Clinical Study
Effects of Converting Tacrolimus Formulation from
Twice-Daily to Once-Daily in Liver Transplantation Recipients
Ashok Thorat,
1
Hong-Shiue Chou,
1
Chen-Fang Lee,
1
Ruey-Shyang Soong,
1
Tsung-Han Wu,
1
Chih-Hsien Cheng,
1
Ting-Jung Wu,
1
Kun-Ming Chan,
1
and Wei-Chen Lee
1,2
1
Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, College of Medicine,
Chang-Gung University, Taoyuan, Taiwan
2
Department of Liver and Transplantation Surgery, Chang-Gung Transplantation Institute, Chang-Gung Memorial Hospital,
5 Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan
Correspondence should be addressed to Wei-Chen Lee; weichen@cgmh.org.tw
Received 10 March 2014; Accepted 3 June 2014; Published 14 July 2014
Academic Editor: Jaime Aranda-Michel
Copyright © 2014 Ashok horat et al. his is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Typically, tacrolimus is administrated twice daily. Prolonged-release tacrolimus is the once-daily formulation and may be more
convenient for patients. Experience with the administration of the once-daily formulation is still limited. his study enrolled 210
liver transplant recipients who had stable liver function and converted tacrolimus from a twice-daily to once-daily formulation on
a 1 mg to 1 mg basis. Among 210 patients, seven patients (3.3%) were withdrawn from the once-daily formulation due to allergy and
fatigue. For the other patients, the trough concentration ater converting to the once-daily formulation was lower than that of the
twice-daily formulation. Liver enzymes were mildly elevated in 3 months ater formulation conversion and serum creatinine and
uric acid were mildly decreased. Seven patients (3.4%) had clinical suspicion of acute rejection ater the formulation conversion
and three of them were caused by nonadherence. 155 patients (76.4%) experienced a more convenient life with an increase of social
activity. Forty-seven patients (23.2%) experienced the convenience of once-daily formulation during overseas trips. In conclusion,
tacrolimus can be safely converted from the twice-daily to the once-daily formulation for most stable liver recipients. Acute rejection
may occur in a minority of patients during formulation conversion and should be carefully monitored.
1. Introduction
Liver transplantation is the only efective treatment for acute
or chronic liver failure. Following liver transplantation, acute
allograt rejection remains a signiicant cause of morbidity
and may lead to grat dysfunction or failure if it is not treated
promptly [1, 2]. By properly conducting immunosuppressive
regimens, maintaining immunosuppression, and carefully
monitoring drug levels, acute rejection can be successfully
prevented or treated. he advances in immunosuppressive
agents play an essential role in long-term allograt and patient
survival [3, 4]. Cyclosporine, a calcineurin inhibitor, was
introduced into transplantation medicine in the late 1970s
and helped achieve great successes in solid organ transplanta-
tion [5]. Tacrolimus is another potent calcineurin inhibitor
introduced in 1989 and becomes one of the most popular
immunosuppressive agents in liver transplantation now [6,
7].
Despite the progression of immunosuppressants, acute
rejection still occurs in long-term survival patients. his
acute rejection may be due to patients’ nonadherence to
immunosuppressive treatment [2, 8, 9]. he incidence of
nonadherence was estimated from 15% to 50% among
solid organ transplant recipients [2, 10]. Conventionally,
tacrolimus dosage is divided and administered orally every
12 hours to maintain stable trough levels of the drug. he
transplant recipients are advised to take tacrolimus on an
empty stomach more than one hour before or two to three
hours ater a meal since oral bioavailability of tacrolimus is
variable and absorption of tacrolimus is reduced by food [11,
12]. his requirement may be bothersome to some recipients
and thus decrease adherence. herefore, attempts to reduce
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 265658, 7 pages
http://dx.doi.org/10.1155/2014/265658