Significant reduction of Tacrolimus trough level after conversion from twice daily Prograf to once daily Advagraf in Chinese renal transplant recipients with or without concomitant diltiazem treatment

Abstract

A dose ratio of 1:1 was recommended for the conversion from Standard-release Tacrolimus (Prograf) to Prolonged-release Tacrolimus (Advagraf). We investigated the trough tacrolimus blood level in Chinese kidney transplant recipients after conversion, including subjects receiving concomitant treatment with diltiazem. Eighteen stable renal allograft recipients were followed prospectively for 12 weeks after conversion from Prograf to Advagraf at the same daily dose. Tacrolimus blood trough level decreased significantly within 8 weeks after conversion (p < 0.01). Twelve patients required escalation of the Advagraf dose by 1.10 ± 0.36 mg. For the whole group the daily tacrolimus dose was increased from 0.057 ± 0.032 mg/kg to 0.068 ± 0.033 mg/kg (p < 0.0001). At week 12 the daily dose of Advagraf was 127 ± 32% of the original daily dose of Prograf. In the subgroup of patients receiving diltiazem, their tacrolimus trough level decreased significantly after conversion (p = 0.001), and the daily tacrolimus dose was increased from 0.060 ± 0.036 mg/kg to 0.073 ± 0.036 mg/kg (p < 0.0001). At week 12, their daily dose of Advagraf was 131 ± 34% of the original daily dose before conversion. To conclude, conversion from Prograf to Advagraf in renal allograft recipients with or without diltiazem co-treatment necessitated an increase in the daily dose by approximately 30% to maintain the target blood trough level unchanged.

High Intrapatient Variability in Tacrolimus Exposure Calculated Over a Long Period Is Associated With De Novo Donor-Specific Antibody Development and/or Late Rejection in Thai Kidney Transplant Patients Receiving Concomitant CYP3A4/5 Inhibitors

“…The mean number of Tac trough levels obtained to calculate IPV [6][7][8][9][10][11][12] and IPV 6-24 was 5.0 6 1.1 and 11.2 6 2.47, respectively. IPV [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] was significantly higher than IPV [6][7][8][9][10][11][12] (P , 0.001); however, IPV [6][7][8][9][10][11][12] was comparable to IPV [13][14][15][16][17][18][19][20][21][22][23]…”

“…16 To minimize CNI costs, several centers in developing countries, including our hospital, continue to prescribe CYP3A4/5 inhibitors (CYPinh) early after KT to increase CNI trough levels, as recommended by Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. 1,17 This strategy increases patient access to transplantation. Evidence regarding the effects of CYPinh use on Tac IPV and data on IPV in the Thai population are currently limited.…”

Extended release once a day tacrolimus

“…Although some have found such conversion to be well tolerated and effective [19][20][21][22], others have expressed concern for increased risk of rejection in stable kidney transplant recipients [23]. One study showed that such a conversion may necessitate an increase in the daily dose of Astagraf/ Advagraf by approximately 30% to maintain the target blood trough level unchanged [24].…”

Tacrolimus in preventing transplant rejection in&nbsp;Chinese patients &ndash; optimizing use

“… 73 The once-daily tacrolimus formulation can significantly improve patient adherence; however, in order to maintain a similar tacrolimus blood concentration, the once-daily dosage of tacrolimus should increase by 30%. 74 …”