped or rapidly reduced in dose.
Warnings and Precautions
Before starting Comtess therapy, inform your doctor if you have, have ever had, or develop any of the following conditions, as additional monitoring or dose adjustments may be required:
- Cardiovascular disease: History of heart attack (myocardial infarction) or any other heart or vascular disease. Your doctor will monitor you carefully, particularly when treatment is first started.
- Medications causing orthostatic hypotension: If you take other medications that may cause dizziness or lightheadedness when standing up, the combination with Comtess and levodopa may intensify these effects.
- Prolonged diarrhea: If you develop persistent or severe diarrhea while taking Comtess, contact your doctor promptly. This may indicate colitis (inflammation of the large intestine), a recognized adverse effect of entacapone that requires medical evaluation.
- Weight loss: If you experience diarrhea, regular weight monitoring is recommended to detect excessive weight loss early.
- Progressive loss of appetite, weakness, fatigue, and weight loss: If you develop these symptoms over a relatively short period, a general medical evaluation including assessment of liver function should be performed.
Comtess, when used with levodopa, may contribute to impulse control disorders including pathological gambling, compulsive shopping or spending, binge eating, and hypersexuality (abnormally increased sex drive). If you or your family/caregiver notice any of these behaviors, inform your doctor immediately, as a review of treatment may be needed.
Because Comtess tablets are always taken together with other levodopa-containing medications, you should also carefully read the patient information leaflets for those medications. When you first start taking Comtess, your doctor may need to adjust the dose of your other Parkinson's disease medications, particularly levodopa. This is because entacapone enhances levodopa’s effects, and the increased levodopa exposure may initially cause or worsen side effects such as dyskinesias (involuntary movements) or nausea.
Comtess taken together with levodopa may cause drowsiness and may occasionally cause sudden onset of sleep. If this occurs, you should not drive or operate machinery. Your doctor may need to adjust your medications to manage this effect.
Pregnancy and Breastfeeding
Comtess should not be used during pregnancy or while breastfeeding. Animal studies have not provided sufficient evidence of safety during pregnancy, and the potential risks to the developing fetus are unknown. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medication. Entacapone may pass into breast milk, and breastfeeding women should not take Comtess. Your doctor will advise you on the appropriate course of action if you need treatment during these periods.
Driving and Operating Machinery
Comtess, when taken together with levodopa, may cause dizziness, lightheadedness (due to low blood pressure), and drowsiness. In some cases, it can cause sudden onset of sleep without warning signs of drowsiness. These effects can significantly impair your ability to drive safely or operate machinery. You must not drive or use machines if you experience these effects, as doing so could endanger yourself and others. Wait until these episodes have completely resolved before resuming such activities.
Important Information About Excipients
Comtess tablets contain soy lecithin as a component of the film coating. If you are allergic to peanuts or soy, you must not use this medication. Soy allergy is a recognized IgE-mediated allergic condition, and even the small amount of soy lecithin present in the tablet coating may trigger an allergic reaction in sensitized individuals. Discuss alternative COMT inhibitors with your doctor if you have these allergies.
How Does Comtess Interact with Other Drugs?
Entacapone can interact with a range of medications due to its effect on catecholamine metabolism. Because COMT is involved in the breakdown of catecholamines (such as epinephrine, norepinephrine, and dopamine), inhibiting this enzyme can potentiate the effects of these substances and related drugs. Always inform your doctor and pharmacist about all medications you are currently taking, including over-the-counter drugs, herbal supplements, and vitamins.
