Efficacy and Safety of Conversion from Twice-daily to Once-daily Tacrolimus in a Large Cohort of Stable Kidney Transplant Recipients

Abstract

Group of new projects in transplantation (Grupo español de actualizaciones en trasplante).Prolonged-release tacrolimus was developed to provide a more convenient once-daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12-month study to describe the efficacy, safety and patient preference of conversion from tacrolimus twice-daily to once-daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg : 1 mg basis (1 mg : 1.1 mg in patients with trough levels <6 ng/mL). The study included 1832 patients (mean age (±SD): 50.0 ± 13.4 years; 62.7% male). After conversion, a modest reduction in tacrolimus trough levels, necessitating an increase in daily dose, was observed (mean changes at 12 months of -9.1% and +1.24%, respectively; p < 0.0001). Mean glomerular filtration rate did not change significantly (56.5 ± 19.7 mL/min at conversion vs. 55.7 ± 20.6 mL/min at 12 months). Proteinuria, blood pressure, lipid, hepatic and glucose parameters remained stable. Eight patients (0.4%) had acute rejection and 34 patients (1.85%) discontinued treatment. Almost all patients (99.4%) preferred the once-daily formulation, because of less frequent dosing (66%) and improved adherence (34%). In conclusion, at similar doses to twice-daily tacrolimus, once-daily formulation provided stable renal function, a low acute rejection rate, and good tolerability in stable kidney transplant recipients in the routine clinical practice setting.

Prevention of organ rejection in renal and liver transplantation with extended release tacrolimus

“…During the study, TAC QD appeared to be efficacious, with only eight patients developing acute rejection and no overall change in eGFR or proteinuria. 42 Other cardiovascular and metabolic parameters also remained unchanged, including blood pressure, lipids, glucose, and liver function tests. 42 Overall 99.4% of patients preferred once-daily tacrolimus and the discontinuation rate was only 1.9%.…”

“…42 Other cardiovascular and metabolic parameters also remained unchanged, including blood pressure, lipids, glucose, and liver function tests. 42 Overall 99.4% of patients preferred once-daily tacrolimus and the discontinuation rate was only 1.9%. 42 Other smaller studies have generally been consistent with these results and, most notably, variously show modest reductions in tacrolimus trough levels with no apparent effect on acute rejection (see Table 3), with follow-up ranging from several weeks to 4 years.…”

“…The largest crossover study, involving 1,832 patients, prospectively analyzed the effect of a 1:1 mg for mg conversion (1:1.1 for patients with known low trough levels) on efficacy, safety, and patient satisfaction. 42 In these patients, the mean trough level was moderately reduced at 12 months (-9.1%) and the mean dose was marginally higher (+1.24%). 42 The persistent reduced level at 12 months raises potential concerns that, over the longer-term, the altered pharmacokinetic profile could increase the risk of subclinical rejection.…”

“…42 In these patients, the mean trough level was moderately reduced at 12 months (-9.1%) and the mean dose was marginally higher (+1.24%). 42 The persistent reduced level at 12 months raises potential concerns that, over the longer-term, the altered pharmacokinetic profile could increase the risk of subclinical rejection. During the study, TAC QD appeared to be efficacious, with only eight patients developing acute rejection and no overall change in eGFR or proteinuria.…”

“…42 Overall 99.4% of patients preferred once-daily tacrolimus and the discontinuation rate was only 1.9%. 42 Other smaller studies have generally been consistent with these results and, most notably, variously show modest reductions in tacrolimus trough levels with no apparent effect on acute rejection (see Table 3), with follow-up ranging from several weeks to 4 years. 18 Note: Tacrolimus-LCP (veloxis Pharmaceuticals, Hørsholm, Denmark).…”