Hypersensitivity Reactions in Serious Adverse Events Reported for Paracetamol in the EudraVigilance Database, 2007–2018

Abstract

Paracetamol is a popular and easily available drug which is used world-wide as analgesic, antipyretic agent. Hypersensitivity reactions to this drug involve a wide range of symptoms of various importance for patient management. The EudraVigilance (EV) database serves as a system for monitoring adverse events (AE) due to drug intake. We retrospectively recorded AE reports for “paracetamol” reported from 1 January 2007 to 1 October 2018 which fulfilled the category of “serious” in EV. For further analysis the retrieved AE reports were selected according to the keywords corresponding to hypersensitivity symptoms. We included in the study 4589 AE reports with 9489 particular AEs. 24.2% of all the AE reports concerned children. The most often reported symptoms were “angioedema,” “rash” and “urticaria” (each of them with a frequency of >10% in the AE reports). An important group of AEs were oedema reported as being located in the head, neck or respiratory tract. We recorded 58 AE reports with fatal outcomes, including 9 Stevens-Johnson syndrome/toxic epidermal necrolysis cases (SJS/TEN), 10 anaphylactic reactions, 21 cases of hepatic failure and a further 18 cases which occurred for other reasons. SJS/TEN, acute generalized exanthematous pustulosis and drug reaction with eosinophilia and systemic symptoms were reported 129, 42 and 25 times, respectively. Prodromes and symptoms of potentially life-threating SJS/TEN appeared in 286 of the AE reports. 380 AE reports pointed to a diagnosis of anaphylaxis. To improve patient safety, healthcare professionals, including pharmacists, can identify warning signs of severe hypersensitivity reactions to paracetamol.

What Do Young Adults Think about the Safety of Over-the-Counter Analgesics? Findings from a Cross-Sectional Survey

“…In Australia, paracetamol is the medication most frequently used in overdoses, and was associated with a 108% increase in paracetamol-related acute liver toxicity between 2007 and 2017 [ 12 ]. Additionally, paracetamol has also been associated with a number of serious hypersensitivity reactions, such as angioedema, Steven–Johnsons syndrome, toxic epidermal necrolysis and anaphylaxis [ 13 ]. Internationally, strategies implemented to minimise paracetamol-related harm include restricted pack size and location of sale, resulting in reduced paracetamol-related calls to poisons centres [ 14 ].…”

Drug-Induced Anaphylaxis: National Database Analysis

“…Our results revealed acetaminophen to be the leader among COX inhibitors in total SRsAs and pediatric SRsAs, but no fatal cases involving acetaminophen were detected. An analysis of the EudraVigilance Database (2007–2018 years) found that acetaminophen-induced anaphylaxis was most common in the age group 18–64 years, and among acetaminophen-induced Ars, anaphylaxis was the second most common cause of death after hepatic failure with shock [ 45 ]. A systematic review of 85 studies reporting hypersensitivity reactions to acetaminophen revealed that acetaminophen hypersensitivity reaction prevalence among children was 10.1% (95% confidence interval 4.5–15.5) [ 46 ].…”

Toxic epidermal necrolysis complicated with respiratory failure in children: A case report

“…Intravenous immunoglobulin (IVIG) therapy has demonstrated notable benefits in the treatment of SJS/TEN by impeding keratinocyte apoptosis [ 11 ]. The combination of glucocorticoids with IVIG therapy has shown the potential to lower mortality rates.…”