Absorption and tolerability of taste‐masked hydrocortisone granules in neonates, infants and children under 6 years of age with adrenal insufficiency

Abstract

SummaryObjectives: There is no licensed, dose-appropriate formulation of hydrocortisone for children with adrenal insufficiency (AI) and patients rely on compounded adult medication. The aim of this study was to evaluate the absorption, palatability and safety of Infacort ® , an immediate-release, granule formulation of hydrocortisone with taste masking. Study design:Single site with satellites attended by a "flying" doctor from investigator site. Open-label, single-dose study in three consecutive child cohorts (n = 24) with AI;Cohort 1, children aged 2 to <6 years (n = 12); Cohort 2, infants aged 28 days to <2 years (n = 6); Cohort 3, neonates aged 1 to <28 days (n = 6). Methods:Fasted children were given a single dose of Infacort ® as dry granules administered directly from a capsule or spoon followed by a drink. The primary end-point was the maximum serum cortisol concentration up to 240 minutes after Infacort ® administration. Secondary end-points were palatability and adverse events (AEs).Results: All children showed an increase in cortisol above baseline after Infacort Conclusions: Infacort ® is well tolerated, easy to administer to neonates, infants and children and shows good absorption, with cortisol levels at 60 minutes after administration similar to physiological cortisol levels in healthy children. K E Y W O R D Sadrenal insufficiency, congenital adrenal hyperplasia, infants, neonates, oral hydrocortisone granules This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Immediate-release granule formulation of hydrocortisone, Alkindi®, for treatment of paediatric adrenal insufficiency (Infacort development programme)

“…Six of the 12 children in the oldest cohort responded to an adjusted palatability questionnaire, with ≥50% subjects reporting that the taste, feel in mouth and ease of swallowing were very good and that they were likely to take the medicine again. No serious adverse events were seen throughout the study, and the adverse events seen were mild (most common reported were diarrhoea, vomiting and rash) and not attributed to investigational product (6).…”

“…The challenge for paediatric patients and their health care providers is that hydrocortisone is only licensed in 10 and 20mg tablet doses in the European Union and children require much smaller doses (of the order of 1-2mg three times daily in infants), and are unable to swallow tablets designed for adults (5). Current clinical practice is for pharmacists to compound hydrocortisone either by tablet crushing or using hydrocortisone base to produce a powder or special solutions of hydrocortisone or in some countries, such as the United Kingdom, for parents to crush tablets (6)(7)(8). All such practice is unlicensed and not subject to the level of regulation and quality control of licensed drug manufacture where Good Manufacturing Practice (GMP) regulations mean that every aspect of manufacturing must be described, controlled and regularly assessed with a quality management system in place at each step.…”

“…Thus, there is a need for a licensed paediatric appropriate formulation of hydrocortisone. diameter, and allows for swallowing of granules even by neonates (15). The granules are presented within a transparent capsule that is opened for dosing, this allows for accurate paediatric dosing with dose strengths of 0.5, 1.0, 2.0, and 5.0 mg ( Figure 1).…”

“…Both cortisol and cortisone are renally excreted and hydrocortisone can be sequentially metabolised to allo-tetrahydrocortisol, tetrahydrocortisol and tetrahydrocortisone, also renally excreted (19). The phase 3 study was undertaken in the Charite hospital in Berlin (6). The study was a sequential age cohort design to maximise subject safety.…”

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“…It can be administered with food, liquids or as dry granules directly onto the child's tongue. It is available in 0.5, 1, 2 and 5 mg doses (69). Infacort® may represent a valid option for precise dosing in paediatric patients with AI.…”