Once-daily LCP-Tacro MeltDose tacrolimus for the prophylaxis of organ rejection in kidney and liver transplantations

Abstract

Tacrolimus is a cornerstone of the immunosuppression regimen for prevention of allograft rejection in kidney and liver transplantations, with efficacy proven in many clinical trials. The currently available and extensively used tacrolimus formulations are flawed by large inter- and intra-individual variability, low bioavailability, wide peak-to-trough fluctuations and a narrow therapeutic index. Drug delivery technology can significantly impact the pharmacologic action of a drug, influencing its pharmacokinetic and subsequent therapeutic profile. LCP-Tacro is a novel, prolonged-release, MeltDose^® formulation of tacrolimus designed for once-daily administration. A hallmark differentiation between this formulation and other once- and twice-daily tacrolimus products is the proprietary MeltDose drug delivery technology which is designed to improve the bioavailability of drugs with low water solubility. Considering the studies conducted to date, once-daily LCP-Tacro has shown improved pharmacokinetic properties, rapid achievement of therapeutic trough levels, consistent exposure, non-inferior efficacy and similar safety, with lower tacrolimus dose than other tacrolimus formulations.

Keywords::

• efficacy
• kidney transplantation
• LCP-Tacro
• liver transplantation
• MeltDose^®
• once-daily administration
• pharmacokinetics
• prolonged-release formulation
• safety
• tacrolimus

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Erratum

Financial & competing interests disclosure

Chiesi Farmaceutici (Parma, Italy) provided funding in support of this manuscript. S Petruzzelli is an employee of Chiesi Farmaceutici. K Kistler (Evidera) provided writing assistance, funded by Chiesi Farmaceutici. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The overwhelming majority (∼91%) of kidney and liver transplant recipients are on a tacrolimus-based immunosuppression regimen.

• Tacrolimus has a narrow therapeutic range/window, and it is essential that patients are within the range to avoid rejection (if too low) and toxicity (if too high).

• Currently available tacrolimus formulations are highly effective but have less than desirable pharmacokinetic characteristics – for example, low bioavailability.

• A novel, prolonged-release, once-daily, MeltDose^®, tacrolimus tablet has been developed for prevention of rejection following kidney and liver transplantation.

• The MeltDose drug delivery technology decrease’s tacrolimus’ particle size to a molecular level which in turn results in significantly improved bioavailability compared to other tacrolimus formulations and a smoother, flatter pharmacokinetic profile compared to other formulations of tacrolimus.

• Rapid achievement of blood levels in de novo transplant patients immediately following Day 1 of dosing.

• LCP-Tacro shows improved bioavailability, lower C_max and less peak-to-trough fluctuation, and higher exposure at equivalent doses to the classical tacrolimus formulation, which results in a lower dosing benefit compared to twice-daily tacrolimus capsules.

• LCP-Tacro is associated with a more rapid achievement of target trough levels, with more constant levels within the therapeutic window.

• Fewer dose adjustments needed over the first 14 days and year post transplant.

• LCP-Tacro is non-inferior in efficacy to twice-daily tacrolimus capsules with similar safety.

• Additional potential benefits of prolonged-release, once-daily, MeltDose, tacrolimus tablet are less pill burden, and the possibility for less peak-related toxicity (e.g., tremor).

Notes