Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.

Abstract

BackgroundDrug regulatory agencies (DRA) support prescription of generic products of intravenous antibiotics assuming therapeutic equivalence from pharmaceutical equivalence. Recent reports of deaths associated with generic heparin and metoprolol have raised concerns about the efficacy and safety of DRA-approved drugs.Methodology/principal findingsTo challenge the assumption that pharmaceutical equivalence predicts therapeutic equivalence, we determined in vitro and in vivo the efficacy of the innovator product and 20 pharmaceutically equivalent generics of gentamicin. The data showed that, while only 1 generic product failed in vitro (MIC = 45.3 vs. 0.7 mg/L, PConclusionPharmaceutical equivalence does not predict therapeutic equivalence of generic gentamicin. Stricter criteria based on solid experimental evidence should be required before approval for human use.