Entacapone

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Entacapone
Skeletal formula
Space-filling model of entacapone
Clinical data
Pronunciation/ˌɛntəkəˈpoʊn/ or /ɛnˈtækəpoʊn/
Trade namesComtan (single ingredient), Stalevo (multi-ingredient)
AHFS/Drugs.comMonograph
MedlinePlusa601236
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability35%
Protein binding98% (binds to serum albumin)
MetabolismHepatic
Elimination half-life0.4–0.7 hours
ExcretionFeces (90%), urine (10%)
Identifiers
  • (2E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide
JSmol)
  • [O-][N+](=O)c1cc(\C=C(/C#N)C(=O)N(CC)CC)cc(O)c1O
  • InChI=1S/C14H15N3O5/c1-3-16(4-2)14(20)10(8-15)5-9-6-11(17(21)22)13(19)12(18)7-9/h5-7,18-19H,3-4H2,1-2H3/b10-5+ checkY
  • Key:JRURYQJSLYLRLN-BJMVGYQFSA-N checkY
  (verify)

Entacapone, sold under the brand name Comtan among others, is a medication commonly used in combination with other medications for the treatment of

levodopa and carbidopa allows levodopa to have a longer effect in the brain and reduces Parkinson's disease signs and symptoms for a greater length of time than levodopa and carbidopa therapy alone.[2]

Entacapone is a selective and

metabolizing levodopa, resulting in an overall increase of levodopa remaining in the brain and body.[2]

Orion Pharma and marketed by Novartis, is a single tablet formulation that contains levodopa, carbidopa, and entacapone.[3]

Medical uses

Entacapone is used

in addition to levodopa and carbidopa for people with Parkinson's disease to treat the signs and symptoms of end-of-dose "wearing-off."[4] "Wearing-off" is characterized by the re-appearance of both motor and non-motor symptoms of Parkinson's disease occurring towards the end of a previous levodopa and carbidopa dose.[5] In clinical trials, entacapone has not been shown to slow progression or reverse Parkinson's disease.[2][5][6]

Entacapone is an orally active drug that can be taken with or without food.[4][6]

Pregnancy and breastfeeding

Pregnancy category C: risk is not ruled out.[2]

Although there have been animal studies that showed that entacapone was

excreted into maternal rat milk, there have been no studies with human breast milk. Caution is advised for mothers taking entacapone while breastfeeding or during pregnancy.[2]

Children

Entacapone safety and efficacy have not been assessed in infants or children.[2]

Liver problems

Biliary excretion is the major route of excretion for entacapone. People with liver dysfunction may require additional caution and more frequent liver function monitoring while taking entacapone.[2]

Kidney problems

There are no significant considerations for people with poor kidney function taking entacapone.[2]

Contraindications

There is a high risk for allergic reactions for people who are hypersensitive to entacapone.[2]

Potential limiting conditions to consider before starting entacapone include:[6]

Side effects

The following

side effects
have been reported by people with Parkinson's disease treated with entacapone:

  • Abdominal pain
  • Nausea
  • Vomiting
  • Fatigue
  • Dry mouth
  • Back ache

Movement problems

The most common side effect of entacapone is movement problems, which occur in 25% of people taking entacapone.[2] This drug may cause or worsen dyskinesia for people with Parkinson's disease treated together with levodopa and carbidopa.[2] In particular, "peak-dose dyskinesias" may occur when levodopa levels are at its peak concentration in the serum plasma.[7][8]

Diarrhea

10% of patients taking entacapone have been shown to experience diarrhea.[2] Diarrhea may occur within 4–12 weeks of initial entacapone use but resolves after discontinuation of the drug. Use of entacapone in the presence of diarrhea can also be associated with weight loss, low potassium levels, and dehydration.[2] In clinical studies, severe diarrhea was the most common reason for discontinuation of entacapone.[9]

Urine color

10% of people taking entacapone experience a change in urine color to orange, red, brown, or black. This side effect is due to entacapone metabolism and excretion in the urine and shown to not be harmful.[9]

Sudden sleep onset

People have reported sudden sleep onset while engaging in daily activities without prior warning of drowsiness. In controlled studies, patients on entacapone had a 2% increased risk of somnolence compared to placebo.[2]

Low blood pressure

Episodes of orthostatic hypotension have been shown to be more common at the start of entacapone use due to increased levels of levodopa.[2]

Behavior problems

mental status, leading to behaviors such as delusions, agitation, confusion, and delirium.[2]

People taking entacapone may experience increased urges to participate in gambling, sexual activities, money spending, and other stimulating reward behaviors.[2]

Interactions

In studies, entacapone has shown a low potential for interaction with other drugs. In theory, it could interact with

INR was seen when combined with entacapone.[10]

Pharmacology

Mechanism of action

Entacapone is a selective and reversible

decarboxylase inhibitor, COMT acts as the major metabolizing enzyme for levodopa and metabolizes it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and in the periphery.[2]

For the treatment of Parkinson's disease, entacapone is given as an adjunct to levodopa and an aromatic amino acid decarboxylase inhibitor, carbidopa. Entacapone inhibits COMT in the periphery (but not, or at most marginally, in the brain[11]) and the metabolism of levodopa, thus increasing plasma levels of levodopa and causing more constant dopaminergic stimulation in order to reduce the signs and symptoms presented in the disease.[2]

Pharmacokinetics

Absorption

The time to highest blood plasma concentrations is approximately one hour. The substance undergoes extensive

first-pass metabolism. Absolute oral bioavailability (F) is 35%.[2][10]

Distribution

The

intravenous injection is approximately 20 liters. 98% of the circulating entacapone is bound to serum albumin, which limits its distribution into tissues.[2][10]

Metabolism and elimination

Entacapone is primarily metabolized to its

Z-isomer.[10] It has a half-life of approximately 0.3–0.7 hours, with only 0.2% being excreted unchanged in the urine.[2]

References

  1. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. ^ a b c d e f g h i j k l m n o p q r s t u v w x y "Comtan Full Prescribing Information-Novartis" (PDF). Pharma.us.novartis.com. July 2014. Archived from the original (PDF) on 15 March 2016. Retrieved 4 November 2015.
  3. ^ "Stalevo- carbidopa, levodopa, and entacapone tablet, film coated". DailyMed. 7 January 2020. Retrieved 14 March 2020.
  4. ^ a b "PubMedHealth". PubMedHealth. 1 October 2015. Retrieved 4 November 2015.
  5. ^
    S2CID 71616140
    .
  6. ^ a b c "Entacapone". Medlineplus - NIH. American Society of Health-System Pharmacist. September 2010. Retrieved 4 November 2015.
  7. ^ "Late (complicated) Parkinson's Disease". National Guideline Clearing House. November 2006. Archived from the original on 24 October 2015. Retrieved 3 November 2015.
  8. PMID 23948989
    .
  9. ^
    ISBN 978-1609137137
    .
  10. ^ a b c d "Comtan: EPAR – Product Information" (PDF). European Medicines Agency. 10 March 2015. Archived from the original (PDF) on 16 March 2018. Retrieved 17 April 2017.
  11. ISBN 978-3-7741-9846-3
    .
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