Effect on Dosage Change and Intrapatient Variability After Conversion From Twice-Daily to Once-Daily Tacrolimus Among Thai Kidney Transplant Patients With and Without CYP3A4/5 Inhibitors.

Background: Converting to once-daily tacrolimus (Advagraf [Adv]) among renal transplant patients results in better drug adherence. Data regarding dosage and intrapatient variability changes after conversion among patients with CYP3A4/5 inhibitors (CYPinh) is lacking.

Method: A retrospective chart review among all kidney transplant recipients at Siriraj Hospital was performed. Patients were enrolled who had been on standard release twice-daily tacrolimus and subsequently replaced it with Adv for at least 6 months with no change in CYPinh type or dosage.

Results: Fifty-three patients were eligible. Conversion occurred at a mean time after transplant of 51.25 (SD, 40.30) months. Ten patients (18.9%) did not receive CYPinh, while 19 (35.8%), 21 (39.6%), and 3 (5.7%) received diltiazem, ketoconazole or fluconazole, and both diltiazem and ketoconazole, respectively. After conversion, median increment of tacrolimus dosage was 14.29% (-50% to 167%), while no significant change in IPV was demonstrated (17.46% [SD, 11.25%] vs 14.83% [SD, 6.78]; P = .11). Patients receiving azole had less dosage increment than those not receiving CYPinh (P = .02). After conversion, 14 of 22 patients with IPV > 17% (63.6%) had reduced IPV to ≤ 17%, while 25.8% of patients with lower IPV had an increase in IPV > 17%.

Conclusion: Conversion to Adv required a dosage increment of 30% to achieve the same trough level. Concomitant use of CYPinh significantly reduced tacrolimus dose increment. A trend was noted toward improved IPV after conversion. Conversion to Adv resulted in better IPV among patients with high IPV while receiving twice-daily tacrolimus.