Intensive drug monitoring program in Argentina: switching from innovator to generic cyclosporine in pediatric renal transplant patients.

SCHAIQUEVICH P; CACERES GUIDO P; LICCIARDONE N; IBAÑEZ J; FERREYRA O; MATO G; MONTEVERDE M

Stuttgart

Congreso; 12 th international congress of therapeutic drug monitoring and clinical toxicology; 2011

IATDMCT

Background: Cyclosporine (Cy) is used as part of the immunosuppressive therapy for pediatric renal transplant patients. Cy is subjected to TDM due to wide inter-inidvidual variability in the pharmacokinetics (PK) and narrow therapeutic range with possible implications in acute rejection, graft loss and severe adverse events (1,2). Factors explaining observed variability arestill under debate. Recent introduction of generic Cy in Argentina may add variability bringing concern among the health care professionals. We implemented the first local intensive drug monitoring program of Cy in pediatric renal transplant patients.Methods: We include pediatric renal transplant patients that receive Cy and are switched from the innovator to the generic formulation due to the provision of the social security. Cy PK (AUC, C2) under the innovator and generic brand and register clinical outcome (absence of acute rejection, graft loss) and adverse events (nephrotoxicty, neurotoxicity, hypertension) is recorded.Patients undergo 2 PK studies. Blood samples are obtained before and at: 1, 2 and 3 h after Cy administration and quantitation is performed by FPIA. The area under the curve (AUC) was calculated by Marquet et al (3).Results: 9 patients were included since the start of the program (follow-up time:2.6 months). The median (range) post-transplant time and age was 8.5 year (5.1-14.0) and 11.5 year (7.9-17.7), respectively. All but 1 patient were concomitantly administered with prednisone and sodium mycophenolic acid. 2 patients declined to switch to the generic formulation. In the evaluable patients, the median (range) percent change in AUC and C2 when switching between formulations was 17.6 % (4.9-35.5) and 17.8 % (5.4-29.1), respectively. Creatinine clearance did not change and no adverse events were observed during the studied period.Conclusion: This is the first report of the implementation of a TDM program in pediatric renal transplant patients in Latin-America facing the problematic of switching between the innovator and generic formulations of Cy. Even if switching between formulations showed a percent change in cyclosporine exposure of up to 35%, no serious adverse events or lack of  efficacy was observed during the studied period. The report reflects the short term results obtained at the start of the present program for immunosuppressive agents and medium to long term follow up of the patients is currently ongoing.