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PATIENT PROFILES
Cushing’s Disease in Different Patients
Since you may see patients at different stages of diagnosis and treatment, there are questions to consider when developing a treatment plan and exploring ISTURISA® (osilodrostat) as an appropriate option.
Select a name to review different patient profiles:
Swipe to review different patient profiles:
Josie S.
Patient with Cushing’s disease (CD)
Age: 36
Race: Caucasian
Cushing’s disease: Mild, recurrent
Time since diagnosis: 3 years
Surgery: Yes
Performed within 1 month of diagnosis.
Status: In remission until 1 month ago.
Beginning to develop symptoms of recurrence.
Symptoms
- Sleep disturbances
- Fatigue
- Anxiety
- Menstrual irregularities
- Acne
Cortisol
-
Urinary free cortisol (UFC): 60 μg/24 h (165.6 nmol/24 h)
- UFC fold upper limit of normal (ULN):
1.2 x ULN mUFC
- UFC fold upper limit of normal (ULN):
Comorbidities
-
Gastroesophageal reflux disease (GERD)
- Current treatment: esomeprazole
Questions to consider when developing a treatment plan
What do you consider to be the appropriate next therapy option for this patient?
How would this patient’s use of a proton pump inhibitor affect your selection of next therapy?
What key concerns do you have that may affect your selection of an appropriate medical therapy for this patient?
Would you consider ISTURISA an appropriate option for this patient? Why or why not?
David A.
Patient with Cushing’s disease (CD)
Age: 32
Race: Caucasian
Cushing’s disease: Recurrent
Time since diagnosis: 2 years
Surgery: Yes
1 month after diagnosis.
Status: Taking glucocorticoid receptor blocker to control hyperglycemia with dosage 1200 mg/24 h.1
Despite dose adjustment to maximum dose, patient reports clinical symptoms of Cushing’s disease persist.a
Symptoms
- Low libido
- Hyperglycemia
- Difficulty losing weight
Cortisol
-
Urinary free cortisol (UFC): 90 μg/24 h (248.4 nmol/24 h) after surgery. Current cortisol level unknown due to mechanism of action of glucocorticoid receptor blocker
- UFC fold upper limit of normal (ULN):
1.8 x ULN mean urinary free cortisol (mUFC)
- UFC fold upper limit of normal (ULN):
Comorbidities
-
Hypertension
- Current treatment: lisinopril 20 mg
-
Type 2 diabetes mellitus
- Current treatment: metformin ER 1000 mg
Questions to consider when developing a treatment plan
What might be your next selection for your patient’s medical therapy?
Would you consider ISTURISA an appropriate option for this patient? Why or why not?
Do you have any concerns about this patient being prescribed other medications, now or in the future, for comorbid conditions?
Jenna M.
Patient with Cushing’s disease (CD)
Age: 40
Race: African American
Cushing’s disease: Medically naive
Time since diagnosis: 1 month
Surgery: None
Tumor not visible, but inferior petrosal sinus sampling (IPSS) shows CD. Patient does not want surgery due to risks.
Symptoms
- Weight gain
- Uncontrolled diabetes
- Fatigue
- Muscle weakness
- Mild depression
Cortisol
-
Urinary free cortisol (UFC): 135 μg/24 h (372.6 nmol/24 h)
- UFC fold upper limit of normal (ULN):
2.7 x ULN mean urinary free cortisol (mUFC)
- UFC fold upper limit of normal (ULN):
Comorbidities
-
Hypertension
- Current treatment: calcium channel blocker
-
Diabetes (glycated hemoglobin [HbA1c] = 8.8)
- Current treatment: multiple medications, including insulin
Questions to consider when developing a treatment plan
What are your key considerations about potential drug-drug interactions when planning the treatment regimen for your medically naive patient?
Is your primary goal to normalize cortisol or resolve signs and symptoms of CD, or do you value them equally?
For a patient with diabetes, would you prefer to block cortisol synthesis at the source or block the cortisol receptor?
Would you consider ISTURISA an appropriate option for this patient? Why or why not?
Tara H.
Patient with Cushing’s disease (CD)
Age: 51
Race: Hispanic
Cushing’s disease: Persistent
Time since diagnosis: 9 months
Surgery: Yes
7 months ago. Surgery was not successful.
Status: Recently discontinued levoketoconazole due to intolerance or lack of response.
Symptoms
- Anxiety
- Weight gain
- Depression
- Easy bruising
Cortisol
-
Urinary free cortisol (UFC): 265 μg/24 h (731.4 nmol/24 h)
- UFC fold upper limit of normal (ULN):
5.3 x ULN mean urinary free cortisol (mUFC)
- UFC fold upper limit of normal (ULN):
Comorbidities
-
Uncontrolled diabetes
- Current treatments: metformin, canagliflozin, and insulin
- Resistant hypertension
-
Child-Pugh A (mild hepatic abnormality)
- Total bilirubin: 2.1 mg/dL
- Alanine aminotransferase (ALT): 1.5 x ULN; Aspartate aminotransferase (AST): 2 x ULN
-
Hirsutism
- Managed with: antiandrogen therapy
Questions to consider when developing a treatment plan
What is your first step for managing this patient’s high cortisol level?
For this patient, would you prefer to block cortisol synthesis at the source or block the cortisol receptor?
Do you have any potential concerns with this patient’s current liver panel, and how might that influence your treatment decision?
Would you consider ISTURISA an appropriate option for this patient? Why or why not?
How would this patient’s likely immunocompromised state influence your treatment selection?
INDICATION(S) AND IMPORTANT SAFETY INFORMATION
INDICATIONS AND USAGE
ISTURISA® (osilodrostat) is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease for whom pituitary 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 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, and edema.
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 the full Prescribing Information.
INDICATION(S) AND IMPORTANT SAFETY INFORMATION
INDICATIONS AND USAGE
ISTURISA® (osilodrostat) is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease for whom pituitary 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 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, and edema.
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 the full Prescribing Information.
Reference: 1. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540.
Reference: 1. Korlym. Package insert. Corcept Therapeutics; 2019.