Extended-release Formulation Of Tacrolimus Research Articles

Effects of switching from twice-daily tacrolimus to once-daily extended-release meltdose tacrolimus on cellular immune response.

LCP-Tacro [LCPT], a novel once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ∼30% dose reduction in contrast to immediate-release tacrolimus (IR-Tac). Once-daily LCPT in de novo kidney transplantation has a comparable efficacy and safety profile to that of IR-Tac with advantages in bioavailability and absorption. The present investigation intends to analyze the effects of conversion from IR-Tac to LCPT on phenotype and function of T-cells and B-cells. 16 kidney transplant patients treated by triple standard immunosuppression with a stable graft function undergoing a switch from IR-Tac to LCPT were included in this observational prospective study. We measured the main immune cell types and performed an in-depth characterization of B cell, dendritic cells and T cells including regulatory T cells of the patients before, 4 and 8 weeks after IR-Tac to LCPT conversion using multi-parameter fl ow cytometry. Additionally, we analyzed T cells by assessing third-party antigens (Tetanus Diphtheria, TD)-reactive T cells, which could be analyzed by restimulation with tetanus vaccine. Overall, we found no significant alterations following LCPT conversion for the most immune cell populations with a few cell populations showing transient quantitative increase. Thus, 4 weeks after conversion, more regulatory T cells could be measured in the patients with a significant shift from memory to naïve Tregs. Furthermore, we found a transient B cell expansion 4 weeks after conversion from IR-Tac to LCPT. There were no changes in the percentage of other basic immune cell types and the antigen-reactive T cells were also not altered after changing the medication to LCP-tacrolimus. Here, we demonstrate first insights into the immune system changes occurred under IR-Tac to LCPT conversion therapy in kidney transplant patients. While phenotypic and functional characteristics of the most immune cell populations did not change, we could observe an a transient expansion of regulatory T cells in peripheral blood following IR-Tac to LCTP conversion, which might additionally contribute to the overall immunosuppressive effect.

Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation

BackgroundExtended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Methods25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. ResultsLCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, −37%, −1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. ConclusionLCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

Comparative Study of 2 Extended-Release Tacrolimus Formulations in Kidney Transplantation

During the 1900s, tacrolimus became the mainstay immunosuppressive agent to prevent rejection after kidney transplant. Subsequently, an extended-release tacrolimus (ER-Tac) formulation was developed to improve adherence, and its generic version has been marketed over the last years. This study examines the differences in efficacy and safety between the generic ER-Tac (Conferoport) and the reference brand-name drug (Advagraf). Prospective, randomized and parallel single-center study (May 2020 to June 2021) with 52 kidney transplant recipients who were randomly assigned to 1 of the following groups: study group (Conferoport, n=31) and control group (Advagraf, n=21). The variables of interest were collected and analyzed to compare tacrolimus efficacy and safety between them. Demographic characteristics of the patients and clinical donor data were homogeneous in both groups (P > .05). No statistically significant differences were found among treatments regarding dosage used, levels, creatinine, and proteinuria (P > .05), with these variables presenting a downward trend during follow-up and, consequently, the improvement of graft function. Analyses also revealed the absence of differences concerning the incidence of acute rejection and intrapatient variability (coefficient of variation) throughout the first year of evolution between both formulations (P > .05). A total of 5 graft losses occurred, 2 resulting from patient death. In our experience, we found no significant differences between the measured parameters in relation to the efficacy and safety profile of both drugs, with generic ER-Tac being an alternative comparable with the reference brand-name ER-Tac.

Significance of CYP3A5 gene *1 allele and obese sarcopenia in renal transplant patients with nephrotoxicity while taking tacrolimus extended-release formulation

Significance of <i>CYP3A5</i> gene ^*<i>1 allele</i> and obese sarcopenia in renal transplant patients with nephrotoxicity while taking tacrolimus extended-release formulation

Conversion from Extended-Dose-Release Tacrolimus to Melt-Dose Tacrolimus in High Metabolizer Patients: Is the New Formulation of LPCT the Best Option for High Metabolizer Kidney Transplanted Patients?

