Skip to main content

Drug Interaction Report

21 potential interactions and/or warnings found for the following 5 drugs:

Add another drug
Filter by interaction and/or warning

Interactions between your drugs

Major

diazePAM fluvoxaMINE

Applies to: diazepam, fluvoxamine

GENERALLY AVOID: One study has reported that fluvoxamine significantly decreases the clearance of diazepam and desmethyldiazepam in healthy volunteers. The mean half-life of diazepam increased from 51 hours to 118 hours. The mechanism is inhibition of hepatic CYP450 metabolism. Other benzodiazepines that are metabolized by this route may also be affected.

MANAGEMENT: The manufacturer states that fluvoxamine and diazepam should not be given together. Lorazepam, oxazepam, and temazepam are metabolized by glucuronidation and are not expected to be affected by fluvoxamine.

References

  1. Fleishaker JC, Hulst LK. A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur J Clin Pharmacol. 1994;46:35-9.
  2. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  3. Perucca E, Gatti G, Cipolla G, Spina E, Barel S, Soback S, Gips M, Bialer M. Inhibition of diazepam metabolism by fluvoxamine: a pharmacokinetic study in normal volunteers. Clin Pharmacol Ther. 1994;56:471-6.

Switch to consumer interaction data

Major

venlafaxine fluvoxaMINE

Applies to: venlafaxine, fluvoxamine

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

  1. Hansen TE, Dieter K, Keepers GA. Interaction of fluoxetine and pentazocine. Am J Psychiatry. 1990;147:949-50.
  2. Achamallah NS. Visual hallucinations after combining fluoxetine and dextromethorphan . Am J Psychiatry. 1992;149:1406.
  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

Switch to consumer interaction data

Major

venlafaxine mirtazapine

Applies to: venlafaxine, mirtazapine

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

  1. Hansen TE, Dieter K, Keepers GA. Interaction of fluoxetine and pentazocine. Am J Psychiatry. 1990;147:949-50.
  2. Achamallah NS. Visual hallucinations after combining fluoxetine and dextromethorphan . Am J Psychiatry. 1992;149:1406.
  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

Switch to consumer interaction data

Major

fluvoxaMINE mirtazapine

Applies to: fluvoxamine, mirtazapine

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity such as selective serotonin reuptake inhibitors (SSRIs) and other antidepressants 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.

MONITOR CLOSELY: Coadministration with fluvoxamine may significantly increase the plasma concentrations of mirtazapine. The proposed mechanism is inhibition by fluvoxamine of CYP450 1A2, 2D6 and 3A4, the isoenzymes responsible for the metabolic clearance of mirtazapine. Increases in serum mirtazapine concentrations by three- to fourfold were observed in two patients following the addition of fluvoxamine. One patient reported feeling more anxious with the combination.

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 receiving mirtazapine with fluvoxamine should have mirtazapine levels measured following the initiation, change of dosage, or withdrawal of fluvoxamine, and 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. 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

  1. Nierenberg DW, Semprebon M. The central nervous system serotonin syndrome. Clin Pharmacol Ther. 1993;53:84-8.
  2. Metz A. Interaction between fluoxetine and buspirone. Can J Psychiatry. 1990;35:722-3.
  3. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705-13.
  4. Insel TR, Roy BF, Cohen RM, Murphy DL. Possible development of the serotonin syndrome in man. Am J Psychiatry. 1982;139:954-5.
  5. 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.
  6. Ruiz F. Fluoxetine and the serotonin syndrome. Ann Emerg Med. 1994;24:983-5.
  7. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  8. Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosomatics. 1995;36:159-60.
  9. Harvey AT, Preskorn SH. Interactions of serotonin reuptake inhibitors with tricyclic antidepressants. Arch Gen Psychiatry. 1995;52:783-4.
  10. Baetz M, Malcolm D. Serotonin syndrome from fluvoxamine and buspirone. Can J Psychiatry. 1995;40:428-9.
  11. Fischer P. Serotonin syndrome in the elderly after antidepressive monotherapy. J Clin Psychopharmacol. 1995;15:440-2.
  12. Corkeron MA. Serotonin syndrome - a potentially fatal complication of antidepressant therapy. Med J Aust. 1995;163:481-2.
  13. George TP, Godleski LS. Possible serotonin syndrome with trazodone addition to fluoxetine. Biol Psychiatry. 1996;39:384-5.
  14. Product Information. Remeron (mirtazapine). Organon. 2001;PROD.
  15. 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.
  16. John L, Perreault MM, Tao T, Blew PG. Serotonin syndrome associated with nefazodone and paroxetine. Ann Emerg Med. 1997;29:287-9.
  17. Mills KC. Serotonin syndrome: A clinical update. Crit Care Clin. 1997;13:763.
  18. 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.
  19. Mathew NT, Tietjen GE, Lucker C. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia. 1996;16:323-7.
  20. 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.
  21. Perry NK. Venlafaxine-induced serotonin syndrome with relapse following amitriptyline. Postgrad Med J. 2000;76:254-6.
  22. Manos GH. Possible serotonin syndrome associated with buspirone added to fluoxetine. Ann Pharmacother. 2000;34:871-4.
  23. 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.
  24. Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49:871-4.
  25. Smith DL, Wenegrat BG. A case report of serotonin syndrome associated with combined nefazodone and fluoxetine. J Clin Psychiatry. 2000;61:146.
  26. Anttila AK, Rasanen I, Leinonen EV. Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold. Ann Pharmacother. 2001;35:1221-3.
  27. Martin TG. Serotonin syndrome. Ann Emerg Med. 1996;28:520-6.
  28. Lane R, Baldwin D. Selective serotonin reuptake inhibitor--induced serotonin syndrome: review. J Clin Psychopharmacol. 1997;17:208-21.
  29. Tissot TA. Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use. Anesthesiology. 2003;98:1511-1512.
  30. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112-20.
  31. 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.
  32. Rang ST, Field J, Irving C. Serotonin toxicity caused by an interaction between fentanyl and paroxetine. Can J Anaesth. 2008;55:521-5.
View all 32 references

