Osilodrostat

What is Osilodrostat?

• Osilodrostat ISTURISA is a cortisol synthesis inhibitor used to treat adults with Cushing’s disease.

What are the uses of this medicine?

This medicine is used to treat adults with Cushing’s disease:

• who cannot have pituitary surgery, or
• who have had pituitary surgery, but the surgery did not cure their Cushing’s disease

How does this medicine work?

• An orally bioavailable inhibitor of both steroid 11beta-hydroxylase (cytochrome P450 (CYP) 11B1) and aldosterone synthase (CYP11B2; steroid 18-hydroxylase), with potential anti-adrenal activity and ability to treat Cushing disease (CD).
• Upon administration, osilodrostat binds to and inhibits the activity of CYP11B1, the enzyme that catalyzes the final step of cortisol synthesis from the precursor 11-deoxycortisol, and CYP11B2, the enzyme that catalyzes aldosterone synthesis from corticosterone and 11-deoxycorticosterone in the adrenal gland.
• The inhibition of CYP11B1 prevents the production of excess cortisol, thereby decreasing and normalizing the levels of cortisol. CD is most often caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

Avoid concomitant use of ISTURISA with fallowing:

• CYP3A4 Inhibitor (e.g., itraconazole, clarithromycin)
• CYP3A4 and CYP2B6 Inducers (e.g., carbamazepine, rifampin, phenobarbital)

Is this medicine FDA approved?

• It was approved for use in the United States in 2020.

How should this medicine be used?

• Correct hypokalemia and hypomagnesemia prior to starting ISTURISA.
• Obtain baseline electrocardiogram (ECG). Repeat ECG within one week after treatment initiation.

Recommended Dosage

• Initiate dosage at 2 mg orally twice daily, with or without food .
• Titrate dosage by 1 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 .
• Maximum recommended dosage is 30 mg twice daily.

Recommended Dosage in Patients with Renal Impairment

• No dose adjustment is required for patients with renal impairment.

Recommended Dosage in Patients with Hepatic Impairment

• For patients with moderate hepatic impairment (Child-Pugh B), the recommended starting dose is 1 mg twice daily.
• For patients with severe hepatic impairment (Child-Pugh C), the recommended starting dose is 1 mg once daily in the evening.
• No dose adjustment is required for patients with mild hepatic impairment(Child-Pugh A).

Administration

• Take ISTURISA exactly as your healthcare provider tells you. Your healthcare provider will tell you exactly how many tablets of ISTURISA to take. Do not change your dose or stop taking ISTURISA unless your healthcare provider tells you to.
• Start ISTURISA by taking 2 mg two times a day by mouth or as directed by your healthcare provider.
• After you have started treatment, your healthcare provider may change your dose, depending on how you respond to the treatment with ISTURISA.
• Take ISTURISA with or without food.
• If you miss a dose of ISTURISA, take the next dose at your regularly scheduled time.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• Tablets: 1 mg, 5 mg, and 10 mg

This medicine is available in fallowing brand namesː

• ISTURISA

What side effects can this medication cause?

Common possible side effects of this medicine include:

• very low cortisol levels (adrenal insufficiency)
• tiredness (fatigue)
• nausea
• headache
• swelling of the legs, ankles or other signs of fluid retention (edema)

ISTURISA can cause serious side effects, including: Low cortisol levels in your blood (hypocortisolism),symptoms of hypocortisolism include

• nausea
• vomiting
• tiredness (fatigue)
• low blood pressure
• stomach (abdominal) pain
• loss of appetite
• dizziness

What special precautions should I follow?

• Monitor patients closely for hypocortisolism and potentially life-threatening adrenal insufficiency. Dosage reduction or interruption may be necessary.
• Perform electrocardiogram in all patients Use with caution in patients with risk factors for QTc prolongation.
• Monitor for hypokalemia, worsening of hypertension, edema, and hirsutism.

What to do in case of emergency/overdose?

• 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.

Management for overdosage

• 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.

Can this medicine be used in pregnancy?

• 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.

Can this medicine be used in children?

• The safety and effectiveness of ISTURISA in pediatric patients have not been established.

What should I know about storage and disposal of this medication?

• Store at room temperature between 68°F to 77°F (20°C to 25°C); excursions permitted 15°C to 30°C (59°F to 86°F); protect from moisture.

• Dailymed label info on Osilodrostat
• FDA Osilodrostat