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Drug Interaction Report

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

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Interactions between your drugs

Major

mirtazapine DULoxetine

Applies to: Remeron (mirtazapine), Cymbalta (duloxetine)

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

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Moderate

clonazePAM gabapentin

Applies to: Klonopin (clonazepam), Neurontin (gabapentin)

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

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Moderate

clonazePAM lamoTRIgine

Applies to: Klonopin (clonazepam), Lamictal (lamotrigine)

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

clonazePAM mirtazapine

Applies to: Klonopin (clonazepam), Remeron (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

clonazePAM DULoxetine

Applies to: Klonopin (clonazepam), Cymbalta (duloxetine)

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

gabapentin mirtazapine

Applies to: Neurontin (gabapentin), Remeron (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

gabapentin DULoxetine

Applies to: Neurontin (gabapentin), Cymbalta (duloxetine)

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. Tegretol (carbamazepine). Novartis Pharmaceuticals. 2002;PROD.
  2. Product Information. Zoloft (sertraline). Roerig Division. 2001;PROD.
  3. Product Information. Prozac (fluoxetine). Dista Products Company. 2001;PROD.
  4. Product Information. Effexor (venlafaxine). Wyeth-Ayerst Laboratories. 2001;PROD.
  5. Product Information. Paxil (paroxetine). GlaxoSmithKline. 2001;PROD.
  6. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  7. Product Information. Celexa (citalopram). Forest Pharmaceuticals. 2001;PROD.
  8. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  9. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  10. Product Information. Cymbalta (duloxetine). Lilly, Eli and Company. 2004.
  11. Cerner Multum, Inc. UK Summary of Product Characteristics.
  12. Product Information. Pristiq (desvenlafaxine). Wyeth Laboratories. 2008.
  13. Product Information. Savella (milnacipran). Forest Pharmaceuticals. 2009.
  14. Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals. 2013.
  15. Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc. 2013.
  16. Belcastro V, Costa C, Striano P. Levetiracetam-associated hyponatremia. Seizure. 2008;17:389-90.
  17. Bavbek N, Alkan R, Uz E, Kaftan O, Akcay A. Hyponatremia associated with sodium valproate in a 22-year-old male. Nephrol Dial Transplant. 2008;23:epub.
  18. Patel KR, Meesala A, Stanilla JK. Sodium valproate-induced hyponatremia: a case report. Prim Care Companion J Clin Psychiatry. 2010;12:epub.
  19. Gandhi S, McArthur E, Mamdani MM, et al. Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies. Epilepsia. 2016;57:2067-79.
  20. 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. 2018;59:28-33.
View all 20 references

Switch to consumer interaction data

Moderate

lamoTRIgine DULoxetine

Applies to: Lamictal (lamotrigine), Cymbalta (duloxetine)

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. Tegretol (carbamazepine). Novartis Pharmaceuticals. 2002;PROD.
  2. Product Information. Zoloft (sertraline). Roerig Division. 2001;PROD.
  3. Product Information. Prozac (fluoxetine). Dista Products Company. 2001;PROD.
  4. Product Information. Effexor (venlafaxine). Wyeth-Ayerst Laboratories. 2001;PROD.
  5. Product Information. Paxil (paroxetine). GlaxoSmithKline. 2001;PROD.
  6. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  7. Product Information. Celexa (citalopram). Forest Pharmaceuticals. 2001;PROD.
  8. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  9. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  10. Product Information. Cymbalta (duloxetine). Lilly, Eli and Company. 2004.
  11. Cerner Multum, Inc. UK Summary of Product Characteristics.
  12. Product Information. Pristiq (desvenlafaxine). Wyeth Laboratories. 2008.
  13. Product Information. Savella (milnacipran). Forest Pharmaceuticals. 2009.
  14. Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals. 2013.
  15. Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc. 2013.
  16. Belcastro V, Costa C, Striano P. Levetiracetam-associated hyponatremia. Seizure. 2008;17:389-90.
  17. Bavbek N, Alkan R, Uz E, Kaftan O, Akcay A. Hyponatremia associated with sodium valproate in a 22-year-old male. Nephrol Dial Transplant. 2008;23:epub.
  18. Patel KR, Meesala A, Stanilla JK. Sodium valproate-induced hyponatremia: a case report. Prim Care Companion J Clin Psychiatry. 2010;12:epub.
  19. Gandhi S, McArthur E, Mamdani MM, et al. Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies. Epilepsia. 2016;57:2067-79.
  20. 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. 2018;59:28-33.
View all 20 references

Switch to consumer interaction data

Minor

gabapentin lamoTRIgine

Applies to: Neurontin (gabapentin), Lamictal (lamotrigine)

Lamotrigine may increase the plasma concentrations of renally excreted drugs that are substrates of OCT 2. Lamotrigine inhibits OCT 2 in vitro. The clinical significance is unknown.

References

  1. Cerner Multum, Inc. UK Summary of Product Characteristics.

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

gabapentin food

Applies to: Neurontin (gabapentin)

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

lamoTRIgine food

Applies to: Lamictal (lamotrigine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P. Evaluation of possible interactions between ethanol and trazodone or amitriptyline. Neuropsychobiology. 1986;15:31-7.
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P. Goodman and Gilman's the Pharmacological Basis of Therapeutics. New York, NY: Pergamon Press Inc. 1990.
  3. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  4. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 4 references

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Moderate

mirtazapine food

Applies to: Remeron (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

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Moderate

DULoxetine food

Applies to: Cymbalta (duloxetine)

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

References

  1. Product Information. Cymbalta (duloxetine). Lilly, Eli and Company. 2004.

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Moderate

clonazePAM food

Applies to: Klonopin (clonazepam)

GENERALLY AVOID: Acute ethanol ingestion may potentiate the 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: Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. 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.
  2. Whiting B, Lawrence JR, Skellern GG, Meier J. Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide. Br J Clin Pharmacol. 1979;7:95-100.
  3. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  4. Juhl RP, Van Thiel DH, Dittert LW, Smith RB. Alprazolam pharmacokinetics in alcoholic liver disease. J Clin Pharmacol. 1984;24:113-9.
  5. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI. Pharmacokinetic noninteraction of triazolam and ethanol. J Clin Psychopharmacol. 1984;4:106-7.
  6. Staak M, Raff G, Nusser W. Pharmacopsychological investigations concerning the combined effects of dipotassium clorazepate and ethanol. Int J Clin Pharmacol Biopharm. 1979;17:205-12.
  7. Nichols JM, Martin F, Kirkby KC. A comparison of the effect of lorazepam on memory in heavy and low social drinkers. Psychopharmacology (Berl). 1993;112:475-82.
View all 7 references

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Drug Interaction Classification

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

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Further information

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