Major Interactions
| Interacting Drug | Effect | Clinical Guidance |
|---|---|---|
| Catecholamines (epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol) | Enhanced catecholamine effects due to COMT inhibition; risk of hypertension, tachycardia, arrhythmias | Use with caution. Monitor blood pressure and heart rate closely. Dose reduction of catecholamines may be needed |
| Certain antidepressants (desipramine, maprotiline, venlafaxine, paroxetine) | Potential additive effects on catecholamine levels; increased risk of adverse cardiovascular and neurological effects | Consult your doctor before combining. Some antidepressants are contraindicated |
| Alpha-methyldopa | Both drugs affect catecholamine metabolism; potential for unpredictable blood pressure changes | Avoid concurrent use if possible. Monitor closely if combination is necessary |
| Apomorphine | Enhanced dopaminergic effects; increased risk of hypotension and other side effects | Use with caution under specialist supervision |
Moderate Interactions
| Interacting Drug | Effect | Clinical Guidance |
|---|---|---|
| Warfarin (and other vitamin K antagonists) | Entacapone may increase the anticoagulant effect of warfarin; potential for increased bleeding risk | Monitor INR closely when starting or stopping entacapone. Warfarin dose adjustment may be needed |
| Iron supplements | Entacapone can chelate iron in the gastrointestinal tract, reducing absorption of both drugs | Take at least 2–3 hours apart. Take iron supplements at a different time of day |
| Rimiterol | Enhanced beta-adrenergic effects due to reduced catecholamine breakdown | Use with caution. Monitor for cardiovascular effects |
This list does not include all possible drug interactions. Always tell your doctor about every medication, supplement, and herbal product you take. Your pharmacist can also help identify potential interactions when dispensing your prescriptions.
What Is the Correct Dosage of Comtess?
Always take Comtess exactly as your doctor or pharmacist has instructed. If you are unsure about your dose, consult your doctor or pharmacist before taking the medication. Comtess is used together with medications containing levodopa (either levodopa/carbidopa preparations or levodopa/benserazide preparations). You may also take other Parkinson's disease medications simultaneously.
Adults
Standard Adult Dosage
The recommended dose is one 200 mg tablet of Comtess taken together with each dose of levodopa/decarboxylase inhibitor. The maximum recommended dose is 10 tablets per day (2,000 mg of entacapone). The dosing frequency of Comtess directly follows the dosing schedule of your levodopa medication. For example, if you take levodopa five times daily, you would take five Comtess tablets daily — one with each levodopa dose.
When you first start taking Comtess, your doctor may need to reduce your levodopa dose. This is because entacapone increases the bioavailability of levodopa, and the enhanced levodopa exposure may initially cause or worsen side effects such as dyskinesias (involuntary movements) or nausea. Follow your doctor's instructions regarding any dose adjustments carefully.
Children and Adolescents
Pediatric Use
Experience with Comtess in patients under 18 years of age is limited. The use of entacapone in children or adolescents is therefore not recommended. Parkinson's disease is extremely rare in children, and the safety and efficacy of entacapone have not been established in the pediatric population.
Patients on Dialysis
If you are undergoing dialysis due to impaired kidney function, your doctor may recommend extending the interval between doses of Comtess. Although entacapone is primarily metabolized by the liver and renal impairment does not significantly affect its pharmacokinetics, dialysis patients may require modified dosing schedules based on their overall clinical status and concomitant medication regimen.
Missed Dose
If you forget to take a Comtess tablet with your levodopa dose, simply continue your treatment by taking the next Comtess tablet together with your next scheduled levodopa dose. Do not take a double dose to compensate for a missed tablet. Since Comtess is taken with each levodopa dose, missing one tablet will have only a temporary and limited effect on your symptom control.
Overdose
In the event of an overdose, contact your doctor, pharmacist, or nearest emergency department immediately. There is no specific antidote for entacapone overdose, and treatment is supportive. The main risks of overdose relate to the enhanced effects of levodopa, including severe nausea, vomiting, dyskinesias, and cardiovascular effects. The maximum dose used in clinical studies was 2,000 mg per day; doses above this have limited clinical experience.
Do not stop taking Comtess without consulting your doctor. When treatment is discontinued, your doctor may need to adjust the dosage of your other Parkinson's disease medications. Abruptly stopping Comtess and other antiparkinsonian medications can result in a dangerous condition called neuroleptic malignant syndrome (NMS), characterized by severe muscle rigidity, high fever, rapid heart rate, and altered consciousness.
What Are the Side Effects of Comtess?
Like all medicines, Comtess can cause side effects, although not everybody experiences them. Most side effects caused by entacapone are mild to moderate in severity. Some side effects are primarily caused by the enhanced effects of levodopa and are most common when treatment with Comtess is first initiated. If you experience such effects, contact your doctor, who may need to adjust your levodopa dose.
At higher entacapone doses (1,400 to 2,000 mg per day), the following side effects become more common: involuntary movements (dyskinesias), nausea, and abdominal pain.
