Entacapone is an active pharmaceutical ingredient in the Other Dopaminergic Agents group (N04BX). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised April 17, 2026[1]
Stacar is indicated for the treatment of adult patients with Parkinson's disease and end-of-dose motor fluctuations not stabilised on levodopa/dopa decarboxylase (DDC) inhibitor treatment.
How to take
GB
CACanada· Health Canada
5 products
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
APO-ENTACAPONE (entacapone) is contraindicated in patients with known hypersensitivity to entacapone or to any of the excipients (see PHARMACEUTICAL INFORMATION – Composition for a complete listing). APO-ENTACAPONE is contraindicated in patients with hepatic impairment.
g. phenelzine and tranylcypromine). The combination of selective MAO-A and selective MAO-B inhibitors is equivalent to non-selective MAO- inhibition, therefore, they should not both be given concomitantly with APO- ENTACAPONE and levodopa preparations.
Non-selective MAO inhibitors must be discontinued at least two weeks prior to initiating therapy with entacapone. g. selegiline 10 mg/day) when co-administered with APO-ENTACAPONE and levodopa (see PRECAUTIONS, Drug Interactions, Selegiline).
APO-ENTACAPONE should not be given to patients with clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematologic, pulmonary (including bronchial asthma), or renal disease. APO-ENTACAPONE is contraindicated in patients with a previous history of Neuroleptic Malignant Syndrome (NMS) and/or non-traumatic rhabdomyolysis.
EUEuropean Union· EMA
4 products
Uses
EUOfficial regulatory label· revised May 7, 2026[3]
Entacapone is indicated as an adjunct to standard preparations of levodopa/benserazide or levodopa/carbidopa for use in adult patients with Parkinson’s disease and end-of-dose motor fluctuations, who cannot be stabilised on those combinations.
How to take
EU
USUnited States· FDA
1 product
Uses
USOfficial regulatory label· revised October 7, 2023[4]
INDICATIONS AND USAGE
Entacapone tablets USP are indicated as an adjunct to levodopa and carbidopa to treat end-of-dose "wearing-off" in patients with Parkinson's disease (see CLINICAL PHARMACOLOGY, Clinical Studies ). Entacapone's effectiveness has not been systematically evaluated in patients with Parkinson's disease who do not experience end-of-dose "wearing-off".
How to take
Drug interactions
Known interactions involving Entacapone. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 307. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PL347710272 · revised April 17, 2026
[2]Health Canada (DPD) · 02321459 · revised March 22, 2025
[3]European Medicines Agency · EMEA/H/C/000171 · revised May 7, 2026
[4]FDA DailyMed · 0bf133e4-1c17-43… · revised October 7, 2023 [PDF]
[5]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
Posology The optimum daily dose must be determined by careful titration of levodopa in each patient. 75 mg/200 mg or 200 mg/50 mg/200 mg levodopa/ carbidopa/ entacapone). Patients should be instructed to take only one Stacar tablet per dose administration.
Patients receiving less than 70-100 mg carbidopa a day are more likely to experience nausea and vomiting. 5 mg/200 mg. 5 mg/200 mg equals 375 mg of carbidopa a day. 75 mg/200 mg is 8 tablets per day and Stacar 200 mg/50 mg/200 mg dose is 7 tablets per day.
Usually Stacar is to be used in patients who are currently treated with corresponding doses of standard release levodopa/DDC inhibitor and entacapone. How to transfer patients taking levodopa/DDC inhibitor (carbidopa or benserazide) preparations and entacapone tablets to Stacar a.
Patients who are currently treated with entacapone and with standard release levodopa/carbidopa in doses equal to Stacar tablet strengths can be directly transferred to corresponding Stacar tablets. 5 mg/200 mg Stacar tablet four times daily in place of their usual levodopa/carbidopa and entacapone doses.
b. 75 mg/200 mg or 200 mg/50 mg/200 mg), Stacar dosing should be carefully titrated for optimal clinical response. At the initiation, Stacar should be adjusted to correspond as closely as possible to the total daily dose of levodopa currently used.
c. When initiating Stacar in patients currently treated with entacapone and levodopa/benserazide in a standard release formulation, the dosing of levodopa/benserazide should be discontinued in the previous night, and Stacar should be started in the next morning.
