Quebec, Canada—Can generic versions of common cardiovascular drugs increase adverse events?

That was the question examined in a recent study in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal. Canadian researchers determined that hospital visits for adverse events jumped up a month after generic versions of three popular angiotensin II receptor blockers (ARBs) became available in Canada.

That conclusion was reached by comparing hospital and emergency department visits among 136,177 patients aged 66 years and older who took one of three medications used for hypertension and heart failure, before and after their generic versions became available—losartan, marketed as Cozaar; valsartan, marketed as Diovan; and candesartan, marketed as Atacand.

Results indicate that, before generic versions were available, the average proportion of adverse events was 10%, but in the month when generics were commercialized, the amplified rates of adverse events ranged from 8% to 14% for patients using generics. The increase was determined to be 8% for losartan, 11.7% for valsartan, and 14% for candesartan, with the rates for losartan remaining elevated throughout the study year.

The study calculated rates of adverse events monthly for the generics—24 months before and 12 months after commercialization of generics.

“Because most users of a brand-name drug are switched to generic versions within 2 or 3 years after it becomes available, the observed increase in adverse events could reflect an acute response to equivalent, but not identical, generic drugs for newly switched patients,” explained coauthor Paul Poirier MD, PhD, Professor of Pharmacy at Laval University in Quebec City.

Poirier pointed out that generic substitutes used by the patients could be “pharmacokinetically 6 to 21% different from the brand-name version that was used. The results must be interpreted cautiously because studies like this assessing adverse events over a fixed time period, combined with differences between patients, make drawing firm conclusions difficult. Also, because the findings were based on medical claims data, there may be inaccuracies.”

The difference in adverse effects declined after the first month, the study authors note, although some variation continued for the length of the study. 

“Although generic drugs are generally considered to be equivalent, patients and their physicians should be aware that they may not have exactly the same effect as their brand-name counterparts, especially during the first month as patients transition to the new medicine,” Poirier said.

Still, economic realities push for the use of generics, the study states.

“As expected, a rapid shift in market shares in favor of generic drugs was observed,” the study authors recount. “The last brand-name ARBs to lose its patent, in our study, was losartan in 2012. It reached 50% of market shares in 2 months, while it took 1 year for generics valsartan and candesartan. This could hypothetically be explained by better confidence of pharmacists to switch patients to a generic formulation because they did not notice major individual problems during previous experiences (valsartan and candesartan). Prescribers were maybe more confident too, for the same reasons, and stopped using the “Do not substitute” writing on prescription labels.”
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