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Interactions between AP-Hist DM and Dexfenfluramine

2 drug interactions and 22 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

dextromethorphan dexfenfluramine

Applies to: AP-Hist DM (brompheniramine / dextromethorphan / phenylephrine) and dexfenfluramine
Monitor closely

Concomitant use of dextromethorphan with other agents that have serotonergic activity such as serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, 5-HT1 receptor agonists, ergot alkaloids, lithium, St. John's wort, phenylpiperidine opioids, 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 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. Some manufacturers consider the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors contraindicated. If concomitant therapy is necessary, patients should be closely monitored for symptoms of serotonin syndrome during treatment. 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 (e.g., fluoxetine). 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 (91)
  1. Hansen TE, Dieter K, Keepers GA (1990) "Interaction of fluoxetine and pentazocine." Am J Psychiatry, 147, p. 949-50
  2. Achamallah NS (1992) "Visual hallucinations after combining fluoxetine and dextromethorphan ." Am J Psychiatry, 149, p. 1406
  3. Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
  4. Metz A (1990) "Interaction between fluoxetine and buspirone." Can J Psychiatry, 35, p. 722-3
  5. Goldberg RJ, Huk M (1992) "Serotonin syndrome from trazodone and buspirone." Psychosomatics, 33, p. 235-6
  6. (2002) "Product Information. D.H.E. 45 (dihydroergotamine)." Sandoz Pharmaceuticals Corporation
  7. Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
  8. Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol, 10, p. 213-7
  9. Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol, 10, p. 48-50
  10. (2001) "Product Information. Zoloft (sertraline)." Roerig Division
  11. (2001) "Product Information. Prozac (fluoxetine)." Dista Products Company
  12. Noble WH, Baker A (1992) "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth, 39, p. 1061-6
  13. Insel TR, Roy BF, Cohen RM, Murphy DL (1982) "Possible development of the serotonin syndrome in man." Am J Psychiatry, 139, p. 954-5
  14. (2001) "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories
  15. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  16. (2001) "Product Information. Paxil (paroxetine)." GlaxoSmithKline
  17. Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ (1994) "Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction." Anesth Analg, 78, p. 593-7
  18. (2001) "Product Information. Imitrex (sumatriptan)." Glaxo Wellcome
  19. Ruiz F (1994) "Fluoxetine and the serotonin syndrome." Ann Emerg Med, 24, p. 983-5
  20. (2001) "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc
  21. Reeves RR, Bullen JA (1995) "Serotonin syndrome produced by paroxetine and low-dose trazodone." Psychosomatics, 36, p. 159-60
  22. Harvey AT, Preskorn SH (1995) "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry, 52, p. 783-4
  23. Fischer P (1995) "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol, 15, p. 440-2
  24. Corkeron MA (1995) "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust, 163, p. 481-2
  25. George TP, Godleski LS (1996) "Possible serotonin syndrome with trazodone addition to fluoxetine." Biol Psychiatry, 39, p. 384-5
  26. Skop BP, Finkelstein JA, Mareth TR, Magoon MR, Brown TM (1994) "The serotonin syndrome associated wtih paroxetine, an over-the-counter cold remedy, and vascular disease." Am J Emerg Med, 12, p. 642-4
  27. Mason BJ, Blackburn KH (1997) "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother, 31, p. 175-7
  28. John L, Perreault MM, Tao T, Blew PG (1997) "Serotonin syndrome associated with nefazodone and paroxetine." Ann Emerg Med, 29, p. 287-9
  29. (2001) "Product Information. Zomig (zolmitriptan)." Astra-Zeneca Pharmaceuticals
  30. (2001) "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company
  31. Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
  32. Bhatara VS, Magnus RD, Paul KL, Preskorn SH (1998) "Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms." Ann Pharmacother, 32, p. 432-6
  33. (2001) "Product Information. Maxalt (rizatriptan)." Merck & Co., Inc
  34. (2001) "Product Information. Celexa (citalopram)." Forest Pharmaceuticals
  35. Gardner DM, Lynd LD (1998) "Sumatriptan contraindications and the serotonin syndrome." Ann Pharmacother, 32, p. 33-8
  36. Mathew NT, Tietjen GE, Lucker C (1996) "Serotonin syndrome complicating migraine pharmacotherapy." Cephalalgia, 16, p. 323-7
  37. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
  38. Egberts AC, ter Borg J, Brodie-Meijer CC (1997) "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol, 12, p. 181-2
  39. Weiner AL (1999) "Meperidine as a potential cause of serotonin syndrome in the emergency department." Acad Emerg Med, 6, p. 156-8
  40. Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
  41. Gordon JB (1998) "SSRI's and St. John's Wort: possible toxicity?" Am Fam Physician, 57, 950,953
  42. Lantz MS, Buchalter E, Giambanco V (1999) "St. John's wort and antidepressant drug interactions in the elderly." J Geriatr Psychiatr Neurol, 12, p. 7-10
  43. Fugh-Berman A (2000) "Herb-drug interactions." Lancet, 355, p. 134-8
  44. (2001) "Product Information. Zyvox (linezolid)." Pharmacia and Upjohn
  45. Perry NK (2000) "Venlafaxine-induced serotonin syndrome with relapse following amitriptyline." Postgrad Med J, 76, p. 254-6
