Published online Mar 24, 2016. doi: 10.5500/wjt.v6.i1.144
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
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.
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.