The Impact of US FDA and Health Canada Warnings Related to the Safety of High-dose Simvastatin

Abstract

Introduction: Between 2010 and 2012, the US Food and Drug Administration and Health Canada issued warnings to healthcare professionals emphasizing the increased risk of muscle problems with high-dose simvastatin. Objective: To measure the impact of the Health Canada safety warning regarding dose-dependent adverse effects of simvastatin on prescribing of low, medium, and high doses of simvastatin. Methods: An interrupted time-series design was used to evaluate the impact of a Health Canada safety warning on 7 November 2012 regarding the safety of high-dose simvastatin. Monthly prescription records were analyzed for beneficiaries of the Nova Scotia Seniors’ Pharmacare Program aged 65 years or older who had received > 1 prescription of simvastatin between 1 January 1997 and 31 March 2015. Autoregressive Integrated Moving Average models were used to test changes in the proportion of beneficiaries dispensed a low dose (< 40 mg), medium dose (40 mg to < 80 mg), or high dose (≥ 80 mg) of simvastatin over time. Results: There were 219 monthly periods, of which 29 periods occurred after the Health Canada warning. On average during the pre-warning periods there were 2944 simvastatin users per month, of whom 71% were dispensed a low dose, 26% a medium dose, and 2% a high dose. The proportion of beneficiaries dispensed low-dose simvastatin increased by 0.9% (one-sided p value 0.035; 90% CI 0.07–1.65), the proportion dispensed medium-dose simvastatin decreased by 0.7% (one-sided p value 0.0496; 90% CI −1.48 to −0), and there was no significant change in the proportion dispensed high-dose simvastatin (−0.15% change, one-sided p value 0.205; 90% CI −0.45 to 0.15). Conclusions: The Health Canada Health Care Professional warning had a small effect on increasing the proportion of beneficiaries dispensed low and medium doses of simvastatin but not high doses of simvastatin. Nevertheless, there remain seniors in Nova Scotia receiving high-dose simvastatin for whom the benefit/risk potential may need to be re-evaluated.