Variability of Drugs with Narrow Therapeutic Window in Transplantology - Potential Costs and Clinical Consequences

Abstract

Demand for organ transplants is growing fast due to the senescence of population and increased incidence of such diseases as diabetes mellitus and viral hepatitis. Resources of health care providers are limited and steadily increasing. Transplant recipients require chronic medical management and life-time immunosuppressant therapy. Patients must take multiple drugs, such as immunosuppressants, anti-infective agents as well as drugs to treat comorbidities. A patient after organ transplantation may take an average of 11 different drugs daily. The aim of treatment of such patients is to avoid loss of a transplant through ensuring high safety level due to monitoring of concentrations of drugs with narrow therapeutic index (tacrolimus, cyclosporine). Potential costs of loss of a transplant include return to dialysis therapy, and in case of a liver or heart - retransplantation or death.

Availability of generic immunosuppressants results in increased availability of these drugs, improved quality of care and sometimes increased patient compliance. Generic formulations of cyclosporine, mycofenolate mofetil (MMF) and tacrolimus received marketing authorization in EU.

Conclusions: Due to the fact that generic formulations of calcineurin inhibitors are becoming available, both health care providers and health care payers must realize that their bioavailability is highly variable and depends on multiple factors that have not yet been taken into account in studies of clinical bioequivalence. Changes in systemic exposure may result in loss of transplant function or toxic effects of an administered drug. Therefore, it is important for the transplant recipient and payer to evaluate evidence for safety and efficacy of any approved alternative formulation that contains a drug with a narrow therapeutic window used in transplantology.