Skip to Content

Acetaminophen / brompheniramine / dextromethorphan / pseudoephedrine Side Effects

Applies to acetaminophen / brompheniramine / dextromethorphan / pseudoephedrine: oral syrup


Two cases hypotension have been reported following the administration of acetaminophen. Both patients experienced significant decreases in blood pressure. One of the two patients required pressor agents to maintain adequate mean arterial pressures. Neither episode was associated with symptoms of anaphylaxis. Neither patient was rechallenged after resolution of the initial episode.

Pseudoephedrine causes vasoconstriction which generally does not produce hypertension, but may be problematic for patients with preexisting hypertension. Arrhythmias may be produced in predisposed patients. Rarely, pseudoephedrine has been reported to cause coronary artery spasm and chest pain.

One report evaluated the effect with 60 mg of pseudoephedrine on individuals in a hyperbaric chamber at 1 atmosphere (simulated scuba dive to 66 feet of sea water). Pseudoephedrine and depth (stimulated) were found to have significant but opposite effects on heart rate, although these effects were unlikely to be clinically significant during diving.[Ref]

Cardiovascular side effects of acetaminophen have included two cases of hypotension.

Cardiovascular effects of brompheniramine have included hypotension, tachycardia, and palpitations.

Cardiovascular side effects of pseudoephedrine have included tachycardia. Some patients have developed hypertension and/or arrhythmias.[Ref]


Dermatologic side effects have included erythematous skin rashes. Acetaminophen associated bullous erythema and purpura fulminans have been reported. One case of toxic epidermal necrolysis associated with acetaminophen administered to a pediatric patient has been reported.[Ref]


Gastrointestinal side effects of acetaminophen have been rare except in alcoholics and after overdose.

Gastrointestinal side effects of brompheniramine have include nausea, dry mouth and constipation.

Gastrointestinal side effects of dextromethorphan have included stomach upset.

Gastrointestinal side effects of pseudoephedrine have included anorexia and gastric irritation in approximately 5% of patients. Dry mouth, nose, or throat have occurred in up to 15% of patients.[Ref]

Alcoholic patients may develop hepatotoxicity after even modest doses of acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is necessary to deplete liver glutathione stores by 70% in a 70 kg person, although hepatotoxicity has been reported with smaller doses. Glutathione concentrations may be repleted by the antidote N-acetylcysteine. One case report has suggested that hypothermia may also be beneficial in decreasing liver damage during overdose. Another study has suggested that acetaminophen may precipitate acute biliary pain and cholestasis. The mechanism for this side effect may be related to inhibition of prostaglandins and alterations in the regulation of the sphincter of Oddi.[Ref]


Hematologic side effects of acetaminophen have included rare cases of thrombocytopenia. Methemoglobinemia with resulting cyanosis has also been observed in the setting of acute overdose.

Hematologic side effects of brompheniramine have included rare cases of hemolytic anemia, thrombocytopenia, and agranulocytosis.[Ref]


Hypersensitivity side effects of acetaminophen have included anaphylaxis and fixed drug eruptions.

Hypersensitivity side effects of dextromethorphan have included rare reports of fixed-drug eruptions.

Hypersensitivity side effects of pseudoephedrine have included fixed drug eruptions.[Ref]

Nervous system

Nervous system side effects of brompheniramine have included central nervous system (CNS) depression, resulting in drowsiness and sedation in nearly 50% of patients treated. This effect has often been transient and ceased with continued use. Motor skills have be impaired and patients should be advised to avoid tasks which require attention. Patients should also avoid concomitant use with alcohol and other sedative-hypnotic drugs. Dyskinesias have rarely been reported following chronic use of brompheniramine.

Nervous system side effects of dextromethorphan have included drowsiness and dizziness. Other side effects such as excitation, mental confusion, and opiate-like respiratory depression have been rare and occurred at higher dosages. In some cases of abuse, patients experienced euphoria, hyperactivity, mania, and auditory and visual hallucinations.