Tacrolimus (FK506) is the most widely used anti-rejection drug in kidney transplantation, especially its extended release Tacrolimus formulation (ER-Tac, Advagraf), which is used when target blood levels can be difficult to reach in high metabolizer patients. In this retrospective monocentric study, we analyzed the effect of a switch from ER-Tac to LifeCycle Pharma Tacrolimus (LPCT, Envarsus) on the dose/level ratio of FK506 in high metabolizer patients that cannot achieve target blood levels in the first 6 months after transplantation.We observed a statistically significant improvement in the level to dose ratio after the switch. Renal function remained stable. We also observed a reduction in the development of tremors.&#x0D; Our data suggest that LPCT can be used in a safer way in high metabolizer kidney transplant recipients.

FRI-370-Application of an extended-release tacrolimus formulation allows dose reduction and stabilizes graft function after liver transplantation

FRI-370-Application of an extended-release tacrolimus formulation allows dose reduction and stabilizes graft function after liver transplantation

Bioavailability and costs of once-daily and twice-daily tacrolimus formulations in de novo kidney transplantation.

The use of once-daily tacrolimus in de novo kidney transplantation is increasingly common. Therefore, we were interested in bioavailability aspects of novel once-daily tacrolimus (LCPT, Envarsus) and once-daily tacrolimus extended-release formulation (ER-Tac, Advagraf) compared with twice-daily immediate-release tacrolimus (IR-Tac, Prograf). Furthermore, we calculated the costs. Kidney allograft recipients on tacrolimus-based immunosuppression within 2 clinical trials were included in a single-center analysis. The tacrolimus formulations were compared with respect to daily doses, doses per body weight, trough levels, and concentration-dose (C/D) ratio over 12months. Intrapatient variability in trough levels and C/D ratios after 3months was calculated. For the calculation of tacrolimus costs, German list prices were used. Eighty patients (21 with LCPT, 23 with IR-Tac, and 36 with ER-Tac) were analyzed. Pharmacokinetic comparisons revealed significantly higher bioavailability of LCPT at all visits. The variability of trough levels and C/D ratios in general was high and highest in LCPT patients. Different dose requirements translated into different costs. Median treatment costs during the first year were 7.825€ (IQR 6.195-8.892€) for LCPT, 9.813€ (IQR 7.630-16.832€) for IR-Tac, and 9.838€ (IQR 7.503- 13.541€) for ER-Tac (Kruskal-Wallis test, P=.003). The 3 tacrolimus formulations exhibit different dose requirements, exposure, and costs in favor of LCPT.

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients

ABSTRACTIntroduction: Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company).Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i.e., basiliximab) in de novo kidney-transplant recipients. To achieve this, we searched for suitable articles through PubMed.Expert commentary: Phases-III and -IV studies comparing Advagraf®/Astagraf XL® to Prograf® in association with mycophenolate mofetil (more than 2,500 patients) have demonstrated overall similar results with regards to patient/graft survival, biopsy-proven acute-rejection rate, and renal function (p > 0.05). A randomized controlled study in maintenance kidney transplant patients has shown (using electronic monitoring) that, as compared to Prograf®, Advagraf® significantly improved adherence to medication. Other studies report that Advagraf®-treated patients receiving a mTOR-inhibitor agent (sirolimus or everolimus) instead of MMF: this was associated with good allograft outcome, and might also prevent late-onset cytomegalovirus infection. Advagraf®-based immunosuppression given to de novo kidney-transplant recipients, with or without an induction therapy, provided excellent results compared to Prograf®; it also increased patients’ adherence to treatment.

Eficacia y seguridad del uso de novo y precoz de tacrolimus de liberación prolongada en el trasplante cardiaco

Introduction and objectivesThe extended-release formulation of tacrolimus (ERT) allows once-daily dosage, thus simplifying the immunosuppressive regimen. This study aimed to describe the safety and efficacy of the de novo and early use of ERT in heart transplantation. MethodsThis was an observational, retrospective, multicenter study comparing the safety and efficacy of the de novo use of ERT (ERT group [n=94]), standard-release tacrolimus (SRT group [n=42]) and early conversion (EC) from SRT to ERT (EC group [n=44]). Extended-release tacrolimus was used between 2007 and 2012. One-year incidence rates of acute rejection, infection, and cytomegalovirus infection were analyzed. Safety parameters were also evaluated. ResultsThere were no significant between-group differences in the daily dose or trough levels of tacrolimus during the first year after transplantation. The rejection incidence rates were 1.05 (95%CI, 0.51-1.54), 1.39 (95%CI, 1.00-1.78), and 1.11 (95%CI, 0.58-1.65) episodes per patient-years in the SRT group, ERT group, and EC group, respectively (P=.48). The infection incidence rates were 0.75 (95%CI, 0.60-0.86), 0.62 (95%CI, 0.52-0.71), and 0.55 (95%CI, 0.40-0.68) in the SRT group, ERT group, and EC group, respectively (P=.46). Cytomegalovirus infection occurred in 23.8%, 20.2%, and 18.2% of the patients, respectively (P=.86). No significant between-group differences were found in laboratory tests or in allograft function. There was 1 death in the SRT group and 2 in the ERT group. ConclusionsBoth de novo and early use of ERT seem to have similar safety and efficacy profiles to conventional SRT-based immunosuppression.Full English text available from: www.revespcardiol.org/en

