Osilodrostat

Osilodrostat is a cortisol synthesis inhibitor. It inhibits 11beta-hydroxylase (CYP11B1), the enzyme responsible for the final step of cortisol biosynthesis in the adrenal gland.

• ISTURISA is indicated for the treatment of endogenous hypercortisolemia in adults with Cushing's syndrome for whom surgery is not an option or has not been curative.

• None.contraindicated

Correct hypokalemia and hypomagnesemia, and obtain baseline electrocardiogram prior to starting ISTURISA ( 2.1 , 5.2 , 5.3 ) Initiate dosage at 2 mg orally twice daily, with or without food ( 2.2 ) Titrate dosage by 1 mg to 2 mg twice daily, no more frequently than every 2 weeks based on rate of cortisol changes, individual tolerability and improvement in signs and symptoms ( 2.2 ) Maximum recommended dosage is 30 mg twice daily ( 2.2 ) See Full Prescribing Information for complete titration, laboratory, and dosage modification recommendations ( 2.1 , 2.2 , 2.3 ) Patients with Hepatic Impairment: Child-Pugh B: Recommended starting dose is 1 mg twice daily ( 2.5 , 8.7 ) Child-Pugh C : Recommended starting dose is 1 mg once daily in the evening ( 2.5 , 8.7 ) 2.1 Laboratory Testing Prior to ISTURISA Initiation Correct hypokalemia and hypomagnesemia prior to starting ISTURISA [see Warnings and Precautions (5.2 , 5.3) ]. Obtain baseline electrocardiogram (ECG) . Repeat ECG within one week after treatment initiation, and as clinically indicated thereafter [see Warnings and Precautions (5.2) ] . 2.2 Recommended Dosage, Titration, and Monitoring Initiate dosing at 2 mg orally twice daily, with or without food. Initially, titrate the dosage by 1 mg to 2 mg twice daily, no more frequently than every 2 weeks based on the rate of cortisol changes, individual tolerability and improvement in signs and symptoms of Cushing's syndrome.

Hypocortisolism : Monitor patients closely for hypocortisolism and potentially life-threatening adrenal insufficiency. Dosage reduction or interruption may be necessary. After interruption or discontinuation of ISTURISA, cortisol suppression may persist and patients should be regularly monitored ( 5.1 ) QTc Prolongation : Perform electrocardiogram in all patients Use with caution in patients with risk factors for QTc prolongation ( 5.2 ) Elevations in Adrenal Hormone Precursors and Androgens: Monitor for hypokalemia, worsening of hypertension, edema, and hirsutism ( 5.3 ) 5.1 Hypocortisolism ISTURISA lowers cortisol levels and can lead to hypocortisolism and sometimes life-threatening adrenal insufficiency. Lowering of cortisol can cause nausea, vomiting, fatigue, abdominal pain, loss of appetite, dizziness. Significant lowering of serum cortisol may result in hypotension, abnormal electrolyte levels, and hypoglycemia [see Adverse Reactions (6) ] . Hypocortisolism can occur at any time during ISTURISA treatment. Evaluate patients for precipitating causes of hypocortisolism (infection, physical stress, etc.). Monitor 24-hour urine free cortisol, serum or plasma cortisol, and patient's signs and symptoms periodically during ISTURISA treatment. Decrease or temporarily discontinue ISTURISA if urine free cortisol levels fall below the target range, there is a rapid decrease in cortisol levels, and/or patients report symptoms of hypocortisolism.

Clinically significant adverse reactions that appear in other sections of the labeling include: Hypocortisolism [see Warnings and Precautions (5.1) ] QT Prolongation [see Warnings and Precautions (5.2) ] Elevations in Adrenal Hormone Precursors and Androgens [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence > 20%) are adrenal insufficiency, fatigue, nausea, headache, edema, decreased appetite, arthralgia, myalgia, and diarrhea ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. The safety of ISTURISA was evaluated in two clinical trials in adults with Cushings disease. Study 1 (NCT02180217) was a 4-period, multicenter study with a 12-week open-label titration period, 12-week open-label maintenance period, 8-week double-blind, placebo-controlled period, and 14 to 24-week open label treatment period in 137 patients with Cushing's disease. Study 2 (NCT02697734) was a 2-period, multicenter study with a 12-week randomized, double-blind, placebo-controlled period and a 36-week open-label treatment period in 74 patients with Cushing's disease [see Clinical Studies (14) ] .

Lactation : Breastfeeding is not recommended during treatment with ISTURISA and for at least one week after treatment ( 8.2 ) 8.1 Pregnancy Risk Summary There are no available data on osilodrostat use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with active Cushing's Syndrome during pregnancy (see Clinical Considerations ). No adverse developmental outcomes were observed in reproduction studies in pregnant rats and rabbits when exposed to osilodrostat during organogenesis at doses that produced maternal exposures of 7 and 0.5-times the 30 mg twice daily maximum clinical dose, by AUC. In rabbits, exposures associated with maternal toxicity at 7-times the maximum clinical dose resulted in decreased fetal viability. No adverse developmental outcomes were observed in a pre- and postnatal development study with administration of osilodrostat to pregnant rats from organogenesis through lactation at 8-times the 30 mg twice daily maximum clinical dose (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Metabolism

Absorption Osilodrostat is absorbed with a time of maximum observed concentration (T max ) of approximately 1 hour. Exposure (AUC inf and C max ) slightly increases over dose-proportionally within the therapeutic dose range of 1 mg to 30 mg.