Nervous system side effects of pseudoephedrine have included insomnia in up to 30% of patients. Tremor, anxiety, nervousness, and headache have also been reported.[Ref]

A few cases of dyskinesias and tremors, often of the face, have been reported in patients whose chronic use of brompheniramine extended over a period of up to 10 years. Some of these cases were only partially relieved by discontinuation of the drug. Haloperidol was successful in relieving symptoms in these patients. Spasmodic torticollis has been reported in a child given brompheniramine over an eight month period.[Ref]


Ocular side effects of brompheniramine have included blurred vision, diplopia, and dry eyes due to anticholinergic effects.[Ref]


Genitourinary side effects of brompheniramine have included dysuria, urinary hesitancy, decrease in urine flow, and, in rare cases, acute urinary retention.[Ref]


Alcoholic patients may develop hepatotoxicity after even modest doses of acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is necessary to deplete liver glutathione stores by 70% in a 70 kg person. However, hepatotoxicity has been reported following smaller doses. Glutathione concentrations may be repleted by the antidote N-acetylcysteine. One case report has suggested that hypothermia may also be beneficial in decreasing liver damage during overdose.

In a recent retrospective study of 306 patients admitted for acetaminophen overdose, 6.9% had severe liver injury but all recovered. None of the 306 patients died.

One study has suggested that acetaminophen may precipitate acute biliary pain and cholestasis. The mechanism of this effect may be related to inhibition of prostaglandin and alterations in the regulation of the sphincter of Oddi.

Cases of acute pancreatitis have been reported rarely.

A 19-year-old female developed hepatotoxicity, reactive plasmacytosis and agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.[Ref]

Hepatic side effects of acetaminophen have included severe and sometimes fatal dose dependent hepatitis in alcoholic patients. Hepatotoxicity has been increased during fasting.[Ref]


Acute tubular necrosis usually occurs in conjunction with liver failure, but has been observed as an isolated finding in rare cases. A possible increase in the risk of renal cell carcinoma has been associated with chronic acetaminophen use as well.

One case-control study of patients with end-stage renal disease suggested that long term consumption of acetaminophen may significantly increase the risk of end-stage renal disease particularly in patients taking more than two pills per day.

However, a recent cohort study of analgesia use of initially healthy men concluded that moderate use of analgesics including acetaminophen was not associated with increased risk of renal disease.[Ref]

Renal side effects of acetaminophen have included acute renal failure, acute tubular necrosis, and interstitial nephritis. Adverse renal effects are most often observed after overdose, after chronic abuse (often with multiple analgesics), or in association with acetaminophen-related hepatotoxicity.[Ref]


Respiratory side effects of acetaminophen have included a case of eosinophilic pneumonia.[Ref]


Metabolic side effects of acetaminophen have included metabolic acidosis following a massive overdose of acetaminophen.[Ref]

In the case of metabolic acidosis, causality is uncertain as more than one drug was ingested. The case of metabolic acidosis followed the ingestion of 75 grams of acetaminophen, 1.95 grams of aspirin, and a small amount of a liquid household cleaner The patient also had a history of seizures which the authors reported may have contributed to an increased lactate level indicative of metabolic acidosis.[Ref]


1. Dickerson J, Perrier D, Mayersohn M, Bressler R "Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man." Eur J Clin Pharmacol 14 (1978): 253-9

2. Mores N, Campia U, Navarra P, Cardillo C, Preziosi P "No cardiovascular effects of single-dose pseudoephedrine in patients with essential hypertension treated with beta-blockers." Eur J Clin Pharmacol 55 (1999): 251-4

3. Covington TR, Lawson LC, Young LL, eds. "Handbook of Nonprescription Drugs. 10th ed." Washington, DC: American Pharmaceutical Association (1993):

4. Knowles SR, Weber E "Dextromethorphan anaphylaxis." J Allerg Clin Immunol 102 (1998): 316-7

5. Schuller DE, Turkewitz D "Adverse effects of antihistamines." Postgrad Med 79 (1986): 75-86

6. Rosen RA "Angina associated with pseudoephedrine ." Ann Emerg Med 10 (1981): 230-1

7. Taylor DM, O'Toole KS, Auble TE, Ryan CM, Sherman DR "The psychometric and cardiac effects of pseudoephedrine in the hyperbaric environment." Pharmacotherapy 20 (2000): 1045-50

