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

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.