Thus, the evidence click here available indicates that many generic formulations are

less well tolerated than the proprietary products and that this leads to poorer adherence, in turn associated with a poorer clinical outcome in terms of effectiveness on BMD [51–53] and ultimately in effectiveness on fracture outcomes [44, 51, 54–56]. Because generic drugs in developed markets are shown to be bioequivalent, it might be assumed that the decrease in effectiveness is a result of the poor adherence. There is some evidence that there may be additional effects on drug efficacy. In the case review of Ringe et al. [50] unequal efficacy of the generic vs. branded alendronate and risedronate was observed in the effect on BMD: significantly lower treatment-induced increases in BMD at the lumbar spine (p < 0.05) and total hip (p < 0.01) were observed after 1 year in the group receiving generic find more alendronate compared to those receiving the two branded bisphosphonates. In the Canadian survey [49], generic treatment was stopped because of a decrease in BMD in a significant minority of patients. Whether some generic products have lower efficacy remains an open question, and poor adherence provides a plausible reason for the apparent reduction in the effectiveness of the generic products. Formulation The question arises whether poor tolerance

is due to differences in the formulation between the generics and their branded equivalents, and there PLX4032 is evidence to suggest that this is indeed the case. Mean disintegration times have been found to be significantly faster for two generic formulations of alendronate available in Canada compared to branded alendronate (with or without

vitamin D) or branded risedronate [57]. Disintegration rates of several of the generics available Phosphoprotein phosphatase in Europe or the USA were similar to those reported for tablets specifically formulated to disintegrate in the mouth (<30 s) [58–60] (Fig. 4). Many other studies have confirmed heterogeneous rates of disintegration [58]. Dissolution rates appear to have much less variability [59–63]. Fig. 4 Disintegration times in vitro of Fosamax 70-mg tablets (R) and ten generic copies from South America [redrawn from 58] In 2005, Epstein showed a greater irritant response in dogs from a generic alendronate compared to the reference product when tablets of the two formulations were placed at the lower oesophagus: the differences were attributed to the excipients, since the active ingredient (alendronate sodium) and the dose in copy alendronate tablets were similar to branded tablets [64]. Rapid disintegration with semi-particulate alendronate may cause poor tolerance by adhering to the oesophageal mucosa. Such an effect of a majority of generic formulations of alendronate, but not the proprietary products, was shown in vitro on the oesophageal mucosa of pigs [65].