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Drug Interaction Report

4 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Major

imipramine venlafaxine

Applies to: imipramine, venlafaxine

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity such as serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists, ergot alkaloids, cyclobenzaprine, lithium, St. John's wort, phenylpiperidine opioids, dextromethorphan, and tryptophan 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, hallucination, 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.

MANAGEMENT: In general, the concomitant use of multiple 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 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. For example, some experts suggest a 5-week washout period following use of fluoxetine and 3 weeks following the use of vortioxetine before administering another serotonergic agent. Individual product labeling for washout periods should be consulted for current recommendations. 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.

References

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  3. Nierenberg DW, Semprebon M. The central nervous system serotonin syndrome. Clin Pharmacol Ther. 1993;53:84-8.
  4. Metz A. Interaction between fluoxetine and buspirone. Can J Psychiatry. 1990;35:722-3.
  5. Goldberg RJ, Huk M. Serotonin syndrome from trazodone and buspirone. Psychosomatics. 1992;33:235-6.
  6. Product Information. D.H.E. 45 (dihydroergotamine). Sandoz Pharmaceuticals Corporation. 2002;PROD.
  7. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705-13.
  8. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions. II. J Clin Psychopharmacol. 1990;10:213-7.
  9. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics. J Clin Psychopharmacol. 1990;10:48-50.
  10. Product Information. Zoloft (sertraline). Roerig Division. 2001;PROD.
  11. Product Information. Prozac (fluoxetine). Dista Products Company. 2001;PROD.
  12. Noble WH, Baker A. MAO inhibitors and coronary artery surgery: a patient death. Can J Anaesth. 1992;39:1061-6.
  13. Insel TR, Roy BF, Cohen RM, Murphy DL. Possible development of the serotonin syndrome in man. Am J Psychiatry. 1982;139:954-5.
  14. Product Information. Effexor (venlafaxine). Wyeth-Ayerst Laboratories. 2001;PROD.
  15. 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.
  16. Product Information. Paxil (paroxetine). GlaxoSmithKline. 2001;PROD.
  17. Product Information. Flexeril (cyclobenzaprine). Merck & Co., Inc. 2001;PROD.
  18. 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. 1994;78:593-7.
  19. Product Information. Imitrex (sumatriptan). Glaxo Wellcome. 2001;PROD.
  20. Ruiz F. Fluoxetine and the serotonin syndrome. Ann Emerg Med. 1994;24:983-5.
  21. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  22. Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosomatics. 1995;36:159-60.
  23. Harvey AT, Preskorn SH. Interactions of serotonin reuptake inhibitors with tricyclic antidepressants. Arch Gen Psychiatry. 1995;52:783-4.
  24. Baetz M, Malcolm D. Serotonin syndrome from fluvoxamine and buspirone. Can J Psychiatry. 1995;40:428-9.
  25. Fischer P. Serotonin syndrome in the elderly after antidepressive monotherapy. J Clin Psychopharmacol. 1995;15:440-2.
  26. Corkeron MA. Serotonin syndrome - a potentially fatal complication of antidepressant therapy. Med J Aust. 1995;163:481-2.
  27. George TP, Godleski LS. Possible serotonin syndrome with trazodone addition to fluoxetine. Biol Psychiatry. 1996;39:384-5.
  28. Skop BP, Finkelstein JA, Mareth TR, Magoon MR, Brown TM. The serotonin syndrome associated wtih paroxetine, an over-the-counter cold remedy, and vascular disease. Am J Emerg Med. 1994;12:642-4.
  29. Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. Ann Pharmacother. 1997;31:175-7.
  30. John L, Perreault MM, Tao T, Blew PG. Serotonin syndrome associated with nefazodone and paroxetine. Ann Emerg Med. 1997;29:287-9.
  31. Product Information. Zomig (zolmitriptan). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  32. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  33. Mills KC. Serotonin syndrome: A clinical update. Crit Care Clin. 1997;13:763.
  34. Bhatara VS, Magnus RD, Paul KL, Preskorn SH. Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms. Ann Pharmacother. 1998;32:432-6.
  35. Product Information. Maxalt (rizatriptan). Merck & Co., Inc. 2001;PROD.
  36. Product Information. Celexa (citalopram). Forest Pharmaceuticals. 2001;PROD.
  37. Gardner DM, Lynd LD. Sumatriptan contraindications and the serotonin syndrome. Ann Pharmacother. 1998;32:33-8.
  38. Mathew NT, Tietjen GE, Lucker C. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia. 1996;16:323-7.
  39. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG. Serotonin syndrome resulting from drug interactions. Med J Aust. 1998;169:523-5.
  40. Egberts AC, ter Borg J, Brodie-Meijer CC. Serotonin syndrome attributed to tramadol addition to paroxetine therapy. Int Clin Psychopharmacol. 1997;12:181-2.
  41. Weiner AL. Meperidine as a potential cause of serotonin syndrome in the emergency department. Acad Emerg Med. 1999;6:156-8.
  42. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  43. Gordon JB. SSRI's and St. John's Wort: possible toxicity? Am Fam Physician. 1998;57:950,953.
  44. Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatr Neurol. 1999;12:7-10.
  45. Fugh-Berman A. Herb-drug interactions. Lancet. 2000;355:134-8.
  46. Product Information. Zyvox (linezolid). Pharmacia and Upjohn. 2001;PROD.
  47. Perry NK. Venlafaxine-induced serotonin syndrome with relapse following amitriptyline. Postgrad Med J. 2000;76:254-6.
  48. Manos GH. Possible serotonin syndrome associated with buspirone added to fluoxetine. Ann Pharmacother. 2000;34:871-4.
  49. Nijhawan PK, Katz G, Winter S. Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission. Crit Care Med. 1996;24:1086-9.
