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Drug Interaction Report

This report displays the potential drug interactions for the following 6 drugs:

  • trazodone
  • Effexor (venlafaxine)
  • Zyprexa (olanzapine)
  • Seroquel (quetiapine)
  • escitalopram
  • Depakote (divalproex sodium)

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Interactions between your drugs

Major

traZODone venlafaxine

Applies to: trazodone, Effexor (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

  1. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther 13 (2006): 550-552
  2. Ruiz F "Fluoxetine and the serotonin syndrome." Ann Emerg Med 24 (1994): 983-5
  3. Dougherty JA, Young H, Shafi T "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother 36 (2002): 1647-1648
  4. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol 10 (1990): 48-50
  5. Bergeron L, Boule M, Perreault S "Serotonin toxicity associated with concomitant use of linezolid." Ann Pharmacother 39 (2005): 956-61
  6. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals, St. Louis, MO.
  7. "Product Information. D.H.E. 45 (dihydroergotamine)." Sandoz Pharmaceuticals Corporation, East Hanover, NJ.
  8. "Product Information. Zoloft (sertraline)." Roerig Division, New York, NY.
  9. Morales N, Vermette H "Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine." Psychosomatics 46 (2005): 274-5
  10. 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 12 (1994): 642-4
  11. Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd "Serotonin syndrome and linezolid." J Am Acad Child Adolesc Psychiatry 43 (2004): 790
  12. "Product Information. Maxalt (rizatriptan)." Merck & Co, Inc, West Point, PA.
  13. "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America, Lincolnshire, IL.
  14. Rang ST, Field J, Irving C "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth 55 (2008): 521-5
  15. Fugh-Berman A "Herb-drug interactions." Lancet 355 (2000): 134-8
  16. "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  17. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories, Philadelphia, PA.
  18. George TP, Godleski LS "Possible serotonin syndrome with trazodone addition to fluoxetine." Biol Psychiatry 39 (1996): 384-5
  19. Metz A "Interaction between fluoxetine and buspirone." Can J Psychiatry 35 (1990): 722-3
  20. Tahir N "Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram." J Am Med Dir Assoc 5 (2004): 111-3
  21. Wigen CL, Goetz MB "Serotonin syndrome and linezolid." Clin Infect Dis 34 (2002): 1651-2
  22. Lane R, Baldwin D "Selective serotonin reuptake inhibitor--induced serotonin syndrome: review." J Clin Psychopharmacol 17 (1997): 208-21
  23. Perry NK "Venlafaxine-induced serotonin syndrome with relapse following amitriptyline." Postgrad Med J 76 (2000): 254-6
  24. "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC, New Haven, CT.
  25. "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company, Whippany, NJ.
  26. Corkeron MA "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust 163 (1995): 481-2
  27. "Product Information. Zomig (zolmitriptan)." Zeneca Pharmaceuticals, Wilmington, DE.
  28. Manos GH "Possible serotonin syndrome associated with buspirone added to fluoxetine." Ann Pharmacother 34 (2000): 871-4
  29. Strouse TB, Kerrihard TN, Forscher CA, Zakowski P "Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine." J Clin Psychopharmacol 26 (2006): 681-683
  30. "Product Information. Flexeril (cyclobenzaprine)." Merck & Co, Inc, West Point, PA.
  31. Mason BJ, Blackburn KH "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother 31 (1997): 175-7
  32. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals, St. Louis, MO.
  33. Gillman PK "Linezolid and serotonin toxicity." Clin Infect Dis 37 (2003): 1274-5
  34. 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 56 (2005): 1176-8
  35. Duggal HS, Fetchko J "Serotonin syndrome and atypical antipsychotics." Am J Psychiatry 159 (2002): 672-3
  36. Taylor JJ, Wilson JW, Estes LL "Linezolid and serotonergic drug interactions: a retrospective survey." Clin Infect Dis 43 (2006): 180-7
  37. Rosebraugh CJ, floxkhart DA, Yasuda SU, Woosley RL "Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient." J Clin Pharmacol 41 (2001): 224-7
  38. Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2
  39. Margolese HC, Chouinard G "Serotonin syndrome from addition of low-dose trazodone to nefazodone." Am J Psychiatry 157 (2000): 1022
  40. Hunter B, Kleinert MM, Osatnik J, Soria E "Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil?" Anesth Analg 102 (2006): 1589
  41. 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 20 (2005): 351-3
  42. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  43. "Product Information. Zyvox (linezolid)" Pharmacia and Upjohn, Kalamazoo, MI.
  44. "Product Information. Prozac (fluoxetine)." Dista Products Company, Indianapolis, IN.
  45. Turkel SB, Nadala JG, Wincor MZ "Possible serotonin syndrome in association with 5-HT3 antagonist agents." Psychosomatics 42 (2001): 258-60
  46. Lee J, Franz L, Goforth HW "Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine." Psychosomatics 50 (2009): 638-9
  47. Dannawi M "Possible serotonin syndrome after combination of buspirone and St John's Wort." J Psychopharmacol 16 (2002): 401
  48. Jones SL, Athan E, O'Brien D "Serotonin syndrome due to co-administration of linezolid and venlafaxine." J Antimicrob Chemother 54 (2004): 289-90