The starting dose of Stacar should provide either the same amount of levodopa or slightly (5-10%) more. How to transfer patients not currently treated with entacapone to Stacar Initiation of Stacar may be considered at corresponding doses to current treatment in some patients with Parkinson's disease and end-of-dose motor fluctuations, who are not stabilised on their current standard release levodopa/DDC inhibitor treatment.
However, a direct switch from levodopa/DDC inhibitor to Stacar is not recommended for patients who have dyskinesias or whose daily levodopa dose is above 800 mg. In such patients it is advisable to introduce entacapone treatment as a separate treatment (entacapone tablets) and adjust the levodopa dose if necessary, before switching to Stacar.
Entacapone enhances the effects of levodopa. It may therefore be necessary, particularly in patients with dyskinesia, to reduce levodopa dose by 10-30% within the first days to first weeks after initiating Stacar treatment. The daily dose of levodopa can be reduced by extending the dosing intervals and/or by reducing the amount of levodopa per dose, according to the clinical condition of the patient.
Dose adjustment during the course of the treatment When more levodopa is required, an increase in the frequency of doses and/or the use of an alternative strength of Stacar should be considered, within the dose recommendations. When less levodopa is required, the total daily dose of Stacar should be reduced either by decreasing the frequency of administration by extending the time between doses, or by decreasing the strength of Stacar at an administration.
If other levodopa products are used concomitantly with a Stacar tablet, the maximum dose recommendations should be followed.
Discontinuation of Stacar therapy:
If Stacar treatment is discontinued and the patient is transferred to levodopa/DDC inhibitor therapy without entacapone, it is necessary to adjust the dosing of other antiparkinsonian treatments, especially levodopa, to achieve a sufficient level of control of the parkinsonian symptoms.
Paediatric population:
The safety and efficacy of Stacar in children aged below 18 years have not been established. No data are available.
Elderly:
No dose adjustment of Stacar is required for elderly.
Hepatic impairment:
It is advised that Stacar should be administered cautiously to patients with mild to moderate hepatic impairment. 2). For severe hepatic impairment see section
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised April 17, 2026[1]
a. Summary of the safety profile The most frequently reported adverse reactions with Stacar are dyskinesias occurring in approximately 19% of patients; gastrointestinal symptoms including nausea and diarrhoea occurring in approximately 15% and 12% of patients, respectively; muscle, musculoskeletal and connective tissue pain occurring in approximately 12% of patients; and harmless reddish-brown discolouration of urine (chromaturia) occurring in approximately 10% of patients.
Serious events of gastrointestinal haemorrhage (uncommon) and angioedema (rare) have been identified from the clinical trials with Levodopa/carbidopa/entacapone or entacapone combined with levodopa/DDC inhibitor. Serious hepatitis with mainly cholestatic features, rhabdomyolysis and neuroleptic malignant syndrome may occur with Levodopa/carbidopa/entacapone although no cases have been identified from the clinical trial data.
b. Tabulated list of adverse reactions The following adverse reactions, listed in Table 1, have been accumulated both from a pooled data of eleven double-blind clinical trials consisting of 3230 patients (1810 treated with Levodopa/carbidopa/entacapone or entacapone combined with levodopa/DDC inhibitor, and 1420 treated with placebo combined with levodopa/DDC inhibitor or cabergoline combined with levodopa/ DDC inhibitor), and from the post-marketing data since the introduction of entacapone into the market for the combination use of entacapone with levodopa/DDC inhibitor.
Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data, since no valid estimate can be derived from clinical trials or epidemiological studies).
