Purpose: Extended release (ER) tacrolimus (tac) has been available as Advagraf® for many years and as Astagraf XL® in the US since 2013. Immediate release (IR) tac (Prograf®) demonstrates excellent absorption in the a.m. and less robust absorption in the p.m., suggesting it could be prescribed once daily (Qday) in the a.m. A tac PK study showed that a 24-hour trough is a sensitive marker of total body drug exposure in patients receiving daily a.m. dosing (AJT 2004). At our center, we commonly switch patients to Qday dosing of tac.

Methods: We performed a retrospective study of adult renal recipients transplanted 1/1/1999-1/1/2013. Patients switched from twice daily (BID) to Qday IR tac were compared to patients that remained on BID tac. The primary outcome was the incidence of acute rejection (AR). Secondary outcomes included death and graft loss. In patients converted to Qday tac, difference in serum creatinine (SCr), blood pressure (BP), glucose glucose (BG), and tac neurotoxicity pre- and post-conversion were also analyzed.

Results: 1830 patients on BID and 119 patients on Qday IR tac were compared. Median time to switch was 8 (0.25-123) months post-transplant. Major reasons for switch were HLA matching (45.4%) and tac toxicity (42.9%). 5.1% in the BID group and 3.4% in the Qday group experienced AR (p=0.40). Graft loss (16.2% BID vs. 15.1% Qday, p=0.75) and death (9.4% BID vs. 8.4% Qday, p=0.72) were similar. In the 119 patients on Qday tac, the median total daily dose 1 month prior to switch was 3.7mg and 1.8mg at 12 months post-switch (p<0.001). Median tac troughs were 4.3ng/mL at 1 month prior, and 3ng/mL at 12 months post-switch (p=0.134). The median SCr improved by 12 months post-switch (1.5 vs. 1.2mg/dL; p=0.134). BP and BG control was similar pre- vs. post-conversion. Neurotoxicity (tremors or insomnia) was present in 30 patients pre-switch and symptoms improved in 90% post-switch. 80.7% remained on Qday tac at a median of 3.7 (0.1-12.7) years post-switch. 35% of those no longer on Qday tac were withdrawn from tac completely due to a 2 haplotype matched kidney transplant.

Conclusions: Qday dosing of IR tac was not associated with an increase in AR. Post-conversion, there was a non-significant decrease in SCr, and improvement in tac-associated neurotoxicity. We believe that generic IR tac is a less costly alternative to the ER formulations without compromising efficacy.

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