INPEFA

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors INPEFA is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure ( 1 ) or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Correct volume status before starting INPEFA at 200 mg daily and titrate to 400 mg as tolerated. ( 2.2 ) In patients with decompensated heart failure, begin dosing when patients are hemodynamically stable. ( 2.1 ) Withhold INPEFA at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. ( 2.3 ) 2.1 Prior to Initiation of INPEFA Assess volume status and, if necessary, correct volume depletion prior to initiation of INPEFA [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.5 , 8.6 )] . Assess renal function prior to initiation of INPEFA and then as clinically indicated [see Warnings and Precautions ( 5.2 )] . For patients with decompensated heart failure, dosing may begin as soon as the patient is hemodynamically stable, including during hospitalization or urgent outpatient treatment or immediately upon discharge. 2.2 Recommended Dosage The recommended starting dose of INPEFA is 200 mg orally once daily not more than one hour before the first meal of the day. Up-titrate after at least 2 weeks to 400 mg orally once daily as tolerated [see Clinical Studies ( 14 )] . Down-titrate to 200 mg as necessary [see Adverse Reactions ( 6.1 ), Warnings and Precautions ( 5 ) and Use in Specific Populations ( 8.6 )]. Swallow tablets whole. Do not cut, crush, or chew tablets. If a dose of INPEFA is missed by more than 6 hours, take the next dose as prescribed the next day. 2.3 Temporary Interruption for Surgery Withhold INPEFA at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. Resume INPEFA when the patient is clinically stable and has resumed oral intake [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )] . Warnings and cautions 5 WARNINGS AND PRECAUTIONS Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue INPEFA if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. ( 5.1 ) Volume Depletion: Before initiating, correct volume status. Monitor for signs and symptoms of hypotension during therapy. ( 5.2 ) Urosepsis and Pyelonephritis: Monitor for signs and symptoms during therapy and treat promptly. ( 5.3 ) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Lower dose of insulin or insulin secretagogue may be required. ( 5.4 ) Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) : Monitor for pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. Discontinue INPEFA and treat urgently. ( 5.5 ) Genital Mycotic Infections : Monitor and treat as appropriate. ( 5.6 ) 5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, INPEFA significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose cotransporter 2 (SGLT2) inhibitors compared to patients who received placebo; this risk may be greater with higher doses of INPEFA. INPEFA is not indicated for glycemic control. Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes using SGLT2 inhibitors. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include acute febrile illness, reduced caloric intake, ketogenic diet, surgery, insulin dose reduction, volume depletion, and alcohol abuse. Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persi