RESUMO
OBJECTIVES: A "chiral switch" occurs in the pharmaceutical market when a drug made up of 2 enantiomer forms is replaced with a purified single-enantiomer version, often in the context of a patent expiration. We studied the prevalence of chiral switching in the United States over the past decade, including trends in use of, and expenditures on, these products in Medicaid. STUDY DESIGN: Retrospective analysis. METHODS: We used US Adopted Names prefixes (lev/levo/ar/es/dex/dextro) to identify all single-enantiomer drugs approved from 2001 to 2011. From publicly available US Food and Drug Administration (FDA) approval documents, we extracted the characteristics of the pivotal premarket trials for the single enantiomers. Specifically, we evaluated whether the single enantiomer was directly compared with the precursor racemic drug and whether there was evidence of superior efficacy. We used quarterly drug expenditure data from each state Medicaid program to chart trends in use of, and spending on, the single-enantiomer products and their racemic precursors during the study period. RESULTS: From 2001 to 2011, the FDA approved 9 single-enantiomer products: dexlansoprazole, levoleucovorin, levocetirizine, armodafinil, arformoterol, eszopiclone, escitalopram, dexmethylphenidate, and esomeprazole. Of those 9 drugs, 3 had at least 1 pre-approval randomized trial that included the racemic precursor as a direct comparator, but there was no evidence of superiority of the single enantiomer over the racemic at comparable doses. Between 2001 and 2011, US Medicaid programs spent approximately $6.3 billion on these 9 single-enantiomer drugs. CONCLUSIONS: Recently approved single-enantiomer drugs showed no evidence of superior efficacy over the older racemic precursors in the pivotal trials leading to their approval, and in a majority of cases, they were not directly compared.
Assuntos
Aprovação de Drogas , Prescrições de Medicamentos/estatística & dados numéricos , Medicaid/economia , Antídotos/química , Antídotos/economia , Compostos Azabicíclicos/química , Compostos Azabicíclicos/economia , Compostos Benzidrílicos/química , Compostos Benzidrílicos/economia , Broncodilatadores/química , Broncodilatadores/economia , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/economia , Cetirizina/química , Cetirizina/economia , Dexlansoprazol/química , Dexlansoprazol/economia , Cloridrato de Dexmetilfenidato/química , Cloridrato de Dexmetilfenidato/economia , Medicamentos Genéricos/economia , Esomeprazol/química , Esomeprazol/economia , Zopiclona , Etanolaminas/química , Etanolaminas/economia , Fumarato de Formoterol , Antagonistas não Sedativos dos Receptores H1 da Histamina/química , Antagonistas não Sedativos dos Receptores H1 da Histamina/economia , Humanos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/economia , Levoleucovorina/química , Levoleucovorina/economia , Modafinila , Patentes como Assunto , Piperazinas/química , Piperazinas/economia , Inibidores da Bomba de Prótons/química , Inibidores da Bomba de Prótons/economia , Estudos Retrospectivos , Estereoisomerismo , Estados Unidos , United States Food and Drug Administration , Promotores da Vigília/química , Promotores da Vigília/economiaRESUMO
A dissolution test for a once daily combination tablet containing 10 mg of cetirizine dihydrochloride (cetirizine HCl) for immediate release and 240 mg of pseudoephedrine hydrochloride (pseudoephedrine HCl) for extended release was developed and validated according to current ICH and FDA guidelines. The cetirizine HCl is contained within an outer layer of the tablet while a semipermeable membrane of cellulose acetate and polyethylene glycol controls the rate at which pseudoephedrine HCl is released from the tablet core. The dissolution method, which uses USP apparatus 2 with paddles rotating at 50 rpm, 1000 ml of deaerated water as the dissolution medium, and reversed-phased HPLC for quantitation, was demonstrated to be robust, discriminating, and transferable. These test conditions were selected after it was demonstrated that the cetirizine HCl portion of the tablet rapidly dissolved in aqueous media over the physiologically relevant pH range of 1.1-7.5, and that the extended-release profile of pseudoephedrine HCl was independent of dissolution conditions (i.e., apparatus, pH, and agitation).