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Drug Interactions between Effexor XR and tramadol

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

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Interactions between your drugs

Major

venlafaxine traMADol

Applies to: Effexor XR (venlafaxine) and tramadol

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

Drug and food/lifestyle interactions

Major

traMADol food/lifestyle

Applies to: tramadol

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur. In addition, alcohol may affect opioid release from sustained-release formulations.

GENERALLY AVOID: Grapefruit or grapefruit juice may increase the plasma concentrations of opioid analgesics by inhibiting CYP450 3A4-mediated metabolism of these agents, although the interaction has not been studied. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with opioid analgesics. Any history of alcohol or illicit drug use should be considered when prescribing an opioid analgesic, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with opioid analgesics should preferably avoid the consumption of grapefruit and grapefruit juice.

References (18)
  1. (2017) "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc
  2. (2024) "Product Information. TraMADol Hydrochloride (traMADol)." Advagen Pharma Ltd
  3. (2024) "Product Information. Jamp Tramadol (tramadol)." Jamp Pharma Corporation
  4. (2025) "Product Information. Tramadol (tramadol)." Sigma Pharmaceuticals Plc
  5. (2024) "Product Information. Tramedo (tRAMadol)." Alphapharm Pty Ltd
  6. (2022) "Product Information. Alfentanil (alfentanil)." Hameln Pharma Ltd
  7. (2024) "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation
  8. (2024) "Product Information. Codeine Sulfate (codeine)." Lannett Company Inc
  9. (2024) "Product Information. Meperidine Hydrochloride (meperidine)." Genus Lifesciences Inc.
  10. (2023) "Product Information. Dsuvia (SUFentanil)." AcelRx Pharmaceuticals
  11. (2024) "Product Information. Dzuveo (sufentanil)." Aguettant Ltd
  12. (2025) "Product Information. Pethidine (pethidine)." Martindale Pharmaceuticals Ltd
  13. (2023) "Product Information. Meperidine Hydrochloride (meperidine)." Sandoz Canada Incorporated
  14. (2024) "Product Information. Pethidine (Juno) (pethidine)." Juno Pharmaceuticals Pty Ltd
  15. Cherrier MM, Shen DD, Shireman L, et al. (2021) "Elevated customary alcohol consumption attenuates opioid effects." Pharmacol Biochem Behav, 4, p. 1-27
  16. Fuhr LM, Marok FZ, Fuhr U, Selzer D, Lehr T (2023) "Physiologically based pharmacokinetic modeling of bergamottin and 6,7-dihydroxybergamottin to describe CYP3A4 mediated grapefruit-drug interactions." Clin Pharmacol Ther, 114, p. 470-82
  17. (2025) "Product Information. TraMADol Hydrochloride ER (traMADol)." Trigen Laboratories Inc
  18. (2025) "Product Information. Codeine Contin (codeine)." Purdue Pharma
Moderate

venlafaxine food/lifestyle

Applies to: Effexor XR (venlafaxine)

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

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

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

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