Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing's Disease.
Ann Pharmacother
; 55(8): 1050-1060, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33143437
ABSTRACT
OBJECTIVE:
To review data on efficacy and safety of osilodrostat (Isturisa), a novel oral steroidogenesis inhibitor for treatment of Cushing's disease (CD), a life-threatening endocrine disorder. DATA SOURCES A PubMed/CINAHL search from inception to September 25, 2020, was performed using the following keywords osilodrostat, 11-beta hydroxylase, pituitary, ACTH hypersecretion, and Cushing's disease. STUDY SELECTION AND DATA EXTRACTION Phase 2 and 3 clinical trials and supplementary documents investigating osilodrostat were obtained from a primary literature search, the manufacturer's website, and the Food and Drug Administration website. These articles evaluated the clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions for osilodrostat. DATASYNTHESIS:
Osilodrostat was efficacious and safe in the treatment of CD in mostly middle-aged Caucasian women. A pivotal phase 3 study revealed a significant difference in 24-hour mean urinary free cortisol (primary end point) between osilodrostat and placebo (86% vs 29%; P < 0.001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE Osilodrostat provides a potent and consistent effect in reducing life-threatening supraphysiological levels of cortisol in patients with CD. Hypocortisolism adverse effects can be mitigated by slowly increasing osilodrostat's dose at ≥2-week intervals. QT interval prolongation was noted; therefore, the QT interval must be monitored by the electrocardiogram. Increased levels of cortisol precursors during treatment with osilodrostat may increase the risk of hypokalemia, edema, and hypertension.CONCLUSIONS:
Osilodrostat was efficacious in decreasing cortisol levels and safe in treating patients who have failed or are ineligible for pituitary surgery. Although risks exist, a pivotal clinical trial revealed efficacy in 86% of participants.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hipersecreção Hipofisária de ACTH
Tipo de estudo:
Clinical_trials
Limite:
Female
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article