• Chen Yiding and Huang Zhongyi.
• Department of Breast Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, China.
• Curr Med Res Opin. 2021 Aug 1; 37 (8): 1421-1433.

AbstractDocetaxel is a widely prescribed chemotherapy drug in oncology and post expiry of its patent, the drug has been marketed as a generic by multiple manufacturers. It is also classified as a narrow therapeutic window drug. Through enhanced permeability and retention effect, polymeric micelles can passively target agents to tumor tissue, thereby decreasing toxicity of the drug in normal tissue. However, various studies have raised concerns that generic docetaxel leads to greater incidences of toxicities among patients with cancer. Thus, we herein review the pharmaceutical challenges associated with different docetaxel formulations and provide insights into the dissimilarities in the quality and safety of branded and generic docetaxel formulations. Literature review reported that 90% of the generic formulations of docetaxel contain inadequate quantity of active drug and high levels of impurities. Higher amounts of solvents such as polysorbate 80 and ethanol in docetaxel formulation lead to severe toxicities such as febrile neutropenia, hematological, and cutaneous toxicities. In most of the studies, even minor changes in excipients, solvents, unbound fraction of docetaxel were associated with adverse events, while in few, the source of docetaxel remained unidentified. One study reported incidence of febrile neutropenia due to a switch in the formulation from branded to generic. The quality, safety, and efficacy of medicines will directly affect the life of patients, and therefore, use of docetaxel formulations that guarantee safety of patients are the necessity of the hour. Being an injectable anti-cancer drug, it is important to determine the consistency of the various formulations of docetaxel globally, conduct bioequivalence studies as per the regulatory standards, taking into account the permissible limits of the excipients or the presence of such unapproved excipients.

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