Very Common
May affect more than 1 in 10 people
- Involuntary movements with difficulty performing voluntary movements (dyskinesias)
- Nausea
- Harmless reddish-brown discoloration of urine
Common
May affect up to 1 in 10 people
- Excessive movements (hyperkinesia), worsening of Parkinson's symptoms, prolonged muscle contractions (dystonia)
- Vomiting, diarrhea, abdominal pain, constipation, dry mouth
- Dizziness, fatigue, increased sweating, falls
- Hallucinations (visual, auditory, tactile, or olfactory), insomnia, vivid dreams, confusion
- Heart or arterial events (e.g., chest pain)
Uncommon
May affect up to 1 in 100 people
- Heart attack (myocardial infarction)
Rare
May affect up to 1 in 1,000 people
- Skin rash
- Abnormal liver function test results
Very Rare
May affect up to 1 in 10,000 people
- Agitation
- Decreased appetite, weight loss
- Skin rash and urticaria (hives)
Not Known
Frequency cannot be estimated from available data
- Colitis (inflammation of the large intestine) — may present as persistent diarrhea
- Hepatitis (liver inflammation) with yellowing of skin and eyes (jaundice)
- Discoloration of skin, hair, beard, and nails
Serious Side Effects Requiring Immediate Medical Attention
Although rare, some side effects of Comtess require immediate medical attention:
- Neuroleptic Malignant Syndrome (NMS): A serious, rare condition characterized by severe muscle rigidity, muscle twitching, tremors, agitation, confusion, unconsciousness, high body temperature, rapid heart rate, and blood pressure fluctuations. This can occur particularly when Comtess and other antiparkinsonian medications are suddenly stopped or rapidly reduced.
- Rhabdomyolysis: A severe, rare muscle condition causing pain, tenderness, and weakness in the muscles, which can lead to kidney damage. Seek immediate medical attention if you experience unexplained muscle pain or dark-colored urine.
- Excessive daytime sleepiness and sudden sleep onset: In rare cases, Comtess together with levodopa can cause extreme drowsiness during the daytime and sudden episodes of falling asleep without warning.
Impulse Control Disorders
You may experience an inability to resist the impulse to perform actions that could be harmful, including:
- Strong impulse to gamble excessively despite serious personal or family consequences
- Altered or increased sexual interest and behavior that significantly concerns you or others
- Uncontrolled excessive shopping or spending
- Binge eating (consuming large amounts of food in a short period) or compulsive eating
Tell your doctor if you experience any of these symptoms. Your doctor will discuss ways to manage or reduce these behaviors, which may include adjusting your medication doses.
How Should You Store Comtess?
Keep Comtess tablets out of the sight and reach of children at all times. No special temperature or humidity conditions are required for storage — store the tablets in the original packaging at normal room temperature.
Do not use Comtess after the expiry date stated on the carton and bottle label. The expiry date refers to the last day of the stated month. When opening the bottle for the first time, open the cap and press the seal with your thumb until it breaks.
Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. These measures help protect the environment and prevent accidental ingestion.
What Does Comtess Contain?
Active Ingredient
The active substance is entacapone. Each film-coated tablet contains 200 mg of entacapone. Entacapone is a nitrocatechol-type COMT inhibitor with a molecular formula of C14H15N3O5 and a molecular weight of 305.29 g/mol.
Inactive Ingredients (Excipients)
Tablet core: microcrystalline cellulose, croscarmellose sodium, povidone, and magnesium stearate.
Film coating: partially hydrolyzed polyvinyl alcohol, talc, macrogol, soy lecithin, yellow iron oxide (E 172), red iron oxide (E 172), and titanium dioxide (E 171).
If you have known allergies to any specific excipients, review the full ingredient list carefully and consult your pharmacist. The presence of soy lecithin in the coating means this product is unsuitable for patients with peanut or soy allergy.
Appearance and Pack Sizes
Comtess 200 mg film-coated tablets are brownish-orange, oval tablets engraved with “COMT” on one side. The tablets are packaged in bottles. Four pack sizes are available: bottles containing 30, 60, 100, or 175 tablets. Not all pack sizes may be marketed in your country.
The marketing authorization holder and manufacturer is Orion Corporation, Orionintie 1, FI-02200 Espoo, Finland. Further information about this medicine is available on the European Medicines Agency website.
Frequently Asked Questions About Comtess
Comtess (entacapone) is used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy in patients with Parkinson's disease who experience end-of-dose motor fluctuations (wearing-off). It is a COMT inhibitor that blocks the peripheral breakdown of levodopa, extending its duration of action and reducing off-time. Comtess has no anti-parkinsonian effect on its own and must always be taken together with levodopa. Clinical trials have shown it increases daily “on-time” by approximately 1–2 hours.
