Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIBYP0FTE)
Drug Name			Lofexidine		Drug Info		Safinamide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Dopaminergic Antiparkinsonism Agents
Structure

Mechanism of Lofexidine-Safinamide Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Lofexidine				Safinamide
Mechanism		Hypotensive effects Alpha-2 adrenergic receptor Agonist				Hypotensive effects Monoamine oxidase-B selective Inhibitor
Key Mechanism Factor 1
		Factor Name		Adrenergic receptor alpha-2				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. Click to Show/Hide
Key Mechanism Factor 2
		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
Mechanism Description		Additive hypotensive effects by the combination of Lofexidine and Safinamide

Recommended Action
Management		Caution is advised during coadministration of MAOIs and other medications with hypotensive effects, especially during the first few weeks of treatment. Close monitoring for development of hypotension is recommended. Ambulatory patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References
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8	Product Information. Matulane (procarbazine). Roche Laboratories, Nutley, NJ.
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11	Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc, Markham, ON.
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13	Schulz R, Antonin KH, Hoffmann E, et al "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36. [PMID: 2510962]