  46. Manos GH (2000) "Possible serotonin syndrome associated with buspirone added to fluoxetine." Ann Pharmacother, 34, p. 871-4
  47. Nijhawan PK, Katz G, Winter S (1996) "Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission." Crit Care Med, 24, p. 1086-9
  48. Laird LK (1996) "Issues in the monopharmacotherapy and polypharmacotherapy of obsessive-compulsive disorder." Psychopharmacol Bull, 32, p. 569-78
  49. Margolese HC, Chouinard G (2000) "Serotonin syndrome from addition of low-dose trazodone to nefazodone." Am J Psychiatry, 157, p. 1022
  50. Mackay FJ, Dunn NR, Mann RD (1999) "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract, 49, p. 871-4
  51. Smith DL, Wenegrat BG (2000) "A case report of serotonin syndrome associated with combined nefazodone and fluoxetine." J Clin Psychiatry, 61, p. 146
  52. Rosebraugh CJ, floxkhart DA, Yasuda SU, Woosley RL (2001) "Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient." J Clin Pharmacol, 41, p. 224-7
  53. Izzo AA, Ernst E (2001) "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs, 61, p. 2163-75
  54. Duggal HS, Fetchko J (2002) "Serotonin syndrome and atypical antipsychotics." Am J Psychiatry, 159, p. 672-3
  55. Wigen CL, Goetz MB (2002) "Serotonin syndrome and linezolid." Clin Infect Dis, 34, p. 1651-2
  56. Hammerness P, Parada H, Abrams A (2002) "Linezolid: MAOI Activity and Potential Drug Interactions." Psychosomatics, 43, p. 248-9
  57. (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
  58. Dougherty JA, Young H, Shafi T (2002) "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother, 36, p. 1647-1648
  59. Turkel SB, Nadala JG, Wincor MZ (2001) "Possible serotonin syndrome in association with 5-HT3 antagonist agents." Psychosomatics, 42, p. 258-60
  60. Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
  61. Lavery S, Ravi H, McDaniel WW, Pushkin YR (2001) "Linezolid and serotonin syndrome." Psychosomatics, 42, p. 432-4
  62. Lane R, Baldwin D (1997) "Selective serotonin reuptake inhibitor--induced serotonin syndrome: review." J Clin Psychopharmacol, 17, p. 208-21
  63. Bernard L, Stern R, Lew D, Hoffmeyer P (2003) "Serotonin syndrome after concomitant treatment with linezolid and citalopram." Clin Infect Dis, 36, p. 1197
  64. Tissot TA (2003) "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology, 98, p. 1511-1512
  65. Hachem RY, Hicks K, Huen A, Raad I (2003) "Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients." Clin Infect Dis, 37, E8-E11
  66. Gillman PK (2003) "Linezolid and serotonin toxicity." Clin Infect Dis, 37, p. 1274-5
  67. Roy S, Fortier LP (2003) "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth, 50, p. 32-5
  68. Giese SY, Neborsky R (2001) "Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl." Plast Reconstr Surg, 107, p. 293-4
  69. Jones SL, Athan E, O'Brien D (2004) "Serotonin syndrome due to co-administration of linezolid and venlafaxine." J Antimicrob Chemother, 54, p. 289-90
  70. Tahir N (2004) "Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram." J Am Med Dir Assoc, 5, p. 111-3
  71. (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
  72. Thomas CR, Rosenberg M, Blythe V, Meyer WJ 3rd (2004) "Serotonin syndrome and linezolid." J Am Acad Child Adolesc Psychiatry, 43, p. 790
  73. Bergeron L, Boule M, Perreault S (2005) "Serotonin toxicity associated with concomitant use of linezolid." Ann Pharmacother, 39, p. 956-61
  74. Morales N, Vermette H (2005) "Serotonin syndrome associated with linezolid treatment after discontinuation of fluoxetine." Psychosomatics, 46, p. 274-5
  75. Morales-Molina JA, Mateu-de Antonio J, Marin-Casino M, Grau S (2005) "Linezolid-associated serotonin syndrome: what we can learn from cases reported so far." J Antimicrob Chemother, 56, p. 1176-8
  76. DeBellis RJ, Schaefer OP, Liquori M, Volturo GA (2005) "Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient." J Intensive Care Med, 20, p. 351-3
  77. Taylor JJ, Wilson JW, Estes LL (2006) "Linezolid and serotonergic drug interactions: a retrospective survey." Clin Infect Dis, 43, p. 180-7
  78. Strouse TB, Kerrihard TN, Forscher CA, Zakowski P (2006) "Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine." J Clin Psychopharmacol, 26, p. 681-683
  79. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S (2006) "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther, 13, p. 550-552
  80. Steinberg M, Morin AK (2007) "Mild serotonin syndrome associated with concurrent linezolid and fluoxetine." Am J Health Syst Pharm, 64, p. 59-62
  81. Packer S, Berman SA (2007) "Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid." Am J Psychiatry, 164, p. 346-7
  82. Shapiro RE, Tepper SJ (2007) "The serotonin syndrome, triptans, and the potential for drug-drug interactions." Headache, 47, p. 266-9
  83. Ailawadhi S, Sung KW, Carlson LA, Baer MR (2007) "Serotonin syndrome caused by interaction between citalopram and fentanyl." J Clin Pharm Ther, 32, p. 199-202
  84. (2008) "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories
  85. Rang ST, Field J, Irving C (2008) "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth, 55, p. 521-5
  86. (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
  87. (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
  88. (2011) "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC
  89. (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
  90. (2013) "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America
  91. (2014) "Product Information. CINFATOS (dextrometorfano)." LABORATORIOS CINFA, S.A.