Efficacy and Safety of de Novo and Early Use of Extended-release Tacrolimus in Heart Transplantation

Introduction and objectivesThe extended-release formulation of tacrolimus (ERT) allows once-daily dosage, thus simplifying the immunosuppressive regimen. This study aimed to describe the safety and efficacy of the de novo and early use of ERT in heart transplantation. MethodsThis was an observational, retrospective, multicenter study comparing the safety and efficacy of the de novo use of ERT (ERT group [n=94]), standard-release tacrolimus (SRT group [n=42]) and early conversion (EC) from SRT to ERT (EC group [n=44]). Extended-release tacrolimus was used between 2007 and 2012. One-year incidence rates of acute rejection, infection, and cytomegalovirus infection were analyzed. Safety parameters were also evaluated. ResultsThere were no significant between-group differences in the daily dose or trough levels of tacrolimus during the first year after transplantation. The rejection incidence rates were 1.05 (95%CI, 0.51-1.54), 1.39 (95%CI, 1.00-1.78), and 1.11 (95%CI, 0.58-1.65) episodes per patient-years in the SRT group, ERT group, and EC group, respectively (P=.48). The infection incidence rates were 0.75 (95%CI, 0.60-0.86), 0.62 (95%CI, 0.52-0.71), and 0.55 (95%CI, 0.40-0.68) in the SRT group, ERT group, and EC group, respectively (P=.46). Cytomegalovirus infection occurred in 23.8%, 20.2%, and 18.2% of the patients, respectively (P=.86). No significant between-group differences were found in laboratory tests or in allograft function. There was 1 death in the SRT group and 2 in the ERT group. ConclusionsBoth de novo and early use of ERT seem to have similar safety and efficacy profiles to conventional SRT-based immunosuppression.

Ten-years data of the first European clinical experience with once-daily tacrolimus extended release formulation in renal transplant recipients

Background: Clinical data about long-term use of tacrolimus QD are lacking. Methods: Ten-years data were collected from 37 renal transplant recipients participating in a Tacrolimus BID (Prograf®) to QD (Advagraf®) conversion study. They were converted at a median of 4.1 years post-transplant (range 1.5-11.4) with a stable renal function (serum creatinine 20% had an immunological or unknown cause of renal failure. Conclusion: Patients on tacrolimus QD have excellent 10-year renal function, patient - and graft survival.

Conversion from Twice-Daily to Once-Daily Tacrolimus Improves Graft Function but has no Influence on Proteinuria in Renal Transplant Recipients

Abstract Introduction. Tacrolimus extended-release formulation enables once-daily use. Although an increasing number of patients have been converted from twice-daily (Tac- BID) to once-daily (Tac-QD) formulation, the available information regarding the initiation and follow-up of Tac- QD is sparse. In the present study we investigated influence of switch from Tac-BID or cyclosporine to Tac-QD on renal allograf function, proteinuria and protein-creatinine (P/C) ratio. Methods. Between October 2012 and October 2014, the switch from Tac-BID or cyclosporine to tacrolimus extended-release formulation was done in 129(38% female, mean age 49 years) renal transplant recipients at different time after transplantation. The analysis focused on markers of graft function (GFR, serum creatinine, proteinuria, P/C ratio), liver function (AST, ALT, γGT, alkaline phosphatase) and blood glucose. Clinical data were obtained at baseline (before conversion), 1 month (V1), 6 months (V6) and 12 months (V12) after conversion. Results. Both serum creatinine and GFR showed a statistically significant improvement. With GFR, signifycant improvement was observed as early as V1 and it continued to increase throughout the study period up to V12 (all between-visit changes were statistically significant). With serum creatinine, mean levels were numerically decreasing throughout the follow-up period, but a significant improvement occurred at V6 and remained significant at V12 (both vs. V0 values). Proteinuria and P/C ratio did not show any significant change through the observation period. In the majority of patients, the baseline values of AST, ALT, GGT, AlP and glucose were within normal limits and did not change significantly through the observation period. Analysis of tacrolimus C0 showed a significant decrease throughout the follow-up period, at practically all visit. This finding was paralleled by a significant tacrolimus dose decrease from baseline to V6 and V12, as well as by a significant decrease of tacrolimus dose/body weight. Conclusions. Conversion from cyclosporine or Tac-BID to extended-release Tac-QD improves graft function in renal transplant recipients, without influence on proteinuria or P/C ratio.