The reddish-brown discoloration of urine is a very common and completely harmless side effect of entacapone. It is caused by the drug and its metabolites being excreted through the kidneys. The color change does not indicate any kidney damage, infection, or other medical problem. This effect occurs in the majority of patients taking entacapone and is fully reversible when the medication is discontinued. No treatment or dose adjustment is needed for this effect.
No, Comtess (entacapone) has no therapeutic effect on Parkinson's symptoms when taken alone. It works exclusively by inhibiting the COMT enzyme that breaks down levodopa in peripheral tissues. Without levodopa present, there is no substrate for COMT to act upon, and entacapone provides no clinical benefit. Each Comtess tablet must be taken at the same time as a dose of levodopa/decarboxylase inhibitor (carbidopa or benserazide). Taking entacapone without concurrent levodopa is pointless and not recommended.
Comtess contains only entacapone (200 mg) and must be taken alongside a separate levodopa/decarboxylase inhibitor tablet. Stalevo is a fixed-dose combination tablet that contains three active ingredients in a single tablet: levodopa, carbidopa, and entacapone. The advantage of Stalevo is the convenience of taking fewer tablets, while Comtess offers more flexibility in adjusting the levodopa and entacapone doses independently. The choice between them depends on your individual dosing needs and your doctor's assessment.
No, you should never stop taking Comtess abruptly without consulting your doctor. Sudden discontinuation of entacapone, especially combined with abrupt withdrawal of other antiparkinsonian medications, can trigger neuroleptic malignant syndrome (NMS), a rare but potentially life-threatening condition characterized by severe muscle rigidity, high fever, altered consciousness, rapid heart rate, and unstable blood pressure. If treatment needs to be stopped, your doctor will gradually reduce the dose and adjust your other Parkinson's medications accordingly.
Yes, Comtess tablets contain soy lecithin in the film coating. This means the product is contraindicated for patients with allergies to peanuts or soy. Even the small amount of soy lecithin present in the tablet coating may trigger an allergic reaction in sensitized individuals. If you have a peanut or soy allergy, inform your doctor immediately so that an alternative COMT inhibitor (such as opicapone, which does not contain soy) can be considered.
References
This article is based on peer-reviewed medical literature, international clinical guidelines, and approved prescribing information. All medical claims are supported by evidence level 1A where available.
- European Medicines Agency (EMA). “Comtess (entacapone) Summary of Product Characteristics.” EMA/CHMP, last updated 2025.
- U.S. Food and Drug Administration (FDA). “Comtan (entacapone) Prescribing Information.” FDA, approved 1999, updated 2024.
- National Institute for Health and Care Excellence (NICE). “Parkinson’s disease in adults: diagnosis and management.” NICE guideline [NG71], updated 2024.
- Movement Disorder Society Evidence-Based Medicine Review. “Treatments for the motor symptoms of Parkinson’s disease.” Movement Disorders, 2023. DOI: 10.1002/mds.29387
- Brooks DJ, Sagar H; UK-Irish Entacapone Study Group. “Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson’s disease.” Journal of Neurology, Neurosurgery & Psychiatry, 2003; 74(8): 1071–1079.
- Stocchi F, Rascol O, Kieburtz K, et al. “Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study.” Annals of Neurology, 2010; 68(1): 18–27.
- Rinne UK, Larsen JP, Siden Å, Worm-Petersen J; NOMECOMT Study Group. “Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations.” Neurology, 1998; 51(5): 1309–1314.
- Parkinson Study Group. “Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients.” Annals of Neurology, 1997; 42(5): 747–755.
- Connolly BS, Lang AE. “Pharmacological treatment of Parkinson disease: a review.” JAMA, 2014; 311(16): 1670–1683.
- British National Formulary (BNF). “Entacapone.” NICE/BNF, 2025.
Editorial Team
This article has been written and reviewed by iMedic's medical editorial team, which includes specialists in neurology, movement disorders, and clinical pharmacology. Our content follows international medical guidelines and the GRADE evidence framework.
iMedic Medical Editorial Team — Specialists in Neurology and Clinical Pharmacology with expertise in movement disorders and Parkinson's disease therapeutics.
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