Dosing algorithms for initiation of immunosuppressive drugs in solid organ transplant recipients

Abstract

Introduction: Starting doses of tacrolimus and ciclosporin are typically chosen on a calculated mg/kg bodyweight basis. After initiation of treatment, doses are adjusted with therapeutic drug monitoring (TDM). This trial-and-error approach has been accepted by most physicians and pharmacists involved in the care of transplanted patients.

Areas covered: Dosing algorithms have only fairly recently been proposed to better individualize the starting dose. This review provides an overview of all the currently available dosing algorithms in adult and children for the starting dose of ciclosporin, tacrolimus and mycophenolic acid. In these algorithms, multiple other covariates influencing the starting dose, such as age, hematocrit, comedication and genotype are taken into account. After selecting the starting dose with an algorithm and after initiation of treatment, TDM will, however, remain necessary. Whether or not implementation of such algorithms will improve clinical outcome remains to be demonstrated.

Expert opinion: First of all an algorithm needs to be validated, against an independent dataset. Second, in a prospective study the algorithm should prove to reduce the time to reach the target concentration, and to reduce the number of patients with drug concentrations (far) outside the therapeutic window. Finally, a clinical trial demonstrating a benefit on clinical outcome will be crucial in achieving broad acceptance of calculating starting dose using individualized dosing algorithms.

Keywords:

• algorithm
• ciclosporin
• dose
• equation
• immunosuppressive drugs
• kidney
• liver
• mycophenolic acid
• pharmacokinetics
• tacrolimus
• therapeutic drug monitoring
• transplantation

Declaration of interest

DA Hesselink has received lecture and consulting fees, as well as grant support from Astellas, Fresenius, Novartis, MSD, Roche and Bristol-Myers Squibb. T van Gelder has received honoraria for presentations or for advisory committees from Astellas, Novartis and Roche. SN de Wildt is supported by a ZonMw Clinical Fellowship and has received investigator-initiated research funding from Novartis and consultancy fees from Koehler Chemie. 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.

Notes

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