  49. Lantz MS, Buchalter E, Giambanco V "St. John's wort and antidepressant drug interactions in the elderly." J Geriatr Psychiatr Neurol 12 (1999): 7-10
  50. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7
  51. Noble WH, Baker A "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth 39 (1992): 1061-6
  52. Hansen TE, Dieter K, Keepers GA "Interaction of fluoxetine and pentazocine." Am J Psychiatry 147 (1990): 949-50
  53. "Product Information. Paxil (paroxetine)." GlaxoSmithKline, Research Triangle Park, NC.
  54. Packer S, Berman SA "Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid." Am J Psychiatry 164 (2007): 346-7
  55. John L, Perreault MM, Tao T, Blew PG "Serotonin syndrome associated with nefazodone and paroxetine." Ann Emerg Med 29 (1997): 287-9
  56. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company, Indianapolis, IN.
  57. "Product Information. Imitrex (sumatriptan)." Glaxo Wellcome, Research Triangle Park, NC.
  58. "Product Information. Oleptro (traZODone)." Labopharm Inc, Laval, AL.
  59. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  60. Harvey AT, Preskorn SH "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry 52 (1995): 783-4
  61. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ "Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction." Anesth Analg 78 (1994): 593-7
  62. Laird LK "Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive disorder." Psychopharmacol Bull 32 (1996): 569-78
  63. Insel TR, Roy BF, Cohen RM, Murphy DL "Possible development of the serotonin syndrome in man." Am J Psychiatry 139 (1982): 954-5
  64. Steinberg M, Morin AK "Mild serotonin syndrome associated with concurrent linezolid and fluoxetine." Am J Health Syst Pharm 64 (2007): 59-62
  65. Smith DL, Wenegrat BG "A case report of serotonin syndrome associated with combined nefazodone and fluoxetine." J Clin Psychiatry 61 (2000): 146
  66. Reeves RR, Bullen JA "Serotonin syndrome produced by paroxetine and low-dose trazodone." Psychosomatics 36 (1995): 159-60
  67. 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 37 (2003): E8-E11
  68. Lavery S, Ravi H, McDaniel WW, Pushkin YR "Linezolid and serotonin syndrome." Psychosomatics 42 (2001): 432-4
  69. Egberts AC, ter Borg J, Brodie-Meijer CC "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol 12 (1997): 181-2
  70. Mathew NT, Tietjen GE, Lucker C "Serotonin syndrome complicating migraine pharmacotherapy." Cephalalgia 16 (1996): 323-7
  71. Bernard L, Stern R, Lew D, Hoffmeyer P "Serotonin syndrome after concomitant treatment with linezolid and citalopram." Clin Infect Dis 36 (2003): 1197
  72. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals, St. Louis, MO.
  73. Izzo AA, Ernst E "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs 61 (2001): 2163-75
  74. Gardner DM, Lynd LD "Sumatriptan contraindications and the serotonin syndrome." Ann Pharmacother 32 (1998): 33-8
  75. "Product Information. Celexa (citalopram)." Forest Pharmaceuticals, St. Louis, MO.
  76. Keegan MT, Brown DR, Rabinstein AA "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs." Anesth Analg 103 (2006): 1466-8
  77. Miller LG "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med 158 (1998): 2200-11
  78. Tissot TA "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology 98 (2003): 1511-1512
  79. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5
  80. Giese SY, Neborsky R "Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl." Plast Reconstr Surg 107 (2001): 293-4
  81. Achamallah NS "Visual hallucinations after combining fluoxetine and dextromethorphan ." Am J Psychiatry 149 (1992): 1406
  82. Gordon JB "SSRI's and St. John's Wort: possible toxicity?" Am Fam Physician 57 (1998): 950,953
  83. Hammerness P, Parada H, Abrams A "Linezolid: MAOI Activity and Potential Drug Interactions." Psychosomatics 43 (2002): 248-9
  84. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  85. Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8
  86. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals, Raritan, NJ.
  87. 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 24 (1996): 1086-9
  88. Roy S, Fortier LP "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth 50 (2003): 32-5
  89. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  90. Mackay FJ, Dunn NR, Mann RD "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract 49 (1999): 871-4
  91. Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20
  92. 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 32 (1998): 432-6
  93. "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc, Marietta, GA.
  94. Weiner AL "Meperidine as a potential cause of serotonin syndrome in the emergency department." Acad Emerg Med 6 (1999): 156-8
  95. Ailawadhi S, Sung KW, Carlson LA, Baer MR "Serotonin syndrome caused by interaction between citalopram and fentanyl." J Clin Pharm Ther 32 (2007): 199-202
  96. Baetz M, Malcolm D "Serotonin syndrome from fluvoxamine and buspirone." Can J Psychiatry 40 (1995): 428-9
  97. Mugele J, Nanagas KA, Tormoehlen LM "Serotonin Syndrome Associated With MDPV Use: A Case Report." Ann Emerg Med (2012):
  98. Shapiro RE, Tepper SJ "The serotonin syndrome, triptans, and the potential for drug-drug interactions." Headache 47 (2007): 266-9
  99. Goldberg RJ, Huk M "Serotonin syndrome from trazodone and buspirone." Psychosomatics 33 (1992): 235-6
View all 99 references

