The Association Between Patient Sociodemographic Characteristics and Generic Drug Use: A Systematic Review and Meta-analysis.

BACKGROUND: Generic drugs are bioequivalent and cost-effective alternatives to brand drugs. In 2014, $254 billion was saved because of the use of generic drugs in the United States. OBJECTIVE: To critically assess evidence on the association between patient characteristics and generic drug use in order to inform the development of educational outreach for improving generic drug use among patients. METHODS: We systematically searched the literature between January 2005 and December 2016 using PubMed, Web of Science, Ovid MEDLINE, Google Scholar, and EBSCO IPA-MEDLINE for potentially relevant studies. The titles and abstracts of identified articles were assessed independently by 2 reviewers. Titles and abstracts that were not written in English, were published before 2005, were not empirical, did not contain sociodemographic data, or were not policy or methodologically relevant to generic drug use were excluded. Data were pooled in a meta-analysis using the RStudio software to assess the association of patient-related factors with generic drug use. RESULTS: Our searches resulted in 11 articles on patient-level factors, and 6 of these articles had sufficient information to conduct meta-analyses in the domains of patients' gender, age, race/ethnicity, and income. Quantitative analysis indicated that no differences in generic drug use existed between subgroups of patients defined by gender, age, or race/ethnicity. However, patients with lower income (i.e., < 200% federal poverty level [FPL]) were more likely to use generic drugs than those with higher income (≥ 200% FPL; pooled OR = 1.32, 95% CI = 1.15-1.52). Heterogeneity was high (I 2 > 75%) for all analyses but income. CONCLUSIONS: Patients with lower income were more likely to use generic drugs, whereas evidence was heterogeneous regarding an association between generic drug use and gender, age, or race/ethnicity. Educational outreach targeting patients with higher incomes to understand their perspectives in generic drugs may help improve generic drug use within that population. DISCLOSURES: Funding for this study was made possible, in part, by the U.S. Food and Drug Administration through grant U01FD005486. Hansen has provided expert testimony for Daiichi Sankyo. No other authors have declared a potential conflict of interest. Views expressed in written materials or publications and by speakers do not necessarily reflect the official policies of the U.S. Department of Health and Human Services, nor does any mention of trade names, commercial practices, or organization imply endorsement by the U.S. government. Study concept and design were contributed by Howard, Harris, Kiptanui, Hansen, and Qian. Frank, Mishuk, Howard, Harris, and Kiptanui collected the data, and data interpretation was performed by Mishuk and Hansen, along with Qian, Harris, and Kiptanui. The manuscript was written and revised primarily by Mishuk, along with Qian and Hansen.

Biowaiver monographs for immediate release solid oral dosage forms: rifampicin.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing rifampicin as the only Active Pharmaceutical Ingredient (API) are reviewed. Rifampicin's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Solubility and absolute BA data indicate that rifampicin is a BCS Class II drug. Of special concern for biowaiving is that many reports of failure of IR solid oral dosage forms of rifampicin to meet BE have been published and the reasons for these failures are yet insufficiently understood. Moreover, no reports were identified in which in vitro dissolution was shown to be predictive of nonequivalence among products. Therefore, a biowaiver based approval of rifampicin containing IR solid oral dosage forms cannot be recommended for either new multisource drug products or for major scale-up and postapproval changes (variations) to existing drug products.

Improvement in seizure control and quality of life in medically refractory epilepsy patients converted from polypharmacy to monotherapy.

In a retrospective chart review, we identified 35 patients with medically refractory epilepsy (MRE) who had been converted from polypharmacy to monotherapy and maintained on monotherapy for at least 12 months. None of the 35 patients had worsening of their seizure frequency after the conversion to monotherapy. Fourteen of the 35 patients (40%) became seizure-free. Nine of 35 patients (26%) had a 50% reduction in seizure frequency. Five of 35 patients (14%) had a 75% reduction in seizure frequency. Twenty-eight (80%) of 35 patients participated in a quality-of-life questionnaire. Quality of life was rated as better on monotherapy as compared with polypharmacy in a number of domains: memory loss, concern over medication long-term effects, difficulty in taking the medications, trouble with leisure time activities, and overall state of health. This improvement reached statistical significance. Conversion to monotherapy in patients with MRE may be successful in achieving a reduction in seizure frequency and an improvement in quality-of-life parameters. A prospective, randomized trial is necessary to validate these findings.

Single-dose oral pharmacokinetics of three formulations of thalidomide in healthy male volunteers.

Thalidomide was recently approved in the United States for the treatment of erythema nodosum leprosum, a complication of leprosy. The present study determined the bioequivalence and pharmacokinetics of Celgene's commercial and clinical trial thalidomide formulations and the Brazilian Tortuga formulation in an open-label, single-dose, three-way crossover design. Seventeen healthy subjects were given 200 mg of thalidomide on three occasions, and blood samples were collected over 48 hours. Pharmacokinetic parameters were determined using compartmental methods for the two Celgene formulations and using noncompartmental methods for all three formulations. All subjects reported adverse events, none of which was serious or unexpected. Celgene formulations were bioequivalent when comparing Cmax, tmax, and AUC. There was significant variability in plasma levels from the Tortuga formulation, giving a mean profile that was distinctly different from the two Celgene formulations with a lower Cmax value and a longer terminal phase. The lower Cmax was probably due to slower absorption. The terminal rate constant for the Tortuga formulation was significantly less, giving rise to a terminal half-life of 15 hours compared to about 5 to 6 hours for the Celgene formulations. Confidence intervals for Cmax between the Tortuga and the Celgene formulations were outside the 80% to 125% range, indicating a lack of bioequivalence. Extent of absorption, as measured by AUC0-infinity, was approximately equal for all three formulations. Terminal half-life for Tortuga was two to three times longer compared to the Celgene formulations and is clear evidence for absorption rate limitations. The two Celgene formulations showed similar pharmacokinetic parameters with profiles that were best described by a one-compartment model with first-order absorption and elimination. The authors conclude that Celgene's clinical trial and commercial thalidomide formulations are similar to each other and distinctly different from the Tortuga formulation and that all three formulations exhibited absorption rate-limited elimination.