isturisa

Correct hypokalemia and hypomagnesemia, and obtain baseline electrocardiogram prior to starting ISTURISA ( 2.1 , 5.2 , 5.3 ) Initiate dosage at 2 mg orally twice daily, with or without food ( 2.2 ) Titrate dosage by 1 mg to 2 mg twice daily, no more frequently than every 2 weeks based on rate of cortisol changes, individual tolerability and improvement in signs and symptoms ( 2.2 ) Maximum recommended dosage is 30 mg twice daily ( 2.2 ) See Full Prescribing Information for complete titration, laboratory, and dosage modification recommendations ( 2.1 , 2.2 , 2.3 ) Patients with Hepatic Impairment: Child-Pugh B: Recommended starting dose is 1 mg twice daily ( 2.5 , 8.7 ) Child-Pugh C : Recommended starting dose is 1 mg once daily in the evening ( 2.5 , 8.7 ) 2.1 Laboratory Testing Prior to ISTURISA Initiation Correct hypokalemia and hypomagnesemia prior to starting ISTURISA [see Warnings and Precautions (5.2 , 5.3) ]. Obtain baseline electrocardiogram (ECG) . Repeat ECG within one week after treatment initiation, and as clinically indicated thereafter [see Warnings and Precautions (5.2) ] . 2.2 Recommended Dosage, Titration, and Monitoring Initiate dosing at 2 mg orally twice daily, with or without food. Initially, titrate the dosage by 1 mg to 2 mg twice daily, no more frequently than every 2 weeks based on the rate of cortisol changes, individual tolerability and improvement…

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…

None. None ( 4 )

Overdosage may result in severe hypocortisolism. Signs and symptoms suggestive of hypocortisolism may include nausea, vomiting, fatigue, low blood pressure, abdominal pain, loss of appetite, dizziness, and syncope. In case of suspected overdosage, ISTURISA should be temporarily discontinued, cortisol levels should be checked, and if necessary, corticosteroid supplementation should be initiated. Close surveillance may be necessary, including monitoring of the QT interval, blood pressure, glucose, fluid, and electrolyte until the patient's condition is stable.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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 ( 7.1 ) 7.1 Effect of Other Drugs on ISTURISA The effect of other drugs on ISTURISA can be found in Table 3. Table 3: Effect of Other Drugs on ISTURISA CYP3A4 Inhibitors Clinical Impact: Concomitant use of ISTURISA with a strong CYP3A4 inhibitor (e.g., itraconazole, clarithromycin) may cause an increase in osilodrostat concentration and may increase the risk of ISTURISA-related adverse reactions [see Clinical Pharmacology (12.3) ] . Intervention : Reduce the dose of ISTURISA by half with concomitant use of a strong CYP3A4 inhibitor. CYP3A4 and CYP2B6 Inducers Clinical Impact: Concomitant use of ISTURISA with strong CYP3A4 and/or CYP2B6 inducers (e.g., carbamazepine, rifampin, phenobarbital) may cause a decrease in osilodrostat concentration and may reduce the efficacy of ISTURISA [see Clinical Pharmacology (12.3) ] . Discontinuation of strong CYP3A4 and/or CYP2B6 inducers while using ISTURISA may cause an increase in osilodrostat concentration and may increase the risk of ISTURISA-related adverse reactions [see Clinical Pharmacology (12.3) ] . Intervention: During concomitant use of ISTURISA with strong CYP3A4 and CYP2B6 inducers, monitor cortisol concentration and patient's signs and symptoms. An increase in ISTURISA dosage may be needed. Upon discontinuation of strong CYP3A4 and CYP2B6 inducers during ISTURISA treatment, monitor cortisol concentration and patient's signs and symptoms. A reduction in ISTURISA dosage may be needed. 7.2 Effect of ISTURISA on Other Drugs ISTURISA should be used with caution when coadministered with CYP1A2 and CYP2C19 substrates with a narrow therapeutic index, such as theophylline, tizanidine, and S-mephenytoin [see Clinical Pharmacology (12.3) ] .