Switch to consumer interaction data

Major

traZODone escitalopram

Applies to: trazodone, escitalopram

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity including selective serotonin reuptake inhibitors, tricyclic antidepressants, 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: Escitalopram can cause dose-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval including tricyclic antidepressants and other antidepressants (e.g., trazodone) may result in additive effects and increased risk of ventricular arrhythmias such as torsade de pointes and sudden death. In a double-blind, placebo-controlled ECG study consisting of 113 healthy subjects, the change from baseline in QTc (Fridericia-corrected) was 4.3 msec for escitalopram 10 mg/day and 10.7 msec for the supratherapeutic dosage of 30 mg/day. Based on the established exposure-response relationship, the predicted QTc change from placebo under the Cmax for 20 mg/day is 6.6 msec. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Also, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

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. 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. Due to the potential for additive effects on the QT interval, ECG monitoring may also be appropriate when escitalopram is used with tricyclic antidepressants or other antidepressants like trazodone. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Insel TR, Roy BF, Cohen RM, Murphy DL "Possible development of the serotonin syndrome in man." Am J Psychiatry 139 (1982): 954-5
  2. Harvey AT, Preskorn SH "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry 52 (1995): 783-4
  3. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  4. Goldberg RJ, Huk M "Serotonin syndrome from trazodone and buspirone." Psychosomatics 33 (1992): 235-6
  5. Smith DL, Wenegrat BG "A case report of serotonin syndrome associated with combined nefazodone and fluoxetine." J Clin Psychiatry 61 (2000): 146
  6. Reeves RR, Bullen JA "Serotonin syndrome produced by paroxetine and low-dose trazodone." Psychosomatics 36 (1995): 159-60
  7. Margolese HC, Chouinard G "Serotonin syndrome from addition of low-dose trazodone to nefazodone." Am J Psychiatry 157 (2000): 1022
  8. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  9. Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2
  10. "Product Information. Paxil (paroxetine)." GlaxoSmithKline, Research Triangle Park, NC.
  11. "Product Information. Prozac (fluoxetine)." Dista Products Company, Indianapolis, IN.
  12. 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 32 (1998): 432-6
  13. Lane R, Baldwin D "Selective serotonin reuptake inhibitor--induced serotonin syndrome: review." J Clin Psychopharmacol 17 (1997): 208-21
  14. "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc, Marietta, GA.
  15. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol 10 (1990): 48-50
  16. Manos GH "Possible serotonin syndrome associated with buspirone added to fluoxetine." Ann Pharmacother 34 (2000): 871-4
  17. 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 24 (1996): 1086-9
  18. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals, St. Louis, MO.
  19. Metz A "Interaction between fluoxetine and buspirone." Can J Psychiatry 35 (1990): 722-3
  20. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  21. George TP, Godleski LS "Possible serotonin syndrome with trazodone addition to fluoxetine." Biol Psychiatry 39 (1996): 384-5
  22. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5
  23. Mackay FJ, Dunn NR, Mann RD "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract 49 (1999): 871-4
  24. Ruiz F "Fluoxetine and the serotonin syndrome." Ann Emerg Med 24 (1994): 983-5
  25. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther 13 (2006): 550-552
  26. 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 12 (1994): 642-4
  27. John L, Perreault MM, Tao T, Blew PG "Serotonin syndrome associated with nefazodone and paroxetine." Ann Emerg Med 29 (1997): 287-9
  28. Dougherty JA, Young H, Shafi T "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother 36 (2002): 1647-1648
  29. "Product Information. Celexa (citalopram)." Forest Pharmaceuticals, St. Louis, MO.
  30. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7
  31. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  32. Corkeron MA "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust 163 (1995): 481-2
  33. Castro VM, Clements CC, Murphy SN, et al. "QT interval and antidepressant use: a cross sectional study of electronic health records." BMJ 346 (2013): f288
  34. Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8
  35. "Product Information. Zoloft (sertraline)." Roerig Division, New York, NY.
View all 35 references

Switch to consumer interaction data

Major

venlafaxine escitalopram

Applies to: Effexor (venlafaxine), escitalopram

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity including selective serotonin reuptake inhibitors, tricyclic antidepressants, 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: Escitalopram can cause dose-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval including tricyclic antidepressants and other antidepressants (e.g., trazodone) may result in additive effects and increased risk of ventricular arrhythmias such as torsade de pointes and sudden death. In a double-blind, placebo-controlled ECG study consisting of 113 healthy subjects, the change from baseline in QTc (Fridericia-corrected) was 4.3 msec for escitalopram 10 mg/day and 10.7 msec for the supratherapeutic dosage of 30 mg/day. Based on the established exposure-response relationship, the predicted QTc change from placebo under the Cmax for 20 mg/day is 6.6 msec. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Also, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

