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World J Transplant. Mar 24, 2016; 6(1): 144-154
Published online Mar 24, 2016. doi: 10.5500/wjt.v6.i1.144
Overview of extended release tacrolimus in solid organ transplantation
Neha Patel, Abigail Cook, Elizabeth Greenhalgh, Megan A Rech, Joshua Rusinak, Lynley Heinrich
Neha Patel, Abigail Cook, Elizabeth Greenhalgh, Megan A Rech, Joshua Rusinak, Lynley Heinrich, Department of Pharmacy, Loyola Medical Center, Maywood, IL 60153, United States
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Neha Patel, PharmD, BCPS, Department of Pharmacy, Loyola Medical Center, 2160 S. First Ave., Maywood, IL 60153, United States. paten@musc.edu
Telephone: +1-843-7922367
Received: August 6, 2015
Peer-review started: August 7, 2015
First decision: October 16, 2015
Revised: November 16, 2015
Accepted: December 29, 2015
Article in press: January 4, 2016
Published online: March 24, 2016
Abstract

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.

Keywords: Tacrolimus, Extended release tacrolimus, Pharmacokinetics, Pharmacoeconomics, Solid-organ transplant

Core tip: Tacrolimus is an immunosuppressive agent to prevent and treat allograft rejection in solid organ transplant recipients. An extended release tacrolimus formulation known as Astagraf XL is now available which allows for once-daily dosing, with the potential to improve adherence. Both tacrolimus formulations have demonstrated comparable steady-state systemic tacrolimus exposure in de novo kidney and liver transplant recipients. The following review will address the pharmacokinetics of extended release tacrolimus, the data in solid-organ transplantation and the phamacoeconomic considerations of extended release tacrolimus compared to twice daily tacrolimus.