Table 1. g. g. g. g. skin, nail, hair, sweat)* Rare: Angioedema Not known: Urticaria* Musculoskeletal and connective tissue disorders Very common: Muscle, musculoskeletal and connective tissue pain* Common: Muscle spasms, arthralgia Not known: Rhabdomyolysis* Renal and urinary disorders Very common: Chromaturia* Common: Urinary tract infection Uncommon: Urinary retention General disorders and administration site conditions Common: Chest pain, peripheral oedema, fall, gait disturbance, asthenia, fatigue Uncommon: Malaise *Adverse reactions that are mainly attributable to entacapone or are more frequent (by the frequency difference of at least 1% in the clinical trial data) with entacapone than levodopa/DDC inhibitor alone.
See section c. 54%, respectively) are derived from an analysis of 13 double- blind studies involving 2082 patients with end-of-dose motor fluctuations receiving entacapone. c. 8b. g. dyskinesia, nausea and vomiting) and occur most commonly at the beginning of the treatment.
Reduction of levodopa dose decreases the severity and frequency of these dopaminergic reactions. Few adverse reactions are known to be directly attributable to the active substance entacapone including diarrhoea and reddish-brown discolouration of urine.
g. skin, nail, hair and sweat. 8b are marked based on either their more frequent occurring (by the frequency difference of at least 1%) in the clinical trial data with entacapone than levodopa/DDCI alone or the individual case safety reports received after the introduction of entacapone into the market.
Convulsions have occurred rarely with levodopa/carbidopa; however a causal relationship to levodopa/carbidopa therapy has not been established. 4). Dopamine Dysregulation Syndrome (DDS) is an addictive disorder seen in some patients treated […]
GBOfficial regulatory label· Warnings and precautions· revised April 17, 2026[1]
Stacar is not recommended for the treatment of drug-induced extrapyramidal reactions. - Stacar therapy should be administered cautiously to patients with ischemic heart disease, severe cardiovascular or pulmonary disease, bronchial asthma, renal or endocrine disease, history of peptic ulcer disease or history of convulsions.
- In patients with a history of myocardial infarction who have residual atrial nodal or ventricular arrhythmias; cardiac function should be monitored with particular care during the period of initial dose adjustments. - All patients treated with Stacar should be monitored carefully for the development of mental changes, depression with suicidal tendencies, and other serious antisocial behaviour.
Patients with past or current psychosis should be treated with caution. - Concomitant administration of antipsychotics with dopamine receptor-blocking properties, particularly D2 receptor antagonists should be carried out with caution, and the patient carefully observed for loss of antiparkinsonian effect or worsening of parkinsonian symptoms.
- Patients with chronic wide-angle glaucoma may be treated with Stacar with caution, provided the intra-ocular pressure is well controlled and the patient is monitored carefully for changes in intra-ocular pressure. - Stacar may induce orthostatic hypotension.
Therefore Stacar should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension. 7). g. dyskinesia, were more common in patients who received entacapone and dopamine agonists (such as bromocriptine), selegiline or amantadine compared to those who received placebo with this combination.
The doses of other antiparkinsonian medicinal products may need to be adjusted when Stacar treatment is substituted for a patient currently not treated with entacapone. - Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been observed rarely in patients with Parkinson's disease.
Therefore, any abrupt dose reduction or withdrawal of levodopa should be carefully observed, particularly in patients who are also receiving neuroleptics. , agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised April 17, 2026[1]
3.
Renal impairment:
Renal impairment does not affect the pharmacokinetics of entacapone. 2). 2). One tablet contains one treatment dose and the tablet may only be administered as whole tablets. 1. - Severe hepatic impairment. - Narrow-angle glaucoma. - Pheochromocytoma.
g. phenelzine, tranylcypromine). 5). - A previous history of Neuroleptic Malignant Syndrome (NMS) and/or non- traumatic rhabdomyolysis.
This is not medical advice. Consult a qualified healthcare professional.
