Introduction
Mechanism of action | Efficacy (%) | Common side effects | |
---|---|---|---|
Ketoconazole | Inhibitor of CYP17A1, CYP11A1, and CYP11B1 | 53–88 | Liver enzyme increase |
Gastrointestinal AEs | |||
Interactions with multiple drugs | |||
Not approved for use during pregnancy | |||
Metyrapone | Inhibitor of CYP11B1, CYP11B2, and CYP17A1 | 75 | Hypokalemia |
Hypertension | |||
Gastrointestinal AEs | |||
Hirsutism | |||
Not approved for use during pregnancy | |||
Etomidate | Inhibitor of CYP11B1, CYP17A1, and CYP11A1 | NR | Hypnosis |
Not approved for use during pregnancy | |||
Mitotane | Inhibitor of CYP11A1, CYP11B1, and CYP11B2 | ~70 | Gastrointestinal AEs |
Neurological side effects | |||
Teratogen (not approved for use during pregnancy) | |||
Osilodrostat (LCI699) | Inhibitor of CYP11B2 and CYP11B1 at higher doses | 78–92 | Nausea |
Hirsutism | |||
Fatigue | |||
Headache | |||
Hypokalemia | |||
Not approved for use during pregnancy | |||
Levoketoconazole (COR-003) | Inhibitor of CYP17A1, CYP11A1, CYP11B1, and CYP21A2 | NR | Headachea
|
Nauseaa
| |||
Mild liver enzyme increasea
| |||
Not approved for use during pregnancy |
Adrenal steroidogenesis inhibitors currently in clinical use
Ketoconazole
Metyrapone
Etomidate
Mitotane
Adrenal steroidogenesis inhibitors in clinical development
Osilodrostat (LCI699)
Levoketoconazole (COR-003)
Clinical considerations for treatment with adrenal steroidogenesis inhibitors in CS
Drug interactions
Medical intervention | Interacts with | Potential for adverse event |
---|---|---|
CYP3A4 | Drug–drug interactions with oral anticoagulants, statins, cyclosporine, and tacrolimus | |
hERG | Possible QT prolongation | |
Use acid-lowering and hepatotoxic drugs with caution | ||
Metyrapone [68] | UGT1 | Drug–drug interactions occur frequently |
Acetaminophen toxicity | ||
CYP11B1 | Etomidate should be given carefully with calcium channel blockers, opioids, and benzodiazepines | |
Mitotane [35] | CYP3A4 | Drug–drug interactions with oral anticoagulants, statins, cyclosporine, and tacrolimus |
Hydrocortisone dose increased | ||
CYP1A2 and CYP2C19 (moderate inhibition) CYP2D6 and CYP3A4 (weakly inhibited) | Drug–drug interactions Possible QT prolongation | |
Levoketoconazole (COR-003) [21] | CYP3A4, CYP3A5 hERG | Drug–drug interactions with oral anticoagulants, statins, cyclosporine, and tacrolimus |
QT prolongation |