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. 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. Due to the potential for additive effects on the QT interval, ECG monitoring may also be appropriate when escitalopram is used with tricyclic antidepressants or other antidepressants like trazodone. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Insel TR, Roy BF, Cohen RM, Murphy DL "Possible development of the serotonin syndrome in man." Am J Psychiatry 139 (1982): 954-5
  2. Harvey AT, Preskorn SH "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry 52 (1995): 783-4
  3. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  4. Goldberg RJ, Huk M "Serotonin syndrome from trazodone and buspirone." Psychosomatics 33 (1992): 235-6
  5. Smith DL, Wenegrat BG "A case report of serotonin syndrome associated with combined nefazodone and fluoxetine." J Clin Psychiatry 61 (2000): 146
  6. Reeves RR, Bullen JA "Serotonin syndrome produced by paroxetine and low-dose trazodone." Psychosomatics 36 (1995): 159-60
  7. Margolese HC, Chouinard G "Serotonin syndrome from addition of low-dose trazodone to nefazodone." Am J Psychiatry 157 (2000): 1022
  8. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  9. Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2
  10. "Product Information. Paxil (paroxetine)." GlaxoSmithKline, Research Triangle Park, NC.
  11. "Product Information. Prozac (fluoxetine)." Dista Products Company, Indianapolis, IN.
  12. 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 32 (1998): 432-6
  13. Lane R, Baldwin D "Selective serotonin reuptake inhibitor--induced serotonin syndrome: review." J Clin Psychopharmacol 17 (1997): 208-21
  14. "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc, Marietta, GA.
  15. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol 10 (1990): 48-50
  16. Manos GH "Possible serotonin syndrome associated with buspirone added to fluoxetine." Ann Pharmacother 34 (2000): 871-4
  17. 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 24 (1996): 1086-9
  18. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals, St. Louis, MO.
  19. Metz A "Interaction between fluoxetine and buspirone." Can J Psychiatry 35 (1990): 722-3
  20. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  21. George TP, Godleski LS "Possible serotonin syndrome with trazodone addition to fluoxetine." Biol Psychiatry 39 (1996): 384-5
  22. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5
  23. Mackay FJ, Dunn NR, Mann RD "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract 49 (1999): 871-4
  24. Ruiz F "Fluoxetine and the serotonin syndrome." Ann Emerg Med 24 (1994): 983-5
  25. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther 13 (2006): 550-552
  26. 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 12 (1994): 642-4
  27. John L, Perreault MM, Tao T, Blew PG "Serotonin syndrome associated with nefazodone and paroxetine." Ann Emerg Med 29 (1997): 287-9
  28. Dougherty JA, Young H, Shafi T "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother 36 (2002): 1647-1648
  29. "Product Information. Celexa (citalopram)." Forest Pharmaceuticals, St. Louis, MO.
  30. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7
  31. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  32. Corkeron MA "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust 163 (1995): 481-2
  33. Castro VM, Clements CC, Murphy SN, et al. "QT interval and antidepressant use: a cross sectional study of electronic health records." BMJ 346 (2013): f288
  34. Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8
  35. "Product Information. Zoloft (sertraline)." Roerig Division, New York, NY.
View all 35 references

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Major

QUEtiapine escitalopram

Applies to: Seroquel (quetiapine), escitalopram

MONITOR CLOSELY: Escitalopram can cause dose-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a double-blind, placebo-controlled ECG study consisting of 113 healthy subjects, the change from baseline in QTc (Fridericia-corrected) was 4.3 msec for escitalopram 10 mg/day and 10.7 msec for the supratherapeutic dosage of 30 mg/day. Based on the established exposure-response relationship, the predicted QTc change from placebo under the Cmax for 20 mg/day is 6.6 msec. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking escitalopram with certain other drugs that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: Caution is recommended if escitalopram is used in combination with other drugs that can prolong the QT interval. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. When escitalopram is used in combination with other drugs that cause CNS and/or respiratory depression, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. 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 doctor if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals, St. Louis, MO.
  2. Health Canada "Antidepressant Cipralex (escitalopram): Updated information regarding dose-related heart risk. Available from: URL: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2012/2012_63-eng.php." ([2012 May 7]):
  3. EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. Available from: URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852" ([2013 - ]):
  4. Canadian Pharmacists Association "e-CPS. Available from: URL: http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink."
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Castro VM, Clements CC, Murphy SN, et al. "QT interval and antidepressant use: a cross sectional study of electronic health records." BMJ 346 (2013): f288
  7. Cerner Multum, Inc. "Australian Product Information." O 0
View all 7 references

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Moderate

traZODone divalproex sodium

Applies to: trazodone, Depakote (divalproex sodium)

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. "Product Information. Belsomra (suvorexant)." Merck & Company Inc, Whitehouse Station, NJ.
  2. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl) 73 (1981): 381-3
  3. Plushner SL "Valerian: valeriana officinalis." Am J Health Syst Pharm 57 (2000): 328-35
  4. Grabowski BS, Cady WJ, Young WW, Emery JF "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol 18 (1980): 317-9
  5. 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 36 (1984): 244-7
  6. Feldman SA, Crawley BE "Interaction of diazepam with the muscle-relaxant drugs." Br Med J 1 (1970): 336-8
  7. Miller LG "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med 158 (1998): 2200-11
  8. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol 11 (1977): 345-9
  9. 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 14 (1982): 791-7
  10. "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company, Whippany, NJ.
  11. Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9
  12. Stovner J, Endresen R "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand 24 (1965): 223-7
  13. Ferslew KE, Hagardorn AN, McCormick WF "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci 35 (1990): 477-82
  14. "Product Information. Seroquel (quetiapine)." Zeneca Pharmaceuticals, Wilmington, DE.
  15. "Product Information. Trileptal (oxcarbazepine)" Novartis Pharmaceuticals, East Hanover, NJ.
  16. Ochs HR, Greenblatt DJ, Verburg-Ochs B "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther 36 (1984): 451-5
  17. Cerner Multum, Inc. "Australian Product Information." O 0
  18. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  19. Sotaniemi EA, Anttila M, Rautio A, et al "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther 29 (1981): 705-10
  20. "Product Information. Iopidine (apraclonidine)." Alcon Laboratories Inc, Fort Worth, TX.
  21. Naylor GJ, McHarg A "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J 2 (1977): 22
  22. "Product Information. Precedex (dexmedetomidine)" Abbott Pharmaceutical, Abbott Park, IL.
  23. 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 43 (1988): 412-9
  24. "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals, Costa Mesa, CA.
  25. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals, St. Louis, MO.
  26. 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 80 Suppl (1989): 95-8
  27. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I "Midazolam-morphine sedative interaction in patients." Anesth Analg 68 (1989): 282-5
  28. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc), Canonsburg, PA.
  29. "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc, Markham, ON.
  30. Stambaugh JE, Lane C "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest 1 (1983): 111-7
  31. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
  32. Greiff JMC, Rowbotham D "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet 27 (1994): 447-61
  33. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.
  34. 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) 96 (1988): 63-6
  35. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories, Wayne, NJ.
  36. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical, Raritan, NJ.
View all 36 references

