Variability of Drugs with Narrow Therapeutic Window in Transplantology - Potential Costs and Clinical Consequences
DOI:
https://doi.org/10.12775/4107Keywords
transplantation, tacrolimus, cyclosporineAbstract
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.
References
European Generic Medicines Association. EGA fact sheet on generic medicines. Available at www.egagenerics.com/doc/ega_factsheet-01.pdf
European Generic Medicines Association. Available at www.egagenerics.com/gen-geneurope.htm
IMS MIDAS-MAT, September 2008.
Alloway RR, Isaacs R, Lake K, et al. Report of the American Society of Transplantation conference on immunosuppressive drugs and the use of generic immunosuppressants. Am J Transplant 2003; 3: 1211-5. http://www.ncbi.nlm.nih.gov/pubmed/14510694
Sabatini S, Ferguson RM, Helderman JH, et al. Drug substitution in transplantation: a National Kidney Foundation White Paper. Am J Kidney Dis 1999; 33: 389-97.
Haroldson JA, Somerville KT, Carlson S, et al. A retrospective assessment of safety, efficacy and pharmacoeconomics of generic azathioprine in heart-transplant recipients. J Heart Lung Transplant 2001; 20: 372-4.
IMS Health, BPI/HPAI/MAT 12/2008.
Simoens S, De Coster S. Sustaining generic medicines markets in Europe; 2006. Available at www.egagenerics.com/doc/simoens-report_2006-04.pdf
Burgermeister J. Generic medicines could rescue EU governments' spending. BMJ 2006; 332: 992.
Danish Drug Agency. Bioequivalence and labelling of medicinal products with regard to generic substitution. Available at www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=64
Agencia Española de Medicamentos y Productos Sanitarios. Ministerstry of Health and Consumer Issues, 18994, regulation datek 12 November 2008.
Perry G. The European generic pharmaceutical market in review: 2006 and beyond. Journal of Generic Medicine 2006; 4: 4-14.
Published
How to Cite
Issue
Section
Stats
Number of views and downloads: 0
Number of citations: 0