Moderate drug interactions

Moderate:

dextromethorphan brompheniramine

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

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

dextromethorphan Food/Lifestyle

Applies to: AP-Hist DM (brompheniramine / dextromethorphan / phenylephrine)
Generally avoid

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

Management

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

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

brompheniramine Food/Lifestyle

Applies to: AP-Hist DM (brompheniramine / dextromethorphan / phenylephrine)
Generally avoid

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

Management

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

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

dexfenfluramine Food/Lifestyle

Applies to: dexfenfluramine
Generally avoid

Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

Management

Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled 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 (3)
  1. Mendelson J, Jones RT, Upton R, Jacob P 3rd (1995) "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther, 57, p. 559-68
  2. (2001) "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn
  3. (2012) "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals
Moderate:

phenylephrine Caffeine

Applies to: AP-Hist DM (brompheniramine / dextromethorphan / phenylephrine)
Monitor

Coadministration of two or more sympathomimetic or noradrenergic agents may increase the risk of nervousness, irritability, tachycardia, and/or increased blood pressure. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic and/or noradrenergic agents, including norepinephrine transporter inhibitors. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

Management

Caution is advised if two or more sympathomimetic or noradrenergic agents are coadministered. Pulse and blood pressure should be closely monitored. Consultation with individual product labeling, as well as relevant institutional protocols, may be advisable for further guidance.

