11β-hydroxylase inhibitor Pregnancy: Should not be used during pregnancy — no or limited human data and reproductive toxicity in animal studies. A pregnancy test before initiating treatment is recommended in women of childbearing potential, who must use effective contraception during treatment and for at least one week after. Should not be used in women of childbearing potential not using contraception. Breast-feeding should be discontinued during treatment and for at least one week after treatment.

Osilodrostat

Brand names: Isturisa

Osilodrostat is an oral cortisol synthesis inhibitor used to treat endogenous Cushing's syndrome.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 2 mg twice daily (recommended starting dose); 1 mg twice daily in patients of Asian ancestry

Route: Oral

Frequency: Twice daily

Max: 30 mg twice daily

Treatment should be initiated and supervised by physicians experienced in endocrinology or internal medicine with access to facilities for monitoring biochemical response, since the dose must be adjusted to normalise cortisol. Titration: gradually titrate, initially by increments of 1 or 2 mg, based on individual response and tolerability; increases should not occur more frequently than once every 1-2 weeks and should be guided by cortisol assessments and clinical response. Monitoring: measure cortisol (e.g. 24-hour urinary free cortisol, serum/plasma cortisol) every 1-2 weeks until adequate clinical response is maintained, then less frequently as clinically indicated. Usual maintenance dose in clinical studies varied between 2 and 7 mg twice daily. Dose reduction or temporary interruption is required if cortisol falls below the lower limit of normal, if there is a rapid fall to the lower part of the normal range, or if there are signs or symptoms of hypocortisolism; treatment may be resumed after resolution of symptoms at a lower dose provided cortisol is above the lower limit of normal without glucocorticoid substitution. Missed dose: take the prescribed dose at the next scheduled time; do not double the next dose. Hepatic impairment: no adjustment in mild impairment (Child-Pugh A); moderate impairment (Child-Pugh B) start 1 mg twice daily; severe impairment (Child-Pugh C) start 1 mg once daily in the evening with initial up-titration to 1 mg twice daily; more frequent monitoring of adrenal function may be required during titration. Elderly: no evidence that dose adjustment is required at 65 years or above, but data are limited and caution is advised. Administration: oral use, with or without food. Paediatric: safety and efficacy in patients under 18 years have not been established, no data available. Before starting, correct any hypokalaemia, hypocalcaemia or hypomagnesaemia and perform an ECG; repeat the ECG within one week of initiation and as clinically indicated (cardiology consultation recommended if QTc exceeds 480 ms).

Dose adjustments

Renal

No dose adjustment is required in renal impairment. Urinary free cortisol levels should be interpreted with caution in moderate to severe renal impairment due to reduced urinary free cortisol excretion; alternative methods of cortisol monitoring should be considered in these patients.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients

Side effects

Adrenal insufficiency / hypocortisolism (very common)
Fatigue and oedema (very common)
Nausea, vomiting, diarrhoea and abdominal pain (very common)
Headache and dizziness (very common)
Hypokalaemia and decreased appetite (very common)
Hypotension and tachycardia (very common); QT prolongation on ECG (common)

Interactions

Strong CYP3A4 inhibitors (e.g. itraconazole, clarithromycin) — increase osilodrostat concentration; reduce the osilodrostat dose by half during concomitant use
Strong CYP3A4 and/or CYP2B6 inducers (e.g. carbamazepine, rifampicin, phenobarbital) — decrease osilodrostat concentration and may reduce efficacy; an increase in osilodrostat dosage may be needed, and a reduction may be needed if the inducer is stopped
Hormonal contraceptives other than the oral combination of ethinylestradiol and levonorgestrel — an additional barrier method of contraception is recommended (§4.6)
Medicines that prolong the QT interval — osilodrostat causes dose-dependent QT prolongation; use with caution and correct electrolytes (§4.4)
(NOTE: eMC §4.5 was not captured in the bundle; the CYP entries above are from section 7 of the US prescribing information in the same bundle)

Clinical monograph

How it works

It inhibits 11-beta-hydroxylase, the enzyme catalysing the final step of cortisol biosynthesis, thereby reducing cortisol production.

Prescribing in practice

Hypocortisolism can occur as cortisol falls, so patients must be monitored and educated to recognise and manage adrenal insufficiency.
It can prolong the QT interval, so an ECG and electrolytes should be checked before and during treatment.
Accumulation of adrenal hormone precursors may cause hypokalaemia, oedema, hypertension and increased androgenic effects such as hirsutism.

Monitoring

Monitor cortisol levels, potassium, blood pressure and ECG (QT interval), titrating the dose to achieve cortisol control without insufficiency.

Counselling the patient

Seek urgent help for symptoms of low cortisol such as severe tiredness, nausea, dizziness or low blood pressure.
Attend all blood tests and heart tracings so the dose can be adjusted safely.
Report palpitations or fainting promptly.

Evidence & guidelines

Osilodrostat is licensed for Cushing's syndrome based on trials demonstrating normalisation of urinary free cortisol.

Reference: NICE TA928 (Osilodrostat); SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways