Skip to Content

Drug interactions between amitriptyline and Trezix

Results for the following 2 drugs:
Trezix (acetaminophen/caffeine/dihydrocodeine)

Interactions between your drugs


amitriptyline dihydrocodeine

Applies to: amitriptyline and Trezix (acetaminophen / caffeine / dihydrocodeine)

Consumer information for this interaction is not currently available.

MONITOR: Opioids may potentiate the effects of serotonergic agents and increase the risk of serotonin syndrome. The interaction has primarily been reported with the phenylpiperidine opioids (e.g., meperidine, fentanyl) and tramadol, which are known to possess some serotonergic activity, although a few cases have involved other opioids such as oxycodone, methadone, morphine, hydromorphone, codeine, and buprenorphine. Serotonin syndrome 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. Since many serotonergic agents can also cause central nervous system depression, concomitant use with opioids may result in increased sedation and impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Caution is advised when opioids are used concomitantly with serotonergic agents such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), other antidepressants/psychotropic agents (e.g., amoxapine, buspirone, lithium, maprotiline, mirtazepine, nefazodone, trazodone, vilazodone), 5-HT1 receptor agonists (triptans), 5-HT3 receptor antagonists, cyclobenzaprine, dextromethorphan, 5-hydroxytryptophan, and St. John's wort. Patients should be monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures. Patients should also be advised of potentially additive central nervous system effects from these agents and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.


  1. Vizcaychipi MP, Walker S, Palazzo M "Serotonin syndrome triggered by tramadol." Br J Anaesth 99 (2007): 919
  2. 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
  3. Mittino D, Mula M, Monaco F "Serotonin syndrome associated with tramadol-sertraline coadministration." Clin Neuropharmacol 27 (2004): 150-1
  4. "Venlafaxine + tramadol: serotonin syndrome." Prescrire Int 13 (2004): 57
  5. Gillman PK "Possible serotonin syndrome with moclobemide and pethidine." Med J Aust 162 (1995): 554
  6. Roy S, Fortier LP "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth 50 (2003): 32-5
  7. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  8. Kesavan S, Sobala GM "Serotonin syndrome with fluoxetine plus tramadol." J R Soc Med 92 (1999): 474-5
  9. Guo SL, Wu TJ, Liu CC, Ng CC, Chien CC, Sun HL "Meperidine-induced serotonin syndrome in a susceptible patient." Br J Anaesth (2009):
  10. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ "Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction." Anesth Analg 78 (1994): 593-7
  11. Das PK, Warkentin DI, Hewko R, Forrest DL "Serotonin syndrome after concomitant treatment with linezolid and meperidine." Clin Infect Dis 46 (2008): 264-5
  12. US Food and Drug Administration (FDA) "FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. Available from: URL:" ([2016, Mar 22]):
  13. 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
  14. Mateo-Carrasco H, Munoz-Aguilera EM, Garcia-Torrecillas JM, Abu Al-Robb H "Serotonin Syndrome Probably Triggered by a Morphine-Phenelzine Interaction." Pharmacotherapy (2015):
  15. Ailawadhi S, Sung KW, Carlson LA, Baer MR "Serotonin syndrome caused by interaction between citalopram and fentanyl." J Clin Pharm Ther 32 (2007): 199-202
  16. Gonzalez-Pinto A, Imaz H, De Heredia JL, Gutierrez M, Mico JA "Mania and tramadol-fluoxetine combination. " Am J Psychiatry 158 (2001): 964-5
  17. Egberts AC, ter Borg J, Brodie-Meijer CC "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol 12 (1997): 181-2
  18. Mason BJ, Blackburn KH "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother 31 (1997): 175-7
  19. Lantz MS, Buchalter EN, Giambanco V "Serotonin syndrome following the administration of tramadol with paroxetine." Int J Geriatr Psychiatry 13 (1998): 343-5
  20. Tissot TA "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology 98 (2003): 1511-1512
  21. Hunter B, Kleinert MM, Osatnik J, Soria E "Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil?" Anesth Analg 102 (2006): 1589
  22. Kitson R, Carr B "Tramadol and severe serotonin syndrome." Anaesthesia 60 (2005): 934-5
  23. Dougherty JA, Young H, Shafi T "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother 36 (2002): 1647-1648
  24. 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
  25. Zornberg GL, Bodkin JA, Cohen BM "Severe adverse interaction between pethidine and selegiline." Lancet 337 (1991): 246
  26. Gnanadesigan N, Espinoza RT, Smith R, Israel M, Reuben DB "Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected?" J Am Med Dir Assoc 6 (2005): 265-9
  27. Hansen TE, Dieter K, Keepers GA "Interaction of fluoxetine and pentazocine." Am J Psychiatry 147 (1990): 949-50
  28. Mahlberg R, Kunz D, Sasse J, Kirchheiner J "Serotonin syndrome with tramadol and citalopram." Am J Psychiatry 161 (2004): 1129
  29. Noble WH, Baker A "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth 39 (1992): 1061-6
  30. Larson KJ, Wittwer ED, Nicholson WT, Weingarten TN, Price DL, Sprung J "Myoclonus in patient on fluoxetine after receiving fentanyl and low-dose methylene blue during sentinel lymph node biopsy." J Clin Anesth 27 (2015): 247-51
  31. Houlihan DJ "Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine." Ann Pharmacother 38 (2004): 411-3
  32. Rang ST, Field J, Irving C "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth 55 (2008): 521-5
  33. Hillman AD, Witenko CJ, Sultan SM, Gala G "Serotonin syndrome caused by fentanyl and methadone in a burn injury." Pharmacotherapy 35 (2015): 112-7
  34. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  35. Meyer D, Halfin V "Toxicity secondary to meperidine in patients on monoamine oxidase inhibitors: a case report and critical review." J Clin Psychopharmacol 1 (1981): 319-21
  36. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  37. Gillman PK "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth (2005):
  38. Abadie D, Rousseau V, Logerot S, Cottin J, Montastruc JL, Montastruc F "Serotonin Syndrome: Analysis of Cases Registered in the French Pharmacovigilance Database." J Clin Psychopharmacol (2015):
  39. Rosebraugh CJ, floxkhart DA, Yasuda SU, Woosley RL "Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient." J Clin Pharmacol 41 (2001): 224-7
  40. Davis JJ, Buck NS, Swenson JD, Johnson KB, Greis PE "Serotonin syndrome manifesting as patient movement during total intravenous anesthesia with propofol and remifentanil." J Clin Anesth 25 (2013): 52-4
View all 40 references

Drug and food interactions


caffeine food

Applies to: Trezix (acetaminophen / caffeine / dihydrocodeine)

Consumer information for this minor interaction is not currently available. Some minor drug interactions may not be clinically relevant in all patients. Minor drug interactions do not usually cause harm or require a change in therapy. However, your healthcare provider can determine if adjustments to your medications are needed.

For clinical details see professional interaction data.

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.

Drug Interaction Classification

The classifications below are a guideline only. The relevance of a particular drug interaction to a specific patient is difficult to determine using this tool alone given the large number of variables that may apply.
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 information available.

Do not stop taking any medications without consulting your healthcare provider.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.