Adverse Reactions
Tacrolimus use is associated with many adverse reactions, including diabetes, nephrotoxicity, hyperglycemia, hyperkalemia, hypomagnesemia, neurotoxicity and alopecia. When compared to other agents in the same class (e.g., cyclosporine), tacrolimus is associated with higher instances of hyperglycemia and diabetes. Children are also at a higher risk of developing infections and lymphoproliferative disorders than adult transplant recipients due to the potentially longer duration of immunosuppression.[2]
A recent study reviewed factors associated with post-transplant diabetes mellitus (PTDM) in children treated with tacrolimus after renal transplantation. Patients without PTDM were matched to patients with PTDM according to age at time of transplantation, sex and follow up duration. All patients were genotyped for SNPs relevant to tacrolimus metabolism, and a pharmacogenetic risk score was constructed to evaluate the potential relationship between risk of PTDM and level of tacrolimus exposure.[10]
Of the 98 children included in the study, 18 (18%) developed PTDM in the first four years after tacrolimus initiation. Of the 18 patients who developed PTDM, 12 (67%) developed PTDM in the first year after initiation of tacrolimus. Tacrolimus dosage at the time of PTDM diagnosis was within the recommended dose range for children after renal transplantation (0.25 +/- 0.12 mg/kg/day). There was a trend between age at transplantation and occurrence of PTDM, with older children developing PTDM earlier than younger children. None of the SNPs tested were significantly associated with PTDM, but the investigators observed a tendency for patients with POR*28 and ABCB1 to have higher rates of PTDM (p = 0.114 and p = 0.066, respectively). A multivariate analysis did not find an association between the risk of PTDM and the initial dose of tacrolimus, previous cyclosporine administration, acute rejection before tacrolimus introduction, or the number of acute rejection episodes while receiving tacrolimus; however, the POR and ABCB1 gene variants were identified as risk factors of PTDM in the population of children with renal transplantation.[10]
Pediatr Pharm. 2018;24(12) © 2018 University of Virginia