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Moderate

traZODone OLANZapine

Applies to: trazodone, Zyprexa (olanzapine)

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Cerner Multum, Inc. "Australian Product Information." O 0
  2. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company, Indianapolis, IN.
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

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Moderate

traZODone QUEtiapine

Applies to: trazodone, Seroquel (quetiapine)

GENERALLY AVOID: Trazodone may cause prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In experimental models, trazodone has been found to inhibit hERG-encoded cardiac potassium channels responsible for the rapid delayed rectifier K+ current (IKr)--an action that is considered a predictor of drug-induced QT prolongation. However, the extent to which trazodone may affect cardiac repolarisation in clinical use has not been adequately studied. There have been postmarketing reports of torsade de pointes associated with immediate-release trazodone following overdose and in the presence of multiple confounding factors, even at dosages of 100 mg/day or less. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalaemia, hypomagnesaemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of trazodone with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. Trazodone should also not be used in patients with risk factors for QT prolongation. Hypokalemia and hypomagnesemia should be corrected prior to initiation of trazodone treatment and periodically monitored. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. When trazodone is used in combination with other drugs that cause CNS and/or respiratory depression, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. 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 doctor if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. "Product Information. Oleptro (traZODone)." Labopharm Inc, Laval, AL.
  2. Mazur A, Strasberg B, Kusniec J, Sclarovsky S "QT prolongation and polymorphous ventricular tachycardia associated with trasodone-amiodarone combination." Int J Cardiol 52 (1995): 27-9
  3. Antonelli D, Atar S, Freedberg NA, Rosenfeld T "Torsade de pointes in patients on chronic amiodarone treatment: contributing factors and drug interactions." Isr Med Assoc J 7 (2005): 163-5
  4. Levenson JL "Prolonged QT interval after trazodone overdose." Am J Psychiatry 156 (1999): 969-70
  5. Dattilo PB, Nordin C "Prolonged QT associated with an overdose of trazodone." J Clin Psychiatry 68 (2007): 1309-10
  6. EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. Available from: URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852" ([2013 - ]):
  7. Goodnick PJ, Jerry J, Parra F "Psychotropic drugs and the ECG: focus on the QTc interval." Expert Opin Pharmacother 3 (2002): 479-98
View all 7 references

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Moderate

venlafaxine divalproex sodium

Applies to: Effexor (venlafaxine), Depakote (divalproex sodium)

MONITOR: The efficacy of anticonvulsants may be diminished during coadministration with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitor (SNRIs). Antidepressants including SSRIs and SNRIs can reduce seizure threshold. In clinical trials, convulsions have typically been reported in 0.1% to 0.3% of patients receiving SSRIs for major depressive disorders. There have been rare reports of prolonged seizures in patients on fluoxetine receiving electroconvulsive therapy (ECT).

MONITOR: Coadministration of SSRIs or SNRIs may potentiate the central nervous system (CNS) adverse effects of anticonvulsants such as somnolence and cognitive and psychomotor impairment.

MONITOR: Coadministration of SSRIs or SNRIs with some anticonvulsants, particularly carbamazepine, eslicarbazepine, oxcarbazepine and valproic acid, may increase the risk of hyponatremia. Treatment with SSRIs or SNRIs has been associated with hyponatremia, which may be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in many cases. While generally reversible following discontinuation of SSRI/SNRI treatment, cases with serum sodium lower than 110 mmol/L have been reported. Hyponatremia and SIADH may also result from treatment with some anticonvulsants. The risk appears to be dose-related, and elderly patients and patients who are volume depleted (e.g., diuretic use) may be at greater risk.

MANAGEMENT: SSRIs and SNRIs should be avoided in patients with unstable epilepsy, and used cautiously in patients with epilepsy controlled with anticonvulsant medications. Treatment with SSRIs and SNRIs should be discontinued if seizures develop or seizure frequency increases. Patients receiving SSRIs or SNRIs with anticonvulsants, particularly carbamazepine, eslicarbazepine, oxcarbazepine and/or valproic acid, should also have serum sodium levels measured regularly and monitored for development of hyponatremia, particularly when higher dosages of these medications are used. Signs and symptoms of hyponatremia include nausea, vomiting, headache, difficulty concentrating, memory impairment, confusion, malaise, lethargy, muscle weakness or spasms, and unsteadiness. In more severe and/or acute cases, hallucination, syncope, seizure, coma, respiratory arrest, and death may occur. Discontinuation of SSRIs and SNRIs should be considered in patients who develop symptomatic hyponatremia, and appropriate medical intervention instituted. All patients receiving concomitant therapy with SSRIs or SNRIs and anticonvulsants should be counseled against driving, operating machinery, or engaging in potentially 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. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals, St. Louis, MO.
  2. Gandhi S, McArthur E, Mamdani MM, et.al "Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies." Epilepsia 57 (2016): 2067-79
  3. Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90
  4. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company, Indianapolis, IN.
  5. "Product Information. Celexa (citalopram)." Forest Pharmaceuticals, St. Louis, MO.
  6. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals, East Hanover, NJ.
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc, Marietta, GA.
  9. "Product Information. Prozac (fluoxetine)." Dista Products Company, Indianapolis, IN.
  10. Patel KR, Meesala A, Stanilla JK "Sodium valproate-induced hyponatremia: a case report." Prim Care Companion J Clin Psychiatry 12 (2010): epub
  11. Falhammar H, Lindh JD, Calissendorff J, et.al "Differences in associations of antiepileptic drugs and hospitalization due to hyponatremia: A population-based case-control study." Seizure 59 (2018): 28-33
  12. "Product Information. Zoloft (sertraline)." Roerig Division, New York, NY.
  13. "Product Information. Trileptal (oxcarbazepine)" Novartis Pharmaceuticals, East Hanover, NJ.
  14. "Product Information. Aptiom (eslicarbazepine)." Sunovion Pharmaceuticals Inc, Marlborough, MA.
  15. Bavbek N, Alkan R, Uz E, Kaftan O, Akcay A "Hyponatremia associated with sodium valproate in a 22-year-old male." Nephrol Dial Transplant 23 (2008): epub
  16. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals, St. Louis, MO.
  17. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories, Philadelphia, PA.
  18. "Product Information. Paxil (paroxetine)." GlaxoSmithKline, Research Triangle Park, NC.
  19. "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  20. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals, St. Louis, MO.
View all 20 references

