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WHY ISTURISA
Safety Profile
The safety of ISTURISA® (osilodrostat) was assessed in 2 phase 3 clinical studies.1,2 Select a study to review adverse reactions.
A well-tolerated safety profile demonstrated through 48 weeks1
Adverse reactions among 137 patients with Cushing’s disease (CD) who received at least 1 dose of ISTURISA in the study3
Adverse reaction
(Frequency >15%)
Adrenal insufficiencya
43.1
Fatigueb
38.7
Nausea
37.2
Headachec
30.7
Edemad
21.2
Nasopharyngitis
19.7
Vomiting
19.0
Arthralgia
17.5
Back pain
15.3
Rashe
15.3
- Among the 43% of patients who were deemed to have experienced adrenal insufficiency, 1/3 had low cortisol levels indicative of adrenal insufficiency3
-
Hypocortisolism was reported at a rate of 31% during weeks 1 to 12 and 18% during weeks 12 to 263
- In most cases, hypocortisolism is addressed by reducing the dose of ISTURISA and/or adding low-dose, short-term glucocorticoid therapy3
- 36% (25/70) of patients with 1 or more hypocortisolism-related event received glucocorticoid supplementation during the duration of the study1
Mild to moderate = severity rated by investigator as 1 or 2 in the LINC 3 clinical trial.4
A well-tolerated safety profile2:
The most common adverse reactions observed during the overall study while on ISTURISA2
Adverse reaction
(Frequency >20%)
Arthralgia
45.2
Decreased appetite
45.2
Fatigue
38.4
Nausea
37.0
Headache
32.9
Myalgia
26.0
Dizziness
26.0
Adrenal insufficiencya
24.7
Increased blood testosterone
24.7
Diarrhea
23.3
Hypertension
21.9
Asthenia
20.5
Upper respiratory tract infection
20.5
Some patients may experience adrenal insufficiency with ISTURISA3,a
- Hypocortisolism was reported at a rate of 31% (42/137) up to 12 weeks in the LINC 3 study.1,3 Adverse reactions potentially related to hypocortisolism were observed at a rate of 14.6% (7/48) up to week 12 in the LINC 4 study2
Counsel patients to recognize and report the symptoms suggestive of hypocortisolism3
- Nausea
- Vomiting
- Fatigue
- Abdominal pain
- Loss of appetite
- Dizziness
- Low blood pressure
- Syncope
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.
References: 1. Pivonello R, Fleseriu M, Newell-Price J, et al; LINC 3 investigators. Efficacy and safety of osilodrostat in patients with Cushing’s disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol. 2020;8(9):748-761. doi:10.1016/S2213-8587(20)30240-0 2. Gadelha M, Bex M, Feelders RA, et al. Randomized trial of osilodrostat for the treatment of Cushing disease. J Clin Endocrinol Metab. 2022;107(7):e2882-e2895. doi:10.1210/clinem/dgac178 3. Isturisa. Package insert. Recordati Rare Diseases Inc; 2023. 4. Pivonello R, Fleseriu M, Newell-Price J, et al. Efficacy and safety of osilodrostat in patients with Cushing’s disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol. 2020;8(9)(suppl). doi:10.1016/S2213- 8587(20)30240-0
References: 1. Pivonello R, Fleseriu M, Newell-Price J, et al; LINC 3 investigators. Efficacy and safety of osilodrostat in patients with Cushing’s disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol. 2020;8(9):748-761. doi:10.1016/S2213-8587(20)30240-0 2. Gadelha M, Bex M, Feelders RA, et al. Randomized trial of osilodrostat for the treatment of Cushing disease. J Clin Endocrinol Metab. 2022;107(7):e2882-e2895. doi:10.1210/clinem/dgac178 3. Isturisa. Package insert. Recordati Rare Diseases Inc; 2023. 4. Fleseriu M, Auchus RJ, Snyder PJ, et al. Effect of dosing and titration of osilodrostat on efficacy and safety in patients with Cushing’s disease (CD): results from two phase III trials (LINC3 and LINC4). Endocr Pract. 2021;27(suppl 6):S112. Abstract #999926. doi:10.1016/j.eprac.2021.04.707