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Carbidopa/levodopa/entacapone

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Carbidopa/levodopa/entacapone
Image
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

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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

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

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

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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.[14]

Mechanism of action

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Image
Carbidopa/levodopa/entercapone's pathway

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

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[edit]

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

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  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. 1 2 3 4 5 6 "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. 1 2 "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. 1 2 "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. ↑ "STALEVO". Health Canada. Archived from the original on 12 July 2024. Retrieved 11 December 2025.
  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. doi:10.1016/j.parkreldis.2025.108006. PMID 40845588.
  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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