References (20)
  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2024) "Product Information. Ephedrine (ephedrine)." Hameln Pharma Ltd
  8. (2023) "Product Information. Ephedrine Hydrochloride (ephedrine)." Wockhardt UK Ltd
  9. (2026) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
  10. (2025) "Product Information. Atomoxetine (atomoxetine)." Zentiva Pharma UK Ltd
  11. (2026) "Product Information. Atomoxetine (Apo) (atomoxetine)." Arrotex Pharmaceuticals Pty Ltd
  12. Angita Pharma, Inc (2026) AG-ATOMOXETINE Product Monograph (Health Canada) https://pdf.hres.ca/dpd_pm/00059014.PDF
  13. (2026) "Product Information. Boots Decongestant (Pseudoephedrine) (pseudoephedrine)." The Boots Company Plc
  14. (2023) "Product Information. Sinus and Nasal Decongestant (Trust) (pseudoephedrine)." Noumed Pharmaceuticals Pty Ltd
  15. (2019) "Product Information. Ephedrine (ephedrine)." Pfizer Australia Pty Ltd
  16. (2024) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Amneal Pharmaceuticals LLC
  17. (2024) "Product Information. Lemsip Cough Max for Mucus Cough and Cold (guaifenesin/paracetamol/phenylephrine)." Reckitt Benckiser Healthcare (UK) Ltd
  18. emc (2026) Product information: sudafed plus blocked nose 1mg/50mg/ml nasal spray. https://www.medicines.org.uk/emc/product/14256/smpc?utm_source=chatgpt.com
  19. (2023) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Baxter Corporation
  20. Neo Health (OTC) Pty Ltd (2026) Product information: pseudoephedrine hydrochloride-paracetamol capsules. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2024-PI-02603-1&d=20260804172310101&d=20260827172310101

Disease interactions

18 potential interactions Applies to: 15 conditions, including Asthma, Benign Prostatic Hyperplasia, COPD, Hypotension, and Hyperthyroidism.

Asthma

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Asthma.

It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.

Benign Prostatic Hyperplasia

Moderate:

AP-Hist DM

The phenylephrine in AP-Hist DM has a moderate potential interaction with Benign Prostatic Hyperplasia.

Sympathomimetic agents may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate.

Cardiovascular Conditions and Disorders

Major:

AP-Hist DM

The phenylephrine in AP-Hist DM has a major potential interaction with Cardiovascular Conditions and Disorders.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Cardiovascular Conditions and Disorders.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

Cerebrovascular Insufficiency

Major:

AP-Hist DM

The phenylephrine in AP-Hist DM has a major potential interaction with Cerebrovascular Insufficiency.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

COPD

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with COPD.

It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.

Diabetes Mellitus

Moderate:

AP-Hist DM

The phenylephrine in AP-Hist DM has a moderate potential interaction with Diabetes Mellitus.

Sympathomimetic agents may cause increases in blood glucose concentrations. These effects are usually transient and slight but may be significant with dosages higher than those normally recommended. Therapy with sympathomimetic agents should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate.

Gastrointestinal Obstruction

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Gastrointestinal Obstruction.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

Glaucoma/Intraocular Hypertension

Moderate:

AP-Hist DM

The phenylephrine in AP-Hist DM has a moderate potential interaction with Glaucoma/Intraocular Hypertension.

Sympathomimetic agents can induce transient mydriasis via stimulation of alpha-1 adrenergic receptors. In patients with anatomically narrow angles or narrow-angle glaucoma, pupillary dilation can provoke an acute attack. In patients with other forms of glaucoma, mydriasis may occasionally increase intraocular pressure. Therapy with sympathomimetic agents should be administered cautiously in patients with or predisposed to glaucoma, particularly narrow-angle glaucoma.

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Glaucoma/Intraocular Hypertension.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

Hyperthyroidism

Major:

AP-Hist DM

The phenylephrine in AP-Hist DM has a major potential interaction with Hyperthyroidism.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Hyperthyroidism.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

Hypotension

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Hypotension.

Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.

Liver Disease

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Liver Disease.

Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.

Pheochromocytoma

Major:

AP-Hist DM

The phenylephrine in AP-Hist DM has a major potential interaction with Pheochromocytoma.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Prostate Tumor, Benign

Moderate:

AP-Hist DM

The phenylephrine in AP-Hist DM has a moderate potential interaction with Prostate Tumor, Benign.

Sympathomimetic agents may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate.

Renal Dysfunction

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Renal Dysfunction.

Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.

Urinary Retention

Moderate:

AP-Hist DM

The brompheniramine in AP-Hist DM has a moderate potential interaction with Urinary Retention.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

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AP-Hist DM

A total of 605 drugs are known to interact with AP-Hist DM.

dexfenfluramine

A total of 312 drugs are known to interact with dexfenfluramine.

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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