Clinical Equivalence between Generic Versus Branded Antibiotics: Systematic Review and Meta-Analysis

Abstract

Regulatory authorities authorize the clinical use of generic drugs (GD) based on bioequivalence studies, which consist of the evaluation of pharmacokinetics after a single dose in vitro or in healthy individuals. There are few data on clinical equivalence between generic and branded antibiotics. Our aim was to synthesize and analyze the available evidence on the clinical efficacy and safety of generic antibiotics compared to their original formulations. A systematic review was performed on Medline (PubMed) and Embase and validated through Epistemonikos and Google Scholar. The last search was conducted on 30 June 2022. Meta-analyses of clinical cure and mortality outcomes were performed. One randomized clinical trial (RCT) and 10 non-randomized intervention studies were included. No differences in clinical cure were observed between groups in the meta-analysis (OR = 0.89, 95% CI [0.61–1.28]; I2 = 70%, p = 0.005). No difference was observed between groups when considering the use of carbapenems for overall mortality (OR = 0.99, 95% CI [0.63–1.55]; I2 = 78%) or death associated with infections (OR = 0.79, 95% CI [0.48–1.29], I2 = 67%). Most of the studies were observational, and the duration of follow-up, the characteristics of the participants, and the sites of infections were heterogeneous. Due to the uncertainty of the evidence, it is not possible to contraindicate the use of generics, which is an important strategy to expand access.

The Effectiveness of Generic Piperacillin/Tazobactam in Managing Gram-Negative Bacillary Bacteremia in Adult Patients at a Tertiary Care Hospital

“…Although the utilization of generics drugs enables access to population, their introduction often leads to controversies concerning discrepancies that may arise compared to the innovative product. PZT is no exception, and several publications corroborate the equivalence or effectiveness of various generic products as well as some that have reported differences in potency or clinical effectiveness [12][13][14].…”

“…However, this leads to an increase in the use of piperacillin/tazobactam and the need to introduce not only the innovative drug but other generics to facilitate access. In the literature, there is controversy about whether the generic PTZ molecules have a different activity to the innovative one, while some studies describe 2 differences in in-vitro or animal models [10,11], in equivalence and clinical studies the data are inconclusive [12][13][14]. It is crucial to conduct real-life evaluations of frequently used generic drugs with high clinical impact, such as PTZ.…”