Ketoconazole in Cushing’s syndrome: a profile of its use

Acknowledgements The manuscript was reviewed by: M. O. Savage, Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK; S. M. Webb, Department of Endocrinology/Medicine, Hospital Sant Pau, Universitat Autònoma de Barcelona, CIBERER group747, Barcelona, Spain. During the peer review process, HRA Pharma, the marketing-authorisation holder of ketoconazole HRA™, was also ofered an opportunity to provide a scientifc accuracy review of their data. Changes resulting from comments received were made on the basis of scientifc and editorial merit.

Declarations

Funding: The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest: M. Shirley is an employee of Adis International Ltd./Springer Nature and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

Ethics approval, Consent to participate, Consent for publication, Availability of data and material, Code availability Not applicable.

Additional information about this Adis Drug Review can be found here.

Abstract

Ketoconazole (Ketoconazole HRA™), an imidazole derivative, is a useful treatment option in the management of endogenous Cushing’s syndrome in adults and adolescents > 12 years of age, based on evidence from more than three decades of use of the drug in clinical practice. Originally developed as an antifungal agent, ketoconazole is a potent steroidogenesis inhibitor. Approximately 60% (range, 45–88% across key studies) of patients with Cushing’s syndrome who are treated with ketoconazole achieve control of hypercortisolism, with efficacy demonstrated in all aetiologies of the disease. Furthermore, reductions in cortisol levels in patients treated with ketoconazole are associated with improvements in clinical and biochemical features of Cushing’s syndrome and common comorbidities. Hepatotoxicity, the main safety concern with ketoconazole, can be managed effectively with careful monitoring of hepatic enzymes, with hepatic enzyme abnormalities generally being mild to moderate, asymptomatic and reversible upon dose reduction or drug withdrawal.

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