Population Pharmacokinetic Modelling and Bayesian Estimation of Tacrolimus Exposure: Is this Clinically Useful for Dosage Prediction Yet?

This review summarises the available data on the population pharmacokinetics of tacrolimus and use of Maximum A Posteriori (MAP) Bayesian estimation to predict tacrolimus exposure and subsequent drug dosage requirements in solid organ transplant recipients. A literature search was conducted which identified 56 studies that assessed the population pharmacokinetics of tacrolimus based on non-linear mixed effects modelling and 14 studies that assessed the predictive performance of MAP Bayesian estimation of tacrolimus area under the plasma concentration-time curve (AUC) from time zero to the end of the dosing interval. Studies were most commonly undertaken in adult kidney transplant recipients and investigated the immediate-release formulation. The pharmacokinetics of tacrolimus were described using one- and two-compartment disposition models with first-order elimination in 61 and 39% of population pharmacokinetic studies, respectively. Variability in tacrolimus whole blood apparent clearance amongst transplant recipients was most commonly related to cytochrome P450 (CYP) 3A5 genotype (rs776746), patient haematocrit, patient weight, post-operative day and hepatic function (aspartate aminotransferase). Bias, as calculated using estimation of the mean predictive error (MPE) or mean percentage predictive error (MPPE) associated with prediction of the tacrolimus AUC, ranged from -15 to 9.95%. Imprecision, as calculated through estimation of the root mean squared error (RMSE) or mean absolute prediction error (MAPE), was generally much poorer overall, ranging from 0.81 to 40. r 2 values ranged from 0.27 to 0.99%. Of the Bayesian forecasting strategies that used two or more tacrolimus concentrations, 71% showed bias of 10% or less; however, only 39% showed imprecision of 10% or less. The combination of sampling times at 0, 1 and 3h post-dose consistently showed bias and imprecision values of less than 15%. No studies to date have examined how closely MAP Bayesian dosage predictions of tacrolimus actually achieve target AUC by comparing dosage prediction from one occasion with a future measured AUC. Further research involving larger prospective studies including more diverse transplant groups and the extended-release formulation of tacrolimus is needed. Several questions require further examination, including the following. Do Bayesian forecasting methods currently use the most appropriate population pharmacokinetic models and optimal sampling times for dosage prediction? Does Bayesian forecasting perform well when applied to make dosage predictions on a subsequent occasion? How can Bayesian forecasting be simplified for use in the clinical setting? And, are patient outcomes improved with dosage prediction based on Bayesian forecasting compared with trough concentration monitoring?

Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method.

Tacrolimus is a poorly water-soluble compound that is used to prevent allograft rejection. We aimed to prepare an extended release formulation of tacrolimus to achieve both an extended release profile and improved solubility of tacrolimus. Extended release granules (ERG) of tacrolimus were prepared with lactose, ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) via the solvent evaporation method. In an in vitro release study, ERG had an extended release profile, and the release rate of tacrolimus was regulated by the quantity of lactose, EC and HPMC in the formulation. HPMC-containing ERG successfully enhanced and maintained supersaturation of tacrolimus even after 24 h in a supersaturated release study. In contrast, the extent of supersaturation rapidly decreased after 4 h and the concentration nearly reached the same level as that of crystalline tacrolimus at 24 h for ERG without HPMC. In vivo absorption characteristics were compared between ERGs and immediate release (IR) formulation of tacrolimus. Successful and sustained absorption of tacrolimus without reducing bioavailability compared with IR formulation was observed for ERG. These results suggest the feasibility of combining an EC-based formulation with solid dispersion utilizing HPMC for the extended release of oral formulations and sustained absorption of tacrolimus.

