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

  • Pharmacoepidemiology and Prescription
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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Acknowledgements

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.

Funding

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.

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Authors and Affiliations

  1. Clinical Pharmacology Unit, Príncipe de Asturias University Hospital, Alcalá de Henares, Madrid, Spain

    Sara Rodríguez-Martín, Victoria Lerma, Antonio Rodríguez-Miguel & Francisco J. de Abajo

  2. Department of Biomedical Sciences, University of Alcalá, Ctra. Alcalá-Meco s/n, 28805, Alcalá de Henares, Madrid, Spain

    Sara Rodríguez-Martín, Antonio Rodríguez-Miguel & Francisco J. de Abajo

  3. Pharmacoepidemiology Research Group, Institute for Health Research IRYCIS, Madrid, Spain

    Sara Rodríguez-Martín, Victoria Lerma, Antonio Rodríguez-Miguel & Francisco J. de Abajo

  4. Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Agency of Medicines and Medical Devices, Madrid, Spain

    Elisa Martín-Merino

  5. Dermatology Department, University Hospital of Getafe, Getafe, Madrid, Spain

    Olga González & Carlos González-Herrada

  6. Clinical Pharmacology Department, La Paz University Hospital, Madrid, Spain

    Elena Ramírez

  7. Drug Hypersensitivity Laboratory, Institute for Health Research IdiPAZ, La Paz University Hospital, Madrid, Spain

    Teresa Bellón

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  1. Sara Rodríguez-Martín
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  2. Elisa Martín-Merino
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  6. Carlos González-Herrada
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  8. Teresa Bellón
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  9. Francisco J. de Abajo
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Corresponding author

Correspondence to Francisco J. de Abajo.

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Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

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

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  • DOI: https://doi.org/10.1007/s00228-018-2569-3

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