APO-ENTACAPONE should not be given when administration of a sympathomimetic amine is contraindicated. APO-ENTACAPONE is contraindicated in patients with pheochromocytoma due to the increased risk of hypertensive crisis. APO-ENTACAPONE should not be given to patients with narrow angle glaucoma.
Because levodopa may activate a malignant melanoma, APO-ENTACAPONE should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma. Page 10 of 54 WARNINGS Sudden Onset of Sleep Patients receiving treatment with APO-ENTACAPONE in combination with levodopa/DDC inhibitor and/or other dopaminergic agents have reported suddenly falling asleep while engaged in activities of daily living, including the driving of a car, which sometimes resulted in accidents.
Although some of the patients reported somnolence while treated with levodopa/DDC inhibitor and APO-ENTACAPONE, others perceived that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event.
Physicians should alert patients of the reported cases of sudden onset of sleep, bearing in mind that these events are NOT limited to initiation of therapy. Patients should also be advised that sudden onset of sleep has occurred without warning signs and should be specifically asked about factors that may increase the risk with APO-ENTACAPONE used in combination with levodopa/decarboxylase DDC inhibitor, such as concomitant medications or the presence of sleep disorders.
Given the reported cases of somnolence and sudden onset of sleep (not necessarily preceded by somnolence), physicians should caution patients about the risk of operating hazardous machinery, including driving motor vehicles, while taking APO- ENTACAPONE in combination with levodopa/decarboxylase DDC inhibitor.
If drowsiness or sudden onset of sleep should occur, patients should be informed to refrain from driving or operating machines and to immediately contact their physician (see PRECAUTIONS- Information for Patients). Episodes of falling asleep while engaged in activities of daily living have also been reported in patients taking other dopaminergic agents, therefore, symptoms may not be alleviated by substituting these products.
While dose reduction clearly reduces the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. Currently, the precise cause of this event is unknown.
It is known that many Parkinson’s disease patients experience alterations in sleep architecture, which results in excessive daytime sleepiness or spontaneous dozing, and that dopaminergic agents can also induce sleepiness.
Skin Melanoma:
Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased Page 11 of 54 risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear.
For the reasons stated above, patients and healthcare providers are advised to monitor for melanomas frequently and on a regular basis when using APO-ENTACAPONE for any indication (see PRECAUTIONS- Information for Patients). , dermatologists).
Prostate Cancer Prostate cancer has been reported in elderly males during the use of entacapone in combination with levodopa/carbidopa in clinical trials. The clinical relevance of these adverse events is not known (see ADVERSE REACTIONS).
Physicians are advised to adhere to the routine examination schedule for all male patients for symptoms and risk factors of prostate cancer including evaluation prior to initiating treatment with APO-ENTACAPONE. Physicians should emphasize to patients the importance of adhering to routine examinations for prostate cancer during extended treatment with entacapone (see PRECAUTIONS- Information for Patients).
Drugs metabolized by Catechol-O-methyltransferase (COMT) When a single 400 mg dose of entacapone was given together with intravenous isoprenaline (isoproterenol) and epinephrine without coadministered levodopa/DDC inhibitor, the overall mean maximal changes in heart rate during infusion were about 50% and 80% higher than with placebo, for isoprenaline and epinephrine, respectively.
Therefore, drugs known to be metabolized by COMT, such as isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine, isoetherine and bitolterol should […]
This is not medical advice. Consult a qualified healthcare professional.
Entacapone should only be used in combination with levodopa/benserazide or levodopa/carbidopa. The prescribing information for these levodopa preparations is applicable to their concomitant use with entacapone. Posology One 200 mg tablet is taken with each levodopa/dopa decarboxylase inhibitor dose.
e. 2,000 mg of entacapone. Entacapone enhances the effects of levodopa. g. dyskinesias, nausea, vomiting and hallucinations, it is often necessary to adjust levodopa dosage within the first days to first weeks after initiating entacapone treatment.