Switch to consumer interaction data

Moderate

diazePAM ALPRAZolam

Applies to: diazepam, alprazolam

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

Moderate

diazePAM venlafaxine

Applies to: diazepam, venlafaxine

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

Moderate

ALPRAZolam venlafaxine

Applies to: alprazolam, venlafaxine

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

Moderate

ALPRAZolam fluvoxaMINE

Applies to: alprazolam, fluvoxamine

MONITOR: Administration of fluvoxamine with certain benzodiazepines may increase CNS depression (e.g., sedation, ataxia). The mechanism appears to be inhibition of the CYP450 3A4 hepatic oxidative metabolism of the benzodiazepine. This interaction has been reported for alprazolam and diazepam, but may also occur with other benzodiazepines.

MANAGEMENT: The patient should be observed for increased CNS depression. Dosage adjustments may be required. Lorazepam, temazepam, and oxazepam, which are not metabolized by oxidative metabolism, may be better alternatives if a benzodiazepine is required.

References

  1. Fleishaker JC, Hulst LK. A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur J Clin Pharmacol. 1994;46:35-9.
  2. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  3. Vonmoltke LL, Greenblatt DJ, Court MH, Duan SX, Harmatz JS, Shader RI. Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. J Clin Psychopharmacol. 1995;15:125-31.

Switch to consumer interaction data

Moderate

diazePAM mirtazapine

Applies to: diazepam, mirtazapine

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

Moderate

ALPRAZolam mirtazapine

Applies to: alprazolam, mirtazapine

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

No other interactions were found between your selected drugs. However, this does not necessarily mean no other interactions exist. Always consult your healthcare provider.

