Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a setting of chemotherapy treatment: An assessment of FDA MedWatch database.

Abstract

e19519 Background: The association of chemotherapy with potentially fatal adverse events such as SJS/TEN has not been systematically examined. Case reports in association with agents such as imatinib and docetaxel have been published in the literature. We applied data mining algorithms to assess the risk of SJS/TEN to chemotherapy. Methods: FDA Safety Information and Adverse Event Reporting Program MedWatch database was searched for cases of SJS and TEN reported in association with FDA-approved chemotherapy agents through December 2009. Proportional reporting ratios (PRR>2) and empirical Bayes geometric mean (EBGM>2) with a case count threshold ≥3 were considered signals of disproportionate reporting. Cases obtained by searching this database included those in which chemotherapeutic agents were used to treat cancer and non-cancer-related diseases. Results: Using our criteria for selection of cases, we have identified 252 TEN cases associated with 11 FDA-approved drugs. Similarly, 71 SJS cases in association with 4 FDA-approved chemotherapy agents were identified (Table). Conclusions: By identifying disproportionally reported agents we demonstrated that multiple chemotherapy agents may be associated with SJS/TEN. Although data mining may not be sufficient to establish causality, this method may serve as a supplemental tool to identify chemotherapy drugs that may warrant further investigation. Drugs Cases Signal n PRR 95% CI EBGM 95% CI SJS Bendamustine 8 6.67 3.34-13.28 5.54 2.33-10.85 Chlorambucil 10 2.66 1.43-4.93 2.21 1.16-3.92 Ibritumomab tiuxetan 17 4.64 2.48-7.65 3.52 1.88-6.03 Temozolomide 36 2.16 1.56-2.99 2.07 1.47-2.82 Total 71 TEN Bendamustine 5 9.53 3.97-23.32 7.21 2.39-16.38 Busulfan 17 3.85 2.39-6.18 3.29 2.00-5.245 Cytarabine 55 2.67 2.05-3.48 2.56 1.94-3.30 Chlorambucil 12 6.19 3.52-10.88 5.67 3.04-9.69 Dactinomycin 8 3.81 1.90-7.60 2.82 1.36-5.57 Fludarabine 40 3.62 2.65-4.93 3.37 2.44-4.56 Ibritumomab tiuxetan 4 2.96 1.11-7.86 1.93 0.69-4.52 Lomustine 14 17.17 10.23-28.79 14.81 7.49-24.27 Procarbazine 24 5.51 3.69-8.2 5.18 3.3-7.62 Thiotepa 8 4.84 2.42-9.66 3.38 1.59-6.81 Vincristine 65 2.12 1.65-2.7 2.06 1.6-2.6 Total 252