Impact of the Commercialization of Three Generic Angiotensin II Receptor Blockers on Adverse Events in Quebec, Canada

Jacinthe Leclerc, Claudia Blais, Louis Rochette, Denis Hamel, Line Guénette, Paul Poirier
2017 Circulation. Cardiovascular Quality and Outcomes  
G eneric drugs are alternatives to brand-name drugs once the patent expires. Known as being generally less expensive, they are economically beneficial for patients, healthcare systems, and third-party payers. 1-4 To achieve substantial healthcare cost reductions, the provincial government of Quebec, Canada, promotes generic substitutions and restricts access to brand-name drugs by economical and administrative strategies. 5 Once generic analogs become available, market is then shared between
more » ... nd-name and generics, but little is published about the rate of this market sharing, neither regarding the clinical impact of generics commercialization. Generic and brand-name drugs are assumed to be clinically equivalent and are used interchangeably once approved Background-Once the patent of a brand-name drug expires, generic drugs are commercialized, and substitution from brand-name to generics may occur. Generic drug equivalence is evaluated through comparative bioavailability studies. Few studies have assessed outcomes after generic drug commercialization at a population level. We evaluated the impact of 3 generic angiotensin II receptor blockers commercialization on adverse events: hospitalizations or emergency room consultations. Methods and Results-This is an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System. Rates of adverse events for losartan, valsartan, and candesartan users (N=136 177) aged ≥66 years were calculated monthly, 24 months before and 12 months after generics commercialization. Periods before and after generics commercialization were compared by negative binomial segmented regression models. Sensitivity analyses were also conducted. For all users, there was a monthly mean rate of 100 adverse events for 1000 angiotensin II receptor blocker users before and after generic commercialization. Among generic users of losartan, valsartan, and candesartan, there was an increase in rates of adverse events of 8.0% ( difference of proportions versus brand-name, 7.5% [95% confidence interval, −0.9% to 15.9%]; P=0.0643), 11.7% (difference of proportions, 17.1% [95% confidence interval, 9.9%-24.3%]; P<0.0001), and 14.0% (difference of proportions, 16.6% [95% confidence interval, 7.9%-25.3%]; P<0.0001), respectively, the month of generic commercialization. The monthly trend of adverse events was affected for generic versus brand-name losartan users only (difference of proportions, 2.0% [0.7%-3.4%]; P=0.0033) ≤1 year after generics commercialization. Similar results were found in sensitivity analyses. Conclusions-Among generic users, immediate or delayed differences in adverse events rates were observed right after generic commercialization for 3 antihypertensive drugs. Rates of adverse events remained higher for generic users. Increases were more pronounced for generic candesartan, which is the studied product with the largest difference in comparative bioavailability. Risk and survival analysis studies controlling for several potential confounding factors are required to better characterize generic substitution. (Circ Cardiovasc Qual Outcomes. 2017;10:e003891.
doi:10.1161/circoutcomes.117.003891 pmid:28974512 fatcat:hj72brtsdfhzplgyrj45wq6yaq