Drug and food interactions

Moderate

diazePAM food

Applies to: diazepam

GENERALLY AVOID: Acute alcohol ingestion may potentiate the CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. However, the interaction seems to affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits intestinal rather than hepatic CYP450 3A4. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy. Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance. Eur J Clin Pharmacol. 1992;42:313-7.
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther. 1991;49:248-55.
  3. Product Information. Valium (diazepam). Roche Laboratories. 2002;PROD.
  4. Bailey DG, Arnold JM, Munoz C, Spence JD. Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. Clin Pharmacol Ther. 1993;53:637-42.
  5. Bailey DG, Arnold JMO, Spence JD. Grapefruit juice and drugs - how significant is the interaction. Clin Pharmacokinet. 1994;26:91-8.
  6. Product Information. Doral (quazepam). Wallace Laboratories. 2001;PROD.
  7. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A. Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation. Pharmazie. 1994;49:522-4.
  8. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD. Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin Pharmacol Ther. 1993;54:589-94.
  9. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG. Drug-food interactions in clinical practice. J Fam Pract. 1995;40:376-84.
  10. Grapefruit juice interactions with drugs. Med Lett Drugs Ther. 1995;37:73-4.
  11. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ. Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice. Clin Pharmacol Ther. 1995;58:127-31.
  12. Min DI, Ku YM, Geraets DR, Lee HC. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers. J Clin Pharmacol. 1996;36:469-76.
  13. Majeed A, Kareem A. Effect of grapefruit juice on cyclosporine pharmacokinetics. Pediatr Nephrol. 1996;10:395.
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS. Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice. Br J Clin Pharmacol. 1996;42:p662.
  15. Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol. 1996;51:189-93.
  16. Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther. 1998;63:397-402.
  17. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A. Interaction between grapefruit juice and diazepam in humans. Eur J Drug Metab Pharmacokinet. 1998;23:55-9.
  18. Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46:101-10.
  19. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans. Clin Pharmacol Ther. 1998;64:248-56.
  20. Garg SK, Kumar N, Bhargava VK, Prabhakar SK. Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy. Clin Pharmacol Ther. 1998;64:286-8.
  21. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther. 1998;64:477-83.
  22. Fuhr U, Maier-Bruggemann A, Blume H, et al. Grapefruit juice increases oral nimodipine bioavailability. Int J Clin Pharmacol Ther. 1998;36:126-32.
  23. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther. 1999;66:118-27.
  24. Eagling VA, Profit L, Back DJ. Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999;48:543-52.
  25. Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol. 1999;48:829-38.
  26. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC. The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study. Clin Ther. 1999;21:1890-9.
  27. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38:41-57.
  28. Gunston GD, Mehta U. Potentially serious drug interactions with grapefruit juice. S Afr Med J. 2000;90:41.
  29. Takanaga H, Ohnishi A, Maatsuo H, et al. Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model. Br J Clin Pharmacol. 2000;49:49-58.
  30. Libersa CC, Brique SA, Motte KB, et al. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br J Clin Pharmacol. 2000;49:373-8.
  31. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther. 2000;68:468-77.
  32. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E. Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers. Ther Drug Monit. 2001;23:369-73.
  33. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol. 1993;44:295-8.
  34. Flanagan D. Understanding the grapefruit-drug interaction. Gen Dent. 2005;53:282-5; quiz 286.
View all 34 references

Switch to consumer interaction data

Moderate

ALPRAZolam food

Applies to: alprazolam

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. Product Information. Xanax (alprazolam). Pharmacia and Upjohn. 2002;PROD.
  2. Product Information. Valium (diazepam). Roche Laboratories. 2002;PROD.
  3. Product Information. Halcion (triazolam). Pharmacia and Upjohn. 2001;PROD.
  4. Grapefruit juice interactions with drugs. Med Lett Drugs Ther. 1995;37:73-4.
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S. Interaction between grapefruit juice and midazolam in humans. Clin Pharmacol Ther. 1995;58:20-8.
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ. Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice. Clin Pharmacol Ther. 1995;58:127-31.
  7. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther. 2000;68:468-77.
View all 7 references

Switch to consumer interaction data

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

Switch to consumer interaction data

Moderate

fluvoxaMINE food

Applies to: fluvoxamine

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

Switch to consumer interaction data

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

  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

Switch to consumer interaction data

Minor

diazePAM food

Applies to: diazepam

One study has reported a 22% reduction in diazepam plasma levels when coadministered with caffeine. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that changes to caffeine consumption habits may impact the efficacy of diazepam therapy.

References

  1. Ghoneim MM, Hinrichs JV, Chiang CK, Loke WH. Pharmacokinetic and pharmacodynamic interactions between caffeine and diazepam. J Clin Psychopharmacol. 1986;6:75-80.

Switch to consumer interaction data

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

Central Nervous System (CNS) Drugs

Therapeutic duplication

The recommended maximum number of medicines in the 'Central Nervous System (CNS) Drugs' category to be taken concurrently is usually three. Your list includes five medicines belonging to the 'Central Nervous System (CNS) Drugs' category:

  • alprazolam
  • diazepam
  • fluvoxamine
  • mirtazapine
  • 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.

Duplication

Psychotropic agents

Therapeutic duplication

The recommended maximum number of medicines in the 'psychotropic agents' category to be taken concurrently is usually three. Your list includes five medicines belonging to the 'psychotropic agents' category:

  • alprazolam
  • diazepam
  • fluvoxamine
  • mirtazapine
  • 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.

Duplication

Antidepressants

Therapeutic duplication

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

  • fluvoxamine
  • mirtazapine
  • 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.

Duplication

Tranquilizers

Therapeutic duplication

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

  • alprazolam
  • diazepam

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.

Duplication

Benzodiazepines

Therapeutic duplication

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

  • alprazolam
  • diazepam

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.

Report options

Loading...
QR code containing a link to this page

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.

Learn more

Further information

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

Medical Disclaimer