Carbidopa/levodopa/entacapone

Carbidopa/levodopa/entacapone
Combination of
CarbidopaDOPA decarboxylase inhibitor
Levodopadopamine precursor
Entacaponecatechol-O-methyltransferase inhibitor
Clinical data
Trade namesStalevo, others
AHFS/Drugs.comProfessional Drug Facts
MedlinePlusa601068
License data
Pregnancy
category
Routes of
administration		oral, subcutaneous, intravenous, intrajejunal infusion[2]
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
  • none
KEGG

Carbidopa/levodopa/entacapone, sold under the brand name Stalevo among others, is a dopaminergic fixed-dose combination medication that contains carbidopa, an inhibitor of aromatic amino acid decarboxylation; levodopa, an aromatic amino acid; and entacapone, an inhibitor of catechol-O-methyltransferase for the treatment of Parkinson's disease.[6]

Medical uses

In the United States, carbidopa/levodopa/entacapone is indicated for the treatment of Parkinson's disease.[6]

In the European Union it is indicated for the treatment of adults with Parkinson's disease and end-of-dose motor fluctuations not stabilized on levodopa/dopa decarboxylase inhibitor treatment.[7]

Side effects

The most common adverse reactions include dyskinesias, hyperkinesia, diarrhea, nausea, abdominal pain, vomiting, dry mouth, and urine discoloration.[1]

In 2015, the US Food and Drug Administration found no evidence of increased risk of heart attacks, stroke, or other cardiovascular events from using entacapone with carbidopa and levodopa for Parkinson’s disease.[9] A 2019 FDA review also reported no increased risk of prostate cancer with this treatment.[10]

Drug interactions

It is contraindicated in people taking a class of antidepressant drugs known as non-selective monoamine oxidase (MAO) inhibitors such as phenelzine and tranylcypromine.[11]

It may be combined with the drugs rasagiline or selegiline. These drugs are a different type of MAO inhibitor known as selective MAO inhibitors that are often prescribed for Parkinson's disease.[12] Many drug interactions involving selegiline are theoretical, primarily based on interactions with non-selective MAO inhibitors; at oral doses the risk of these interactions may be very low. However, transdermal selegiline, known by its trade name Emsam, is still contraindicated.[11] Transdermal selegiline results in higher plasma levels at which it behaves like a non-selective MAO inhibitor.

Concominant use of entacapone, a component of carbidopa/levodopa/entacapone, with MAO inhibitors may increase toxicity of MAO inhibitors. Levodopa, also a component of carbidopa/levodopa/entacapone, in combination with MAO inhibitors may result in hypertensive reactions.[13]

Iron salts or multivitamins containing iron should be administered with caution. They can form chelates with levodopa, carbidopa, and entacapone, which may reduce the bioavailability of these medications.[2][14]

Mechanism of action

Main articles: Levodopa, Carbidopa, and Entacapone

Levodopa can cross the blood-brain barrier[6] and it serves as the immediate precursor to dopamine,[6] which cannot cross the barrier.[6] Once levodopa enters the brain, it is converted to dopamine by the enzyme called aromatic L-amino acid decarboxylase (AADC), or to 3-O-methyldopa by catechol-O-methyltransferase.

Carbidopa is an inhibitor of AADC and does not cross the blood-brain barrier. As a result, it does not influence levodopa metabolism in the central nervous system. By inhibiting AADC, carbidopa prevents the conversion of levodopa to dopamine in the peripheral nervous system, allowing a larger amount of levodopa to reach the central nervous system.[15]

History

Carbidopa/levodopa/entacapone was approved for medical use in the United States in June 2003.[16][17] Levodopa-entacapone-carbidopa intestinal gel (LECIG) was first approved in Sweden in 2018,[18] followed by Denmark, Finland, and Norway in 2019, Austria, Belgium, Germany, the Netherlands, Romania, and Slovenia in 2020.[19]