Overview of extended release tacrolimus in solid organ transplantation.

Tacrolimus (Prograf(©), Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf(©), Astagraf XL(©)) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patient's due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher.

Limited Sampling Strategies for Predicting Tacrolimus Exposure With Once Daily Extended Formulation in Kidney Transplant Recipients and Optimal Pre-Dosing Schedule.

Pharmacokinetics (PK) and optimal dosing of tacrolimus extended-release formulation (TACER)re not well evaluated. We have validated the use of single and limited sampling strategies to estimate tacrolimus exposure with TACER. Patients and Methods: Thirty-three Living-donor kidney transplant recipients were prospectively involved in PK-study measuring tacrolimus area under curve profiles (TAC-AUC) 0-24 by 9 points sampling following the trapezoidal rule at 1, 2 and 3 weeks after transplant. All recipients received 0.2mg/day of TACER 7 days before transplant, followed by mycophenolate mofetile (MMF), prednisolone and basiliximab after transplant. Targeted trough level of tacrolimus was 8-10ng/ml in the first month, 6-8ng/ml until 3 months and 4-6ng/ml thereafter. MMF was started with 1250mg bid and reduced to 750mg bid at 2 weeks after transplant. 1) Optimal pre-dosing schedule, 2) clinical efficiency and CNI toxicity evaluated by protocol biopsy at 6 and 12 months after transplant, 3) Correlation between single sampling/limited sampling strategies and measured TAC-AUC 0-24 were evaluated respectively. Results: 1) With a mean observation of 45 months (40-53), patients and graft survival are 100%. 2) Subclinical and clinical T cell mediated rejection were observed in 2(6.1%) and 2(6.1%). 3) CNI toxicity were observed in 7(21.2%) by protocol biopsies and mean eGFR maintained above 50ml/min/1.73m2 at 3 years after transplant. 4) Trough level of tacrolimus did not correlated with AUC0-24 (R=0.79), nor other single sampling data. Limited sampling strategy principles well correlated with AUC 0-24 as shown in Table1.Table: No Caption available.Conclusions: This study suggests that tacrolimus exposure with TACER can be accurately estimated only using limited sampling strategy. And lower targeted trough level of tacrolimus could be tested based on low rejection and high toxicity rate with standard exposure of tacrolimus with TACER.

C12 Measurement With Nocturnal Dosing of Tacrolimus Extended-Release Formulation Shows High Correlation to Daily Exposure.

C12 Measurement With Nocturnal Dosing of Tacrolimus Extended-Release Formulation Shows High Correlation to Daily Exposure.

236 The once-daily tacrolimus extended-release formulation provides similar drug exposure in non-CF and CF lung transplant recipients when compared to the conventional twice-daily formulation

236 The once-daily tacrolimus extended-release formulation provides similar drug exposure in non-CF and CF lung transplant recipients when compared to the conventional twice-daily formulation

Conversion from twice-daily to once-daily extended-release tacrolimus in renal transplant recipients: 2-year results and review of the literature.

Tacrolimus extended-release formulation has been approved for use in Canada since October 2008. In initial studies, efficacy and safety profile were demonstrated as similar for both formulations (twice-daily tacrolimus and extended-release formula tacrolimus). To validate the safety and efficacy of extended-release formula tacrolimus, we conducted a prospective observational study. At our institution, between January 2009 and January 2010, the switch from tacrolimus to extended-release formula tacrolimus was done in 130 stable kidney recipients. Clinical data were accessed at baseline (data before conversion), 1 to 2 weeks, 1 month, 3 months, 6 months, 12 months, and 24 months after conversion. One hundred thirty renal transplant recipients were included in the current study. During the observation period, we saw no acute rejection and no change in graft function (mean serum creatinine levels remained stable). However, compared with baseline, mean tacrolimus trough levels were significantly reduced at 1 to 2 weeks, at 1 month, 6 months, 12 months, and at 24 months after conversion. Regarding the safety profile, no significant changes were noted in blood glucose, potassium, and magnesium. Approximately 35% of recipients preferred the extended-release formula tacrolimus to twice-daily tacrolimus. Conversion from twice-daily tacrolimus to extended-release once-daily tacrolimus appears to be safe and convenient up to 2 years after conversion in some recipients.

