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From the Comprehensive Epilepsy Center, Department of Neurology (H.A., D.W., S.K., C.S.-H., C.W.B., S.R.R., L.J.H.), and Department of Biostatistics, Mailman School of Public Health (R.B.), Columbia University, New York, NY.
Address correspondence and reprint requests to Dr. Lawrence J. Hirsch, Comprehensive Epilepsy Center, Columbia University, Neurological Institute, Box NI-135, 710 W. 168th St., New York, NY 10032 ljh3{at}columbia.edu
Objective: To determine predictors and relative incidence of antiepileptic drug (AED)–related rash in patients taking all common AEDs.
Methods: We reviewed 1,890 outpatients. Eighty-one variables were tested as potential predictors of rash. We compared the rate of rash attributed to each AED (AED rash) with the average rate of rash attributed to the other AEDs in all adults (aged 
16 years; n = 1,649) when taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproate (VPA), or zonisamide (ZNS). We repeated this analysis for patients with and without the identified nondrug predictors of AED rash.
Results: The average rate of AED rash was 2.8%. The only nondrug predictor significant in multivariate analysis was occurrence of another AED rash (odds ratio 3.1, 95% CI 1.8 to 5.1; p < 0.0001); the rate of rash in this subgroup was 8.8%, vs 1.7% in those without another AED rash. Higher AED rash rates were seen with PHT (5.9% overall, p = 0.0008; 25.0% in those with another AED rash, p = 0.001), LTG (4.8%, p = 0.00095; 14.4%, p = 0.025), and CBZ (3.7%, not significant; 16.5%, p = 0.01). Lower rates were seen with LEV (0.6% overall; p = 0.00042), GBP (0.3%, p = 0.00035), and VPA (0.7%, p = 0.01). Rash rates were also low (<1% overall) with FBM, PRM, TPM, and VGB (not significant). These AED differences remained similar in patients with and without other AED rashes. There were four cases of Stevens–Johnson syndrome involving four AEDs.
Conclusions: The rate of an antiepileptic drug (AED) rash is approximately five times greater in patients with another AED rash (8.8%) vs those without (1.7%). Rash rates were highest with phenytoin, lamotrigine, and carbamazepine and low (<1%) with several AEDs.
Supplemental data at www.neurology.org
Dr. Hirsch has received honoraria for speaking from GlaxoSmithKline, Eisai, Abbott, and UCB Pharma and research support from GlaxoSmithKline, UCB Pharma, and Abbott. Dr. Hirsch is on the speakers' bureau for GlaxoSmithKline, Eisai, and UCB Pharma. Dr. Resor has received honoraria for speaking from GlaxoSmithKline and consultation fees from Elan, Ortho-McNeil, and Shire Pharmaceuticals. Dr. Bazil has received research support from UCB Pharma and Pfizer and honoraria for consulting and/or lecturing from UCB Pharma, Pfizer, GlaxoSmithKline, and Eisai.
The Columbia AED Database has been funded by Abbott, Elan, GlaxoSmithKline, Novartis, Ortho-McNeil, Pfizer, and UCB Pharma.
Received May 25, 2006. Accepted in final form January 10, 2007.
This article has been cited by other articles:
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  A Rash Decision with Antiepileptic Drugs Journal Watch Psychiatry, July 2, 2007; 2007(702): 2 - 2. [Full Text]
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