Basic Information
ID DDInter254 and DDInter1186
Interaction Coadministration of methylene blue with serotonergic agents may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Current research suggests that methylene blue has structural properties similar to monoamine oxidase inhibitors (MAOIs). As such, it may enhance serotonergic effects by inhibiting serotonin metabolism.
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.
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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. Available from: URL: http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm." ([2011 July 26]): [7] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 [8] Gillman PK "Methylene blue and serotonin toxicity: definite causal link." Psychosomatics 51 (2010): 448-9 [9] Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20 [10] 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 [11] "Product Information. Savella (milnacipran)." Forest Pharmaceuticals, St. Louis, MO. [12] Krivy J, Wiener J "Sertraline and platelet counts in idiopathic thrombocytopenia purpura." Lancet 345 (1995): 132 [13] Ottervanger JP, Stricker BH, Huls J, Weeda JN "Bleeding attributed to the intake of paroxetine." Am J Psychiatry 151 (1994): 781-2 [14] Skop BP, Brown TM "Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors." Psychosomatics 37 (1996): 12-6 [15] Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9 [16] "Product Information. Paxil (paroxetine)." GlaxoSmithKline, Research Triangle Park, NC. [17] Cerner Multum, Inc. "Australian Product Information." O 0 [18] Layton D, Clark DWJ, Pearce GL, Shakir SAW "Is there an association between selective serotonin reuptake inhibitors and risk of abnormal bleeding? Results from a cohort study based on prescription event monitoring in England." Eur J Clin Pharmacol 57 (2001): 167-76 [19] Pai VB, Kelly MW "Bruising associated with the use of fluoxetine." 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"Does concurrent prescription of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?" Aliment Pharmacol Ther 22 (2005): 175-81 [27] "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America, Lincolnshire, IL. [28] Hergovich N, Aigner M, Eichler HG, Entlicher J, Drucker C, Jilma B "Paroxetine decreases platelet serotonin storage and platelet function in human beings." Clin Pharmacol Ther 68 (2000): 435-42 [29] de Abajo FJ, Rodriguez LA, Montero D "Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study." BMJ 319 (1999): 1106-9 [30] Woolfrey S, Gammack NS, Dewar MS, Brown PJ "Fluoxetine-warfarin interaction." BMJ 307 (1993): 241 [31] Messiha FS "Fluoxetine - adverse effects and drug-drug interactions." 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Alternative for Buspirone N05B
Alprazolam Chlordiazepoxide Clobazam Meprobamate Oxazepam Clorazepic acid
Lorazepam Hydroxyzine Halazepam Diazepam
Alternative for Methylene blue V03A
Sodium cellulose phosphate Dimercaprol Iron sucrose Flumazenil Palifermin Nitrous acid
Deferoxamine Sodium zirconium cyclosilicate Levoleucovorin Ipecac Magnesium carbonate
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.