Compounded hydrocortisone capsules fail quality standards

By Eleanor McDermid
Eur J Endocrinol 2017; Advance online publication
01 June 2017

medwireNews: Researchers have found that compounded hydrocortisone capsules used to treat congenital adrenal hyperplasia (CAH) and other causes of adrenal insufficiency in children contain inconsistent amounts of the hormone, highlighting the need for licensed paediatric formulations.

Oliver Blankenstein (Charité-Universitätsmedizin Berlin, Germany) and co-researchers note that the lowest hydrocortisone doses available in the USA and Europe are 5.0 mg and 10.0 mg, respectively, whereas the doses needed to treat paediatric patients can be as low as 0.5 mg, making compounded hydrocortisone unavoidable.

The team undertook their study after encountering a 5-year-old CAH patient who developed accelerated growth and elevated androgens, attributed to a poor batch of compounded hydrocortisone capsules.

“Poor compliance is often blamed for poor disease control in children with CAH and this causes considerable distress to children and parents,” the researchers write in the European Journal of Endocrinology.

“However, as we show here this might also be due to the lack of content uniformity in compounded hydrocortisone.”

The team found that a quarter of the 56 batches they analysed, containing 1125 hydrocortisone capsules, failed the European Pharmacopoeia criteria for acceptable mass and content uniformity.

Specifically, seven (12.5%) batches failed content uniformity criteria (>10% of capsules deviated by ≥15% or at least one capsule deviated by ≥25%). And nine (16.0%) batches failed net mass criteria (corresponding thresholds of ≥10% and ≥20%).

In all, 21.4% of batches failed to meet the criteria for either content or mass (7.1% for both), and two batches did not contain detectable hydrocortisone, meaning that 25.0% were substandard.

“These patients require hydrocortisone replacement therapy to avoid life-threatening adrenal crises and careful titration of therapy to control androgen excess and optimize growth and development,” say Blankenstein and team.

They stress the need for licensed paediatric formulations, approved by the European Medicines Agency and the US Food and Drug Administration.

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