Back to Search
Start Over
Hepatic safety of ketoconazole in Cushing's syndrome: results of a Compassionate Use Programme in France.
- Source :
-
European journal of endocrinology [Eur J Endocrinol] 2018 May; Vol. 178 (5), pp. 447-458. Date of Electronic Publication: 2018 Feb 22. - Publication Year :
- 2018
-
Abstract
- Objective: Ketoconazole (KTZ) is one of few available treatments for Cushing's syndrome (CS). Although KTZ has been associated with severe hepatotoxicity, little information is available about hepatic safety in CS. The aim of this study was to document changes in liver function in patients with CS treated with KTZ.<br />Design: An observational prospective French cohort study (Compassionate Use Programme (CUP)).<br />Methods: Enrolled patients were stratified into a KTZ-naive cohort and a cohort already treated by another formulation of ketoconazole (KTZ-switch cohort). Liver function markers (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, γ-glutamyltransferase and bilirubin) were monitored at regular intervals. Patients with ALT > 3 × ULN (upper limit of normal), total bilirubin > 2 × ULN or both ALP > 2 × ULN and ALT > ULN were considered to have liver injury.<br />Results: Overall, 108 patients were analysed (47 KTZ-naïve; 61 KTZ-switch). The median KTZ dose was 600 mg/day. Most abnormalities observed were asymptomatic mild increases of liver enzymes. Four patients in the KTZ-naïve cohort (8.5%) and two in the KTZ-switch cohort (3.3%) developed liver injury, considered related to KTZ in three cases (all KTZ-naïve in the first month of treatment). Five patients had mild liver function abnormalities at baseline and two had proven liver metastases. Two patients recovered on discontinuation of KTZ and the remaining patient died of unrelated causes.<br />Conclusions: These findings highlight the need for close monitoring of liver enzymes especially during the first six months of treatment. Liver enzyme abnormalities usually occurred within four weeks were asymptomatic and could be reversed on timely discontinuation of KTZ.<br /> (© 2018 European Society of Endocrinology.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Chemical and Drug Induced Liver Injury diagnosis
Chemical and Drug Induced Liver Injury metabolism
Child
Cohort Studies
Compassionate Use Trials adverse effects
Cushing Syndrome metabolism
Cytochrome P-450 CYP3A Inhibitors adverse effects
Cytochrome P-450 CYP3A Inhibitors therapeutic use
Female
France epidemiology
Humans
Ketoconazole adverse effects
Liver drug effects
Liver metabolism
Longitudinal Studies
Male
Middle Aged
Prospective Studies
Young Adult
Chemical and Drug Induced Liver Injury epidemiology
Compassionate Use Trials methods
Cushing Syndrome drug therapy
Cushing Syndrome epidemiology
Ketoconazole therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1479-683X
- Volume :
- 178
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- European journal of endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 29472378
- Full Text :
- https://doi.org/10.1530/EJE-17-0886