Extended-release Hydrocortisone Formulations-Is There a Clinically Meaningful Benefit?

Abstract

Despite best practice replacement therapy with corticosteroids, patients with adrenal insufficiency report diminished quality of life and face increased mortality and morbidity. Conventional formulations of hydrocortisone have short half-lives (about 90 minutes) requiring multiple dosing during the day. Since 2011, extended-release hydrocortisone (ER-HC) formulations have been available enabling once-, sometimes twice-daily dosing. Most studies comparing ER-HC formulations with conventional hydrocortisone therapy report reduction in body weight, blood pressure and glucose levels, and improved quality of life. However, it is still unclear if the reported beneficiary effects are due to differences in cortisol exposure or alterations in pharmacokinetics. Here, we review studies comparing conventional and ER-HC treatment in adrenal insufficiency and discuss whether these novel formulations are safe and offer clinically significant benefits.

Keywords: Addison's disease; adrenal insufficiency; extended-release hydrocortisone (ER-HC); glucocorticoid replacement therapy; immediate-release hydrocortisone (IR-HC).

Figure 1.

Cortisol profiles in healthy subjects and during replacement therapy. (A) Cortisol and adrenocorticotropic hormone profiles in blood of a healthy subject revealing circadian and ultradian rhythmicity (modified from Lightman and Conway-Campbell, Nature Review Neuroscience, 11, 710-18, 2010). (B) Serum cortisol during trice daily immediate release hydrocortisone (mean of 64 patients, dosing interval 20-40 mg per day, modified from Johannsson et al, J Clin Endocrinol Metabol, 97(2):473-81). (C) Serum cortisol profiles during treatment with once daily Plenadren in the morning (mean of 64 patients, dosing interval 20-40 mg per day, modified from Johannsson et al, J Clin Endocrinol Metabol, 97(2):473-81). (D) Serum cortisol profiles during twice daily Chronocort, 20 mg at 23:00 hours and 10 mg at 07:00 hours (modified from DeBono et al J Clin Endocrinol Metabol, 94(5):1548-54). Reproduced with permission from the copyright owners and authors.