Sequential Substitution from Sandimmune to Implanta and from Implanta to its Microemulsion Formulation, Neoplanta as Cyclosporine Preparations in Renal Transplant Patients

Song, Seung Chan; Kim, Ho Jung

Abstract

Clinical trial of cyclosporines produced from two different manufacturers were performed in thirty three renal transplant patients for 16 months divided into 2 phases. A 1:1 conversion on a milligram-to- milligram basis was used for switching from Sandimmune(Sandoz Pharma Ltd, Switzerland) to Implanta(Hanmi Pharma Co, Korea) as the first phase and from Implanta to its microemulsion formulation, Neoplanta, as the second phase. Throughout two phases, the cyclosporine dose, blood pressure and hemoglobin were not changed significantly. Serum creatinine was reduced from the baseline(1.76+/-0.5mg/dL) only during the middle 2 months of the first phase(month 3 : 1.57+/-0.4mg/dL, P<0.05, month 5 : 1.58+/-0.4mg/dL, P<0.05), but it was not changed significantly during the second phase at all. However, blood urea nitrogen(BUN) was increased from baseline throughout the second phase, significantly. Cyclosporine trough level was reduced from baseline(180.87+/-57.5 ng/mL) during the late 3 months of the first phase(month 6 : 131.69+/-61.2ng/mL, P<0.05, month 7 : 137.27+/-82.1ng/mL, P<0.05, month 8 : 135.06+/-58.2ng/mL, P<0.05), while those were increased from baseline to during the early 2 months (month 1 : 172.48+/-64.1ng/mL, P<0.05, month 2 : 170.12+/-49.6ng/mL, P<0.05) and returned to baseline during the remaining 6 months of the second phase. No one developed rejection, but 8 admissions in 7 patients occurred due to cyclosporine nephrotoxicity related elevation of serum creatinine(n=2 in the first phase, n=3 in the second phase), cellulitis in leg(n= 1), partial colectomy for colon cancer(n=1) and reduction of fractured arm(n=1), respectively. Mild abdominal discomfort in 2 patients and nausea with fishy smell on cyclosporine intakes in 3 patients during the early first phase were noted transiently, but no one developed such adverse side effects during the second phase. In conclusion, there were no discernible differences in safety and effectiveness in cyclosporine products from two different manufacturers. Furthermore, the comparable effects between the conventional cyclosporine(Implants) and the microemulsion formulation(Neoplanta) were noted without requiring the dose reduction after the 1:1 conversion.