References

  1. ^ "Carbidopa / entacapone / levodopa Use During Pregnancy". Drugs.com. 14 October 2019. Archived from the original on 28 November 2020. Retrieved 19 May 2020.
  2. ^ "The device-aided intrajejunal delivery of levodopa–entacapone–carbidopa intestinal gel the treatment of Parkinson's disease: overview of efficacy and safety". Expert Review of Medical Devices. 9 September 2019. Retrieved 14 November 2025.
  3. ^ "Stalevo 75/18.75/200 levodopa/carbidopa (as monohydrate)/entacapone tablet bottle (160686)". Therapeutic Goods Administration (TGA). 27 May 2022. Retrieved 30 April 2023.
  4. ^ "Carlevent levodopa/carbidopa/entacapone 100/25/200 mg tablet bottle (195747)". Therapeutic Goods Administration (TGA). 26 May 2022. Retrieved 1 May 2023.
  5. ^ "Stalevo 100 mg/25 mg/200 mg Film-coated Tablets - Summary of Product Characteristics (SmPC)". (emc). 9 September 2019. Archived from the original on 2 December 2021. Retrieved 19 May 2020.
  6. ^ a b c d e f "Stalevo- carbidopa, levodopa, and entacapone tablet, film coated". DailyMed. 30 July 2021. Archived from the original on 6 December 2021. Retrieved 1 May 2023.
  7. ^ a b "Stalevo EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 31 October 2020. Retrieved 25 May 2020.
  8. ^ "Corbilta". European Medicines Agency (EMA). 16 January 2023. Archived from the original on 3 February 2023. Retrieved 1 May 2023.
  9. ^ "FDA Drug Safety Communication: FDA review found no increased cardiovascular risks with Parkinson's disease drug entacapone". U.S. Food and Drug Administration (FDA). 9 February 2019.
  10. ^ "FDA review finds no increased risk of prostate cancer with Parkinson's disease medicines containing entacapone (Comtan, Stalevo)". U.S. Food and Drug Administration (FDA). 20 December 2019.
  11. ^ a b "Stalevo: Dosing, contraindications, side effects, and pill pictures". Epocrates Online. Archived from the original on 5 February 2022. Retrieved 30 April 2023.
  12. ^ "Carbidopa, entacapone, and levodopa Advanced Patient Information". Drugs.com. 9 December 2022. Archived from the original on 5 July 2022. Retrieved 1 May 2023.
  13. ^ Leikin JB, Paloucek FP (2007). Poisoning and toxicology handbook (4th ed.). Informa Health Care. p. 610. ISBN 978-1-4200-4479-9. Archived from the original on 1 May 2023. Retrieved 6 December 2020.
  14. ^ Government of Canada, Health Canada, Health Products and Food Branch. "Drug Details - Drug and Health Product Register". hpr-rps.hres.ca. Archived from the original on 12 July 2024. Retrieved 11 December 2025.{{cite web}}: CS1 maint: multiple names: authors list (link)
  15. ^ Miyaue N, Nagai M (October 2025) [2025-08-19]. "Sex differences in the pharmacokinetics of levodopa and carbidopa in patients with Parkinson's disease". Parkinsonism & Related Disorders. 139 108006: 108006. doi:10.1016/j.parkreldis.2025.108006. PMID 40845588.{{cite journal}}: CS1 maint: article number as page number (link)
  16. ^ "Drug Approval Package: Stalevo 50, 100 & 150 (carbidopa/ levodopa/ entacapone) Tablets NDA #021485". U.S. Food and Drug Administration (FDA). Archived from the original on 7 April 2021. Retrieved 1 May 2023.
  17. ^ "Carbidopa, entacapone, and levodopa Uses, Side Effects & Warnings". Drugs.com. 4 October 2022. Archived from the original on 13 January 2023. Retrieved 1 May 2023.
  18. ^ Öthman M, Widman E, Nygren I, Nyholm D (March 2021). "Initial Experience of the Levodopa-Entacapone-Carbidopa Intestinal Gel in Clinical Practice". Journal of Personalized Medicine. 11 (4): 254. doi:10.3390/jpm11040254. PMC 8067183. PMID 33807308.
  19. ^ Auffret M, Weiss D, Stocchi F, Vérin M, Jost WH (November 2023) [12 July 2023]. "Access to device-aided therapies in advanced Parkinson's disease: navigating clinician biases, patient preference, and prognostic uncertainty". Journal of Neural Transmission. 130 (11): 1411–1432. doi:10.1007/s00702-023-02668-9. PMC 10645670. PMID 37436446.
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