Alkindi (hydrocortisone granules): risk of acute adrenal insufficiency in children when switching from hydrocortisone tablet formulations to granules
When children receiving replacement therapy for adrenal insufficiency are being switched from hydrocortisone tablets to Alkindi granules, parents or carers should be informed of the need to be extra vigilant for symptoms of adrenal insufficiency.
Advice for healthcare professionals:
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adrenal crisis has been reported in an infant who was switched from hydrocortisone soluble tablets to Alkindi (hydrocortisone granules)
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acute adrenal insufficiency could also occur when switching from crushed hydrocortisone tablets to Alkindi granules due to a potential risk of inaccurate dosing
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if the child is switching to Alkindi granules, parents or carers should be advised to carefully observe the child during the first week for symptoms of adrenal insufficiency, such as tiredness, floppiness, unstable temperature, headache and vomiting
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counsel parents or carers on what to do if the child develops symptoms of adrenal insufficiency, including the need to seek immediate medical advice and administer extra doses of Alkindi if appropriate
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if a child requires additional doses during the first week after switching to Alkindi, a long-term increase in the daily dose of Alkindi should be considered
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report suspected adverse drug reactions associated with hydrocortisone medicines on a Yellow Card
Case of severe adrenal insufficiency
Alkindi hydrocortisone granules are indicated for replacement therapy of adrenal insufficiency in infants, children and adolescents (from birth to age 18 years).
A single case has been reported of an infant developing severe adrenal insufficiency when switched from hydrocortisone soluble tablets to Alkindi granules. The child experienced an adrenal crisis approximately 48 hours after starting Alkindi. The child had no evidence of transient illness such as severe infection and there was no indication that Alkindi had been administered incorrectly, nor any symptoms of malabsorption.
Due to the low solubility of hydrocortisone, preparing hydrocortisone soluble tablets not in accordance with the manufacturer’s instructions may risk variable dosing and make conversion to other forms of hydrocortisone in younger children difficult.
Similarly, variable dosing could also potentially occur with the use of crushed hydrocortisone tablets in younger children, resulting in the starting dose of Alkindi not corresponding to the actual dose of hydrocortisone previously being taken.
New safety advice to parents or carers
When converting children from oral hydrocortisone formulations, such as soluble or crushed tablets, to Alkindi granules, parents or carers should be advised to observe the child carefully in the first week after the switch. This is especially important in younger children less able to communicate symptoms of adrenal insufficiency.
The prescriber should instruct parents and carers what to do if the child develops any symptoms of adrenal insufficiency such as tiredness, floppiness, temperature instability, headache, or vomiting. This could include giving the child extra doses of Alkindi, in accordance with the recommendations in the Summary of Product Characteristics. In addition, carers and patients should be advised to seek immediate medical advice if such symptoms occur.
If a child requires additional dosing during the first week after transferring from oral hydrocortisone formulations, such as crushed or soluble tablets, to Alkindi, an increase in the daily dose of Alkindi should be considered.
These risks have been considered by a European safety review and the product information for Alkindi will be updated with appropriate advice. A letter has been sent to healthcare professionals.
Report on a Yellow Card
Please continue to report suspected adverse drug reactions to the Yellow Card scheme.
Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:
- the Yellow Card website
- the Yellow Card app; download from the Apple App Store or Google Play Store
- some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)
When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.
Report suspected side effects to medicines, vaccines or medical device and diagnostic adverse incidents used in coronavirus (COVID-19) using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app. See the MHRA website for the latest information on medicines and vaccines for COVID-19.
Article citation: Drug Safety Update volume 14, issue 7: February 2021: 3.