Single Center Experiences of Conversion from Twice-daily Tacrolimus (Prograf) to Once-daily Tacrolimus (Advagraf) in Stable Liver Transplant Recipients

Tae-Seok Kim; Keun Soo Ahn; Yong Hoon Kim; Hyoung Tae Kim; Koo Jeong Kang

doi:10.4285/jkstn.2016.30.2.77

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Kim, Ahn, Kim, Kim, and Kang: Single Center Experiences of Conversion from Twice-daily Tacrolimus (Prograf) to Once-daily Tacrolimus (Advagraf) in Stable Liver Transplant Recipients

Original Article

J Korean Soc Transplant 2016;30(2):77-81.

Published online: 19 January 2016

DOI: https://doi.org/10.4285/jkstn.2016.30.2.77

Single Center Experiences of Conversion from Twice-daily Tacrolimus (Prograf) to Once-daily Tacrolimus (Advagraf) in Stable Liver Transplant Recipients

Tae-Seok Kim, M.D., Keun Soo Ahn, M.D., Yong Hoon Kim, M.D., Hyoung Tae Kim, M.D., Koo Jeong Kang, M.D.

Department of Surgery, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea

Corresponding author: Koo Jeong Kang Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, 56 Dalseong-ro, Jung-gu, Daegu 41931, Korea Tel: 82-53-250-7655, Fax: 82-53-250-7322 E-mail: kjkang@dsmc.or.kr

Received 5 January 2016 Revised 9 June 2016 Accepted 9 June 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Patient adherence to immunosuppressant regimens after organ transplant is crucial to preserve graft function, and simplifying the regimen improves adherence. In this study, our experience of conversion from twice-daily (b.i.d.) to once-daily (q.d.) tacrolimus (TAC) in stable liver transplant recipients is reviewed and the proper conversion regimen is investigated.

Methods:

Between November 2011 and August 2012, the regimen was converted in 32 stable liver transplant recipients, and data on the conversions gathered retrospectively from medical records. TAC trough level, dose, and laboratory findings were evaluated at preconversion and 1 to 12 months after conversion.

Results:

Conversion from b.i.d. to q.d. regimen was based on 1:1 proportion in 16 patients and dose escalation in 16 patients. The mean conversion time after transplant was 56.8 months (range; 21∼94). Reconversion to b.i.d. regimen was needed in nine patients. Among these patients, seven patients needed titration due to elevated liver enzyme. The trough level decreased significantly after conversion (from 4.7 to 3.1 ng/mL) in patients with conversion at 1:1 proportion, while increasing slightly without statistical significance (3.7 to 4.0 ng/mL) in patients with dose escalation. At 1 year after conversion, dose adjustment was required to preserve trough level and graft function in 14 patients.

Conclusions:

Based on our results, TAC q.d. formulation can be a useful option to improve adherence in stable liver transplant recipients. However, dose titration should be considered for preserving proper trough level in case of low TAC level or TAC single regimen.

Keywords: Tacrolimus, Immunosuppression, Once-daily tacrolimus

REFERENCES

1). Chapman JR. Compliance: the patient, the doctor, and the medication? Transplantation. 2004. 77:782–6.

2). Lieber SR., Volk ML. Non-adherence and graft failure in adult liver transplant recipients. Dig Dis Sci. 2013. 58:824–34.

3). Dumortier J., Guillaud O., Boillot O. Conversion from twice daily tacrolimus to once daily tacrolimus in long-term stable liver transplant recipients: a single-center experience with 394 patients. Liver Transpl. 2013. 19:529–33.

4). Beckebaum S., Iacob S., Sweid D., Sotiropoulos GC., Saner F., Kaiser G, et al. Efficacy, safety, and immunosuppressant adherence in stable liver transplant patients converted from a twice-daily tacrolimus-based regimen to once-daily tacrolimus extended-release formulation. Transpl Int. 2011. 24:666–75.

5). Alloway RR., Eckhoff DE., Washburn WK., Teperman LW. Conversion from twice daily tacrolimus capsules to once daily extended-release tacrolimus (LCP-Tacro): phase 2 trial of stable liver transplant recipients. Liver Transpl. 2014. 20:564–75.

6). Giannelli V., Rossi M., Giusto M., Lucidi C., Lattanzi B., Ruffa A, et al. Conversion from twice-daily to once-daily Tacrolimus administration in liver transplant patient: results of long term follow-up. Eur Rev Med Pharmacol Sci. 2013. 17:2718–20.

7). Valente G., Rinaldi L., Sgambato M., Piai G. Conversion from twice-daily to once-daily tacrolimus in stable liver transplant patients: effectiveness in a real-world setting. Transplant Proc. 2013. 45:1273–5.

8). Jannot M., Masson I., Alamartine E., Mariat C. Early conversion from twice-daily tacrolimus to once-daily extended formulation in renal transplant patients before hospital discharge. Ann Transplant. 2014. 19:320–4.

