Incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis among new users of different individual drugs in a European population: a case-population study

Eur J Clin Pharmacol. 2019 Feb;75(2):237-246. doi: 10.1007/s00228-018-2569-3. Epub 2018 Oct 8.

Abstract

Purpose: To estimate the specific incidences of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) among new users of drugs frequently reported to be associated with this serious event.

Methods: We performed a case-population approach, which combined data from a registry of SJS/TEN cases from the Madrid region (numerator) during the study period 2005-2015 and a primary healthcare database from the same catchment population. The proportion of new users of drugs estimated in the primary healthcare database was stratified by calendar year, sex and age (5-year bands), and then applied to the same strata of Madrid's population census to compute the number of new users (denominator). Incidences were re-estimated using only cases in which the concerned drug had a probable or very probable causal relationship.

Results: A total of 44 SJS/TEN cases aged > 14 years were registered during the study period. The highest SJS/TEN incidence was found for phenytoin with 68.9 per 100,000 new users (95% CI 27.7-141.9), followed by dexamethasone (5.48; 1.49-14.03), allopurinol (3.29; 1.07-7.67) and cotrimoxazole (3.19; 0.87-8.16). Considering only probable and very probable cases, the incidences hardly changed, except for dexamethasone, which was left without cases. Pantoprazole, levofloxacin and lorazepam showed incidences between 1 per 100,000 and 1 per 1,000,000 new users. Ibuprofen, amoxicillin-clavulanic acid, metamizole, amoxicillin, paracetamol and omeprazole showed incidences around 1 per one million new users.

Conclusions: Phenytoin was the drug with the highest incidence of SJS/TEN, followed by allopurinol and cotrimoxazole. For the rest of the drugs, the estimated incidences were below 1 in 100,000 new users.

Keywords: Case-population study; Hypersensitivity; SCAR; Stevens-Johnson syndrome; Toxic epidermal necrolysis.

MeSH terms

  • Adolescent
  • Adult
  • Databases, Factual
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Europe
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Pharmaceutical Preparations / administration & dosage*
  • Registries
  • Stevens-Johnson Syndrome / etiology*
  • Young Adult

Substances

  • Pharmaceutical Preparations