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

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.

Single Center Experiences of Conversion from Twice-daily Tacrolimus (Prograf) to Once-daily Tacrolimus (Advagraf) in Stable Liver Transplant Recipients / 대한이식학회지

BACKGROUND: Patient adherence to immunosuppressant regimens after organ transplant is crucial to preserve graft function, and simplifying the regimen improves adherence. In this study, our experience of conversion from twice-daily (b.i.d.) to once-daily (q.d.) tacrolimus (TAC) in stable liver transplant recipients is reviewed and the proper conversion regimen is investigated. METHODS: Between November 2011 and August 2012, the regimen was converted in 32 stable liver transplant recipients, and data on the conversions gathered retrospectively from medical records. TAC trough level, dose, and laboratory findings were evaluated at preconversion and 1 to 12 months after conversion. RESULTS: Conversion from b.i.d. to q.d. regimen was based on 1:1 proportion in 16 patients and dose escalation in 16 patients. The mean conversion time after transplant was 56.8 months (range; 21~94). Reconversion to b.i.d. regimen was needed in nine patients. Among these patients, seven patients needed titration due to elevated liver enzyme. The trough level decreased significantly after conversion (from 4.7 to 3.1 ng/mL) in patients with conversion at 1:1 proportion, while increasing slightly without statistical significance (3.7 to 4.0 ng/mL) in patients with dose escalation. At 1 year after conversion, dose adjustment was required to preserve trough level and graft function in 14 patients. CONCLUSIONS: Based on our results, TAC q.d. formulation can be a useful option to improve adherence in stable liver transplant recipients. However, dose titration should be considered for preserving proper trough level in case of low TAC level or TAC single regimen.