J Korean Med Sci.  2016 Nov;31(11):1711-1716. 10.3346/jkms.2016.31.11.1711.

Risk Factors for the Adverse Events after Conversion from Twice-Daily to Once-Daily Tacrolimus in Stable Liver Transplantation Patients

• Suh SW
• Lee KW
• Jeong J
• Kim H
• Yi NJ
• Suh KS

• KMID: 2470265
• DOI: http://doi.org/10.3346/jkms.2016.31.11.1711

Abstract

Despite the therapeutic equivalence between twice-daily and once-daily tacrolimus, patient safety after conversion is still a concern. We reviewed 218 liver transplantation (LT) patients who converted twice-daily to once-daily tacrolimus between May 2011 and January 2014. Thirty (13.8%) patients had adverse events after conversion, with a liver function test (LFT) abnormality being the most common adverse event (n = 17). Despite the decrease in serum tacrolimus of > 30% after conversion, none of the patients who were converted to a dosage ratio (once-daily tacrolimus dosage: twice-daily tacrolimus dosage) > 1 had an LFT abnormality. Most patients with an LFT abnormality improved after increasing the once-daily tacrolimus dosage (n = 2), returned to a previous medication, and/or added another immunosuppressant (n = 15). One patient had acute cellular rejection, which improved after steroid pulse treatment, and another patient had graft failure. In patients with a dosage ratio ≤ 1, the conversion time within 5 years after LT was the only significant risk factor for an LFT abnormality after conversion (odds ratio: 11.850, 95% confidence interval: 1.321-106.325, P = 0.027). In conclusion, the dosage ratio and time after LT should be carefully considered during conversion from twice-daily to once-daily tacrolimus.

Keyword

Once-daily Tacrolimus; Twice-daily Tacrolimus; Conversion; Liver Transplantation; Adverse Events

MeSH Terms

Adolescent
Adult
Aged
Child
Drug Administration Schedule
Female
Graft Rejection/*prevention & control
Humans
Immunosuppressive Agents/blood/*therapeutic use
Liver Failure/therapy
Liver Function Tests
Liver Transplantation/*adverse effects
Male
Middle Aged
Multivariate Analysis
Odds Ratio
Retrospective Studies
Risk Factors
Tacrolimus/blood/*therapeutic use
Young Adult

Figure

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  Fig. 1 Dosage vs. trough level after conversion. DR = dosage ratio, Similar = < 30% decrease of tacrolimus level after conversion, Decrement = ≥ 30% decrease of tacrolimus trough level after conversion.

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  Fig. 2 Proportion of LFT abnormality after conversion by conversion time and dosage ratio. (A) LFT abnormality after conversion in patients who had DR > 1. There was no patient with LFT abnormality after conversion. (B) LFT abnormality after conversion in patients who had DR = 1. 7 (11.3%) patients in Group B and 4 (4.5%) patients in Group C had LFT abnormality after conversion. (C) LFT abnormality after conversion in patients who had DR < 1. 4 (33.3%) patients in Group B and 2 (15.4%) patients in Group C had LFT abnormality after conversion (P = 0.003). Group A = LFT normal, Group B = LFT abnormality in patient with ≥ 30% decrease of tacrolimus level after conversion, Group C = LFT abnormality in patient with < 30% decrease tacrolimus level after conversion, LFT = liver function test, DR = dosage ratio.

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