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Drug Interactions between milnacipran and Tramadol Hydrochloride ER

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

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Interactions between your drugs

Major

traMADol milnacipran

Applies to: Tramadol Hydrochloride ER (tramadol) and milnacipran

GENERALLY AVOID: Due to its serotonergic activity, coadministration of tramadol with serotonin-enhancing drugs such as SSRIs and SNRIs 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 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

  1. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  2. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7
  3. "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories PROD (2001):
  4. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  5. Mason BJ, Blackburn KH "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother 31 (1997): 175-7
  6. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  7. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5
  8. Egberts AC, ter Borg J, Brodie-Meijer CC "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol 12 (1997): 181-2
  9. Duggal HS, Fetchko J "Serotonin syndrome and atypical antipsychotics." Am J Psychiatry 159 (2002): 672-3
  10. Lange-Asschenfeldt C, Weigmann H, Hiemke C, Mann K "Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated symptomatology." J Clin Psychopharmacol 22 (2002): 440-1
  11. Kesavan S, Sobala GM "Serotonin syndrome with fluoxetine plus tramadol." J R Soc Med 92 (1999): 474-5
  12. Gonzalez-Pinto A, Imaz H, De Heredia JL, Gutierrez M, Mico JA "Mania and tramadol-fluoxetine combination." Am J Psychiatry 158 (2001): 964-5
  13. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  14. Houlihan DJ "Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine." Ann Pharmacother 38 (2004): 411-3
  15. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  16. Freeman WD, Chabolla DR "36-Year-old woman with loss of consciousness, fever, and tachycardia." Mayo Clin Proc 80 (2005): 667-70
  17. Kitson R, Carr B "Tramadol and severe serotonin syndrome." Anaesthesia 60 (2005): 934-5
  18. Cerner Multum, Inc. "Australian Product Information." O 0
  19. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories (2008):
  20. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals (2009):
  21. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  22. "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC (2011):
  23. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals (2013):
View all 23 references

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Drug and food interactions

Moderate

traMADol food

Applies to: Tramadol Hydrochloride ER (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

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

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Moderate

milnacipran food

Applies to: milnacipran

GENERALLY AVOID: Use of milnacipran in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Milnacipran alone can increase serum transaminase levels. In placebo-controlled fibromyalgia trials, increases in ALT were more frequently observed in patients treated with milnacipran 100 mg/day (6%) and 200 mg/day (7%) compared to patients treated with placebo (3%). One patient receiving milnacipran 100 mg/day (0.2%) had an increase in ALT greater than 5 times the upper limit of normal (ULN) but did not exceed 10 times the ULN. Increases in AST were also more frequently observed in patients treated with milnacipran 100 mg/day (3%) and 200 mg/day (5%) than in patients treated with placebo (2%). There have been reported cases of increased liver enzymes and severe liver injury, including fulminant hepatitis, from foreign postmarketing experience with milnacipran. Significant underlying clinical conditions and/or use of multiple concomitant medications were present in the cases of severe liver injury.

MANAGEMENT: Due to the risk of liver injury, patients prescribed milnacipran should be counseled to avoid excessive use of alcohol. Milnacipran should generally not be prescribed to patients with substantial alcohol use.

References

  1. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals (2009):

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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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