Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIH0F8EDV)
Drug Name			Safinamide		Drug Info		Valbenazine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Dopaminergic Antiparkinsonism Agents				Vmat2 Inhibitors
Structure

Mechanism of Safinamide-Valbenazine Interaction (Severity Level: Major)
Additive serotonergic effects Click to Show/Hide Mechanism Graph

Drug Name		Safinamide				Valbenazine
Mechanism		Serotonergic effects Monoamine oxidase-B selective Inhibitor				Serotonergic effects Vesicular monoamine transporter 2 Inhibitor
Key Mechanism Factor 1
		Factor Name		Monoamine oxidase type B				× Structure Sequence MSNKCDVVVVGGGISGMAAAKLLHDSGLNVVVLEARDRVGGRTYTLRNQKVKYVDLGGSYVGPTQNRILRLAKELGLETYKVNEVERLIHHVKGKSYPFRGPFPPVWNPITYLDHNNFWRTMDDMGREIPSDAPWKAPLAEEWDNMTMKELLDKLCWTESAKQLATLFVNLCVTAETHEVSALWFLWYVKQCGGTTRIISTTNGGQERKFVGGSGQVSERIMDLLGDRVKLERPVIYIDQTRENVLVETLNHEMYEAKYVISAIPPTLGMKIHFNPPLPMMRNQMITRVPLGSVIKCIVYYKEPFWRKKDYCGTMIIDGEEAPVAYTLDDTKPEGNYAAIMGFILAHKARKLARLTKEERLKKLCELYAKVLGSLEALEPVHYEEKNWCEEQYSGGCYTTYFPPGILTQYGRVLRQPVDRIYFAGTETATHWSGYMEGAVEAGERAAREILHAMGKIPEDEIWQSEPESVDVPAQPITTTFLERHLPSVPGLLRLIGLTTIFSATALGFLAHKRGLLVRV
		Gene Name		MAOB
		Uniprot ID		AOFB_HUMAN
		KEGG Pathway		hsa:4129
		Protein Family		Flavin monoamine oxidase family
		Protein Function		Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079). Preferentially degrades benzylamine and phenylethylamine (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079). Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Synaptic vesicle amine transporter				× Structure Sequence MALSELALVRWLQESRRSRKLILFIVFLALLLDNMLLTVVVPIIPSYLYSIKHEKNATEIQTARPVHTASISDSFQSIFSYYDNSTMVTGNATRDLTLHQTATQHMVTNASAVPSDCPSEDKDLLNENVQVGLLFASKATVQLITNPFIGLLTNRIGYPIPIFAGFCIMFVSTIMFAFSSSYAFLLIARSLQGIGSSCSSVAGMGMLASVYTDDEERGNVMGIALGGLAMGVLVGPPFGSVLYEFVGKTAPFLVLAALVLLDGAIQLFVLQPSRVQPESQKGTPLTTLLKDPYILIAAGSICFANMGIAMLEPALPIWMMETMCSRKWQLGVAFLPASISYLIGTNIFGILAHKMGRWLCALLGMIIVGVSILCIPFAKNIYGLIAPNFGVGFAIGMVDSSMMPIMGYLVDLRHVSVYGSVYAIADVAFCMGYAIGPSAGGAIAKAIGFPWLMTIIGIIDILFAPLCFFLRSPPAKEEKMAILMDHNCPIKTKMYTQNNIQSYPIGEDEESESD
		Gene Name		SLC18A2
		Uniprot ID		VMAT2_HUMAN
		KEGG Pathway		hsa:6571
		Protein Family		Major facilitator superfamily
		Protein Function		Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles (PubMed:23363473). Requisite for vesicular amine storage prior to secretion via exocytosis. Click to Show/Hide
Mechanism Description		Additive serotonergic effects by the combination of Safinamide and Valbenazine

Recommended Action
Management		The use of valbenazine with MAOIs should generally be avoided. If concomitant use is required, caution and close clinical and laboratory monitoring are recommended. alternative treatment may be required if an interaction is suspected.

References
1	Product Information. Ingrezza (valbenazine). Neurocrine Biosciences, Inc., San Diego, CA.
2	Product Information. Matulane (procarbazine). Roche Laboratories, Nutley, NJ.
3	Product Information. Zyvox (linezolid) Pharmacia and Upjohn, Kalamazoo, MI.