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Drug Interactions between mirtazapine and tramadol

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

traMADol mirtazapine

Applies to: tramadol and mirtazapine

GENERALLY AVOID: Due to its serotonergic activity, coadministration of tramadol with serotonin-enhancing drugs such as SSRIs, SNRIs, nefazodone, trazodone, and mirtazapine 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. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. Patients receiving tramadol with serotonin-enhancing drugs may also have an increased risk of seizures due to additive epileptogenic effects of these agents.

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 (28)
  1. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  2. Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol, 10, p. 213-7
  3. (2001) "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories
  4. (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
  5. Mason BJ, Blackburn KH (1997) "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother, 31, p. 175-7
  6. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  7. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
  8. Egberts AC, ter Borg J, Brodie-Meijer CC (1997) "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol, 12, p. 181-2
  9. Duggal HS, Fetchko J (2002) "Serotonin syndrome and atypical antipsychotics." Am J Psychiatry, 159, p. 672-3
  10. Lange-Asschenfeldt C, Weigmann H, Hiemke C, Mann K (2002) "Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated symptomatology." J Clin Psychopharmacol, 22, p. 440-1
  11. Kesavan S, Sobala GM (1999) "Serotonin syndrome with fluoxetine plus tramadol." J R Soc Med, 92, p. 474-5
  12. Gonzalez-Pinto A, Imaz H, De Heredia JL, Gutierrez M, Mico JA (2001) "Mania and tramadol-fluoxetine combination." Am J Psychiatry, 158, p. 964-5
  13. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  14. Houlihan DJ (2004) "Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine." Ann Pharmacother, 38, p. 411-3
  15. (2004) "Venlafaxine + tramadol: serotonin syndrome." Prescrire Int, 13, p. 57
  16. Mahlberg R, Kunz D, Sasse J, Kirchheiner J (2004) "Serotonin syndrome with tramadol and citalopram." Am J Psychiatry, 161, p. 1129
  17. Mittino D, Mula M, Monaco F (2004) "Serotonin syndrome associated with tramadol-sertraline coadministration." Clin Neuropharmacol, 27, p. 150-1
  18. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
  19. Freeman WD, Chabolla DR (2005) "36-Year-old woman with loss of consciousness, fever, and tachycardia." Mayo Clin Proc, 80, p. 667-70
  20. Lantz MS, Buchalter EN, Giambanco V (1998) "Serotonin syndrome following the administration of tramadol with paroxetine." Int J Geriatr Psychiatry, 13, p. 343-5
  21. Kitson R, Carr B (2005) "Tramadol and severe serotonin syndrome." Anaesthesia, 60, p. 934-5
  22. (2008) "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories
  23. (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
  24. (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
  25. (2011) "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC
  26. (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
  27. Shakoor M, Ayub S, Ahad A, Ayub Z (2014) "Transient serotonin syndrome caused by concurrent use of tramadol and selective serotonin reuptake inhibitor." Am J Case Rep, 15, p. 562-4
  28. US Food and Drug Administration (FDA) (2018) FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM491302.pdf

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Drug and food interactions

Moderate

traMADol food

Applies to: tramadol

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc

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Moderate

mirtazapine food

Applies to: mirtazapine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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