Cyclosporin pediatric patients

Drug absorption is highly variable in neonates and infants [21,22]. Older children appear to have absorption patterns similar to adults unless chronic illness or surgical procedures alter absorption. Differences in bile excretion, bowel length, and surface area probably contribute to the reduced bioavailability of cyclosporine seen in pediatric liver transplant patients [22a]. Impaired absorption has also been observed in severely malnourished children [22b]. A rapid GI transit time may contribute to the malabsorption of carbamazepine tablets, which has been reported in a child [23]. Selection of a more readily available bioavailable dosage form, such as chewable tablets or liquids, should be promoted for pediatric patients. 

An order was written for 30 mg Cyclosporine (immunosuppressant) oral solution to be administered to a pediatric patient. However, for several days, the nurse administered 300 mg believing that the syringe was calibrated in mg not mL. The oral solution is available as 100 mg/mL. As the pharmacist reviewed the error, he noted that the syringes accompanying the medication were never designed for pediatrics. It is not possible to calculate any dose less than 50 mg. It is imderstandable how the nurse assumed that the 3 mark was for 30 mg since it is positioned between 2,5 and 3,5 (which are European style for the decimals 2.5 and 3.5). To harmonize products in the global market, the manufacturer chose to follow European convention for expressing numbers which uses commas and decimals in the reverse manner as in the United States. 

McLellan RA, Drobitch RK, McLellan H, Acott PD, Crocker JF, Renton KW. Norfloxacin interferes with cyclosporine disposition in pediatric patients undergoing renal transplantation. Clin Pharmacol Ther 1995 58(3) 322-7. 

Cyclosporine has been used in adult and pediatric patients. The drug decreases lymphokine production by activated T lymphocytes and thereby reduces proteinuria by reversing the lymphokine-induced alterations in the anionic charge and permeability of the GBM to albumin. Cyclosporine can also reduce proteinuria by improving the permselectivity of the GBM. 

Tacrolimus is indicated for the prophylaxis of solid-organ allograft rejection in a manner akin to cyclosporine and as rescue therapy in patients with rejection despite therapeutic levels of cyclosporine. Dosages are intended to achieve blood trough levels of 5-15-ng/mL. Pediatric patients generally require higher doses than do adults. 

Brunner LJ, Pai KS, Munar MY, Lande MB, Olyaei AJ, Mowry JA. Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients. Pediatr Transplant 2000 4(4) 313-321. 

Kale, A.S., Ferry, G.D., Hawkins, E.R End-stage renal disease in a patient with cholesteryl ester storage disease following successful hver transplantation and cyclosporine immunosuppression. J. Pediatr. Gastroenterol. Nutrit. 1995 20 95-97... 

Charbit M, Gubler MC, Dechaux M, Gagnadoux MF, Grunfeld JP, Niaudet P. Cyclosporin therapy in patients with Alport syndrome. Pediatr Nephrol 2007 22 57-63. 

Nakamura T, Nozu K, lijima K, Yoshikawa N, Moriya Y, Yamamori M, Kako A, Matsuo M, Sakurai A, Okamura N, Ishikawa T, Oku-mura K, Sakaeda T. Association of cumulative cyclosporine dose with its irreversible nephrotoxicity in Japanese patients with pediatric-onset autoimmune diseases. Biol Pharm Bull 2007 30 2371-2375. 

The current example is drawn from results of a PK study that was designed to evaluate the pharmacokinetics of cyclosporine in stable pediatric transplant patients receiving chronic oral dosing. Since many of the subjects had evaluations from two separate formulations, a secondary objective of the study was to evaluate the relative absorption characteristics of the two formulations. The study included 32 children and adolescents, a typical size for a pediatric Phase 1-2 study. This modest number of subjects in a pediatric PK study is common but reduces the power to... 

The efficacy of tacrolimus as a primary immunosuppressant for the prophylaxis of rejection and for rescue therapy following failure of conventional cyclosporin-based rejection prophylaxis has been demonstrated in numerous clinical studies in adults and pediatrics using various types of combination therapy since 1989. Tacrolimus is now well established not only as a primary immunosuppressant in organ transplantation but also an excellent rescue agent for patients experiencing posttransplant rejection while on cyclosporin-based regimens [44]. 

Results of a randomized comparative study in pediatric liver transplantation between tacrolimus and cyclosporin showed equal patient survival (80% vs. 81%), graft survival (70% vs. 71%), and retransplantation rate (17% vs. 19%) at 1 year after transplantation. Of note, however, was a trend favoring tacrolimus in the prevention of acute rejection (52% vs. 79%) [52]. An additional benefit of tacrolimus in children is its steroid-sparing effect allowing for them to achieve more normal growth. In addition, the lack of gingival hyperplasia and hirsutism has made tacrolimus particularly valuable in the treatment of children undergoing liver transplantation. 

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