107 Evaluation of the efficacy, safety and utilization of racemic mixtures versus single enantiomers in British Columbia primary care: a comprehensive review

Objectives The primary objective of this focused literature review was to determine whether clinically significant differences exist in the efficacy and safety of commonly prescribed racemic mixtures compared to their corresponding single enantiomers in British Columbia (BC). We aimed to assess whether the theoretical pharmacological advantages of single enantiomers translate into meaningful clinical benefits in practice. As a secondary objective, we analyzed drug utilization patterns and associated expenditures within primary care settings in BC, with a focus on evaluating the cost differences between single enantiomers and their racemic counterparts. Furthermore, we critically evaluated the credibility of manufacturers’ claims regarding the clinical superiority of single enantiomers. By addressing these objectives, we aimed to provide a comprehensive evaluation of the clinical outcomes associated with racemic mixtures and single enantiomers, ensuring that any additional financial burden placed on patients is justified by meaningful clinical benefit. Method The top 200 most prescribed drugs in BC, from January 1 to May 31, 2024, based on patient count and prescription volume, were reviewed to identify currently marketed racemic mixture and single enantiomer drug pairs. To be eligible, at least one drug had to appear among the top 200 list. A systematic literature search was conducted using MEDLINE, Embase, PubMed, Epistemonikos, and Cochrane CENTRAL from their inception dates to June 2024. We included head-to-head randomized trials comparing the efficacy and safety of equipotent doses of racemic mixtures versus single enantiomers. Studies conducted solely in healthy participants were excluded. Two authors independently screened all search results for eligibility and conducted a critical appraisal of included studies using the Cochrane RoB2 tool. The Fragility Index was calculated for reported dichotomous outcomes. Additionally, we reviewed US FDA and Health Canada drug assessments, BC Ministry of Health expenditure data, and Canadian product monographs. Results After reviewing the top 200 most prescribed drugs in BC, we identified five racemic mixture and single enantiomer pairs: omeprazole/esomeprazole, citalopram/escitalopram, lansoprazole/dexlansoprazole, zopiclone/eszopiclone, and mixed amphetamine salts/dextroamphetamine. 26 studies comparing these pairs at equipotent doses were iden]fied. All studies were assessed to have a high risk of bias. 24 studies reported on efficacy; only seven reported statistically significant differences favouring the enantiomer, though fragility index calculations revealed five were statistically fragile. 24 studies assessed safety; 23 found no difference in adverse events risk, and one favoured the racemic mixture. Manufacturers’ claims regarding enantiomers’ superiority were not supported by robust evidence. Additionally, our assessment of drug expenditures in BC demonstrated that residents incurred substan]ally higher costs for single enantiomer drugs. For instance, in 2024 private payers spent more than $16 million and $14 million on esomeprazole and escitalopram, respectively, compared to their less expensive racemic counterparts. Conclusions Claims regarding the superiority of single enantiomers are primarily based on pharmacodynamic and pharmacokinetic studies, as well as studies comparing drug pairs at non-equivalent doses. Our study indicated that the proposed pharmacological advantages of single enan]omers do not translate into superior clinical efficacy or improved safety profiles. Although our financial assessment exclusively compared drug expenditures in the province of British Columbia, single enantiomer are often considered clinically superior to their racemic mixtures worldwide. It should be noted that the findings of this study could lead to significant cost savings for governments, private payers, and individuals, and could support the development of optimized prescribing plaeorms for primary care providers to promote cost-effective prescribing.

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