The daily dose of levodopa should be reduced by about 10–30% by extending the dosing intervals and/or by reducing the amount of levodopa per dose, according to the clinical condition of the patient. If entacapone treatment is discontinued, it is necessary to adjust the dosing of other antiparkinsonian treatments, especially levodopa, to achieve a sufficient level of control of the parkinsonian symptoms.
Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide preparations slightly (5–10%) more than from standard levodopa/carbidopa preparations. Hence, patients who are taking standard levodopa/benserazide preparations may need a larger reduction of levodopa dose when entacapone is initiated.
3 Renal impairment Renal insufficiency does not affect the pharmacokinetics of entacapone and there is no need for dose adjustment. 2). Hepatic impairment See section
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised May 7, 2026[3]
Summary of the safety profile The most frequent adverse reactions caused by entacapone relate to the increased dopaminergic activity and occur most commonly at the beginning of treatment. Reduction of levodopa dosage decreases the severity and frequency of these reactions.
The other major class of adverse reactions are gastrointestinal symptoms, including nausea, vomiting, abdominal pain, constipation and diarrhoea. Urine may be discoloured reddish-brown by entacapone, but this is a harmless phenomenon.
Usually the adverse reactions caused by entacapone are mild to moderate. g. g. 7%). 2%) were reported significantly more often with entacapone than with placebo in pooled data from clinical studies involving 406 patients taking the medicinal product and 296 patients taking placebo.
Some of the adverse reactions, such as dyskinesia, nausea, and abdominal pain, may be more common with the higher doses (1,400 to 2,000 mg per day) than with the lower doses of entacapone. Tabulated list of adverse reactions The following adverse reactions, listed below in Table 1, have been accumulated both from clinical studies with entacapone and since the introduction of entacapone into the market.
g. 4) Skin and subcutaneous tissue disorders Rare: Erythematous or maculopapular rash Very rare: Urticaria Not known: Skin, hair, beard and nail discolourations Renal and urinary disorders Very common: Urine discolouration 7 General disorders and administration site conditions Common: Fatigue, sweating increased, fall Very rare: Weight decrease * Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data, since no valid estimate can be derived from clinical trials or epidemiological studies).
54%, respectively) are derived from an analysis of 13 double-blind studies involving 2,082 patients with end-of- dose motor fluctuations receiving entacapone. Description of selected adverse reactions Entacapone in association with levodopa has been associated with isolated cases of excessive daytime somnolence and sudden sleep onset episodes.
4). Isolated cases of NMS have been reported following abrupt reduction or discontinuation of entacapone and other dopaminergic treatments. Isolated cases of rhabdomyolysis have been reported. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
EUOfficial regulatory label· Warnings and precautions· revised May 7, 2026[3]
Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been observed rarely in patients with Parkinson’s disease. g. agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase.
In individual cases, only some of these symptoms and/or findings may be evident. Neither NMS nor rhabdomyolysis have been reported in association with entacapone treatment from controlled trials in which entacapone was discontinued abruptly.
Since the introduction into the market, isolated cases of NMS have been reported, especially following abrupt reduction or discontinuation of entacapone and other concomitant dopaminergic medicinal products. When considered necessary, withdrawal of entacapone and other dopaminergic treatment should proceed slowly, and if signs and/or symptoms occur despite a slow withdrawal of entacapone, an increase in levodopa dosage may be necessary.
Entacapone therapy should be administered cautiously to patients with ischaemic heart disease. Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal 4 products containing a catechol group and potentiate their action.
g. 5). Entacapone is always given as an adjunct to levodopa treatment. Hence, the precautions valid for levodopa treatment should also be taken into account for entacapone treatment. Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide preparations 5–10% more than from standard levodopa/carbidopa preparations.
8). 8). Entacapone may aggravate levodopa-induced orthostatic hypotension. Entacapone should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension. g. dyskinesia, were more common in patients who received entacapone and dopamine agonists (such as bromocriptine), selegiline or amantadine compared to those who received placebo with this combination.
