Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDISMQA6TB)
  Drug Name Entacapone Drug Info Levodopa Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiparkinson Agents Dopaminergic Antiparkinsonism Agents
  Structure

 Mechanism of Entacapone-Levodopa Interaction (Severity Level: Moderate)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Entacapone Levodopa
      Mechanism Catechol-O-methyl-transferase inhibitor Catechol-O-methyl-transferase substrate
      Key Mechanism Factor 1
Factor Name Catechol-O-methyl-transferase
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Structure Sequence
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRILNHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCGYSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKYDVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFECTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
Gene Name COMT
Uniprot ID COMT_HUMAN
KEGG Pathway hsa:1312
Protein Family Class I-like SAM-binding methyltransferase superfamily
Protein Function
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Levodopa caused by Entacapone mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management Although COMT inhibitors are intended for use with levodopa/carbidopa, clinicians should be aware that dose reduction of levodopa may be necessary during coadministration. This is especially true if the patient is experiencing dyskinesia induced by levodopa. Use with caution in patients with severe dyskinesia or dystonia. Likewise, when discontinuing a COMT inhibitor, monitor patients and consider adjustment of other dopaminergic therapies as needed. In addition, some authorities advise that opicapone should be administered as a once-daily dose at least one hour before or after combinations containing levodopa so as to avoid any interaction with the absorption of levodopa (AU, UK).

References
1 Dingemanse J, Jorga K, Zurcher G, Schmitt M, Sedek G, Da Prada M, Van Brummelen P "Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa." Br J Clin Pharmacol 40 (1995): 253-62. [PMID: 8527287]
2 Product Information. Comtan (entacapone) Novartis Pharmaceuticals, East Hanover, NJ.
3 Product Information. Ongentys (opicapone). Neurocrine Biosciences, Inc., San Diego, CA.
4 Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals, Costa Mesa, CA.
5 Sedek G, Jorga K, Schmitt M, Burns RS, Leese P "Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers." Clin Neuropharmacol 20 (1997): 531-41. [PMID: 9403227]
6 Svetel M, Tomic A, Kresojevic N, Kostic V "Pharmacokinetic drug evaluation of opicapone for the treatment of Parkinson's disease." Expert Opin Drug Metab Toxicol 14 (2018): 353-60. [PMID: 29345156]
7 Baas H, Beiske AG, Ghika J, Jackson M, Oertel WH, Poewe W, Ransmayr G "Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuatin parkinsonian patients." J Neurol Neurosurg Psychiatry 63 (1997): 421-8. [PMID: 9343116]