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.
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.
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.
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.
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We are grateful to all members of the PIELenRed Consortium and patients who take part in this study. The authors would like to acknowledge the excellent collaboration of primary care practitioners taking part in BIFAP and the BIFAP staff for their collaboration and provision of resources to access the database. All views expressed in this article are those of the authors and do not necessarily represent the views of their institutions.
The present study was supported by a research grant from the Instituto de Salud Carlos III - Ministerio de Economía y Competitividad (no. PI12/02267), co-founded by FEDER. The Spanish Agency of Medicinal Products and Medical Devices supports the management of the PIELenRed registry and is the owner of the database BIFAP.
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all prospective individual participants or legal representatives. For retrospective cases, the Ethics Research Committee granted us an exemption. BIFAP is a fully anonymised database, and according to the Spanish law, an informed consent is not required when no personal data is collected.
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Rodríguez-Martín, S., Martín-Merino, E., Lerma, V. et al. 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 75, 237–246 (2019). https://doi.org/10.1007/s00228-018-2569-3
- Toxic epidermal necrolysis
- Stevens-Johnson syndrome
- Case-population study