The doses of other antiparkinsonian medicinal products may need to be adjusted when entacapone treatment is initiated. 7). For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid potential excessive weight decrease.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised May 7, 2026[3]
3. Elderly (≥65 years) No dosage adjustment of entacapone is required for older people. Paediatric population The safety and efficacy of Comtan in children below age 18 have not been established. No data are available. Method of administration Entacapone is administered orally and simultaneously with each levodopa/carbidopa or levodopa/benserazide dose.
2). 1. - Hepatic impairment. - Phaeochromocytoma. g. phenelzine, tranylcypromine). 5). - A previous history of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis.
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised October 7, 2023[4]
DOSAGE AND ADMINISTRATION
The recommended dose of entacapone is one 200 mg tablet administered concomitantly with each levodopa and carbidopa dose to a maximum of 8 times daily (200 mg × 8 = 1,600 mg per day). Clinical experience with daily doses above 1,600 mg is limited.
Entacapone should always be administered in association with levodopa and carbidopa. Entacapone has no antiparkinsonian effect of its own. In clinical studies, the majority of patients required a decrease in daily levodopa dose if their daily dose of levodopa had been greater than or equal to 800 mg or if patients had moderate or severe dyskinesia before beginning treatment.
To optimize an individual patient's response, reductions in daily levodopa dose or extending the interval between doses may be necessary. In clinical studies, the average reduction in daily levodopa dose was about 25% in those patients requiring a levodopa dose reduction.
) Entacapone can be combined with both the immediate and sustained-release formulations of levodopa and carbidopa. Entacapone may be taken with or without food (see CLINICAL PHARMACOLOGY ). Patients With Impaired Hepatic Function Patients with hepatic impairment should be treated with caution.
The AUC and C max of entacapone approximately doubled in patients with documented liver disease, compared to controls. However, these studies were conducted with single-dose entacapone without levodopa and dopa decarboxylase inhibitor coadministration, and therefore the effects of liver disease on the kinetics of chronically administered entacapone have not been evaluated (see CLINICAL PHARMACOLOGY, Pharmacokinetics of Entacapone ).
Withdrawing Patients from Entacapone Rapid withdrawal or abrupt reduction in the entacapone dose could lead to emergence of signs and symptoms of Parkinson's disease (see CLINICAL PHARMACOLOGY, Clinical Studies ), and may lead to hyperpyrexia and confusion, a symptom complex resembling NMS (see PRECAUTIONS, Other Events Reported With Dopaminergic Therapy ).
This syndrome should be considered in the differential diagnosis for any patient who develops a high fever or severe rigidity. If a decision is made to discontinue treatment with entacapone, patients should be monitored closely and other dopaminergic treatments should be adjusted as needed.
Although tapering entacapone has not been systematically evaluated, it seems prudent to withdraw patients slowly if the decision to discontinue treatment is made.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 352 reports total. [5]
Hallucination 61
Fall 43
Death 41
Dyskinesia 33
On And Off Phenomenon 33
Drug Ineffective 24
Urinary Tract Infection 23
Tremor 20
Fatigue 19
Gait Disturbance 19
Nausea 18
Parkinson^S Disease 18
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised October 7, 2023[4]
ADVERSE REACTIONS
Because clinical studies are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment per total number of patients treated) observed in the clinical studies of a drug cannot be directly compared to the incidence of adverse reactions in the clinical studies of another drug and may not reflect the incidence of adverse reactions observed in practice.
A total of 1,450 patients with Parkinson's disease were treated with entacapone in premarketing clinical studies. Included were patients with fluctuating symptoms, as well as those with stable responses to levodopa therapy. All patients received concomitant treatment with levodopa preparations, however, and were similar in other clinical aspects.
