داباجليف 10مجم 14 قرص

12.1 Mechanism of Action Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Dapagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose and thereby promotes urinary glucose excretion. Dapagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity, and decreased intraglomerular pressure which is believed to be mediated by increased tubuloglomerular feedback.

FARXIGA (dapagliflozin) is indicated: • To reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular (CV) death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression. • To reduce the risk of CV death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established CV disease or multiple CV risk factors. • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. Limitations of Use • FARXIGA is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see (5.1) ] . • FARXIGA is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m 2 . FARXIGA is likely to be ineffective in this setting based upon its mechanism of action. • FARXIGA is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. FARXIGA is not expected to be effective in these populations. FARXIGA is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated: • To reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular (CV) death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression. (1) • To reduce the risk of CV death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure. (1) • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established CV disease or multiple CV risk factors. (1) • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. (1) Limitations of use: • Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. (1) • Not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m 2 . FARXIGA is likely to be ineffective in this setting based upon its mechanism of action....

• Assess renal function prior to initiation and then as clinically indicated. Assess volume status and correct volume depletion before initiating. (2.1) • To improve glycemic control, the recommended starting dosage is 5 mg orally once daily. Dosage can be increased to 10 mg orally once daily for additional glycemic control. (2.2) • For all other indications, the recommended dosage is 10 mg orally once daily. ( 2.3 ) • See full prescribing information for dosage recommendations in patients with renal impairment. ( 2.2 , 2.3 ) • Withhold FARXIGA for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. ( 2.4 ) 2.1 Testing Prior to Initiation of FARXIGA • Assess renal function prior to initiation of FARXIGA and then as clinically indicated [see (5.2) ]. • Assess volume status. In patients with volume depletion, correct this condition before initiating FARXIGA [see (5.2) and (8.5 , 8.6) ] . 2.2 Recommended Dosage for Glycemic Control in Adults and Pediatric Patients Aged 10 Years and Older with Type 2 Diabetes Mellitus In adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus, the recommended starting dosage of FARXIGA is 5 mg orally once daily to improve glycemic control. For additional glycemic control, the dosage can be increased to 10 mg orally once daily. For Adult and Pediatric Patients with Type 2 Diabetes Mellitus and Renal Impairment: • The recommended dosage for FARXIGA in patients with an eGFR greater than or equal to 45 mL/min/1.73 m 2 is the same as the recommended dosage in patients with normal renal function. • FARXIGA is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m 2 . FARXIGA is likely to be ineffective to improve glycemic control in this setting based upon its mechanism of action. 2.3 Recommended Dosage for Other Indications in Adults The recommended dosage of FARXIGA is 10 mg orally once daily in adults for the following indications: • To reduce the risk of sustained eGFR decline, end-stage kidney disease (ESKD), CV death, and hospitalization for heart failure (hHF) in patients with chronic kidney disease at risk of progression. • To reduce the risk of CV death, hHF, and urgent heart failure visit in patients with heart failure. • To reduce the risk of hHF in patients with type 2 diabetes mellitus and either established CV disease or multiple CV risk factors....

The following important are described below and elsewhere in the labeling: • Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see (5.1) ] • Volume Depletion [see (5.2) ] • Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections [see (5.3) ] • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see (5.4) ] • Most common (5% or greater incidence) were female genital mycotic infections, nasopharyngitis, and urinary tract infections. ( 6.1) To report SUSPECTED , contact AstraZeneca at 1-800-236-9933 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 the clinical trials of another drug and may not reflect the rates observed in clinical practice. FARXIGA has been evaluated in clinical trials in adult and pediatric patients aged 10 years and older with type 2 diabetes mellitus, in adult patients with heart failure, and in adult patients with chronic kidney disease. The overall safety profile of FARXIGA was consistent across the studied indications. No new were identified in the DAPA-HF and DELIVER heart failure trials, or in the DAPA-CKD trial in patients with chronic kidney disease. Severe hypoglycemia and diabetic ketoacidosis (DKA) were observed only in patients with diabetes mellitus. Clinical Trials for Glycemic Control in Adult Patients with Type 2 Diabetes Mellitus Pool of 12 Placebo-Controlled Adult Trials for FARXIGA 5 and 10 mg for Glycemic Control The data in Table 1 is derived from 12 glycemic control placebo-controlled trials in adult patients with type 2 diabetes mellitus ranging from 12 to 24 weeks. In 4 trials FARXIGA was used as monotherapy, and in 8 trials FARXIGA was used as add-on to background antidiabetic therapy or as combination therapy with metformin [see Clinical Studies (14.1) ] . These data reflect exposure of 2338 adult patients to FARXIGA with a mean exposure duration of 21 weeks. Patients received placebo (N=1393), FARXIGA 5 mg (N=1145), or FARXIGA 10 mg (N=1193) once daily. The mean age of the population was 55 years and 2% were older than 75 years of age. Fifty percent (50%) of the population were male; 81% were White, 14% were Asian, and 3% were Black or African American....

FARXIGA is contraindicated in patients with a history of a serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA. Serious hypersensitivity reactions, including anaphylaxis and angioedema have been reported with FARXIGA [see (6.1) ] . • History of serious hypersensitivity reaction to dapagliflozin or any of the excipients in FARXIGA. (4)