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Moderate

venlafaxine OLANZapine

Applies to: Effexor (venlafaxine), Zyprexa (olanzapine)

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Cerner Multum, Inc. "Australian Product Information." O 0
  2. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company, Indianapolis, IN.
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

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Moderate

venlafaxine QUEtiapine

Applies to: Effexor (venlafaxine), Seroquel (quetiapine)

GENERALLY AVOID: There is some concern that quetiapine may have additive cardiovascular effects in combination with other drugs that are known to prolong the QT interval of the electrocardiogram. In clinical trials, quetiapine was not associated with a persistent increase in QT intervals, and there was no statistically significant difference between quetiapine and placebo in the proportions of patients experiencing potentially important changes in ECG parameters including QT, QTc, and PR intervals. However, QT prolongation and torsade de pointes have been reported during postmarketing use in cases of quetiapine overdose and in patients with risk factors such as underlying illness or concomitant use of drugs known to cause electrolyte imbalance or increase QT interval. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, certain agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants) may have additive parasympatholytic and central nervous system-depressant effects when used in combination with quetiapine. Excessive parasympatholytic effects may include paralytic ileus, hyperthermia, mydriasis, blurred vision, tachycardia, urinary retention, psychosis, and seizures.

MANAGEMENT: Coadministration of quetiapine with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. In addition, if combination therapy with agents with anticholinergic properties is required, caution is advised, particularly in the elderly and those with underlying organic brain disease. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

References

  1. Glassman AH, Bigger JT Jr "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry 158 (2001): 1774-82
  2. EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. Available from: URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852" ([2013 - ]):
  3. Canadian Pharmacists Association "e-CPS. Available from: URL: http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink."
  4. Vieweg WV, Schneider RK, Wood MA "Torsade de pointes in a patient with complex medical and psychiatric conditions receiving low-dose quetiapine." Acta Psychiatr Scand 112 (2005): 318-22
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. "Product Information. Seroquel (quetiapine)." Zeneca Pharmaceuticals, Wilmington, DE.
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Vieweg WV "New generation antipsychotic drugs and QTc interval prolongation." Prim Care Companion J Clin Psychiatry 5 (2003): 205-15
  9. Sala M, Vicentini A, Brambilla P, et al. "QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy." Ann Gen Psychiatry 4 (2005): 1
View all 9 references

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Moderate

divalproex sodium OLANZapine

Applies to: Depakote (divalproex sodium), Zyprexa (olanzapine)

MONITOR: Concurrent use of olanzapine and valproic acid may potentiate the risk of hepatotoxicity. The exact mechanism of interaction is unknown. In a retrospective study of 52 children, combined treatment with olanzapine and divalproex was associated with more frequent elevations of hepatic enzymes than either agent alone, and mean and peak hepatic enzyme levels during the observed course of treatment were also higher. All 12 patients who received combined treatment had at least one peak enzyme elevation above the normal range, versus 10 of 17 who received olanzapine alone and 6 of 23 who received divalproex alone. With the exception of 2 patients who required discontinuation of combination treatment (due to development of pancreatitis in one and steatohepatitis in the other), the observed peak and mean enzyme levels were less than 3 times the upper limit of normal (ULN) and were asymptomatic. The long-term significance of these findings is unknown.

MANAGEMENT: The authors of the study recommend monitoring liver function tests every 3 to 4 months during the first year of treatment with either olanzapine or valproic acid, at least in pediatric patients. If no elevations of liver enzymes or marked weight gain occur after one year, a decrease in frequency of monitoring to every 6 months can be considered. Patients should be advised to notify their physician if they experience signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice.

References

  1. Gonzalez-Heydrich J, Raches D, Wilens TE, Leichtner A, Mezzacappa E "Retrospective study of hepatic enzyme elevations in children treated with olanzapine, divalproex, and their combination." J Am Acad Child Adolesc Psychiatry 42 (2003): 1227-33

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Moderate

divalproex sodium QUEtiapine

Applies to: Depakote (divalproex sodium), Seroquel (quetiapine)