The most commonly observed adverse reactions (incidence at least 3% greater than placebo) in double-blind, placebo-controlled studies (N=1,003) associated with the use of entacapone were: dyskinesia, urine discoloration, diarrhea, nausea, hyperkinesia, abdominal pain, vomiting, and dry mouth.
Approximately 14% of the 603 patients given entacapone in the double-blind, placebo-controlled studies discontinued treatment due to adverse reactions, compared to 9% of the 400 patients who received placebo. The most frequent causes of discontinuation in decreasing order were: psychiatric disorders (2% vs.
1%), diarrhea (2% vs. 0%), dyskinesia and hyperkinesia (2% vs. 1%), nausea (2% vs. 1%), and abdominal pain (1% vs. 0%). Adverse Event Incidence in Controlled Clinical Studies Table 4 lists treatment-emergent adverse events that occurred in at least 1% of patients treated with entacapone participating in the double-blind, placebo-controlled studies and that were numerically more common in the entacapone group, compared to placebo.
In these studies, either entacapone or placebo was added to levodopa and carbidopa (or levodopa and benserazide).
Table 4:
Summary of Patients with Adverse Events after Start of Trial Drug Administration At least 1% in Entacapone Group and Greater Than Placebo SYSTEM ORGAN CLASS Entacapone Placebo Preferred term (n = 603) % of patients (n = 400)) % of patients SKIN AND APPENDAGES DISORDERS Sweating increased 2 1 MUSCULOSKELETAL SYSTEM DISORDERS Back pain 2 1 CENTRAL AND PERIPHERAL NERVOUS SYSTEM DISORDERS Dyskinesia 25 15 Hyperkinesia 10 5 Hypokinesia 9 8 Dizziness 8 6 SPECIAL SENSES, OTHER DISORDERS Taste perversion 1 0 PSYCHIATRIC DISORDERS Anxiety 2 1 Somnolence 2 0 Agitation 1 0 GASTROINTESTINAL SYSTEM DISORDERS Nausea 14 8 Diarrhea 10 4 Abdominal pain 8 4 Constipation 6 4 Vomiting 4 1 Mouth dry 3 0 Dyspepsia 2 1 Flatulence 2 0 Gastritis 1 0 Gastrointestinal disorders 1 0 RESPIRATORY SYSTEM DISORDERS Dyspnea 3 1 PLATELET, BLEEDING AND CLOTTING DISORDERS Purpura 2 1 URINARY SYSTEM DISORDERS Urine discoloration 10 0 BODY AS A WHOLE - GENERAL DISORDERS Back pain 4 2 Fatigue 6 4 Asthenia 2 1 RESISTANCE MECHANISM DISORDERS Infection bacterial 1 0 Effects of Gender and Age on Adverse Reactions No differences were noted in the rate of adverse events attributable to entacapone by age or gender.
Postmarketing Reports The following spontaneous reports of adverse events temporally associated with entacapone have been identified since market introduction and are not listed in Table 4. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish causal relationship to entacapone exposure.
Hepatitis with mainly cholestatic features has been reported.
USOfficial regulatory label· Warnings and precautions· revised October 7, 2023[4]
WARNINGS
Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines. , phenelzine and tranylcypromine) would result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism.
For this reason, patients should ordinarily not be treated concomitantly with entacapone and a non-selective MAO inhibitor. , selegiline). Drugs Metabolized By Catechol-O-Methyltransferase (COMT) When a single 400 mg dose of entacapone was given with intravenous isoprenaline (isoproterenol) and epinephrine without coadministered levodopa and dopa decarboxylase inhibitor, the overall mean maximal changes in heart rate during infusion were about 50% and 80% higher than with placebo, for isoprenaline and epinephrine, respectively.
Therefore, drugs known to be metabolized by COMT, such as isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine, isoetherine, and bitolterol should be administered with caution in patients receiving entacapone regardless of the route of administration (including inhalation), as their interaction may result in increased heart rates, possible arrhythmias, and excessive changes in blood pressure.
