Drug substitution in transplantation: A National Kidney Foundation white paper

Specific safeguards to guide the approval process and substitution practice s for generic immunosuppressive agents are necessary for the effective deli very of patient care. Currently, the Food and Drug Administration (FDA) req uires the demonstration of bioequivalence of generic drugs to innovator dru gs in normal healthy subjects, a, criterion that may be insufficient for cr itical-dose drugs. For generic equivalents of critical-dose drugs and for i nnovator critical-dose drugs, there should be a requirement for replicate s tudies measuring intrasubject variability and subject-treatment interaction s to establish that bioequivalence holds true. Extensive testing of generic drugs in all target patient types is impractical and should not be require d. However, when evidence suggests that the bioavailability of a critical-d ose drug may vary substantially in certain subgroups, the FDA should requir e a demonstration of bioequivalence of generic versions to innovator produc ts in these representative target populations. Changes in the approval proc ess for generics should be accompanied by more consistent substitution prac tices. Pharmacists should notify the prescribing physician and patient when ever a critical-dose drug (generic or brand name) is dispensed in a differe nt formulation from the one the patient has been taking. Therapeutic substi tution for such drugs should not be made unless the prescribing physician h as granted approval. The health care provider should consider instituting a ppropriate monitoring whenever patients are switched between generic formul ations or between innovator drugs and generic formulations. Patients should be well informed about generic substitutes so that they can participate in treatment choices. (C) 1999 by the National Kidney Foundation, Inc.