9). Laederach-Hofmann K., Bunzel B. Noncompliance in organ transplant recipients: a literature review. Gen Hosp Psychiatry. 2000. 22:412–24.

10). Ichimaru N., Kakuta Y., Abe T., Okumi M., Imamura R., Isaka Y, et al. Treatment adherence in renal transplant recipients: a questionnaire survey on immunosuppressants. Transplant Proc. 2008. 40:1362–5.

11). Trunecka P., Boillot O., Seehofer D., Pinna AD., Fischer L., Ericzon BG, et al. Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation. Am J Transplant. 2010. 10:2313–23.

12). Kim SH., Lee SD., Kim YK., Park SJ. Conversion of twice-daily to once-daily tacrolimus is safe in stable adult living donor liver transplant recipients. Hepatobiliary Pancreat Dis Int. 2015. 14:374–9.

13). Dopazo C., Rodriguez R., Llado L., Calatayud D., Castells L., Ramos E, et al. Successful conversion from twice-daily to once-daily tacrolimus in liver transplantation: observational multicenter study. Clin Transplant. 2012. 26:E32–7.

14). Sanko-Resmer J., Boillot O., Wolf P., Thorburn D. Renal function, efficacy and safety postconversion from twice- to once-daily tacrolimus in stable liver recipients: an open-label multicenter study. Transpl Int. 2012. 25:283–93.

Fig. 1.

Trough level change at 1 month after conversion (n=32).

Table 1.

Patients characteristics at the time of conversion (n=32)

Characteristic	Value
Sex (males/female)	24/8
Age at conversion (yr)	55±9.9 (18∼72)
Time from LT to conversion	56.8±19.49 (21∼94)
Immunosuppressant regimen
TAC single	30
TAC+MMF	2
History of rejection episode	5 (16)
Indications for LT
Hepatitis B virus	18 (56)
Hepatocellular carcinoma	10 (31)
Others	4 (13)
Mean TAC dose (mg/day)	2.03±0.60 (1∼4)
Baseline mean trough level (ng/mL)	4.2±1.50 (1.9∼7.4)
Reconversion to TAC twice-daily	9 (28)
Time from conversion to reconversion	4.4±4.12 (0.9∼11.4)
Cause of reconversion
Elevated AST or ALT (1:1/escalation)	7 (5/2)
Uncontrolled trough level	1
Neurologic symptom^a	1

Data are presented as mean±SD (range) or number (%).

Abbreviations: LT, liver transplant; MMF, mycophenolate mofetil; TAC, tacrolimus; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

^a Perioral numbness.

Table 2.

Liver function, kidney function, serum trough level, and dose of TAC in patients with successful conversion at baseline and after the conversion from TAC twice-daily to TAC once-daily (n=23)

Variable	Time (mo)					P-value
Variable	Baseline	1	3	6	12	P-value
ALP (U/L)	254±124	246±115	228±114	232±99	235±105	0.001
AST (U/L)	22±6	21±5	22±6	22±5	23±6	0.727
ALT (U/L)	21±12	20±10	21±9	22±10	23±10	0.819
Total bilirubin (mg/dL)	0.9±0.3	0.9±0.4	1.0±0.4	1.0±0.5	0.9±0.4	0.640
Serum Cr (mg/dL)	0.9±0.3	0.9±0.2	1.0±0.2	1.0±0.2	0.9±0.2	0.178
eGFR (mL/min)	94±28	93±26	87±24	88±25	91±27	0.095
TAC level (ng/mL)	3.9±1.4	3.2±1.5	3.4±1.5	3.6±1.1	3.8±1.6	0.254
TAC dose (mg)	2.1±0.6	2.4±0.8	2.5±0.8	2.5±0.8	2.6±0.8	0.001

Data are presented as mean±SD.

Abbreviations: TAC, tacrolimus; ALP, alkaline phosphatase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; eGFR, estimated glomerular filtration rate.

Table 3.

Comparison of characteristics and results between 1:1 dose group and escalation group

Characteristic	1:1 Group	Escalation group	P-value
Sex (male/female)	12/4	12/4
Age at conversion (yr)	54±11.6	56±8.1	0.577
Time from LT to conversion (mo)	56.5±23.4	57.2±15.3	0.926
History of rejection	3 (19)	2 (13)	0.632
Mean TAC dose (mg/day)	2.0±0.5	2.1±0.7	0.772
Mean conversion dose (mg/day)	2.0±0.5	2.7±0.8	0.013
Baseline mean trough level (ng/mL)	4.7±1.5	3.7±1.4	0.056
Mean trough level after conversion (ng/mL)	3.1±1.3	4.0±1.8	0.110
Reconversion to TAC twice-daily	5 (31)	4 (25)	0.699
Reconversion due to elevated AST or ALT	5 (31)	2 (13)	0.207

Data are presented as mean±SD or number (%). Abbreviations: LT, liver transplant; TAC, tacrolimus; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

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