Overdosage may result in severe hypocortisolism. Signs and symptoms suggestive of hypocortisolism may include nausea, vomiting, fatigue, low blood pressure, abdominal pain, loss of appetite, dizziness, and syncope. In case of suspected overdosage, ISTURISA should be temporarily discontinued, cortisol levels should be checked, and if necessary, corticosteroid supplementation should be initiated. Close surveillance may be necessary, including monitoring of the QT interval, blood pressure, glucose, fluid, and electrolyte until the patient's condition is stable.

• Mar 6, 2020NDANDA212801Recordati Rare

1. 1Off Label Use31816%
2. 2Fatigue27714%
3. 3Nausea23112%
4. 4Headache1286.6%
5. 5Death1186.0%
6. 6Asthenia1115.7%
7. 7Adrenal Insufficiency1105.6%
8. 8Diarrhoea1095.6%
9. 9Dizziness1065.4%
10. 10Decreased Appetite1025.2%
11. 11Vomiting985.0%
12. 12Cortisol Decreased814.1%
13. 13Covid-19713.6%
14. 14Arthralgia673.4%
15. 15Disease Progression623.2%

The 10 most recently updated of 22 ClinicalTrials.gov registrations naming Osilodrostat as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Combination Osilodrostat and Cabergoline in Cushing's Disease
  Enrolling by invitation · Phase 4 · Interventional · 50 enrolled · University of Basrah
  NCT07603466updated 2026-05-22
• Pharmacokinetic (PK), Pharmacodynamic (PD) and Tolerability of Osilodrostat in Pediatric Patients With Cushing's Syndrome
  Recruiting · Phase 2 · Interventional · 12 enrolled · RECORDATI GROUP
  NCT03708900updated 2026-03-27
• Isturisa Treatment in Mild Autonomous Cortisol Secretion( MACS)
  Recruiting · Phase 4 · Interventional · 10 enrolled · Johns Hopkins University
  NCT07247058updated 2026-03-05
• Impact of 1 mg Osilodrostat Therapy on Mild Autonomous Cortisol Secretion (MACS)
  Recruiting · Phase 2 · Interventional · 15 enrolled · Mayo Clinic
  NCT07104812updated 2026-02-11
• Osilodrostat in Patients With Hypertension Caused by Hypercortisolaemia Due to Cushing's Syndrome
  Not yet recruiting · Phase 4 · Interventional · 63 enrolled · RECORDATI GROUP
  NCT07247162updated 2025-12-10
• Metyrapone Versus Osilodrostat in Patients With Metabolic Autonomous Cortisol Secretion (MACS)
  Recruiting · Phase 4 · Interventional · 150 enrolled · Laikο General Hospital, Athens
  NCT07268222updated 2025-12-05
• Non-interventional Study on Osilodrostat in Patients With Endogenous Cushing's Syndrome
  Active not recruiting · Observational · 206 enrolled · RECORDATI GROUP
  NCT05382156updated 2025-11-20
• A Block-and-Replace Therapy With Osilodrostat and Concomitant Glucocorticoid Replacement
  Recruiting · Observational · 12 enrolled · University of Michigan
  NCT06430528updated 2025-08-20
• Osilodrostat for the Treatment of Non-Cushing's Disease Cushing's Syndrome
  Completed · Observational · 103 enrolled · RECORDATI GROUP
  NCT05633953updated 2025-02-10
• Roll-over Study in Patients With Endogenous Cushing's Syndrome for LCI699
  Completed · Phase 2 · Interventional · 127 enrolled · RECORDATI GROUP
  NCT03606408updated 2024-12-18

Frequently asked questions

How does Osilodrostat work?

Osilodrostat is a cortisol synthesis inhibitor. It inhibits 11beta-hydroxylase (CYP11B1), the enzyme responsible for the final step of cortisol biosynthesis in the adrenal gland.

What is Osilodrostat used for?

According to FDA labeling, Osilodrostat carries indications including: ISTURISA is indicated for the treatment of endogenous hypercortisolemia in adults with Cushing's syndrome for whom surgery is not an option or has not been curative.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Osilodrostat?

Osilodrostat is classified as Anticorticosteroids, Cortisol Synthesis Inhibitor, Adrenal Steroid Synthesis Inhibitors, Cytochrome P450 11B1 Inhibitors, Cytochrome P450 1A2 Inhibitors, Cytochrome P450 2C19 Inhibitors, Cytochrome P450 2D6 Inhibitors, Cytochrome P450 3A4 Inhibitors, Cytochrome P450 3A5 Inhibitors, Cytochrome P450 Inhibitors, Adrenal Cortical Activity Alteration.

What are the brand names for Osilodrostat?

Osilodrostat is marketed under brand names including Isturisa.

What are the contraindications for Osilodrostat?

Osilodrostat labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.