Optimal dosing of intravenous tacrolimus following pediatric heart transplantation

Blair V. Robinson, Gerard J. Boyle, Susan A. Miller, Yuk M. Law, John Myers, Bartley P. Griffith, Steven A. Webber

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Early experience with intravenous tacrolimus at high doses (0.1-0.15 mg/kg/day) was associated with frequent clinical toxicity. The optimal dosing regimen after pediatric heart transplantation is unknown.Methods We retrospectively reviewed data on the last 45 pediatric heart transplant recipients to document the time required to achieve therapeutic blood levels and the safety of 2 differing intravenous dosing regimens (tacrolimus 0.03 and 0.05 mg/kg/day as continuous IV infusion). Target plasma levels were (1.2-1.7 ng/ml) with levels >2.0 ng/ml considered toxic, and target whole blood levels were 15-20 ng/ml with levels >25 ng/ml considered toxic.Results Mean age at transplantation was 7.5 ± 5.6 years (0.1-18), and 14 were infants. Intravenous tacrolimus was commenced at a mean of 7 ± 3 hours (range 2-16) after arrival in the ICU. Eight patients were excluded from analysis because of protocol modifications. Of the remaining 37 pts, 9 received initial infusion at 0.03 mg/kg/day; 3 (33%) achieved 'therapeutic' levels within 48 hours and 1 patient had a toxic level (27 ng/ml) at 36 hours. Twenty-eight patients received 0.05 mg/kg/day; 18 (64%) achieved therapeutic levels within 48 hours and 9 (32%) developed toxic levels. Patients with toxic whole blood levels had higher tacrolimus levels on first blood assay compared to those who did not develop toxicity (16.4 ± 3.4 vs 9.3 ± 3.9, p < .0001; level >10 ng/ml on first assay in 7/7 toxic patients vs 7/19 without toxicity, p = .004). Patients receiving the higher dose regimen had fewer episodes of moderate or severe rejection (≥Grade 3A) at first biopsy than those receiving the lower dose infusion (32% vs 75%; p = .046). No patient required renal dialysis.ConclusionsDosing below 0.05 mg/kg/day may result in clinically important delay in achieving therapeutic levels. Toxicity may be reduced by frequent monitoring of levels for the first 48 hours after transplantation especially when the initial level is >10 ng/ml. Copyright (C) 1999 International Society for Heart and Lung Transplantation.

Original languageEnglish (US)
Pages (from-to)786-791
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume18
Issue number8
DOIs
StatePublished - Jan 1 1999

Fingerprint

Tacrolimus
Heart Transplantation
Poisons
Pediatrics
Transplantation
Blood Safety
Therapeutics
Renal Dialysis
Biopsy

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Robinson, Blair V. ; Boyle, Gerard J. ; Miller, Susan A. ; Law, Yuk M. ; Myers, John ; Griffith, Bartley P. ; Webber, Steven A. / Optimal dosing of intravenous tacrolimus following pediatric heart transplantation. In: Journal of Heart and Lung Transplantation. 1999 ; Vol. 18, No. 8. pp. 786-791.
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title = "Optimal dosing of intravenous tacrolimus following pediatric heart transplantation",
abstract = "Background: Early experience with intravenous tacrolimus at high doses (0.1-0.15 mg/kg/day) was associated with frequent clinical toxicity. The optimal dosing regimen after pediatric heart transplantation is unknown.Methods We retrospectively reviewed data on the last 45 pediatric heart transplant recipients to document the time required to achieve therapeutic blood levels and the safety of 2 differing intravenous dosing regimens (tacrolimus 0.03 and 0.05 mg/kg/day as continuous IV infusion). Target plasma levels were (1.2-1.7 ng/ml) with levels >2.0 ng/ml considered toxic, and target whole blood levels were 15-20 ng/ml with levels >25 ng/ml considered toxic.Results Mean age at transplantation was 7.5 ± 5.6 years (0.1-18), and 14 were infants. Intravenous tacrolimus was commenced at a mean of 7 ± 3 hours (range 2-16) after arrival in the ICU. Eight patients were excluded from analysis because of protocol modifications. Of the remaining 37 pts, 9 received initial infusion at 0.03 mg/kg/day; 3 (33{\%}) achieved 'therapeutic' levels within 48 hours and 1 patient had a toxic level (27 ng/ml) at 36 hours. Twenty-eight patients received 0.05 mg/kg/day; 18 (64{\%}) achieved therapeutic levels within 48 hours and 9 (32{\%}) developed toxic levels. Patients with toxic whole blood levels had higher tacrolimus levels on first blood assay compared to those who did not develop toxicity (16.4 ± 3.4 vs 9.3 ± 3.9, p < .0001; level >10 ng/ml on first assay in 7/7 toxic patients vs 7/19 without toxicity, p = .004). Patients receiving the higher dose regimen had fewer episodes of moderate or severe rejection (≥Grade 3A) at first biopsy than those receiving the lower dose infusion (32{\%} vs 75{\%}; p = .046). No patient required renal dialysis.ConclusionsDosing below 0.05 mg/kg/day may result in clinically important delay in achieving therapeutic levels. Toxicity may be reduced by frequent monitoring of levels for the first 48 hours after transplantation especially when the initial level is >10 ng/ml. Copyright (C) 1999 International Society for Heart and Lung Transplantation.",
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Optimal dosing of intravenous tacrolimus following pediatric heart transplantation. / Robinson, Blair V.; Boyle, Gerard J.; Miller, Susan A.; Law, Yuk M.; Myers, John; Griffith, Bartley P.; Webber, Steven A.

