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

• Published in: European journal of clinical pharmacology 2019-02, Vol.75 (2), p.237-246
• Main Authors: Rodríguez-Martín, Sara, Martín-Merino, Elisa, Lerma, Victoria, Rodríguez-Miguel, Antonio, González, Olga, González-Herrada, Carlos, Ramírez, Elena, Bellón, Teresa, de Abajo, Francisco J.
• Format: Article
• Language: English
• Subjects: Allopurinol; Amoxicillin; Biomedical and Life Sciences; Biomedicine; Clavulanic acid; Cotrimoxazole; Dexamethasone; Drugs; Ibuprofen; Incidence; Levofloxacin; Lorazepam; Omeprazole; Paracetamol; Pharmacoepidemiology and Prescription; Pharmacology/Toxicology; Phenytoin; Population; Population studies; Skin diseases; Stevens-Johnson syndrome; Toxic epidermal necrolysis
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-018-2569-3

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.