Complete adverse effect profile including incidence rates and management
Important Safety Information
This is not a complete list of all possible side effects. Contact your healthcare provider if you experience any unexpected symptoms. For serious or life-threatening side effects, seek emergency medical attention immediately.
6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Hypocortisolism [see Warnings and Precautions (5.1) ] QT Prolongation [see Warnings and Precautions (5.2) ] Elevations in Adrenal Hormone Precursors and Androgens [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence > 20%) are adrenal insufficiency, fatigue, nausea, headache, edema, decreased appetite, arthralgia, myalgia, and diarrhea ( 6 ) 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.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
The safety of ISTURISA was evaluated in two clinical trials in adults with Cushings disease.
Study 1 (NCT02180217) was a 4-period, multicenter study with a 12-week open-label titration period, 12-week open-label maintenance period, 8-week double-blind, placebo-controlled period, and 14 to 24-week open label treatment period in 137 patients with Cushing's disease.
Study 2 (NCT02697734) was a 2-period, multicenter study with a 12-week randomized, double-blind, placebo-controlled period and a 36-week open-label treatment period in 74 patients with Cushing's disease [see Clinical Studies (14) ] .
Study 1 The adverse reactions that occurred with frequency higher than 10% during the core 48-week period are shown in Table
Table 1: Adverse Reactions With a Frequency of More Than 10% in 48-week Clinical Study 1 in Adults with Cushing's Disease Adverse Reaction Type (N = 137) % Adrenal insufficiency Adrenal insufficiency includes glucocorticoid deficiency, adrenocortical insufficiency acute, steroid withdrawal syndrome, cortisol free urine decreased, cortisol decreased.
One-third of the subjects with this event had low cortisol levels indicative of Adrenal Insufficiency.
The majority of subjects had normal cortisol levels suggesting a cortisol withdrawal syndrome.
5 WARNINGS AND PRECAUTIONS Hypocortisolism : Monitor patients closely for hypocortisolism and potentially life-threatening adrenal insufficiency.
Dosage reduction or interruption may be necessary.
After interruption or discontinuation of ISTURISA, cortisol suppression may persist and patients should be regularly monitored ( 5.1 ) QTc Prolongation : Perform electrocardiogram in all patients Use with caution in patients with risk factors for QTc prolongation ( 5.2 ) Elevations in Adrenal Hormone Precursors and Androgens: Monitor for hypokalemia, worsening of hypertension, edema, and hirsutism ( 5.3 ) 5.1 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, dizziness.
Significant lowering of serum cortisol may result in hypotension, abnormal electrolyte levels, and hypoglycemia [see Adverse Reactions (6) ] .
Like all medications, Isturisa can cause side effects. However, not everyone who takes this medication will experience them. Many side effects are dose-dependent and may improve as your body adjusts to the medication. Others may require dose adjustment or medical attention.
Contact your healthcare provider promptly if you experience:
Seek immediate emergency medical care if you experience signs of: