Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIDB4VMWS)
  Drug Name Linezolid Drug Info Dexfenfluramine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antibiotics Appetite Depressants
  Structure

 Mechanism of Linezolid-Dexfenfluramine Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Linezolid Dexfenfluramine
      Mechanism Serotonergic effects
Monoamine oxidase non-selective  Inhibitor 		Serotonergic effects
Serotonin transporter  Inhibitor
      Key Mechanism Factor 1
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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      Key Mechanism Factor 2
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.
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      Mechanism Description
  • Additive serotonergic effects by the combination of Linezolid and Dexfenfluramine 

Recommended Action
      Management Concomitant use of linezolid and serotonergic agents should be avoided unless no alternatives exist and close monitoring for the development of serotonin syndrome can be provided. In general, most serotonergic psychiatric drugs should be stopped 1 to 2 weeks (i.e., 4 to 5 half-lives) prior to treatment with an MAOI, while others such as fluoxetine may require discontinuation up to 5 weeks in advance due to its prolonged half-life. Treatment with serotonergic medications may be resumed 24 hours after the last dose of linezolid.

References
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3 Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20. [PMID: 15784664]
4 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
5 Clark DB, Andrus MR, Byrd DC "Drug interactions between linezolid and selective serotonin reuptake inhibitors: case report involving sertraline and review of the literature." Pharmacotherapy 26 (2006): 269-76. [PMID: 16466332]
6 DeBellis RJ, Schaefer OP, Liquori M, Volturo GA "Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient." J Intensive Care Med 20 (2005): 351-3. [PMID: 16280409]
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9 Hachem RY, Hicks K, Huen A, Raad I "Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients." Clin Infect Dis 37 (2003): E8-E11. [PMID: 12830431]
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11 Jones SL, Athan E, O'Brien D "Serotonin syndrome due to co-administration of linezolid and venlafaxine." J Antimicrob Chemother 54 (2004): 289-90. [PMID: 15140859]
12 Lavery S, Ravi H, McDaniel WW, Pushkin YR "Linezolid and serotonin syndrome." Psychosomatics 42 (2001): 432-4. [PMID: 11739912]
13 Lorenz RA, Vandenberg AM, Canepa EA "Serotonergic antidepressants and linezolid: a retrospective chart review and presentation of cases." Int J Psychiatry Med 38 (2008): 81-90. [PMID: 18624020]
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16 Morales N, Vermette H "Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine." Psychosomatics 46 (2005): 274-5. [PMID: 15883150]
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18 Morrison EK, Rowe AS "Probable drug-drug interaction leading to serotonin syndrome in a patient treated with concomitant buspirone and linezolid in the setting of therapeutic hypothermia." J Clin Pharm Ther 37 (2012): 610-3. [PMID: 22452676]
19 Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8. [PMID: 8257462]
20 Packer S, Berman SA "Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid." Am J Psychiatry 164 (2007): 346-7. [PMID: 17267801]
21 Product Information. Zyvox (linezolid) Pharmacia and Upjohn, Kalamazoo, MI.
22 Shapiro RE, Tepper SJ "The serotonin syndrome, triptans, and the potential for drug-drug interactions." Headache 47 (2007): 266-9. [PMID: 17300366]
23 Steinberg M, Morin AK "Mild serotonin syndrome associated with concurrent linezolid and fluoxetine." Am J Health Syst Pharm 64 (2007): 59-62. [PMID: 17189581]
24 Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13. [PMID: 2035713]
25 Strouse TB, Kerrihard TN, Forscher CA, Zakowski P "Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine." J Clin Psychopharmacol 26 (2006): 681-683. [PMID: 17110838]
26 Tahir N "Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram." J Am Med Dir Assoc 5 (2004): 111-3. [PMID: 14984623]
27 Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd "Serotonin syndrome and linezolid." J Am Acad Child Adolesc Psychiatry 43 (2004): 790. [PMID: 15213578]
28 Wigen CL, Goetz MB "Serotonin syndrome and linezolid." Clin Infect Dis 34 (2002): 1651-2. [PMID: 12032904]
29 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.".