Pharmacokinetic and Pharmacovigilance Studies in Pediatric Renal Transplant Patients When Switching Between Innovator and Generic Cyclosporine Formulations. Riva N.

RIVA NATALIA; CACERES GUIDO P; ROUSSEAU M; CAMBACERES C; LICCIARDONE N; MONTEVERDE M; SCHAIQUEVICH P

Congreso; 24th International Congress of The Transplantation Society; 2012

International Congress of The Transplantation Society

Introduction: Cyclosporine (Cy) is used as part of the immunosuppressive therapy for pediatric renal transplant patients. Cy pharmacokinetics shows high inter-individual variability and a narrow therapeutic range with possible implications in acute rejection, graft loss and severe adverse events. Due to the previously established relationship between Cy plasma concentration and efficacy an exhaustive monitoring of the patient is carried out to assure the efficacy and safety of the pharmacological treatment. Recent introduction of generic Cy in Argentina may add variability to a vulnerable population such as renal transplant pediatric patients. Thus, we developed and implemented the first regional intensive monitoring program of Cy in pediatric renal transplant patients involving pharmacokinetics and pharmacovigilance studies. Materials and methods: The program includes pediatric renal transplant patients that receive Cy and are switched from the brand name (R) to the generic formulation (T) due to the provision of the social security. A data base was developed to register the most frequent and serious adverse events to calcineurin inhibitors, the associated biochemical parameters and Cy concentration after 2 hours (C2). The protocol was approved by the IRB. Patients undergo two pharmacokinetic studies after receiving R and T. Blood samples are obtained before and at: 1, 2 and 3 hours after Cy administration and quantitation is performed by FPIA. Cy pharmacokinetic parameters are calculated (Area Under the Curve, AUC; C2). Clinical outcome (absence of acute rejection, graft loss) and adverse events (nephrotoxicity, neurotoxicity, hypertension) is recorded. Pharmacokinetic parameters were compared between groups (T and R) by means of Wilcoxon matched paird test (p0.05). The most frequent adverse events observed were hypertension, gingival hyperplasia, and no acute rejection or graft loss was registered in patients under both trademarks. Discussion: This is the first intensive vigilance program of immunosuppressants in pediatric renal transplant patients in Latin-America facing the problematic of switching between the innovator and generic formulations of Cy. Even if a percent change of Cy exposure of up to 35 % was observed, no serious adverse events or lack of efficacy was recorded during the studied period. A long-term follow up is currently undergoing. Evaluation of adverse events and therapeutic Cy monitoring is needed for optimizing pediatric renal transplant patient pharmacological treatment.