Generic Docetaxel.

Abstract

We read with great interest the article by N. Al Faqeer et al on the retrospective comparison of generic and branded formulations of docetaxel in terms of incidence of febrile neutropenia resulting in hospital admission.1 The authors found a higher incidence of febrile neutropenia with generic formulations compared with branded docetaxel and stated that the lower cost of generics should be balanced with the expenditure relative to complications. This kind of study is rather uncommon because approved generics and branded drugs have the same clinical activity. The approval of intravenous generic drugs is based on pharmaceutical equivalence, and clinical trials are not required by drug regulatory agencies. In fact, they are useless because the active entity is the same. In short, comparing generic drugs and their branded reference is the same as comparing various batches of the branded drug.2 Suspicion about generic drugs is often related to case reports or isolated observations. We do not think that this study proves than docetaxel generics are clinically different from the branded reference because of the several limitations highlighted by the authors (retrospective design, no check of drug–drug interactions). Docetaxel is cleared by CYP3A-mediated metabolism, and huge variations of elimination have been found among patients.3,4 In addition, docetaxel clearance has been related to CYP3A activity5 and has also been found to be an independent predictor of febrile neutropenia.3 So the difference of febrile neutropenia might have been simply related to the variations of metabolic elimination and not to the source of the docetaxel. At last, if a higher incidence of severe neutropenia really exists between the different formulations of docetaxel, it suggests that the generic vials are overdosed. Consequently, the drug agencies and the manufacturers should be alerted and the vials checked and eventually withdrawn. Otherwise, what can we do with this information, apart from casting doubts on generics and fear among patients?