Premium
The risk of Stevens‐Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs
Author(s) -
Frey Noel,
Bodmer Michael,
Bircher Andreas,
Rüegg Stephan,
Jick Susan S.,
Meier Christoph R.,
Spoendlin Julia
Publication year - 2017
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13925
Subject(s) - lamotrigine , toxic epidermal necrolysis , carbamazepine , topiramate , phenytoin , medicine , clonazepam , clobazam , levetiracetam , odds ratio , pregabalin , dermatology , epilepsy , gabapentin , zonisamide , confidence interval , pediatrics , anesthesia , psychiatry , pathology , alternative medicine
Summary Objective Older antiepileptic drugs ( AEDs ) are known to cause Stevens‐Johnson syndrome and toxic epidermal necrolysis ( SJS / TEN ). However, evidence for newer AED is sparse. We quantified risks of SJS / TEN in association with use of all AED s in the United Kingdom. Methods In a matched case‐control study of 480 previously validated SJS / TEN cases (1995–2013) we used conditional logistic regression to calculate odds ratios ( ORs ) with 95% confidence intervals ( CIs ), and calculated absolute risks of SJS / TEN within separate cohorts of new users of 28 AED s. We assessed causality between drugs and SJS / TEN in each exposed case, using an adapted version of the algorithm of drug causality for epidermal necrolysis ( ALDEN ) score. Results We observed a strong association between SJS / TEN and new use of carbamazepine ( OR 92.57, 95% CI 19.89–∞), phenytoin ( OR 49.96, 95% CI 10.13–∞), and lamotrigine ( OR 26.90, 95% CI 4.88–∞), where causality, according to the ALDEN score, was very probable or probable for most exposed cases. Absolute risks for SJS / TEN were highest for phenytoin (45.86 cases/100,000 exposed), lamotrigine (44.17 cases/100,000 exposed), and carbamazepine (20.38 cases/100,000 exposed). Despite increased OR s for valproate (40,941 exposed), gabapentin (116,037 exposed), pregabalin (59,967 exposed), and clobazam (4,300 exposed), ALDEN suggested no causal association. There were no observed cases of SJS / TEN among new users of levetiracetam (n = 96,77), clonazepam (n = 18,075), or topiramate (n = 11,307). Significance The results of our study are consistent with those of previous studies of SJS / TEN , which found increased risks of SJS / TEN in new use of carbamazepine, phenytoin, and lamotrigine. Despite frequent use, no ALDEN ‐score confirmed cases were observed in new users of valproate, gabapentin, pregabalin, levetiracetam, topiramate, or clonazepam.