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. "Product Information. Belsomra (suvorexant)." Merck & Company Inc, Whitehouse Station, NJ.
  2. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl) 73 (1981): 381-3
  3. Plushner SL "Valerian: valeriana officinalis." Am J Health Syst Pharm 57 (2000): 328-35
  4. Grabowski BS, Cady WJ, Young WW, Emery JF "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol 18 (1980): 317-9
  5. 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 36 (1984): 244-7
  6. Feldman SA, Crawley BE "Interaction of diazepam with the muscle-relaxant drugs." Br Med J 1 (1970): 336-8
  7. Miller LG "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med 158 (1998): 2200-11
  8. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol 11 (1977): 345-9
  9. 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 14 (1982): 791-7
  10. "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company, Whippany, NJ.
  11. Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9
  12. Stovner J, Endresen R "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand 24 (1965): 223-7
  13. Ferslew KE, Hagardorn AN, McCormick WF "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci 35 (1990): 477-82
  14. "Product Information. Seroquel (quetiapine)." Zeneca Pharmaceuticals, Wilmington, DE.
  15. "Product Information. Trileptal (oxcarbazepine)" Novartis Pharmaceuticals, East Hanover, NJ.
  16. Ochs HR, Greenblatt DJ, Verburg-Ochs B "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther 36 (1984): 451-5
  17. Cerner Multum, Inc. "Australian Product Information." O 0
  18. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  19. Sotaniemi EA, Anttila M, Rautio A, et al "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther 29 (1981): 705-10
  20. "Product Information. Iopidine (apraclonidine)." Alcon Laboratories Inc, Fort Worth, TX.
  21. Naylor GJ, McHarg A "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J 2 (1977): 22
  22. "Product Information. Precedex (dexmedetomidine)" Abbott Pharmaceutical, Abbott Park, IL.
  23. 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 43 (1988): 412-9
  24. "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals, Costa Mesa, CA.
  25. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals, St. Louis, MO.
  26. 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 80 Suppl (1989): 95-8
  27. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I "Midazolam-morphine sedative interaction in patients." Anesth Analg 68 (1989): 282-5
  28. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc), Canonsburg, PA.
  29. "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc, Markham, ON.
  30. Stambaugh JE, Lane C "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest 1 (1983): 111-7
  31. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
  32. Greiff JMC, Rowbotham D "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet 27 (1994): 447-61
  33. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.
  34. 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) 96 (1988): 63-6
  35. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories, Wayne, NJ.
  36. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical, Raritan, NJ.
View all 36 references

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Moderate

divalproex sodium escitalopram

Applies to: Depakote (divalproex sodium), escitalopram

MONITOR: The efficacy of anticonvulsants may be diminished during coadministration with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitor (SNRIs). Antidepressants including SSRIs and SNRIs can reduce seizure threshold. In clinical trials, convulsions have typically been reported in 0.1% to 0.3% of patients receiving SSRIs for major depressive disorders. There have been rare reports of prolonged seizures in patients on fluoxetine receiving electroconvulsive therapy (ECT).

MONITOR: Coadministration of SSRIs or SNRIs may potentiate the central nervous system (CNS) adverse effects of anticonvulsants such as somnolence and cognitive and psychomotor impairment.

MONITOR: Coadministration of SSRIs or SNRIs with some anticonvulsants, particularly carbamazepine, eslicarbazepine, oxcarbazepine and valproic acid, may increase the risk of hyponatremia. Treatment with SSRIs or SNRIs has been associated with hyponatremia, which may be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in many cases. While generally reversible following discontinuation of SSRI/SNRI treatment, cases with serum sodium lower than 110 mmol/L have been reported. Hyponatremia and SIADH may also result from treatment with some anticonvulsants. The risk appears to be dose-related, and elderly patients and patients who are volume depleted (e.g., diuretic use) may be at greater risk.

MANAGEMENT: SSRIs and SNRIs should be avoided in patients with unstable epilepsy, and used cautiously in patients with epilepsy controlled with anticonvulsant medications. Treatment with SSRIs and SNRIs should be discontinued if seizures develop or seizure frequency increases. Patients receiving SSRIs or SNRIs with anticonvulsants, particularly carbamazepine, eslicarbazepine, oxcarbazepine and/or valproic acid, should also have serum sodium levels measured regularly and monitored for development of hyponatremia, particularly when higher dosages of these medications are used. Signs and symptoms of hyponatremia include nausea, vomiting, headache, difficulty concentrating, memory impairment, confusion, malaise, lethargy, muscle weakness or spasms, and unsteadiness. In more severe and/or acute cases, hallucination, syncope, seizure, coma, respiratory arrest, and death may occur. Discontinuation of SSRIs and SNRIs should be considered in patients who develop symptomatic hyponatremia, and appropriate medical intervention instituted. All patients receiving concomitant therapy with SSRIs or SNRIs and anticonvulsants should be counseled against driving, operating machinery, or engaging in potentially 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. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals, St. Louis, MO.
  2. Gandhi S, McArthur E, Mamdani MM, et.al "Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies." Epilepsia 57 (2016): 2067-79
  3. Belcastro V, Costa C, Striano P "Levetiracetam-associated hyponatremia." Seizure 17 (2008): 389-90
  4. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company, Indianapolis, IN.
  5. "Product Information. Celexa (citalopram)." Forest Pharmaceuticals, St. Louis, MO.
  6. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals, East Hanover, NJ.
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc, Marietta, GA.
  9. "Product Information. Prozac (fluoxetine)." Dista Products Company, Indianapolis, IN.
  10. Patel KR, Meesala A, Stanilla JK "Sodium valproate-induced hyponatremia: a case report." Prim Care Companion J Clin Psychiatry 12 (2010): epub
  11. Falhammar H, Lindh JD, Calissendorff J, et.al "Differences in associations of antiepileptic drugs and hospitalization due to hyponatremia: A population-based case-control study." Seizure 59 (2018): 28-33
  12. "Product Information. Zoloft (sertraline)." Roerig Division, New York, NY.
  13. "Product Information. Trileptal (oxcarbazepine)" Novartis Pharmaceuticals, East Hanover, NJ.
  14. "Product Information. Aptiom (eslicarbazepine)." Sunovion Pharmaceuticals Inc, Marlborough, MA.
  15. Bavbek N, Alkan R, Uz E, Kaftan O, Akcay A "Hyponatremia associated with sodium valproate in a 22-year-old male." Nephrol Dial Transplant 23 (2008): epub
  16. "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals, St. Louis, MO.
  17. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories, Philadelphia, PA.
  18. "Product Information. Paxil (paroxetine)." GlaxoSmithKline, Research Triangle Park, NC.
  19. "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
  20. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals, St. Louis, MO.
View all 20 references

