Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIFD4OU3H)
  Drug Name Methadone Drug Info Safinamide Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Dopaminergic Antiparkinsonism Agents
  Structure

 Mechanism of Methadone-Safinamide Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Methadone Safinamide
      Mechanism Serotonergic effects
5-HT 3 receptor  Antagonist 		Serotonergic effects
Monoamine oxidase non-selective  Inhibitor
      Key Mechanism Factor 1
Factor Name 5-HT 3 receptor Structure Sequence
Protein Family Ligand-gated ion channel (TC 1.A.9) family
Protein Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
    Click to Show/Hide
      Key Mechanism Factor 2
Factor Name Monoamine oxidase Structure Sequence
Protein Family Flavin monoamine oxidase family
Protein Function
Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Additive serotonergic effects by the combination of Methadone and Safinamide 

Recommended Action
      Management Because the interaction may involve a class-effect of MAOIs, concomitant administration of the selective MAO-B inhibitor, safinamide, with certain opioids such as meperidine, methadone, propoxyphene, and tramadol is considered contraindicated. Some authorities suggest that at least 7 to 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with opioids. Although morphine may also have significant CNS interactions with MAOIs, it is generally considered a safer alternative in patients treated with MAOIs who require a narcotic analgesic. A sensitivity test should be performed in which repeated, small, incremental doses of morphine are administered over the course of several hours while overall clinical status and vital signs are carefully monitored.

References
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25 Product Information. Furoxone (furazolidone). Roberts Pharmaceutical Corporation, Eatontown, NJ.
26 Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
27 Product Information. Matulane (procarbazine). Roche Laboratories, Nutley, NJ.
28 Product Information. Meperidine Hydrochloride Injection, USP (meperidine) Astra-Zeneca Pharmaceuticals, Wilmington, DE.
29 Product Information. Methylene Blue (methylene blue). American Regent Laboratories Inc, Shirley, NY.
30 Product Information. Nardil (phenelzine). Parke-Dvis, Morris Plains, NJ.
31 Product Information. Parnate (tranylcypromine). SmithKline Beecham, Philadelphia, PA.
32 Product Information. Xadago (safinamide). US WorldMeds LLC, Louisville , KY.
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