Tacrolimus Concentration in Pediatric Compounded Suspensions Under Conditions Mimicking Real‐Life Use

ABSTRACT Background Tacrolimus is an immunosuppressant drug with a narrow therapeutic index used to treat children following solid organ transplantation as well as those with other immune‐mediated conditions. While tacrolimus exists as a child‐friendly commercially prepared formulation in many countries, such formulation adapted to children's needs is unavailable in Canada. Hence, pharmacists must resort to preparing tacrolimus compounded suspensions (TCS) for children unable to swallow tablets/capsules. The aim of this pilot study was to evaluate tacrolimus concentration in TCS over time under various conditions mimicking real‐life use. Methods In this study, we used ultra‐high performance liquid chromatography (UHPLC) to measure tacrolimus concentrations in nine bottles of TCS over time, under various handling and storage conditions mimicking real‐life use, and compared these with the expected TCS concentration of 0.5 mg/mL. Results The initial concentration of tacrolimus was found to be less than 90% of the expected concentration in two bottles and less than 95% in six bottles. In addition, for the six bottles mimicking real‐life use, with twice daily samplings for 28 days, four bottles on day 7 and five on days 14, 21, and 28 had concentrations of tacrolimus less than 90% of expected (range at day 28, −4.4% to −31.4% variation). Conclusions Compounding, storage, and handling can affect tacrolimus concentration in compounded suspensions, potentially leading to therapeutic inefficacy or toxicity due to inadvertent under‐ or overdosing. The results of this study should not only raise concerns for TCS but for all other liquid compounded drugs. Despite the international availability of commercially prepared pediatric formulations, including tacrolimus granules, Canada as well as other countries remain reliant on compounding as a means of administering tacrolimus along with numerous other medications to young children. Our results provide new data to fuel ongoing advocacy work for improving access to commercial pediatric formulations.