pharmacopeia
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Mechanism of action

Sourced from openFDA

Entacapone is a selective and reversible inhibitor of COMT. In mammals, COMT is distributed throughout various organs with the highest activities in the liver and kidney.

Catechol O-Methyltransferase

Indications

Sourced from openFDA
  • 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".ICD-10: G20

Contraindications

Sourced from openFDA
  • Entacapone is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.contraindicated

Dosage & administration

Sourced from openFDA

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. (More than 58% of patients with levodopa doses above 800 mg daily required such a 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.

Warnings & precautions

Sourced from openFDA

Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines. It is theoretically possible, therefore, that the combination of entacapone and a non-selective MAO inhibitor (e.g., 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. Entacapone can be taken concomitantly with a selective MAO-B inhibitor (e.g., 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.

Adverse reactions

Sourced from openFDA

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%).

Use in specific populations

Sourced from openFDA

Pregnancy Pregnancy Category C In embryofetal development studies, entacapone was administered to pregnant animals throughout organogenesis at doses of up to 1,000 mg/kg/day in rats and 300 mg/kg/day in rabbits. Increased incidences of fetal variations were evident in litters from rats treated with the highest dose, in the absence of overt signs of maternal toxicity. The maternal plasma drug exposure (AUC) associated with this dose was approximately 34 times the estimated plasma exposure in humans receiving the maximum recommended daily dose (MRDD) of 1,600 mg. Increased frequencies of abortions, late and total resorptions, and decreased fetal weights were observed in the litters of rabbits treated with maternally toxic doses of 100 mg/kg/day (plasma AUCs 0.4 times those in humans receiving the MRDD) or greater. There was no evidence of teratogenicity in these studies. However, when entacapone was administered to female rats prior to mating and during early gestation, an increased incidence of fetal eye anomalies (macrophthalmia, microphthalmia, anophthalmia) was observed in the litters of dams treated with doses of 160 mg/kg/day (plasma AUCs 7 times those in humans receiving the MRDD) or greater, in the absence of maternal toxicity.

Pharmacokinetics

Sourced from openFDA
Metabolism
Effect on the Pharmacokinetics of Levodopa and its Metabolites When 200 mg entacapone is administered together with levodopa and carbidopa, it increases the area under the curve (AUC) of levodopa by approximately 35% and the elimination half-life of levodopa is prolonged from 1.3 hours to 2.4 hours. In general, the average peak levodopa plasma concentration and the time of its occurrence (T max of 1 hour) are unaffected.

Overdosage

Sourced from openFDA

The postmarketing data include several cases of overdose. The highest reported dose of entacapone was at least 40,000 mg. The acute symptoms and signs commonly seen in these cases included somnolence and decreased activity, states related to depressed level of consciousness (e.g., coma, confusion and disorientation) and discolorations of skin, tongue, and urine, as well as restlessness, agitation, and aggression. COMT inhibition by entacapone treatment is dose-dependent. A massive overdose of entacapone (entacapone) may theoretically produce a 100% inhibition of the COMT enzyme in humans, thereby preventing the metabolism of endogenous and exogenous catechols. The highest daily dose given to humans was 2,400 mg, administered in one study as 400 mg six times daily with levodopa and carbidopa for 14 days in 15 Parkinson's disease patients, and in another study as 800 mg three times daily for 7 days in 8 healthy volunteers. At this daily dose, the peak plasma concentrations of entacapone averaged 2.0 mcg/mL (at 45 minutes, compared to 1.0 mcg/mL and 1.2 mcg/mL with 200 mg entacapone at 45 minutes).

Approval history

Sourced from openFDA
  • Oct 19, 1999NDANDA020796Orion Pharma
  • Jun 11, 2003NDANDA021485Orion Pharma
  • Jun 19, 2015ANDAANDA203437Aurobindo Pharma Ltd
  • Jun 5, 2017ANDAANDA207210Macleods Pharms Ltd
  • Aug 31, 2017ANDAANDA205792Ajanta Pharma Ltd
  • Oct 3, 2018ANDAANDA206669Sunshine
  • Jan 4, 2022ANDAANDA212601Alembic
  • Jan 25, 2022ANDAANDA213212Rising

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
4,523 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Hallucination53012%
  2. 2Fall52312%
  3. 3Dyskinesia49611%
  4. 4Death3838.5%
  5. 5Drug Ineffective3798.4%
  6. 6Parkinson^s Disease3177.0%
  7. 7Confusional State2826.2%
  8. 8Gait Disturbance2766.1%
  9. 9Tremor2706.0%
  10. 10On And Off Phenomenon2505.5%
  11. 11Somnolence2114.7%
  12. 12Fatigue2074.6%
  13. 13Constipation2054.5%
  14. 14Dizziness2024.5%
  15. 15Nausea2004.4%

Clinical trials

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The 10 most recently updated of 76 ClinicalTrials.gov registrations naming Entacapone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Entacapone work?
Entacapone is a selective and reversible inhibitor of COMT. In mammals, COMT is distributed throughout various organs with the highest activities in the liver and kidney.
What is Entacapone used for?
According to FDA labeling, Entacapone carries indications including: 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".. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Entacapone?
Entacapone is classified as Other dopaminergic agents, Catechol-O-Methyltransferase Inhibitor, Catechol O-Methyltransferase Inhibitors, Increased Central Nervous System Dopamine Activity.
What are the brand names for Entacapone?
Entacapone is marketed under brand names including Comtan, Stalevo.
What are the contraindications for Entacapone?
Entacapone labeling lists contraindications including: Entacapone is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.. Always consult the full prescribing information and a clinician.
Note. Data for entacapone is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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