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Moderate

OLANZapine QUEtiapine

Applies to: Zyprexa (olanzapine), Seroquel (quetiapine)

MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

References

  1. Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82
  2. Mann SC, Boger WP "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry 135 (1978): 1097-100
  3. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm 2 (1983): 174-8
  4. Warnes H, Lehmann HE, Ban TA "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J 96 (1967): 1112-3
  5. Zelman S, Guillan R "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry 126 (1970): 1787-90
  6. Cohen MA, Alfonso CA, Mosquera M "Development of urinary retention during treatment with clozapine and meclizine [published erratum appears in Am J Psychiatry 1994 Jun;151(6):952]." Am J Psychiatry 151 (1994): 619-20
  7. Gershon S, Neubauer H, Sundland DM "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther 6 (1965): 749-56
  8. Sarnquist F, Larson CP Jr "Drug-induced heat stroke." Anesthesiology 39 (1973): 348-50
  9. Lee BS "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry 47 (1986): 571
  10. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories, Wayne, NJ.
  11. Johnson AL, Hollister LE, Berger PA "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry 42 (1981): 313-7
  12. Stadnyk AN, Glezos JD "Drug-induced heat stroke." Can Med Assoc J 128 (1983): 957-9
  13. Forester D "Fatal drug-induced heat stroke." JACEP 7 (1978): 243-4
  14. "Product Information. Cogentin (benztropine)." Merck & Co, Inc, West Point, PA.
  15. Moreau A, Jones BD, Banno V "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry 31 (1986): 339-41
View all 15 references

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Moderate

OLANZapine escitalopram

Applies to: Zyprexa (olanzapine), escitalopram

MONITOR: It is uncertain whether olanzapine causes clinically significant prolongation of the QT interval. In pooled studies of adults as well as pooled studies of adolescents, there were no significant differences between olanzapine and placebo in the proportion of patients experiencing potentially important changes in ECG parameters, including QT, QTcF (Fridericia-corrected), and PR intervals. In clinical trials, clinically meaningful QTc prolongations (QTcF >=500 msec at any time post-baseline in patients with baseline QTcF <500 msec) occurred in 0.1% to 1% of patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. Published studies have generally reported no significant effect of olanzapine on QTc interval, although both QTc prolongation and QTc shortening have also been reported. There have been a few isolated case reports of QT prolongation in patients receiving olanzapine. However, causality is difficult to establish due to confounding factors such as concomitant use of drugs that cause QT prolongation and underlying conditions that may predispose to QT prolongation (e.g., hypokalemia, congenital long QT syndrome, preexisting conduction abnormalities).

MANAGEMENT: Some authorities recommend caution when olanzapine is used with drugs that are known to cause QT prolongation. ECG monitoring may be advisable in some cases, such as in patients with a history of cardiac arrhythmias or congenital or family history of long QT syndrome. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Cerner Multum, Inc. "Australian Product Information." O 0
  2. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company, Indianapolis, IN.
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

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

Drug and food interactions

Moderate

traZODone food

Applies to: trazodone

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. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  2. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.
  3. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
View all 4 references

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Moderate

venlafaxine food

Applies to: Effexor (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. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  2. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.
  3. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
View all 4 references

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Moderate

divalproex sodium food

Applies to: Depakote (divalproex sodium)

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. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  2. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.
  3. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
View all 4 references

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Moderate

OLANZapine food

Applies to: Zyprexa (olanzapine)

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. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  2. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.
  3. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
View all 4 references

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Moderate

escitalopram food

Applies to: escitalopram

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. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):
  2. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.
  3. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
View all 4 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

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 six medicines belonging to the 'Central Nervous System (CNS) Drugs' category:

  • trazodone
  • Effexor (venlafaxine)
  • Zyprexa (olanzapine)
  • Seroquel (quetiapine)
  • escitalopram
  • Depakote (divalproex sodium)

Note: The benefits of taking this combination of medicines may outweigh any risks associated with therapeutic duplication. This information does not take the place of talking to your doctor. Always check with your healthcare provider to determine if any adjustments to your medications are needed.

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:

  • trazodone
  • Effexor (venlafaxine)
  • Zyprexa (olanzapine)
  • Seroquel (quetiapine)
  • escitalopram

Note: The benefits of taking this combination of medicines may outweigh any risks associated with therapeutic duplication. This information does not take the place of talking to your doctor. Always check with your healthcare provider to determine if any adjustments to your medications are needed.

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:

  • trazodone
  • Effexor (venlafaxine)
  • escitalopram

Note: The benefits of taking this combination of medicines may outweigh any risks associated with therapeutic duplication. This information does not take the place of talking to your doctor. Always check with your healthcare provider to determine if any adjustments to your medications are needed.

Duplication

Antipsychotics

Therapeutic duplication

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

  • Zyprexa (olanzapine)
  • Seroquel (quetiapine)

Note: The benefits of taking this combination of medicines may outweigh any risks associated with therapeutic duplication. This information does not take the place of talking to your doctor. Always check with your healthcare provider to determine if any adjustments to your medications are needed.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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

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