Cost containment-driven drug substitution, whether generic or therapeutic, is defined as switching to another drug because it is cheaper. So far, such substitutions have drawn their public legitimacy from the general belief that they would not compromise the clinical interests of patients and certainly not violate their right to decline them if they did. This article does not enter the debate on whether or not such substitutions must give exclusive priority to the patient's interests and choices in order to be ethical. Indeed, it acknowledges the plurality of views on this matter. It simply argues that when such substitutions involve a cheaper drug that is known to have different effects and side effects, or even a drug whose effects and side effects are unknown, they are potentially deleterious to the patient, and that no competent and well-informed patient would ever consent to them. Such substitutions are thus unethical in their very own terms.

Introduction: Dissolution is an example of in-vitro test which can be used to identify formulations that may present potential bioequivalence problems. It is defined as the amount of substance that goes into solution per unit time under standardised conditions of liquid/solid interface, solvent composition and temperature. It is considered one of the most important tools to predict the in-vivo bioavailability and in some cases replacing clinical studies to determine bioequivalence. Aim: To compare the differences in the dissolution behaviour between two anticancer formulations, Xeloda ® 500 mg (reference product) and Capeda 500 mg (test product). Methods: Four replicates for each batch of the tested medicines were carried out using a PT-DT70 dissolution tester (Pharma Test) to detect any differences in their dissolution behaviour. Samples at nine time intervals were tested according to the US Pharmacopeia with the rate of dissolution determined by ultraviolet spectrophotometery. Results: All the tested medicines complied with the pharmacopoeial specifications, the EMA and the FDA guidance for industry when achieved 85% dissolution in 60 minutes. However, Capeda 500 mg (test product) showed slower, different and incomplete dissolution rate compared to Xeloda ® 500 mg (reference product) at both 60 and 120 minutes. Other visual differences in the weight, size, clarity of solution, presence of un-dissolved residue and particles during the dissolution test were also detected. Conclusion: Results in this study clearly raise a question about the interchangeability between Xeloda ® 500 mg and its Intended copy Capeda 500 mg. Awareness of these scientific concerns should be considered when a clinical choice between these two drugs is required. Differences between the innovator and copy medicines with regard to pharmacokinetics, clinical efficacy and safety may exist. Thereby, patients' monitoring after performing drug substitution of these two medicines is strongly recommended.