Osilodrostat
Adrenal steroid synthesis inhibitors
Adrenal steroid synthesis inhibitors
An oral blocker of the last enzyme in cortisol synthesis. It lowers cortisol in Cushing's syndrome when surgery is not possible or has failed.
Quick facts
- Group
- Adrenal steroid synthesis inhibitors
- Target
- 11-beta-hydroxylase (CYP11B1), and aldosterone synthase (CYP11B2)
- Used for
- Endogenous Cushing's syndrome
- Key effects
- Nausea · Headache and tiredness · Swelling of the legs
- Monitor
- Cortisol levels · ECG before and during treatment
- ATC
- H02CA02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows osilodrostat bound to the heme of human aldosterone synthase (CYP11B2), a very similar enzyme that osilodrostat also inhibits; CYP11B1, its main target for cortisol, has the same kind of site.
Osilodrostat is a non-steroidal inhibitor of 11-beta-hydroxylase (CYP11B1), which converts 11-deoxycortisol to cortisol, and of aldosterone synthase (CYP11B2). Cortisol falls. Precursors before the block accumulate: 11-deoxycortisol and deoxycorticosterone (mineralocorticoid effects: low potassium, oedema, high blood pressure) and adrenal androgens (hirsutism, acne). Too much effect causes adrenal insufficiency.
- Osilodrostat binds the heme of CYP11B1 (and CYP11B2)
- 11-deoxycortisol is not converted to cortisol
- Cortisol falls; precursors and androgens accumulate
- Doses are titrated to avoid adrenal insufficiency
Indications
- Endogenous Cushing's syndrome (including Cushing's disease) when pituitary surgery is not possible or has not cured it Cushing syndrome →
Adverse effects
Common
- Nausea, vomiting, diarrhoea, abdominal pain and reduced appetite
- Headache and tiredness
- Swelling of the legs (oedema)
- Excess hair growth and acne in women
- Dizziness on standing
Contraindications
- Hypersensitivity to osilodrostat
- Caution: long QT, other heart disease, uncorrected low potassium or magnesium
Key interactions
- Other drugs that prolong the QT interval
- Additive QT prolongation; ECG monitoring
- Other medicines in general
- Doses may need adjusting or closer monitoring; a full medication list is reviewed
What is monitored
- Cortisol levels (urine or serum) during dose titration
- ECG before and during treatment
- Potassium and magnesium
- Blood pressure and signs of adrenal insufficiency
Administration and safety
- Oral tablets on a regular schedule; started low and adjusted gradually
- Low potassium and magnesium are corrected before starting
- Not stopped without the prescriber, who may lower or interrupt it if cortisol falls too far
Pregnancy and breastfeeding
Data in pregnancy are limited; the prescriber is told about pregnancy plans. Breastfeeding is avoided during treatment and for a week after the last dose.
Nursing care
- Teach the signs of low cortisol: nausea, vomiting, tiredness, abdominal pain, loss of appetite, dizziness
- Check ECG and electrolyte results
- Advise rising slowly from lying or sitting
- Laboratory staff are told the person takes osilodrostat
Pharmacokinetics
- Absorption
- Taken by mouth, with or without food
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme does osilodrostat mainly inhibit to lower cortisol?
11-beta-hydroxylase (CYP11B1), the final step from 11-deoxycortisol to cortisol; it also inhibits aldosterone synthase.
Why can osilodrostat cause hypokalaemia and oedema?
Precursors before the block, such as deoxycorticosterone, accumulate and have mineralocorticoid activity.
Which cardiac test is done before and during osilodrostat?
An ECG, because the drug can prolong the QT interval.
Connections
← Back to the class: Adrenal steroid synthesis inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Osilodrostat: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.