• Cushing’s disease in patients in whom pituitary surgery is not an option or has not been curative.

Contraindicated in:

• Lactation: Lactation.

Use Cautiously in:

• Congenital long QT syndrome, HF, bradyarrhythmias, hypokalemia, or hypomagnesemia (↑ risk of QT interval prolongation)
• Concurrent use of QT interval prolonging medications (↑ risk of QT interval prolongation)
• Moderate or severe hepatic impairment (↓ dose)
• OB: Safety not established in pregnancy
• Pedi: Safety and effectiveness not established in children.

CV: edema, hypotension, hypertension, QT interval prolongation, tachycardia.

Derm: rash, acne (females), alopecia, hirsutism, hypertrichosis.

EENT: nasopharyngitis.

Endo: hypocortisolism, ↑testosterone levels, hypoglycemia.

F and E: hypokalemia.

GI: abdominal pain, diarrhea, nausea, vomiting, dyspepsia, ↑ liver enzymes.

GU: urinary tract infection.

Hemat: anemia.

Metab: ↓appetite.

MS: arthralgia, myalgia.

Neuro: dizziness, headache, anxiety, depression, insomnia, syncope.

Resp: cough.

Misc: fatigue, fever.

Drug-Drug:

• QT interval prolonging medications may ↑ risk of QT interval prolongation and torsade de pointes.
• Strong CYP3A4 inhibitors, including clarithromycin and itraconazole may ↑ levels and risk of toxicity; ↓ dose of osilodrostat by 50%.
• CYP3A4 inducers and CYP2B6 inducers, including carbamazepine, phenobarbital, or rifampin, may ↓ levels and effectiveness; may need to ↑ osilodrostat dose based on urine free cortisol levels.
• May ↑ levels and risk of toxicity of CYP1A2 substrates and CYP2C19 substrates with a narrow therapeutic index, including theophylline and tizanidine.

• Tablets: 1 mg; 5 mg; 10 mg;

• PO (Adults): 2 mg twice daily; may ↑ by 1–2 mg twice daily every 2 wk based on urine free cortisol levels, tolerability, and signs/symptoms. If patient continues to have elevated urine free cortisol levels while taking 10 mg twice daily, may ↑ by 5 mg twice daily every 2 wk (max dose = 30 mg twice daily).

Isturisa

• Inhibits 11–beta-hydroxylase, an enzyme responsible for the final step of cortisol synthesis in the adrenal gland.

• Reduction in urine free cortisol levels.

Therapeutic Classification: n/a

Pharmacologic Classification: cortisol synthesis inhibitors

Absorption: High-fat meals may delay and reduce extent of absorption.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Metabolized by CYP3A4, CYP2B6, and CYP2D6 isoenzymes as well as UDP-glucuronosyltransferases. Primarily excreted in urine (91%; 5% as unchanged drug), with minimal excretion in feces.

Half-life: 4 hr.

(plasma concentrations)

• Instruct patient to take osilodrostat as directed. Omit missed doses; take next dose at regularly scheduled time. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• Advise patient to notify health care professional if signs and symptoms of low cortisol levels (nausea, abdominal pain, vomiting, loss of appetite, tiredness, dizziness, low blood pressure) occur.
• Inform patient of possibility of hyperandrogenism. Advise patient to notify health care professional if signs and symptoms (hirsutism, hypertrichosis, acne in females, swelling of legs and ankles) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep: Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during and for 1 wk after final dose.
• Emphasize importance of regular lab test to monitor for side effects.

oh-SIL-oh-DROE-stat