Acetaminophen / guaifenesin / pseudoephedrine Side Effects
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 may cause 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 side effects of pseudoephedrine have included significant increases in heart rate. Hypertension and arrhythmias have also been problematic in susceptible 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. 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]
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]
Gastrointestinal side effects of acetaminophen have been rare except in alcoholics and after overdose.
Gastrointestinal side effects of guaifenesin have included stomach upset and vomiting with higher than recommended doses. Doses recommended for expectoration have rarely been associated with gastrointestinal 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]
Renal side effects of acetaminophen have been rare and 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]
Acute tubular necrosis with acetaminophen 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]
Hypersensitivity side effects of acetaminophen have included anaphylaxis and fixed drug eruptions.
Hypersensitivity side effects of pseudoephedrine have included fixed drug eruptions.[Ref]
Dermatologic side effects of acetaminophen have included rare reports of 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. Acetaminophen has been associated with a risk of rare but potentially fatal serious skin reactions known as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).
Dermatologic side effects of guaifenesin have included rare reports of rash.[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]
Nervous system side effects of guaifenesin have occasionally included dizziness and headache.
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]
1. 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
2. Covington TR, Lawson LC, Young LL, eds. "Handbook of Nonprescription Drugs. 10th ed." Washington, DC: American Pharmaceutical Association (1993):
3. Gordon RD, Ballantine DM, Bachmann AW "Effects of repeated doses of pseudoephedrine on blood pressure and plasma catecholamines in normal subjects and in patients with phaeochromocytoma." Clin Exp Pharmacol Physiol 19 (1992): 287-90
4. 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
5. 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
6. Brown G "Acetaminophen-induced hypotension." Heart Lung 25 (1996): 137-40
7. Lyon CC, Turney JH "Pseudoephedrine toxicity in renal failure." Br J Clin Pract 50 (1996): 396-7
8. 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
9. Mariani PJ "Pseudoephedrine-induced hypertensive emergency: treatment with labetalol." Am J Emerg Med 4 (1986): 141-2
10. 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
11. Rosen RA "Angina associated with pseudoephedrine ." Ann Emerg Med 10 (1981): 230-1
12. 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
13. 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
14. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
15. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
16. 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
17. Block R "Liver failure induced by paracetamol." BMJ 306 (1993): 457
18. Wong V, Daly M, Boon A, Heatley V "Paracetamol and acute biliary pain with cholestasis." Lancet 342 (1993): 869
19. 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
20. Lee WM "Acute liver failure." Am J Med 96 (1994): 3-9
21. 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
22. Kumar S, Rex DK "Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics." Arch Intern Med 151 (1991): 1189-91
23. 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
24. Cheung L, Meyer KC "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1311-2
25. Hartleb M "Do thyroid hormones promote hepatotoxicity to acetaminophen?" Am J Gastroenterol 89 (1994): 1269-70
26. McJunkin B, Barwick KW, Little WC, Winfield JB "Fatal massive hepatic necrosis following acetaminophen overdose." JAMA 236 (1976): 1874-5
27. Block R, Jankowski JA, Lacoux P, Pennington CR "Does hypothermia protect against the development of hepatitis in paracetamol overdose?" Anaesthesia 47 (1992): 789-91
28. Rumore MM, Blaiklock RG "Influence of age-dependent pharmacokinetics and metabolism on acetaminophen hepatotoxicity." J Pharm Sci 81 (1992): 203-7
29. Minton NA, Henry JA, Frankel RJ "Fatal paracetamol poisoning in an epileptic." Hum Toxicol 7 (1988): 33-4
30. Lee WM "Medical progress: drug-induced hepatotoxicity." N Engl J Med 333 (1995): 1118-27
31. Keaton MR "Acute renal failure in an alcoholic during therapeutic acetaminophen ingestion." South Med J 81 (1988): 1163-6
