To the Editor:
We present a patient with an unusual reaction to paracetamol (acetaminophen).
1. Case report
The patient was 57 years old and had had asthma since childhood. He had advanced gastric carcinoma and was referred to the palliative care team for worsening epigastric pain. He developed florid urticaria and wheeze one hour after taking co-codamol, which was prescribed by his general practitioner. The patient was admitted to hospital where he was treated for bronchospasm and urticaria (with steroids, antihistamines, and β2-agonists) and pain (with subcutaneous diamorphine and oral paracetamol). His urticaria worsened ten minutes after the diamorphine injection, and it was thought that his anaphylactoid response was due to opioid-induced histamine release from mast cells. Oxycodone was started because it causes less histamine release than morphine.
1.
Two days later, the patient was readmitted, with angio-edema and severe urticaria, which started about one hour after taking oxycodone. He was treated with steroids and antihistamines. Phenazocine was used instead of oxycodone. Its chemical structure is most remote from the thebaines group (containing codeine, diamorphine, and oxycodone).
2.
It is short acting, minimizing the potential problems of any further reaction. He was monitored as an inpatient while the dose was titrated. This was uneventful. The patient was discharged home on phenazocine 10 mg every four hours, and supplied with adrenaline for self-administration.Two weeks later, finding the burden of taking “all these tablets' too great, he decided to stop the phenazocine. When his pain returned, he simply took paracetamol. Within an hour he developed urticaria and angio-edema. He was admitted to a different hospital, and was commenced on regular-release morphine. He was converted to sustained-release morphine, 40 mg every twelve hours.
It was only then that the patient admitted to taking paracetamol intermittently throughout this period, although a detailed drug history had been taken on each occasion. He had not mentioned it earlier because it had not been prescribed. He thought that because it was a common drug, and safe, it was not important.
We assumed that this patient was allergic to paracetamol. We did not feel it appropriate to re-expose him to paracetamol, given the risks of bronchospasm. He avoided paracetamol thereafter and had no further episodes of urticaria. He died eleven months later.
2. Comment
Paracetamol is the most commonly used non-prescription analgesic in the UK, with sales more than ten times that of aspirin and four times that of ibuprofen. More than 300 million tablets (166 tons) were sold over the counter in 2000.
3.
It is considered one of the safest nonopioid analgesics at therapeutic doses.How many people use retail analgesics? 2002; [6 screens]. Available at: http://www.jr2.ox.ac.uk/bandolier/band106/b106-6.html. Accessed September 24, 2003.
4.
However, allergic reactions to paracetamol have been reported, ranging from rashes
5.
to bronchospasm6.
, 7.
and anaphylactic shock.8.
, 9.
Most of these case reports are published in the specialist journals of allergy, immunology, and dermatology.The mechanism of paracetamol allergy is uncertain. There is occasional correlation with nonsteroidal anti-inflammatory drug hypersensitivity,
10.
suggesting that inhibition of cyclo-oxygenase may be responsible. However, some patients are not sensitive to other nonsteroidal anti-inflammatory drugs.11.
Paracetamol-specific IgE is detectable in some sufferers.11.
This indicates that the mechanism is type I hypersensitivity rather than inhibition of prostaglandin synthesis. Re-challenging—using an oral provocation test—is considered to be the most accurate method of confirming the diagnosis.12.
This is not always available. Paracetamol-specific IgE detection and skin-prick testing7.
have also been used, but are less sensitive.The exact prevalence of paracetamol allergy is unknown, due to the imprecise information of the number of users and under-reporting of cases. National drug safety monitoring systems provide some data,
8.
, 13.
but are reliant on practitioners reporting adverse reaction. In the UK, the Committee on Safety of Medicines requests that all suspected adverse reactions be reported for medications showing the black triangle symbol (newly-licensed medicines). For established medicines, all serious suspected adverse reactions should be reported. These include reactions that are “fatal, life-threatening, disabling, incapacitating or which result in or prolong hospitalization.”14.
Such information may identify unexpected side effects or indicate that certain side effects occur more commonly than previously believed. It may also show which patients are most susceptible to adverse reactions.The Yellow Card Scheme: Who can report. [3 screens]. Available at: http://www.mca.gov.uk/aboutagency/regframework/csm/csmhome.htm. Accessed September 24, 2003.
15.
It is estimated that less than 10% of all serious and 2–4% of non-serious adverse reactions are reported.Monitoring the safety and quality of medicines: Pharmacovigilance. [3 screens]. Available at http://www.mca.gov.uk/ourwork/monitorsafequalmed/pharmacovigilance/pharmacovigilance.htm. Accessed September 23, 2003.
16.
This case study emphasises the importance of taking a thorough drug history, including over-the-counter medications. Even the safest of medications can be harmful for some patients and there is value in reporting serious adverse reactions to determine the incidence of these rare but important events.
References
- Comparison of histamine release in human skin mast cells induced by morphine, fentanyl and oxymorphone.Anesthesiology. 1985; 62: 124-129
- Analgesic selection when the patient is allergic to codeine.Clin Pharm. 1991; 10: 658
How many people use retail analgesics? 2002; [6 screens]. Available at: http://www.jr2.ox.ac.uk/bandolier/band106/b106-6.html. Accessed September 24, 2003.
- Comparative safety evaluation of non-narcotic analgesics.J Clin Epidemiol. 1998; 51: 1357-1365
- Urticaria from paracetamol.Clin Exp Dermatol. 1985; 10: 404
- Occurrence of allergic conditions in asthmatics with analgesic intolerance.Allergy. 1999; 54: 428-435
- Anaphylaxis to paracetamol.Allergol Immunopathol (Madr). 1998; 26 (Erratum in: Allergol Immunopathol (Madr) 1998;26(5):2832): 199-200
- Acute hypersensitivity reactions to paracetamol.Br Med J (Clin Res Ed). 1985; 291: 938-939
- Anaphylactic shock induced by paracetamol.Eur J Clin Pharmacol. 1990; 38: 389-390
- Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects.J Allergy Clin Immunol. 1995; 96: 480-485
- Paracetamol (acetaminophen) hypersensitivity.Ann Allergy Asthma Immunol. 2000; 85: 508-511
- The accuracy of the diagnosis of suspected paracetamol (acetaminophen) hypersensitivity: results of a single-blinded trial.Clin Exp Allergy. 2002; 32: 1366-1369
- Aspirin or acetaminophen? A comparison from data collected by the Spanish Drug Monitoring System.J Clin Epidemiol. 1996; 49: 255-261
The Yellow Card Scheme: Who can report. [3 screens]. Available at: http://www.mca.gov.uk/aboutagency/regframework/csm/csmhome.htm. Accessed September 24, 2003.
Monitoring the safety and quality of medicines: Pharmacovigilance. [3 screens]. Available at http://www.mca.gov.uk/ourwork/monitorsafequalmed/pharmacovigilance/pharmacovigilance.htm. Accessed September 23, 2003.
- Pharmacovigilance: paradise lost, regained or postponed? The William Withering Lecture 1994.JR Coll Physicians Lond. 1995; 29 (Erratum in: JR Coll Physicians Lond 1995;29(2):118): 41-49
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© 2004 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc.