In: Journal of Heart and Lung Transplantation, Vol. 18, No. 8, 01.01.1999, p. 786-791.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Optimal dosing of intravenous tacrolimus following pediatric heart transplantation

AU - Robinson, Blair V.

AU - Boyle, Gerard J.

AU - Miller, Susan A.

AU - Law, Yuk M.

AU - Myers, John

AU - Griffith, Bartley P.

AU - Webber, Steven A.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Background: Early experience with intravenous tacrolimus at high doses (0.1-0.15 mg/kg/day) was associated with frequent clinical toxicity. The optimal dosing regimen after pediatric heart transplantation is unknown.Methods We retrospectively reviewed data on the last 45 pediatric heart transplant recipients to document the time required to achieve therapeutic blood levels and the safety of 2 differing intravenous dosing regimens (tacrolimus 0.03 and 0.05 mg/kg/day as continuous IV infusion). Target plasma levels were (1.2-1.7 ng/ml) with levels >2.0 ng/ml considered toxic, and target whole blood levels were 15-20 ng/ml with levels >25 ng/ml considered toxic.Results Mean age at transplantation was 7.5 ± 5.6 years (0.1-18), and 14 were infants. Intravenous tacrolimus was commenced at a mean of 7 ± 3 hours (range 2-16) after arrival in the ICU. Eight patients were excluded from analysis because of protocol modifications. Of the remaining 37 pts, 9 received initial infusion at 0.03 mg/kg/day; 3 (33%) achieved 'therapeutic' levels within 48 hours and 1 patient had a toxic level (27 ng/ml) at 36 hours. Twenty-eight patients received 0.05 mg/kg/day; 18 (64%) achieved therapeutic levels within 48 hours and 9 (32%) developed toxic levels. Patients with toxic whole blood levels had higher tacrolimus levels on first blood assay compared to those who did not develop toxicity (16.4 ± 3.4 vs 9.3 ± 3.9, p < .0001; level >10 ng/ml on first assay in 7/7 toxic patients vs 7/19 without toxicity, p = .004). Patients receiving the higher dose regimen had fewer episodes of moderate or severe rejection (≥Grade 3A) at first biopsy than those receiving the lower dose infusion (32% vs 75%; p = .046). No patient required renal dialysis.ConclusionsDosing below 0.05 mg/kg/day may result in clinically important delay in achieving therapeutic levels. Toxicity may be reduced by frequent monitoring of levels for the first 48 hours after transplantation especially when the initial level is >10 ng/ml. Copyright (C) 1999 International Society for Heart and Lung Transplantation.

AB - Background: Early experience with intravenous tacrolimus at high doses (0.1-0.15 mg/kg/day) was associated with frequent clinical toxicity. The optimal dosing regimen after pediatric heart transplantation is unknown.Methods We retrospectively reviewed data on the last 45 pediatric heart transplant recipients to document the time required to achieve therapeutic blood levels and the safety of 2 differing intravenous dosing regimens (tacrolimus 0.03 and 0.05 mg/kg/day as continuous IV infusion). Target plasma levels were (1.2-1.7 ng/ml) with levels >2.0 ng/ml considered toxic, and target whole blood levels were 15-20 ng/ml with levels >25 ng/ml considered toxic.Results Mean age at transplantation was 7.5 ± 5.6 years (0.1-18), and 14 were infants. Intravenous tacrolimus was commenced at a mean of 7 ± 3 hours (range 2-16) after arrival in the ICU. Eight patients were excluded from analysis because of protocol modifications. Of the remaining 37 pts, 9 received initial infusion at 0.03 mg/kg/day; 3 (33%) achieved 'therapeutic' levels within 48 hours and 1 patient had a toxic level (27 ng/ml) at 36 hours. Twenty-eight patients received 0.05 mg/kg/day; 18 (64%) achieved therapeutic levels within 48 hours and 9 (32%) developed toxic levels. Patients with toxic whole blood levels had higher tacrolimus levels on first blood assay compared to those who did not develop toxicity (16.4 ± 3.4 vs 9.3 ± 3.9, p < .0001; level >10 ng/ml on first assay in 7/7 toxic patients vs 7/19 without toxicity, p = .004). Patients receiving the higher dose regimen had fewer episodes of moderate or severe rejection (≥Grade 3A) at first biopsy than those receiving the lower dose infusion (32% vs 75%; p = .046). No patient required renal dialysis.ConclusionsDosing below 0.05 mg/kg/day may result in clinically important delay in achieving therapeutic levels. Toxicity may be reduced by frequent monitoring of levels for the first 48 hours after transplantation especially when the initial level is >10 ng/ml. Copyright (C) 1999 International Society for Heart and Lung Transplantation.

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