Tacrolimus Extended Release Formulation Given As An Alternative To Ciclosporine A In Case Of Renal Impairment After Allogeneic HSCT: Results From a Prospective Pilot Study

Introduction Tacrolimus is a widely used calcineurin inhibitor in allogeneic HCST for prophylaxis and treatment of GvHD. This molecule is now available in both standard-release (Prograf, twice-daily tacrolimus, Astellas Pharma) and extended-release (Advagraf, once-daily tacrolimus, Astellas Pharma) formulations. Compared with the standard-release formulation, the extended-release (ER) tacrolimus has been shown in previous pharmacological studies to provide bioequivalent drug exposure, efficacy and safety. Moreover, this formulation of tacrolimus was followed by a clinically significant improvement in kidney graft function for kidney recipients. Based on these observations, we have conducted a prospective study in wich ciclosporine A (CsA) (Neoral) is switched for tacrolimus ER (Advagraf) in case of renal impairment after alloHSCT. Method We enrolled 16 consecutive patients with renal impairment (serum creatinine &gt;110 µMol/L) from May 2012 to May 2013 during the follow-up at outpatient clinic, the conversion dose was established on an mg:mg basis 1:100 from CsA total oral daily dose to a single dose of oral tacrolimus ER formulation. The dose was readjusted to obtain a tacrolimus blood trough level between 5 and 15 µg/L. Tacrolimus ER was given at noon in a single dose one hour before lunch. We evaluated the tacrolimus blood trough level changes after switch, serum creatinine, glycemia, potassium, acute and chronic GvHD. A satisfaction survey for tacrolimus ER treatment was performed 3 months after the switch, the questionnaire included administration compliance questions. Results All patients in this cohort had hematological malignancies, the median age was 52 years (range, 28-66). Eight patients (50%) had a matched related donor, 7 patients (43.75%) had a HLA-10/10 matched unrelated donor and 1 patient underwent alloHSCT with two cord blood units. Seven patients (43.75%) received a myeloablative regimen with 12 Gy TBI and 9 patients (56.25%) a reduced intensity regimen. The stem cell source was bone marrow for 7 patients (43.75%), PBSC for 8 patients (50%) and cord blood for one patient. The status at transplantation was CR1 for 6 patients (37.5%), CR2 or more for 6 patients (37.5%) and partial response for 4 patients (25%). The median follow-up of the cohort was 7 months (range,2-14). Non-parametric tests such as exact Wilcoxon Mann-Whitney test or Kruskal Wallis were performed for the analysis of the physiological parameters. The median of serum creatinine was 112 µmol/L (range, 51-262) with CsA and 87 µmol/L (range, 50-125) with tacrolimus ER (p&lt;.0001) (Figure). The median of potassium level was 4.2 (range, 3.5-5.2) with CsA and 4.0 (3.4-4.5) with tacrolimus ER (p =.001) (Figure). The median time of switch was 45 days (10-162) and the median of serum creatinine in which the switch was realized was 138 µmol/L (range,110-262). Nor patient had diabetes mellitus neither elevation of potassium &gt; 4.5 mmol/L after the switch for tacrolimus ER. The median blood trough level was 300 µg/L (range,100-438) for CsA 14 days after starting and 7.2 (range,3-15) for tacrolimus ER 20 days after starting (Figure). The cumulative incidence of aGvHD grade &gt;1 at 3 months was 25% (95%CI,14-36). After the switch for tacrolimus ER, no patient developped aGvHD. Eight patients (50%) developed aGvHD grade &gt;1 during the prophylaxis with CsA. For 6 patients (37.5%), aGvHD was resolutive after the switch for tacrolimus ER with an association of tacrolimus ER and prednisone or tacrolimus ER alone. For 2 patients (12.5%), aGvHD was resolutive with CsA and prednisone before the switch for tacrolimus ER. Two patients in this study developed severe chronic GvHD after the discontinuation of prophylaxis (5 months and 10 months). One patient received tacrolimus ER with a complete resolution of cGvHD and the second patient is now on therapy with everolimus. All patients in this cohort are alive and all patients except two are still in complete response. Moreover, the satisfaction survey demonstrated that the patients were satisfied with the switch and the one daily formulation of tacrolimus. Conclusion The conversion from oral CsA to oral tacrolimus ER formulation was followed by a clinically significant improvement in kidney function with stable tacrolimus blood trough levels. The patients were satisfied with this formulation of tacrolimus. We have now extended this study to several centers in the aim to confirm these observations. Disclosures: No relevant conflicts of interest to declare.