Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI6YZLADW)
  Drug Name Duloxetine Drug Info Methylene blue Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antidotes/Mao Inhibitors
  Structure

 Mechanism of Duloxetine-Methylene blue Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Duloxetine Methylene blue
      Mechanism Serotonergic effects
Serotonin transporter  Inhibitor 		Serotonergic effects
Monoamine oxidase non-selective  Inhibitor
      Key Mechanism Factor 1
Factor Name Serotonin transporter
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Structure Sequence
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTRHSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLPYTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIMAWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIHRSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGATLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVTLTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRICWVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIITPGTFKERIIKSITPETPTEIPCGDIRLNAV
Gene Name SLC6A4
Uniprot ID SC6A4_HUMAN
KEGG Pathway hsa:6532
Protein Family Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
Protein Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
    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).
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      Mechanism Description
  • Additive serotonergic effects by the combination of Duloxetine and Methylene blue 

Recommended Action
      Management Serotonergic agents should not be used in patients receiving methylene blue intravenously. Most serotonergic psychiatric drugs should be stopped 1 to 2 weeks (i.e., 4 to 5 half-lives) prior to treatment with methylene blue if possible, while others such as fluoxetine may require discontinuation up to 5 weeks in advance due to its prolonged half-life.

References
1 Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20. [PMID: 15784664]
2 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3 Gillman PK "Methylene blue and serotonin toxicity: definite causal link." Psychosomatics 51 (2010): 448-9. [PMID: 20833947]
4 Gillman PK "Methylene blue is a potent monoamine oxidase inhibitor." Can J Anaesth 55 (2008): 311-2 author reply 312. [PMID: 18451123]
5 Heritier Barras AC, Walder B, Seeck M "Serotonin syndrome following Methylene Blue infusion: a rare complication of antidepressant therapy." J Neurol Neurosurg Psychiatry 81 (2010): 1412-3. [PMID: 20547626]
6 Khavandi A, Whitaker J, Gonna H "Serotonin toxicity precipitated by concomitant use of citalopram and methylene blue." Med J Aust 189 (2008): 534-5. [PMID: 18976207]
7 Ng BK, Cameron AJ "The role of methylene blue in serotonin syndrome: a systematic review." Psychosomatics 51 (2010): 194-200. [PMID: 20484716]
8 Ng BK, Cameron AJ, Liang R, Rahman H. Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review.?Can J Anaesth. 2008;55(1):36-41. [PMID: 18166746]
9 FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Serious CNS reactions possible when linezolid (Ayvox) is given to patients taking certain psychiatric medications.".
10 FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications.".