Md Motiur Rahman1, Yasser Alatawi2, Ning Cheng3, Jingjing Qian4, Annya V Plotkina5, Peggy L Peissig6, Richard L Berg7, David Page8, Richard A Hansen9. 1. Auburn University, Harrison School of Pharmacy, Department of Health Outcomes Research and Policy, Auburn, AL, USA. Electronic address: mzr0042@auburn.edu. 2. Auburn University, Harrison School of Pharmacy, Department of Health Outcomes Research and Policy, Auburn, AL, USA. Electronic address: yma0002@tigermail.auburn.edu. 3. Auburn University, Harrison School of Pharmacy, Department of Health Outcomes Research and Policy, Auburn, AL, USA. Electronic address: nzc0026@auburn.edu. 4. Auburn University, Harrison School of Pharmacy, Department of Health Outcomes Research and Policy, Auburn, AL, USA. Electronic address: jzq0004@auburn.edu. 5. Auburn University, Harrison School of Pharmacy, Department of Health Outcomes Research and Policy, Auburn, AL, USA. Electronic address: avp0004@tigermail.auburn.edu. 6. Marshfield Clinic Research Foundation, Biomedical Informatics Research Center, Marshfield, WI, USA. Electronic address: Peissig.Peggy@mcrf.mfldclin.edu. 7. Marshfield Clinic Research Foundation, Biomedical Informatics Research Center, Marshfield, WI, USA. Electronic address: Berg.Richard@mcrf.mfldclin.edu. 8. University of Wisconsin, School of Medicine and Public Health, Department of Biostatistics and Medical Informatics, and Department of Computer Science, Madison, WI, USA. Electronic address: page@biostat.wisc.edu. 9. Auburn University, Harrison School of Pharmacy, Department of Health Outcomes Research and Policy, Auburn, AL, USA. Electronic address: rah0019@auburn.edu.
Abstract
OBJECTIVE: Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. METHODS: Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected P<0.01. RESULTS: A total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P<0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P<0.01. SIGNIFICANCE: Similar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study.
OBJECTIVE: Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. METHODS: Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected P<0.01. RESULTS: A total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P<0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P<0.01. SIGNIFICANCE: Similar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study.
Authors: Jerry J Shih; Julia B Whitlock; Nicole Chimato; Emily Vargas; Steven C Karceski; Ryan D Frank Journal: Epilepsy Behav Date: 2017-02-23 Impact factor: 2.937
Authors: Md Motiur Rahman; Yasser Alatawi; Ning Cheng; Jingjing Qian; Peggy L Peissig; Richard L Berg; David C Page; Richard A Hansen Journal: Clin Drug Investig Date: 2017-12 Impact factor: 2.859