Standard dosing of tacrolimus leads to overexposure in pediatric renal transplantation recipients

Pediatric Transplantation
Joshua Y KausmanStephen D Marks

Abstract

Tacrolimus dosage in pediatric RTRs is empirically based on weight. There is evidence that adolescents are at greater risk of toxicity than young children on this dosing regimen. We investigated the rate of tacrolimus overexposure within the first three wk post-transplantation in pediatric RTRs receiving tacrolimus 0.15 mg/kg twice daily. Of 63 RTRs studied, 41 (65.1%) experienced a tacrolimus level above the therapeutic range (supratherapeutic), the majority (48.8%) on days two to four post-transplant. Patients with supratherapeutic levels were older (14.2 vs. 9.9 yr, p = 0.016), taller (146.7 vs. 126.5 cm, p = 0.029), larger (1.36 vs. 1.01 m(2), p = 0.039) and heavier (44.1 vs. 29.3 kg, p = 0.043) and by day 12 were receiving much lower tacrolimus doses than those without supratherapeutic levels (0.425 vs. 0.198 mg/kg/day, p = 0.0002). Supratherapeutic levels were more common among white (British) children than other ethnic groups (74 vs. 45%, p = 0.02). There were no observed differences in rates of patient or graft survival, or acute rejection during the three-yr study period. Adolescent patients appear to be at greater risk of excessive tacrolimus dosing on a standard regimen. We therefore outline a regimen restricting tac...Continue Reading

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Citations

Feb 24, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Nicholas Ware
Jun 27, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Paul D RobinsonHelen Spencer
Nov 21, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Rajiv SinhaStephen D Marks
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Apr 14, 2015·Expert Opinion on Drug Metabolism & Toxicology·Louise M AndrewsTeun van Gelder
Dec 18, 2008·Pediatric Transplantation·Christian BendenStephen D Marks
Dec 18, 2013·Transplant International : Official Journal of the European Society for Organ Transplantation·Chrysothemis C BrownStephen D Marks
Aug 30, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·J J KimS D Marks
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Nov 25, 2014·Archives of Disease in Childhood·Pauline LanciaWei Zhao
Oct 30, 2009·Clinical Pharmacology and Therapeutics·W ZhaoE Jacqz-Aigrain
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Sep 19, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Gabriel ChanPatrick du Souich
Jun 1, 2013·Personalized Medicine·Lisa Ca D'Alessandro, Seema Mital
Apr 12, 2013·Acta Paediatrica·Rajiv Sinha, Stephen D Marks
Dec 22, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xiang-Qian GuQiang Xia

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