Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDISHIDPN7)
  Drug Name Tramadol Drug Info Dexfenfluramine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Appetite Depressants
  Structure

 Mechanism of Tramadol-Dexfenfluramine Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tramadol Dexfenfluramine
      Mechanism 1 Serotonergic effects
Serotonin transporter  Inhibitor 		Serotonergic effects
Serotonin transporter  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
      Mechanism Description
  • Additive serotonergic effects by the combination of Tramadol and Dexfenfluramine 
     Increased risk of lowers seizure threshold Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tramadol Dexfenfluramine
      Mechanism 2 Lower seizure threshold Lower seizure threshold
      Key Mechanism Factor 2
Factor Name Lowers seizure threshold
Factor Description The combination of medications that lower the seizure threshold is a factor that makes people with epilepsy more likely to have seizures. A seizure is a sudden, uncontrolled electrical disturbance in the brain that can cause changes in your behavior, movements or sensations, and level of consciousness.
      Mechanism Description
  • Increased risk of lowers seizure threshold by the combination of Tramadol and Dexfenfluramine 

Recommended Action
      Management In general, the use of tramadol in combination with highly serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when initiating or increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life.

References
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17 Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
18 Product Information. Effexor (venlafaxine). Wyeth-Ayerst Laboratories, Philadelphia, PA.
19 Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals, St. Louis, MO.
20 Product Information. Nucynta (tapentadol). PriCara Pharmaceuticals, Raritan, NJ.
21 Product Information. Pristiq (desvenlafaxine). Wyeth Laboratories, Philadelphia, PA.
22 Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
23 Product Information. Ultram (tramadol). McNeil Pharmaceutical, Raritan, NJ.
24 Product Information. Viibryd (vilazodone). Trovis Pharmaceuticals LLC, New Haven, CT.
25 Shakoor M, Ayub S, Ahad A, Ayub Z "Transient serotonin syndrome caused by concurrent use of tramadol and selective serotonin reuptake inhibitor." Am J Case Rep 15 (2014): 562-4. [PMID: 25540831]
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27 Venlafaxine + tramadol: serotonin syndrome. Prescrire Int 13 (2004): 57. [PMID: 15148976]
28 US Food and Drug Administration (FDA) "FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines requires label changes.".