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Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency.

European journal of endocrinology (2014-06-20)
A G Nilsson, C Marelli, D Fitts, R Bergthorsdottir, P Burman, P Dahlqvist, B Ekman, B Edén Engström, T Olsson, O Ragnarsson, M Ryberg, J Wahlberg, H Lennernäs, S Skrtic, G Johannsson
ABSTRACT

The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden. Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness). In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure. This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
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Hydrocortisone solution, 50 μM, sterile-filtered, BioXtra, suitable for cell culture
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Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
Supelco
Cortisol solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
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Hydrocortisone, Pharmaceutical Secondary Standard; Certified Reference Material
Hydrocortisone, European Pharmacopoeia (EP) Reference Standard
USP
Hydrocortisone, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Hydrocortisone for peak identification, European Pharmacopoeia (EP) Reference Standard
Supelco
Hydrocortisone, VETRANAL®, analytical standard