8. Gill ND, Shield A, Blazevich AJ, Zhou S, Weatherby RP "Muscular and cardiorespiratory effects of pseudoephedrine in human athletes." Br J Clin Pharmacol 50 (2000): 205-13

9. Stroh JE, Jr Ayars GH, Bernstein IL, Kemp JP, Podleski WK, Prenner BM, Schoenwetter WF, Salzmann JK "A comparative tolerance study of terfenadine-pseudoephedrine combination tablets and pseudoephedrine tablets in patients with allergic or vasomotor rhinitis." J Int Med Res 16 (1988): 420-7

10. Brown G "Acetaminophen-induced hypotension." Heart Lung 25 (1996): 137-40

11. Lyon CC, Turney JH "Pseudoephedrine toxicity in renal failure." Br J Clin Pract 50 (1996): 396-7

12. Lima JJ, Jusko WJ "Determination of procainamide acetylator status." Clin Pharmacol Ther 23 (1978): 25-9

13. Wiener I, Tilkian AG, Palazzolo M "Coronary artery spasm and myocardial infarction in a patient with normal coronary arteries: temporal relationship to pseudoephedrine ingestion." Cathet Cardiovasc Diagn 20 (1990): 51-3

14. Halevi A, BenAmitai D, Garty BZ "Toxic epidermal necrolysis associated with acetaminophen ingestion." Ann Pharmacother 34 (2000): 32-4

15. Filipe PL, Freitas JP, Decastro JC, Silva R "Drug eruption induced by acetaminophen in infectious mononucleosis." Int J Dermatol 34 (1995): 220-1

16. Thomas RH, Munro DD "Fixed drug eruption due to paracetamol." Br J Dermatol 115 (1986): 357-9

17. Guccione JL, Zemtsov A, Cobos E, Neldner KH "Acquired purpura fulminans induced by alcohol and acetaminophen - successful treatment with heparin and vitamin-k." Arch Dermatol 129 (1993): 1267-9

18. Brotodihardjo AE, Batey RG, Farrell GC, Byth K "Hepatotoxicity from paracetamol self-poisoning in Western Sydney: a continuing challenge." Med J Aust 157 (1992): 382-5

19. Keaton MR "Acute renal failure in an alcoholic during therapeutic acetaminophen ingestion." South Med J 81 (1988): 1163-6

20. Dowd J, Bailey D, Moussa K, Nair S, Doyle R, CulpepperMorgan JA "Ischemic colitis associated with pseudoephedrine: Four cases." Am J Gastroenterol 94 (1999): 2430-4

21. Wolfe TR, Caravati EM "Massive dextromethorphan ingestion and abuse." Am J Emerg Med 13 (1995): 174-6

22. Lee WM "Medical progress: drug-induced hepatotoxicity." N Engl J Med 333 (1995): 1118-27

23. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404

24. Johnson GK, Tolman KG "Chronic liver disease and acetaminophen." Ann Intern Med 87 (1977): 302-4

25. Shriner K, Goetz MB "Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6

26. Whitcomb DC "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1311

27. Cheung L, Potts RG, Meyer KC "Acetaminophen treatment nomogram." N Engl J Med 330 (1994): 1907-8

28. Wong V, Daly M, Boon A, Heatley V "Paracetamol and acute biliary pain with cholestasis." Lancet 342 (1993): 869

29. Smilkstein MJ, Douglas Dr, Daya MR "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1310-1

30. Block R "Liver failure induced by paracetamol." BMJ 306 (1993): 457

31. Blamoutier J "Comparative trial of two antihistamines, mequitazine and brompheniramine." Curr Med Res Opin 5 (1978): 366-70

32. Simons FE, Frith EM, Simons KJ "The pharmacokinetics and antihistaminic effects of brompheniramine." J Allergy Clin Immunol 70 (1982): 458-64