Ventricular tachycardia was noted in one 32-year-old healthy male volunteer in an interaction study after epinephrine infusion and oral entacapone administration. Treatment with propranolol was required. A causal relationship to entacapone administration appears probable but cannot be attributed with certainty.
Falling Asleep During Activities of Daily Living and Somnolence Patients with Parkinson's disease treated with entacapone, which increases plasma levodopa levels, or with levodopa have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (including the operation of motor vehicles).
Some of these episodes resulted in accidents. Although many of these patients reported somnolence while on entacapone, some did not perceive warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event.
Some of these events have been reported as late as one year after initiation of treatment. The risk of somnolence was increased (entacapone 2% and placebo 0%) in controlled studies. It has been reported that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised October 7, 2023[4]
CONTRAINDICATIONS
Entacapone is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.
This is not medical advice. Consult a qualified healthcare professional.
In individual cases, only some of these symptoms and/or findings may be evident. The early diagnosis is important for the appropriate management of NMS. A syndrome resembling the neuroleptic malignant syndrome including muscular rigidity, elevated body temperature, mental changes and increased serum creatine phosphokinase has been reported with the abrupt withdrawal of antiparkinsonian agents.
Neither NMS nor rhabdomyolysis have been reported in association with entacapone treatment from controlled trials in which entacapone was discontinued abruptly. Since the introduction of entacapone into the market, isolated cases of NMS have been reported, especially following abrupt reduction or discontinuation of entacapone and other concomitant dopaminergic medicinal products.
When considered necessary, the replacement of Stacar with levodopa and DDC inhibitor without entacapone or other dopaminergic treatment should proceed slowly and an increase in levodopa dose may be necessary. - If general anaesthesia is required, therapy with Stacar may be continued for as long as the patient is permitted to take fluids and medicinal products by mouth.
If therapy has to be stopped temporarily, Stacar may be restarted as soon as oral medicinal products can be taken at the same daily dose as before. - Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy with Stacar.
- For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid potential excessive weight decrease. Prolonged or persistent diarrhoea appearing during use of entacapone may be a sign of colitis. In the event of prolonged or persistent diarrhoea, the drug should be discontinued and appropriate medical therapy and investigations considered.
- Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including Stacar.
Review of treatment is recommended if such symptoms develop. - Dopamine Dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product seen in some patients treated with carbidopa/levodopa. 8). - For patients who experience progressive anorexia, asthenia and weight decrease within a relatively short period of time, a general medical evaluation including liver function should be considered.
- Levodopa/carbidopa may cause false positive result when a dipstick is used to test for urinary ketone and this reaction is not altered by boiling the urine sample. The use of glucose oxidase methods may give false negative results for glycosuria.
Prolonged or persistent diarrhoea appearing during use of entacapone may be a sign of colitis. In the event of prolonged or persistent diarrhoea, the medicinal product should be discontinued and appropriate medical therapy and investigations considered.
Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments such as Comtan in association with levodopa.
Review of treatment is recommended if such symptoms develop. For patients who experience progressive anorexia, asthenia and weight decrease within a relatively short period of time, a general medical evaluation including liver function should be considered.
Comtan tablets contain sucrose. Therefore, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. 3 mg sodium per tablet. The maximum recommended daily dose (10 tablets) contains 73 mg sodium, equivalent to 4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
For this reason, prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.
Patients should be advised to exercise caution while driving, operating machines, or working at heights during treatment with entacapone. Patients who have already experienced somnolence and/or an episode of sudden sleep onset should not participate in these activities during treatment with entacapone.
Before initiating treatment with entacapone, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase this risk such as concomitant use of sedating medications and the presence of sleep disorders.
), entacapone should ordinarily be discontinued (see DOSAGE AND ADMINISTRATION for guidance on discontinuing entacapone). If the decision is made to continue entacapone, patients should be advised not to drive and to avoid other potentially dangerous activities.
There is insufficient information to establish whether dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.