Accuracy of hydrocortisone dose administration via nasogastric tube

Daniel, Eleni; Whitaker, Martin J.; Keevil, Brian; Wales, Jerry; Ross, Richard

doi:10.1111/cen.13876

Cited by 9 publications

(9 citation statements)

References 26 publications

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“…However, these doses are not appropriate to treat neonates, infants, and young children with adrenal insufficiency who require a daily dose of 10–15 mg/m² with single doses as low as 0.5 mg ( 27 ). Crushed hydrocortisone tablets suspended in water are often used in some countries ( 26 ), though accurate dosing is not possible as hydrocortisone does not dissolve well in water and may adhere to plastic material when applied with syringes ( 28 , 29 ). Another common practice in pharmacies is to compound hydrocortisone often mixed with sucrose to overcome the inherent bitterness of hydrocortisone.…”

Section: Optimized Hydrocortisone Dosing In Childrenmentioning

confidence: 99%

Clinical advances in the pharmacotherapy of congenital adrenal hyperplasia

Prete

Auchus

Ross

2022

European Journal of Endocrinology

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Background Patients with 21-hydroxylase deficiency congenital adrenal hyperplasia (21OHD-CAH) have poor health outcomes with increased mortality, short stature, impaired fertility, and increased cardiovascular risk factors such as obesity. To address this, there are therapies in development that target the clinical goal of treatment, which is to control excess androgens with an adrenal replacement dose of glucocorticoid. Methods Narrative review of publications on recent clinical developments in the pharmacotherapy of congenital adrenal hyperplasia. Summary Therapies in clinical development target different levels of the hypothalamo–pituitary–adrenal axis. Two corticotrophin-releasing factor type 1 (CRF1) receptor antagonists, Crinecerfont and Tildacerfont, have been trialled in poorly controlled 21OHD-CAH patients, and both reduced ACTH and androgen biomarkers while patients were on stable glucocorticoid replacement. Improvements in glucocorticoid replacement include replacing the circadian rhythm of cortisol that has been trialled with continuous s.c. infusion of hydrocortisone and Chronocort, a delayed-release hydrocortisone formulation. Chronocort optimally controlled 21OHD-CAH in 80% of patients on an adrenal replacement dose of hydrocortisone, which was associated with patient-reported benefits including restoration of menses and pregnancies. Adrenal-targeted therapies include the steroidogenesis-blocking drug Abiraterone acetate, which reduced adrenal androgen biomarkers in poorly controlled patients. Conclusions CRF1 receptor antagonists hold promise to avoid excess glucocorticoid replacement in patients not controlled on standard or circadian glucocorticoid replacement such as Chronocort. Gene and cell therapies are the only therapeutic approaches that could potentially correct both cortisol deficiency and androgen excess.

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Section: Optimized Hydrocortisone Dosing In Childrenmentioning

confidence: 99%

Clinical advances in the pharmacotherapy of congenital adrenal hyperplasia

Prete

Auchus

Ross

2022

European Journal of Endocrinology

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“…Parent and caregiver concern about accuracy of doses prepared in this way causes distress, with carers describing the difficulties of manipulating medicines vital for their young children, and resultant worry, on top of the other stresses of parenthood [15]. Hydrocortisone is virtually insoluble in water and may adhere to plastics used during preparation [16], however, attempting to dissolve hydrocortisone in water to obtain low doses for pediatric patients is common [14]. A laboratory study concluded that liquid hydrocortisone in water is a suspension rather than a solution, the volume used does not correlate with dose delivered, and in one case the delivered dose was more than 250% of the target dose [14].…”

Section: Overview Of the Adrenal Insufficiency Marketmentioning

confidence: 99%

“…Hydrocortisone administration via nasogastric (NG) tube is required in sick children with adrenal insufficiency, in some cases of sepsis and occasionally in premature infants; however, use of hydrocortisone granules directly down the NG tube is contraindicated due to risk of blocking fine bore NG tubes. This finding came from an in vitro study to measure hydrocortisone recovery after passing through NG tubes for three formulations; suspension, crushed tablets in water, and hydrocortisone granules in capsules for opening [16]. Even before passage through the NG tube, hydrocortisone recovery was low for all formulations examined; between 30%-78%, presumably due to hydrocortisone sticking to the syringes.…”

Section: Administration Via Nasogastric Tubesmentioning

confidence: 99%

Hydrocortisone granules in capsules for opening (Alkindi) as replacement therapy in pediatric patients with adrenal insufficiency

Coope

Parviainen

Withe

et al. 2021

Expert Opinion on Orphan Drugs

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Introduction: Treatment of pediatric adrenal insufficiency (AI) has been challenging due to a lack of dose and age appropriate hydrocortisone preparations for children. Hydrocortisone granules in capsules for opening (Alkindi) is the only licensed replacement therapy specifically designed for use in pediatric adrenal insufficiency. Areas Covered: The high unmet need of the pediatric AI patient population for a licensed, doseappropriate hydrocortisone formulation and the development and approval of hydrocortisone granules in capsules for opening for pediatric AI. Expert opinion: To date, treatment of children with AI has relied on parents or pharmacists crushing tablets of hydrocortisone. Pediatric patients have suffered from over-and under-treatment with poor health outcomes. Hydrocortisone granules in capsules for opening provides accurate, age-appropriate dosing, allowing appropriate dose titration for the growing child. The granule-based formulation is taste masked to hide the bitterness of hydrocortisone, and in clinical trials was well tolerated and easily administered to children. The granules can be administered either directly to the mouth or sprinkled onto soft food or yogurt. Hydrocortisone granules in capsules for opening provides the first licensed treatment option specifically designed for pediatric patients with AI.

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“…Hydrocortisone is poorly soluble in aqueous solutions and suspensions have been shown not to be bioequivalent to the hydrocortisone tablet (14). Furthermore, suspensions are viscous and may adsorb to equipment used in compounding (15). Studies of compounded hydrocortisone report that up to 25% of batches from pharmacies and 50% by parents were out of specification leading to clinically evident under-or over-treatment including iatrogenic Cushing's syndrome (16,17,18).…”

Section: Introductionmentioning

confidence: 99%

Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young children

Michelet

Melin

Parra-Guillén

et al. 2020

European Journal of Endocrinology

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Context: Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing`s syndrome and adrenal crisis. Objective: To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens. Design and methods: Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate 7 different hydrocortisone treatment regimens. Results: Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the 7 treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC24h within the 90% reference range for healthy children except in neonates where 2 regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 hours were outside the 90% reference range for healthy individuals in 50%, 55% - 65% and 70% - 75% for children, infants and neonates, respectively, with low cortisol levels being most prevalent. Conclusions: Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC24h but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.

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Accuracy of hydrocortisone dose administration via nasogastric tube

Cited by 9 publications

References 26 publications

Clinical advances in the pharmacotherapy of congenital adrenal hyperplasia

Clinical advances in the pharmacotherapy of congenital adrenal hyperplasia

Hydrocortisone granules in capsules for opening (Alkindi) as replacement therapy in pediatric patients with adrenal insufficiency

Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young children

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