Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI9C6TMGN)
Drug Name			Levodopa		Drug Info		Opicapone		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Dopaminergic Antiparkinsonism Agents				Dopaminergic Antiparkinsonism Agents
Structure

Mechanism of Levodopa-Opicapone Interaction (Severity Level: Moderate)
Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph

Drug Name		Levodopa				Opicapone
Mechanism		Catechol-O-methyl-transferase substrate				Catechol-O-methyl-transferase inhibitor
Key Mechanism Factor 1
		Factor Name		Catechol-O-methyl-transferase				× 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 Opicapone 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]