Issues in cyclosporine drug substitution: implications for patient management

Substantial improvements in short-term and long-term outcomes for kidney transplant recipients have resulted from better use of existing immunosuppressive agents and newer treatment options. Calcineurin inhibitors (e.g., cyclosporine and tacrolimus) remain the foundation of immunosuppressive therapy. These agents are considered critical-dose drugs because of their narrow therapeutic range, variable pharmacokinetics, formulation-dependent bioavailability, and negative clinical consequences of underdosing or overdosing. With the recent introduction of a new cyclosporine formulation, concern exists that current bioequivalence guidelines for generic approval may not provide adequate assessment of the safety and efficacy of critical-dose drugs. Transplant experts at 2 recent conferences recommended more rigorous criteria for bioequivalence testing of critical-dose drugs and adoption of consistent drug substitution practices. Additional recommendations included specifying the intended formulation and instituting appropriate monitoring whenever formulations are switched. A summary of the outcomes of these conferences and practice implications for transplant coordinators is discussed.