32. 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
33. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
34. Whitcomb DC "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1311
35. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
36. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
37. 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
38. Smilkstein MJ, Douglas Dr, Daya MR "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1310-1
39. Bray GP "Liver failure induced by paracetamol." BMJ 306 (1993): 157-8
40. Johnson GK, Tolman KG "Chronic liver disease and acetaminophen." Ann Intern Med 87 (1977): 302-4
41. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
42. Cheung L, Potts RG, Meyer KC "Acetaminophen treatment nomogram." N Engl J Med 330 (1994): 1907-8
43. Shriner K, Goetz MB "Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6
44. 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
45. Goldberg M "Analgesic nephropathy in 1981: which drug is responsible?" JAMA 247 (1982): 64-5
46. Vanchieri C "Australian study links certain analgesics to renal cancers." J Natl Cancer Inst 85 (1993): 262-3
47. 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
48. 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
49. Curry RW, Robinson JD, Sughrue MJ "Acute renal failure after acetaminophen ingestion." JAMA 247 (1982): 1012-4
50. Duchene A, Chadenas D, Marneffe-Lebrequier H "Insuffisance renale aigue isolee apres intoxication volontaire par le paracetamol." Presse Med 20 (1991): 1684-5
51. Eguia L, Materson BJ "Acetaminophen-related acute renal failure without fulminant liver failure." Pharmacotherapy 17 (1997): 363-70
52. Segasothy M, Suleiman AB, Puvaneswary M, Rohana A "Paracetamol: a cause for analgesic nephropathy and end-stage renal disease." Nephron 50 (1988): 50-4
53. Boyer TD, Rouff SL "Acetaminophen-induced hepatic necrosis and renal failure." JAMA 218 (1971): 440-1
54. 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
55. Leung R, Plomley R, Czarny D "Paracetamol anaphylaxis." Clin Exp Allergy 22 (1992): 831-3
56. 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
57. Quan MB, Chow WC "Nonpigmenting fixed drug eruption after pseudoephedrine." Int J Dermatol 35 (1996): 367-70
58. Kalyoncu AF "Acetaminophen hypersensitivity and other analgesics." Ann Allergy 72 (1994): 285
59. Halevi A, BenAmitai D, Garty BZ "Toxic epidermal necrolysis associated with acetaminophen ingestion." Ann Pharmacother 34 (2000): 32-4
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. Vidal C, Prieto A, PerezCarral C, Armisen M "Nonpigmenting fixed drug eruption due to pseudoephedrine." Ann Allergy Asthma Immunol 80 (1998): 309-10
62. Settipane RA, Stevenson DD "Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma." J Allergy Clin Immunol 84 (1989): 26-33
63. Doan T "Acetaminophen hypersensitivity and other analgesics - response." Ann Allergy 72 (1994): 285
64. Tomb RR, Lepoittevin JP, Espinassouze F, Heid E, Foussereau J "Systemic contact dermatitis from pseudoephedrine." Contact Dermatitis 24 (1991): 86-8
65. Camisa C "Fixed drug eruption due to pseudoephedrine." Cutis 41 (1988): 339-40
66. Doan T, Greenberger PA "Nearly fatal episodes of hypotension, flushing, and dyspnea in a 47- year-old woman." Ann Allergy 70 (1993): 439-44
67. Van Diem L, Grilliat JP "Anaphylactic shock induced by paracetamol." Eur J Clin Pharmacol 38 (1990): 389-90
68. Shoenfeld Y, Shaklai M, Livni E, Pinkhas J "Thrombocytopenia from acetaminophen." N Engl J Med 303 (1980): 47
69. Thomas RH, Munro DD "Fixed drug eruption due to paracetamol." Br J Dermatol 115 (1986): 357-9
70. Filipe PL, Freitas JP, Decastro JC, Silva R "Drug eruption induced by acetaminophen in infectious mononucleosis." Int J Dermatol 34 (1995): 220-1
71. "Product Information. Robitussin (guaifenesin)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
72. 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
73. "Product Information. Robitussin (guaifenesin)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
74. Kondo K, Inoue Y, Hamada H, Yokoyama A, Kohno N, Hiwada K "Acetaminophen-induced eosinophilic pneumonia." Chest 104 (1993): 291-2
75. Koulouris Z, Tierney MG, Jones G "Metabolic acidosis and coma following a severe acetaminophen overdose." Ann Pharmacother 33 (1999): 1191-4
76. Loizou LA, Hamilton JG, Tsementzis SA "Intracranial haemorrhage in association with pseudoephedrine overdose." J Neurol Neurosurg Psychiatry 45 (1982): 471-2
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Some side effects may not be reported. You may report them to the FDA.