Osilodrostat oral tablets for adults with Cushing’s disease

Martino, Marianna; Aboud, Nairus; Lucchetti, Beatrice; Salvio, Gianmaria; Arnaldi, Giorgio

doi:10.1080/17446651.2022.2044789

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…Commonly used maintenance dose is 4–14 mg twice daily with a maximum dose of 30 mg twice daily. [ 1 ] Osilodrostat has three active metabolites [M34.5 (51%), M16.5 (9%), and M24.9 (7%) of administered dose], which have longer half-lives making twice daily dosing feasible, which significantly improves patient compliance and satisfaction vis a viz four doses/day and six doses/day for ketoconazole and metyrapone respectively. [ 21 ] Hirsutism and acne (androgenic side effects) may limit the long-term use of osilodrostat in women, similar to that of metyrapone.…”

Section: Discussionmentioning

confidence: 99%

“…Osilodrostat (oral medication; peak blood levels at 1 h; half-life of 4 h), is a potent reversible inhibitor of 2 major enzymes involved in adrenal steroidogenesis [11β-hydroxylase cytochrome P450 family 11 subfamily B member 1 (CYP11B1): catalyses the hydroxylation of 11-deoxycortisol to cortisol and of 11-deoxycorticosterone to corticosterone; and 18-hydroxylase (aldosterone synthase, CYP11B2): catalyses the conversion of corticosterone to aldosterone]. [ 1 ] Thus, osilodrostat happens to be a dual inhibitor of glucocorticoid and mineralocorticoid biosynthetic pathways. In-vitro studies have documented a threefold higher affinity for CYP11B1 with osilodrostat as compared to metyrapone, another drug having a similar mechanism of action.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Osilodrostat in Managing Cushing’s Syndrome: A Systematic Review and Meta-Analysis

Nagendra,

Dutta,

Raizada

et al. 2024

Indian Journal of Endocrinology and Metabolism

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No meta-analysis has holistically analysed and summarized the efficacy and safety of osilodrostat, a novel dual 11β-hydroxylase (cytochrome P450 family 11 subfamily B member 1 [CYP11B1]) and 18-hydroxylase (aldosterone synthase, CYP11B2) inhibitor in managing Cushing’s syndrome (CS). We undertook this meta-analysis to address this knowledge gap. Electronic databases were searched for randomized controlled trials (RCTs) involving patients with CS receiving osilodrostat in the intervention arm. The primary outcome was to evaluate changes in urine free cortisol (UFC) levels. Secondary outcomes were to evaluate alterations in cortisol levels, androgen levels, mineralocorticoid levels, and adverse events. From initially screened 109 articles, data from 2 RCTs involving 144 patients was analysed. After 8–12 weeks of therapy, the odds of achieving a normal 24-hour UFC was higher in patients receiving oslidrostat as compared to placebo. [odds ratio (OR) 21.94 (95% CI: 8.53–56.43); P < 0.00001; I2 = 0%]. The occurrence of adverse events [OR 1.35 (95% CI: 0.52–3.53); P = 0.54; I2 = 0%; low heterogeneity (LH); High certainty of evidence (HCE)], serious adverse events (SAEs) [OR 1.32 (95% CI: 0.30–5.79); P = 0.72; I2 = 0%; LH; HCE], adrenal insufficiency [OR 5.38 (95% CI: 0.91–31.78); P = 0.06; I2 = 0%; LH; HCE], headache [OR 0.98 (95% CI: 0.35–2.76); P = 0.97; I2 = 0%; LH; HCE], hyperandrogenism [OR 3.68 (95% CI: 0.59–22.80); P = 0.16; I2 = 0%; LH; HCE] and deaths [OR 0.32 (95% CI: 0.01–8.00); P = 0.48; I2 = 0%; LH; HCE] was comparable among the groups. The occurrence of nausea [OR 4.25 (95% CI: 1.26–14.30); P = 0.02; I2 = 0%; LH] and arthralgia [OR 6.54 (95% CI: 1.64–26.13); P = 0.008; I2 = 0%; LH; HCE] was significantly higher in the osilodrostat group as compared to placebo. Osilodrostat has good efficacy and safety in CS and was well tolerated over 48 weeks of use.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Osilodrostat in Managing Cushing’s Syndrome: A Systematic Review and Meta-Analysis

Nagendra,

Dutta,

Raizada

et al. 2024

Indian Journal of Endocrinology and Metabolism

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Treatment of Cushing’s syndrome with osilodrostat: practical applications of recent studies with case examples

Fleseriu

2022

Pituitary

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Endogenous Cushing’s syndrome (CS) is a rare endocrine condition frequently caused by a tumor resulting in elevated cortisol levels. Cushing’s disease (CD) caused by an adrenocorticotropic hormone–secreting pituitary adenoma is the most common form of endogenous CS. Medical therapy for CD is mostly used as second-line treatment after failed surgery or recurrence and comprises several pituitary-directed drugs, adrenal steroidogenesis inhibitors, and a glucocorticoid receptor blocker, some of which are US Food and Drug Administration (FDA)–approved for this condition. The recent Pituitary Society consensus guidelines for diagnosis and management of CD described osilodrostat, an oral inhibitor of 11β-hydroxylase, as an effective, FDA-approved medical therapy for CD. Because clinical experience outside clinical trials is limited, we provide here a review of published data about osilodrostat and offer example case studies demonstrating practical considerations on the use of this medication. Recommendations regarding osilodrostat are provided for the following situations: specific assessments needed before treatment initiation; monitoring for adrenal insufficiency, hypokalemia, and changes in QTc; the potential value of a slow up-titration in patients with mild disease; managing temporary treatment cessation for patients with CD who have acquired coronavirus disease 2019; monitoring for increased testosterone levels in women; exercising caution with concomitant medication use; considering whether a higher dose at nighttime might be beneficial; and managing cortisol excess in ectopic and adrenal CS. This review highlights key clinical situations that physicians may encounter when using osilodrostat and provides practical recommendations for optimal patient care when treating CS, with a focus on CD.

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The role of ARMC5 in adrenal pathology: a brief review

Smith

2022

Diagnostic Histopathology

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Osilodrostat oral tablets for adults with Cushing’s disease

Cited by 3 publications

References 34 publications

Efficacy and Safety of Osilodrostat in Managing Cushing’s Syndrome: A Systematic Review and Meta-Analysis

Efficacy and Safety of Osilodrostat in Managing Cushing’s Syndrome: A Systematic Review and Meta-Analysis

Treatment of Cushing’s syndrome with osilodrostat: practical applications of recent studies with case examples

The role of ARMC5 in adrenal pathology: a brief review

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