  50. Laird LK. Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive disorder. Psychopharmacol Bull. 1996;32:569-78.
  51. Margolese HC, Chouinard G. Serotonin syndrome from addition of low-dose trazodone to nefazodone. Am J Psychiatry. 2000;157:1022.
  52. Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49:871-4.
  53. Smith DL, Wenegrat BG. A case report of serotonin syndrome associated with combined nefazodone and fluoxetine. J Clin Psychiatry. 2000;61:146.
  54. 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. 2001;41:224-7.
  55. Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs. 2001;61:2163-75.
  56. Duggal HS, Fetchko J. Serotonin syndrome and atypical antipsychotics. Am J Psychiatry. 2002;159:672-3.
  57. Wigen CL, Goetz MB. Serotonin syndrome and linezolid. Clin Infect Dis. 2002;34:1651-2.
  58. Hammerness P, Parada H, Abrams A. Linezolid: MAOI Activity and Potential Drug Interactions. Psychosomatics. 2002;43:248-9.
  59. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  60. Dougherty JA, Young H, Shafi T. Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine. Ann Pharmacother. 2002;36:1647-1648.
  61. Turkel SB, Nadala JG, Wincor MZ. Possible serotonin syndrome in association with 5-HT3 antagonist agents. Psychosomatics. 2001;42:258-60.
  62. Martin TG. Serotonin syndrome. Ann Emerg Med. 1996;28:520-6.
  63. Lavery S, Ravi H, McDaniel WW, Pushkin YR. Linezolid and serotonin syndrome. Psychosomatics. 2001;42:432-4.
  64. Lane R, Baldwin D. Selective serotonin reuptake inhibitor--induced serotonin syndrome: review. J Clin Psychopharmacol. 1997;17:208-21.
  65. Bernard L, Stern R, Lew D, Hoffmeyer P. Serotonin syndrome after concomitant treatment with linezolid and citalopram. Clin Infect Dis. 2003;36:1197.
  66. Dannawi M. Possible serotonin syndrome after combination of buspirone and St John's Wort. J Psychopharmacol. 2002;16:401.
  67. Tissot TA. Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use. Anesthesiology. 2003;98:1511-1512.
  68. Hachem RY, Hicks K, Huen A, Raad I. Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Clin Infect Dis. 2003;37:E8-E11.
  69. Gillman PK. Linezolid and serotonin toxicity. Clin Infect Dis. 2003;37:1274-5.
  70. Roy S, Fortier LP. Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine. Can J Anaesth. 2003;50:32-5.
  71. Giese SY, Neborsky R. Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl. Plast Reconstr Surg. 2001;107:293-4.
  72. Jones SL, Athan E, O'Brien D. Serotonin syndrome due to co-administration of linezolid and venlafaxine. J Antimicrob Chemother. 2004;54:289-90.
  73. Tahir N. Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram. J Am Med Dir Assoc. 2004;5:111-3.
  74. Product Information. Cymbalta (duloxetine). Lilly, Eli and Company. 2004.
  75. Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd. Serotonin syndrome and linezolid. J Am Acad Child Adolesc Psychiatry. 2004;43:790.
  76. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112-20.
  77. Bergeron L, Boule M, Perreault S. Serotonin toxicity associated with concomitant use of linezolid. Ann Pharmacother. 2005;39:956-61.
  78. Morales N, Vermette H. Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine. Psychosomatics. 2005;46:274-5.
  79. Morales-Molina JA, Mateu-de Antonio J, Marin-Casino M, Grau S. Linezolid-associated serotonin syndrome: what we can learn from cases reported so far. J Antimicrob Chemother. 2005;56:1176-8.
  80. DeBellis RJ, Schaefer OP, Liquori M, Volturo GA. Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient. J Intensive Care Med. 2005;20:351-3.
  81. Hunter B, Kleinert MM, Osatnik J, Soria E. Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil? Anesth Analg. 2006;102:1589.
  82. Taylor JJ, Wilson JW, Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006;43:180-7.
  83. Strouse TB, Kerrihard TN, Forscher CA, Zakowski P. Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine. J Clin Psychopharmacol. 2006;26:681-683.
  84. Keegan MT, Brown DR, Rabinstein AA. Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs. Anesth Analg. 2006;103:1466-8.
  85. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S. Rare case of serotonin syndrome with therapeutic doses of paroxetine. Am J Ther. 2006;13:550-552.
  86. Steinberg M, Morin AK. Mild serotonin syndrome associated with concurrent linezolid and fluoxetine. Am J Health Syst Pharm. 2007;64:59-62.
  87. Packer S, Berman SA. Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid. Am J Psychiatry. 2007;164:346-7.
  88. Shapiro RE, Tepper SJ. The serotonin syndrome, triptans, and the potential for drug-drug interactions. Headache. 2007;47:266-9.
  89. Ailawadhi S, Sung KW, Carlson LA, Baer MR. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther. 2007;32:199-202.
  90. Product Information. Pristiq (desvenlafaxine). Wyeth Laboratories. 2008.
  91. Rang ST, Field J, Irving C. Serotonin toxicity caused by an interaction between fentanyl and paroxetine. Can J Anaesth. 2008;55:521-5.
  92. Product Information. Savella (milnacipran). Forest Pharmaceuticals. 2009.
  93. Product Information. Nucynta (tapentadol). PriCara Pharmaceuticals. 2009.
  94. Lee J, Franz L, Goforth HW. Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine. Psychosomatics. 2009;50:638-9.
  95. Product Information. Viibryd (vilazodone). Trovis Pharmaceuticals LLC. 2011.
  96. Mugele J, Nanagas KA, Tormoehlen LM. Serotonin Syndrome Associated With MDPV Use: A Case Report. Ann Emerg Med. 2012.
  97. Product Information. Oleptro (trazodone). Labopharm Inc. 2012.
  98. Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals. 2013.
  99. Product Information. Brintellix (vortioxetine). Takeda Pharmaceuticals America. 2013.
  100. Product Information. Exxua (gepirone). Mission Pharmacal Company. 2023;1.
View all 100 references

