ISTURISA (osilodrostat phosphate)

AbsorptionOsilodrostat is absorbed with a time of maximum observed concentration (T max ) of approximately 1 hour. Exposure (AUC inf and C max ) slightly increases over dose-proportionally within the therapeutic dose range of 1 mg to 30 mg. Effect of Food In a healthy volunteer study (N = 20), subjects administered with a single, 30 mg oral dose of ISTURISA film-coated tablets with a high-fat meal resulted in reduction of AUC by 11% and C max by 21%, respectively. The median T max was delayed f...

The safety and efficacy of ISTURISA was evaluated in 2 multicenter clinical studies,

Study 1(NCT02180217) and

Study 2(NCT02697734), in adults with persistent or recurrent Cushing's disease despite pituitary surgery or de novo patients for whom surgery was not indicated or who had refused surgery. Study 1 was a 48-week study that included an 8-week, double-blind, randomized withdrawal period at Weeks 26 to 34 in the study. After Week 48, patients who maintained clinical benefit on ISTURISA could continue in a long-term extension period until the last patient reached Week 72. Study 2 was a 48-...

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 REACTI...

None. None ( 4 )

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: Mo...

7 DRUG INTERACTIONS CYP3A4 Inhibitor: Reduce the dose of ISTURISA by half with concomitant use of a strong CYP3A4 inhibitor ( 7.1 ) 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 (...