INDICATIONS AND USAGE
ISTURISA® (osilodrostat) 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.
IMPORTANT SAFETY INFORMATION
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, and dizziness. Significant lowering of serum cortisol may result in
hypotension, abnormal electrolyte levels, and hypoglycemia.
Hypocortisolism can occur at any time during ISTURISA treatment. Evaluate patients
for precipitating causes of hypocortisolism (infection, physical stress, etc.). Monitor 24-hr 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. Stop ISTURISA
and administer exogenous glucocorticoid replacement therapy if serum or plasma cortisol levels are below
target range and patients have symptoms of adrenal insufficiency. After ISTURISA interruption or
discontinuation, cortisol
suppression may persist beyond the 4-hour half-life of ISTURISA.
Educate patients on the symptoms associated with hypocortisolism and advise them to contact a healthcare
provider if they occur.
QTc Prolongation: ISTURISA is associated with a dose-dependent QT interval prolongation
which may cause cardiac arrhythmias. Perform an ECG to obtain a baseline QTc interval measurement prior to
initiating therapy with ISTURISA and monitor for an effect on the QTc interval thereafter.
Correct hypokalemia and/or hypomagnesemia prior to ISTURISA initiation and monitor periodically during
treatment with ISTURISA. Use with caution in patients with risk factors for QT prolongation and consider
more frequent ECG monitoring.
Elevations in Adrenal Hormone Precursors and Androgens: ISTURISA blocks cortisol synthesis
and may increase circulating levels of cortisol and aldosterone precursors and androgens. This may
activate mineralocorticoid receptors and cause hypokalemia, edema and hypertension. Hypokalemia should be
corrected prior to initiating ISTURISA. Monitor patients treated with ISTURISA for hypokalemia, worsening of
hypertension and edema. Inform patients of the symptoms associated with hyperandrogenism and advise them to
contact a healthcare provider if they occur.
The most common adverse reactions (incidence >20%) are adrenal insufficiency, fatigue,
nausea, headache, edema, decreased appetite, arthralgia, myalgia, and diarrhea.
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.
Drug Interactions:
- CYP3A4 Inhibitor: Reduce the dose of ISTURISA by half with concomitant use of a strong
CYP3A4 inhibitor.
- CYP3A4 and CYP2B6 Inducers: An increase of ISTURISA dosage may be needed if ISTURISA is
used concomitantly with strong CYP3A4 and CYP2B6 inducers. A reduction in ISTURISA dosage may be needed
if strong CYP3A4 and CYP2B6 inducers are discontinued while using ISTURISA.
Use in Specific Populations:
- Lactation: Breastfeeding is not recommended during treatment with ISTURISA and for at
least one week after treatment.
Dosage Interruptions and Modifications: If treatment is interrupted, re-initiate ISTURISA at
a lower dose when cortisol levels are within target ranges and patient symptoms have been resolved.
ISTURISA® (osilodrostat) tablets, for oral use, is available as 1 mg and 5 mg tablets.
Please see full Prescribing
Information.
June 23