33. Bonkovsky HL, Kane RE, Jones DP, Galinsky RE, Banner B "Acute hepatic and renal toxicity from low doses of acetaminophen in the absence of alcohol abuse or malnutrition - evidence for increased susceptibility to drug toxicity due to cardiopulmonary and renal insufficiency." Hepatology 19 (1994): 1141-8

34. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7

35. Cheung L, Meyer KC "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1311-2

36. Lee WM "Acute liver failure." Am J Med 96 (1994): 3-9

37. Bray GP "Liver failure induced by paracetamol." BMJ 306 (1993): 157-8

38. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50

39. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301

40. Rumore MM, Blaiklock RG "Influence of age-dependent pharmacokinetics and metabolism on acetaminophen hepatotoxicity." J Pharm Sci 81 (1992): 203-7

41. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301

42. Mofenson HC, Caraccio TR, Nawaz H, Steckler G "Acetaminophen induced pancreatitis." Clin Toxicol 29 (1991): 223-30

43. McJunkin B, Barwick KW, Little WC, Winfield JB "Fatal massive hepatic necrosis following acetaminophen overdose." JAMA 236 (1976): 1874-5

44. Block R, Jankowski JA, Lacoux P, Pennington CR "Does hypothermia protect against the development of hepatitis in paracetamol overdose?" Anaesthesia 47 (1992): 789-91

45. Minton NA, Henry JA, Frankel RJ "Fatal paracetamol poisoning in an epileptic." Hum Toxicol 7 (1988): 33-4

46. Kumar S, Rex DK "Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics." Arch Intern Med 151 (1991): 1189-91

47. Singer AJ, Carracio TR, Mofenson HC "The temporal profile of increased transaminase levels in patients with acetaminophen-induced liver dysfunction." Ann Emerg Med 26 (1995): 49-53

48. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23

49. Keays R, Harrison PM, Wendon JA, et al "Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial." BMJ 303 (1991): 1026-9

50. Hartleb M "Do thyroid hormones promote hepatotoxicity to acetaminophen?" Am J Gastroenterol 89 (1994): 1269-70

51. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73

52. Shoenfeld Y, Shaklai M, Livni E, Pinkhas J "Thrombocytopenia from acetaminophen." N Engl J Med 303 (1980): 47

53. Van Diem L, Grilliat JP "Anaphylactic shock induced by paracetamol." Eur J Clin Pharmacol 38 (1990): 389-90

54. Doan T "Acetaminophen hypersensitivity and other analgesics - response." Ann Allergy 72 (1994): 285

55. Camisa C "Fixed drug eruption due to pseudoephedrine." Cutis 41 (1988): 339-40

56. Leung R, Plomley R, Czarny D "Paracetamol anaphylaxis." Clin Exp Allergy 22 (1992): 831-3

57. Doan T, Greenberger PA "Nearly fatal episodes of hypotension, flushing, and dyspnea in a 47- year-old woman." Ann Allergy 70 (1993): 439-44

58. Kawada A, Hiruma M, Noguchi H, Ishibashi A "Fixed drug eruption induced by acetaminophen in a 12-year-old girl." Int J Dermatol 35 (1996): 148-9

59. Quan MB, Chow WC "Nonpigmenting fixed drug eruption after pseudoephedrine." Int J Dermatol 35 (1996): 367-70

60. Shelley WB, Shelley ED "Nonpigmenting fixed drug eruption as a distinctive reaction pattern: examples caused by sensitivity to pseudoephedrine hydrochloride and tetrahydrozoline." J Am Acad Dermatol 17 (1987): 403-7

61. Kalyoncu AF "Acetaminophen hypersensitivity and other analgesics." Ann Allergy 72 (1994): 285

62. Vidal C, Prieto A, PerezCarral C, Armisen M "Nonpigmenting fixed drug eruption due to pseudoephedrine." Ann Allergy Asthma Immunol 80 (1998): 309-10

63. Stubb S, Reitamo S "Fixed-drug eruption due to dextromethorphan ." Arch Dermatol 126 (1990): 970-1

64. Settipane RA, Stevenson DD "Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma." J Allergy Clin Immunol 84 (1989): 26-33

