Bioequivalence between generic tacrolimus products marketed in Spain by adjusted indirect comparison

Abstract

Not only are the generic products bioequivalent with the reference product, but also with each other.

Influence of point estimates and study power of bioequivalence studies on establishing bioequivalence between generics by adjusted indirect comparisons

“…The authors concluded that even with the Bworse^scenario of 9.5 % non-bioequivalent products, this low value provides reassurance of the BE of two generic products that have been shown to be bioequivalent to the same reference product. However, this does not seem to be the worst scenario, but a very favorable one, because point estimate differences between generics can be larger [5,16]. Karalis et al (2013) plotted the probability of accepting BE between generics as a function of their point estimates and concluded that although two generics are bioequivalent to the reference product, this does not ensure that they are bioequivalent to one another [8].…”

“…Combining 57 possible differences between point estimates from 0 to 14 % in 0.25 % increments and 16 14,592 scenarios were computed, although some scenarios were repetitive (e.g., where the first study has 80 % power and the second has 90 % power is the same scenario as where the first study has 90 % power and the second one has 80 % power).…”

De novo use of generic tacrolimus in liver transplantation – a single center experience with one‐yr follow‐up

“…However, since 2010, the European Medicines Agency (EMA) has stipulated that for bioequivalence to be demonstrated for drugs like tacrolimus that have a narrow therapeutic index, pharmacokinetic parameters should lie within 90-111% of the innovator drug (3). Despite the fact that it is well known that the pharmacokinetic properties of tacrolimus are affected by a number of patient related variables, such as gut function, concomitant medication, and liver function, there is as yet no requirement for bioequivalence to be demonstrated in patients, nor does bioequivalence need to be demonstrated between different generic formulations of the same drug (4). Therefore, for dose critical drugs, such as tacrolimus, where maintenance of stable levels is imperative to ensure stable graft function and avoid complications, there is a need to demonstrate similar clinical outcomes with the use of generic vs. innovator formulations (5).…”

Efficacy and Safety of Glaucoma Patients' Switch from a 2% Dorzolamide/0.5% Timolol Fixed-Combination Brand-Name Drug to Its Generic Counterpart

“…3 Generic drugs have been used in a variety of ways, such as cardiovascular medicines, anticonvulsant medicines, nonsteroidal anti-inflammatory drugs, levothyroxine, oral contraceptives, and proton pump inhibitors. [4][5][6][7][8] This trend is also true for the antiglaucoma ophthalmic solutions. [9][10][11] The 2% dorzolamide/0.5% timolol fixed-combination (DTFC) drug has been widely used for the treatment of glaucoma because of its highly intraocular pressure (IOP)-lowering effect and the increased compliance with it due to its ease of use.…”