What's new? Isomers, metabolites and prodrugs, oh my!

Abstract

The terms racemic mixtures, single isomers, prodrugs, active metabolites, extended-release mechanisms were once remembered as the topics of early pharmacy school curriculum. Now they are often the source of confusion for practitioners and, sometimes, big money for manufacturers. Since 2011, nearly ten percent of the top 100 medications by sales were “new and improved” versions of previously released products with 4-5% being revised psychotropics. Since these “new” products are released as brand name agents under patent protection, they are often priced much higher than their predecessors. Clinical evidence is limited to approval trials – a handful of placebo-controlled and/or active-controlled efficacy studies. Rarely, if ever, are the new agents compared head-to-head with predecessor products. Clinicians are faced with marketing claims that, while true statements (e.g., “The starting dose is the proven effective dose”), may not have data to support clinical impact (i.e., differences in response or remission rates). In a time of financial strain for the healthcare system as a whole, the high cost of these new agents can be a hard pill to swallow. Evaluation of clinical utility must include efficacy, safety and cost as with any new medication. As head-to-head trials are extremely rare with these “new” medications, evidence-based comparisons may be limited to pharmacokinetic and pharmacodynamic properties of products. It is also important to use clinical common sense to compare new agents to their predecessors.