Keiko Hosohata1, Ayaka Inada2, Saki Oyama2, Iku Niinomi2, Tomohito Wakabayashi2, Kazunori Iwanaga2. 1. Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan. hosohata@gly.oups.ac.jp. 2. Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
Abstract
BACKGROUND AND OBJECTIVE: Adverse cutaneous drug reactions associated with antiepileptic drugs (AEDs) are a serious problem in the clinical setting. New-generation AEDs have been reported to be better tolerated than old-generation forms; however, information about the risks of adverse cutaneous drug reactions to new-generation AEDs is limited. OBJECTIVE: The purpose of this study was to clarify the association of AEDs with adverse cutaneous drug reactions using a spontaneous reporting database. METHODS: We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and January 2017 were analyzed. Based on reports of all adverse events, we obtained 4805 reports of adverse cutaneous drug reactions associated with AEDs, and calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for drug rash, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). RESULTS: Individual AEDs had variable signals for drug rash, SJS, and TEN. The strongest signals were detected for drug rash caused by lamotrigine (ROR 9.18, 95% CI 8.65-9.74), SJS caused by zonisamide (ROR 9.85, 95% CI 8.23-11.78), and TEN caused by phenobarbital (ROR 14.08, 95% CI 11.28-17.57). CONCLUSION: There are clear differences in the risk of cutaneous reactions among AEDs, and further studies are needed to confirm these findings.
BACKGROUND AND OBJECTIVE: Adverse cutaneous drug reactions associated with antiepileptic drugs (AEDs) are a serious problem in the clinical setting. New-generation AEDs have been reported to be better tolerated than old-generation forms; however, information about the risks of adverse cutaneous drug reactions to new-generation AEDs is limited. OBJECTIVE: The purpose of this study was to clarify the association of AEDs with adverse cutaneous drug reactions using a spontaneous reporting database. METHODS: We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and January 2017 were analyzed. Based on reports of all adverse events, we obtained 4805 reports of adverse cutaneous drug reactions associated with AEDs, and calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for drug rash, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). RESULTS: Individual AEDs had variable signals for drug rash, SJS, and TEN. The strongest signals were detected for drug rash caused by lamotrigine (ROR 9.18, 95% CI 8.65-9.74), SJS caused by zonisamide (ROR 9.85, 95% CI 8.23-11.78), and TEN caused by phenobarbital (ROR 14.08, 95% CI 11.28-17.57). CONCLUSION: There are clear differences in the risk of cutaneous reactions among AEDs, and further studies are needed to confirm these findings.
Authors: Dean J Naisbitt; John Farrell; Gavin Wong; Jan P H Depta; Charlotte C Dodd; Josephine E Hopkins; Claire A Gibney; David W Chadwick; Werner J Pichler; Munir Pirmohamed; B Kevin Park Journal: J Allergy Clin Immunol Date: 2003-06 Impact factor: 10.793
Authors: Anthony G Marson; Asya M Al-Kharusi; Muna Alwaidh; Richard Appleton; Gus A Baker; David W Chadwick; Celia Cramp; Oliver C Cockerell; Paul N Cooper; Julie Doughty; Barbara Eaton; Carrol Gamble; Peter J Goulding; Stephen J L Howell; Adrian Hughes; Margaret Jackson; Ann Jacoby; Mark Kellett; Geoffrey R Lawson; John Paul Leach; Paola Nicolaides; Richard Roberts; Phil Shackley; Jing Shen; David F Smith; Philip E M Smith; Catrin Tudur Smith; Alessandra Vanoli; Paula R Williamson Journal: Lancet Date: 2007-03-24 Impact factor: 79.321