65. Tomb RR, Lepoittevin JP, Espinassouze F, Heid E, Foussereau J "Systemic contact dermatitis from pseudoephedrine." Contact Dermatitis 24 (1991): 86-8

66. Polles A, Griffith JL "Dextromethorphan-induced mania." Psychosomatics 37 (1996): 71-4

67. Lewith GT, Davidson F "Dystonic reactions to Dimotapp elixir." J R Coll Gen Pract 31 (1981): 241

68. Bostwick JM "Dextromethorphan-induced manic symptoms in a bipolar patient on lithium." Psychosomatics 37 (1996): 571-2

69. Murray S, Brewerton T "Abuse of over-the-counter dextromethorphan by teenagers." South Med J 86 (1993): 1151-3

70. Helfer J, Kim OM "Psychoactive abuse potential of Robitussin-DM." Am J Psychiatry 147 (1990): 672-3

71. Thach BT, Chase TN, Bosma JF "Oral facial dyskinesia associated with prolonged use of antihistaminic decongestants." N Engl J Med 293 (1975): 486-7

72. Hall RC, Beresford TP, Stickney SK, Nasdahl CS, Coleman JH "Psychiatric reactions produced by respiratory drugs." Psychosomatics 26 (1985): 605-8,616-7

73. Gursoy M, Haznedaroglu IC, Celik I, Sayinalp N, Ozcebe OI, Dundar SV "Agranulocytosis, plasmacytosis, and thrombocytosis followed by a leukemoid reaction due to acute acetaminophen toxicity." Ann Pharmacother 30 (1996): 762-5

74. Kleinman JG, Breitenfield RV, Roth DA "Transient cholestatic hepatitis in a neonate associated with carbamazepine exposure during pregnancy and breast-feeding." Clin Nephrol 14 (1980): 201-5

75. Curry RW, Robinson JD, Sughrue MJ "Acute renal failure after acetaminophen ingestion." JAMA 247 (1982): 1012-4

76. Duchene A, Chadenas D, Marneffe-Lebrequier H "Insuffisance renale aigue isolee apres intoxication volontaire par le paracetamol." Presse Med 20 (1991): 1684-5

77. Eguia L, Materson BJ "Acetaminophen-related acute renal failure without fulminant liver failure." Pharmacotherapy 17 (1997): 363-70

78. Segasothy M, Suleiman AB, Puvaneswary M, Rohana A "Paracetamol: a cause for analgesic nephropathy and end-stage renal disease." Nephron 50 (1988): 50-4

79. Perneger TV, Whelton PK, Klag MJ "Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs." N Engl J Med 331 (1994): 1675-79

80. McCredie M, Stewart JH, Day NE "Different roles for phenacetin and paracetamol in cancer of the kidney and renal pelvis." Int J Cancer 53 (1993): 245-9

81. Vanchieri C "Australian study links certain analgesics to renal cancers." J Natl Cancer Inst 85 (1993): 262-3

82. Drenth JP, Frenken LA, Wuis EW, Van der Meer JW "Acute renal failure associated with paracetamol ingestion in an alcoholic patient." Nephron 67 (1994): 483-5

83. Goldberg M "Analgesic nephropathy in 1981: which drug is responsible?" JAMA 247 (1982): 64-5

84. Boyer TD, Rouff SL "Acetaminophen-induced hepatic necrosis and renal failure." JAMA 218 (1971): 440-1

85. Kondo K, Inoue Y, Hamada H, Yokoyama A, Kohno N, Hiwada K "Acetaminophen-induced eosinophilic pneumonia." Chest 104 (1993): 291-2

86. Koulouris Z, Tierney MG, Jones G "Metabolic acidosis and coma following a severe acetaminophen overdose." Ann Pharmacother 33 (1999): 1191-4

Some side effects of acetaminophen / brompheniramine / dextromethorphan / pseudoephedrine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

More about acetaminophen/brompheniramine/dextromethorphan/pseudoephedrine

Related treatment guides

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.