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Drug and food interactions

Moderate

venlafaxine food

Applies to: 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

  1. Warrington SJ, Ankier SI, Turner P. Evaluation of possible interactions between ethanol and trazodone or amitriptyline. Neuropsychobiology. 1986;15:31-7.
  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

imipramine food

Applies to: imipramine

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References

  1. Dorian P, Sellers EM, Reed KL, et al. Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction. Eur J Clin Pharmacol. 1983;25:325-31.
  2. Warrington SJ, Ankier SI, Turner P. Evaluation of possible interactions between ethanol and trazodone or amitriptyline. Neuropsychobiology. 1986;15:31-7.
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R. Biotransformation of amitriptyline in alcoholic depressive patients. Eur J Clin Pharmacol. 1983;24:615-21.
  4. Ciraulo DA, Barnhill JG, Jaffe JH. Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers. Clin Pharmacol Ther. 1988;43:509-18.
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M. Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving. Clin Pharmacol Ther. 1975;17:515-22.
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF. Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls. J Stud Alcohol. 1990;51:366-72.
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA. Imipramine disposition in alcoholics. J Clin Psychopharmacol. 1982;2:2-7.
View all 7 references

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antidepressants

Therapeutic duplication

The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antidepressants' category:

  • imipramine
  • venlafaxine

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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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.

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Further information

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

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