US FDA Approves Expanded FARXIGA and XIGDUO XR Labels for Use in Patients with Type 2 Diabetes and Moderate Renal Impairment
Updated label confirms the well-established efficacy and safety profile for FARXIGA and XIGDUO XR
WILMINGTON, Del.-AstraZeneca today announced that the US Food and Drug Administration (FDA) has approved a label update for?FARXIGA??(dapagliflozin) and XIGDUO??XR (dapagliflozin and metformin HCl extended-release) expanding use in patients with type 2 diabetes (T2D) and moderate renal impairment (chronic kidney disease with an estimated glomerular filtration rate [eGFR] of 45-59 mL/min/1.73 m2). FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. XIGDUO XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both dapagliflozin and metformin is appropriate.
The updated?labels lower the eGFR threshold to 45 mL/min/1.73 m2?from 60 mL/min/1.73 m2, expanding the potential population of patients with T2D and impaired renal function who may benefit from the medicine. FARXIGA and XIGDUO XR are not recommended when the eGFR is less than 45 mL/min/1.73 m2?and remains contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or in patients on dialysis.
The updates were based on the results of?DERIVE, a Phase 3 study of patients with inadequately controlled T2D (HbA1c 7.0%-11.0%) and an eGFR of 45 to 59 mL/min/1.73 m2?who received either FARXIGA (dapagliflozin 10 mg) or placebo over 24 weeks. At Week 24, FARXIGA (dapagliflozin 10 mg) provided statistically significant reductions in HbA1c compared with placebo. The safety profile following a treatment duration of 24 weeks was similar to that seen in the overall FARXIGA (dapagliflozin) clinical trial program.
Jim McDermott, PhD., Vice President, US Medical Affairs, Diabetes at AstraZeneca, said: ?The DERIVE study, which further confirmed the well-established efficacy and safety profile for?FARXIGA and XIGDUO XR, has resulted in important label changes for patients with type 2 diabetes that enable a broader population with impaired renal function to potentially benefit from these important treatment options.?
According to the Centers for Disease Control and Prevention, 30.3 million people in the US have diabetes, and T2D accounts for 90% to 95% of all diabetes cases.?Diabetes is the leading cause of kidney disease, and approximately 1 in 4 adults with diabetes has kidney disease.
Indication and Limitations of Use for FARXIGA??(dapagliflozin)
FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Important Safety Information for FARXIGA??(dapagliflozin)
Contraindications
- Prior serious hypersensitivity reaction to FARXIGA
- Severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
- Hypotension:?FARXIGA causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating FARXIGA in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for hypotension
- Ketoacidosis?has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
- Acute Kidney Injury and?Impairment in Renal Function:?FARXIGA causes intravascular volume contraction and renal impairment, with reports of acute kidney injury requiring hospitalization and dialysis. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue and promptly treat. FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Before initiating FARXIGA, evaluate renal function and monitor periodically. FARXIGA is not recommended when the eGFR is <45 mL/min/1.73 m2
- Urosepsis and Pyelonephritis:?SGLT2 inhibitors increase the risk for urinary tract infections [UTIs] and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
- Hypoglycemia:?FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
- Necrotizing Fasciitis of the Perineum (Fournier?s Gangrene):?Rare but serious, life-threatening cases have been reported in patients receiving SGLT2 inhibitors including FARXIGA. Cases have been reported in females and males. Serious outcomes have included hospitalization, surgeries, and death. Assess patients presenting with pain or tenderness, erythema, swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue FARXIGA.
- Genital Mycotic Infections:?FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
- Increases in Low-Density Lipoprotein Cholesterol (LDL-C)?occur with FARXIGA. Monitor LDL-C and treat per standard of care
- Bladder cancer:?An imbalance in bladder cancers was observed in clinical trials.?There were too few cases to determine whether the emergence of these events is related to FARXIGA, and insufficient data to determine whether FARXIGA has an effect on pre-existing bladder tumors. FARXIGA should not be used in patients with active bladder cancer. Use with caution in patients with a history of bladder cancer
- Macrovascular Outcomes:?There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with FARXIGA
- Pregnancy:?Advise females of potential risk to a fetus especially during the second and third trimesters.
- Lactation:?FARXIGA is not recommended when breastfeeding.
- Severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
- Prior serious hypersensitivity reaction to dapagliflozin or hypersensitivity to metformin hydrochloride
- Metabolic acidosis, including diabetic ketoacidosis
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