With regard to generic medicines for oral use that contain cyclosporine or tacrolimus, it has so far been possible to label these as generically substitutable if the medicines were assessed to be therapeutically interchangeable. Provided, however, that bioequivalence between the generic version and the original product is established based on stringent criteria.
Following a reassessment, the Danish Medicines Agency now considers that generic substitution should no longer be possible for these to active substances.
The termination of generic substitution is effective from 25 July 2011.
Generic substitution is terminated because the calcineurin inhibitors cyclosporine and tacrolimus have a narrow therapeutic interval and because one of the products' treatment areas is immunosuppression to prevent rejection of vital organs in transplant patients.
Above all, it has been taken into account that therapeutic failure as a result of insufficient exposure to the medicine and subsequent rejection of organs, such as the heart, liver and lungs will have severe and often fatal outcomes for the patients concerned.
Generic substitution requires that an 'automatic' switch to another product can take place relatively unproblematically for the vast majority of patients, regardless of indication.
In any event, the physician responsible for the medical treatment of transplant patients will unproblematically in compliance with practice and recommendations in many countries unproblematically often choose to monitor the patient at more frequent intervals if patients receiving cyclosporine or tacrolimus are switched from e.g. one pharmaceutical form to another, from an original product to a generic product or from a generic product to another. Monitoring at more frequent intervals typically involves the taking of extra blood samples to measure concentrations of the medicine in the blood. Such intervention is not considered compatible with generic substitution.
The Danish Medicines Agency is aware that immunosuppressants in Denmark are mostly all dispensed to transplant patients by public hospitals. It is also known that cyclosporine and tacrolimus are used for the treatment of other immunologically-mediated diseases in which case therapeutic failure will not have as severe consequences as it has in transplant patients. In the case of tacrolimus, such use is exclusively 'off-label', i.e. used for unauthorised indications.
In its reassessment, the Danish Medicines Agency has attached great importance to the fact that the authorised indications for cyclosporine and tacrolimus (for the latter product only) cover immunosuppression in transplant patients and to the possibility that transplant patients are dispensed the products at a pharmacy.
For further information on bioequivalence and labelling of medicines with regard to generic substitution, please see the box to the right.