Important Safety Information For Farxiga

Contraindications

  • Prior serious hypersensitivity reaction to FARXIGA...Read More
  • Severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis

Warnings and Precautions

  • 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 in patients with an eGFR persistently between 30 and <60 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
  • 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

Adverse Reactions

In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).

Use in Specific Populations

  • Pregnancy: Advise females of potential risk to a fetus especially during the second and third trimesters

  • Lactation: FARXIGA is not recommended when breastfeeding

INDICATION AND LIMITATIONS OF USE

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.

Please read US Full Prescribing Information and Medication Guide for FARXIGA.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

A TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS, IN ADDITION TO DIET AND EXERCISE

FARXIGA 10 mg Initial Combination Therapy With Metformin XR*

Select a category or scroll to learn more.

A1C Reductions

 

SIGNIFICANT REDUCTION IN A1C LEVELS WITH 10 MG DOSE1

Primary end point: Mean reduction in A1C levels at 24 weeks1,2,a

Mean reduction in A1C levels with FARXIGA® (dapagliflozin) at 24 weeks Mean reduction in A1C levels with FARXIGA® (dapagliflozin) at 24 weeks

aThe median metformin XR dose was 2000 mg per day.

bP<0.0001 vs FARXIGA 10 mg or metformin XR.

BL=baseline.

Values are last observation (prior to rescue for rescued patients) carried forward and represent adjusted mean change from baseline.

Weight Reductions >

WEIGHT REDUCTIONS†

 

SIGNIFICANT WEIGHT REDUCTION WITH 10 MG DOSE1

A secondary end point: Mean weight reduction at 24 weeks1,2,c

Mean reduction in A1C levels with FARXIGA® (dapagliflozin) at 24 weeks Mean reduction in A1C levels with FARXIGA® (dapagliflozin) at 24 weeks

cThe median metformin XR dose was 2000 mg per day.

dP<0.0001 vs metformin XR monotherapy.

BL=baseline.

Values are last observation (prior to rescue for rescued patients) carried forward and represent adjusted mean change from baseline.

FARXIGA is not indicated for weight loss.

*Recommended starting dose of FARXIGA is 5 mg once daily. In patients tolerating 5 mg who require additional glycemic control, the dose can be increased to 10 mg once daily.

Weight reduction was a secondary end point.

Study Design >

Study Design

 

STUDY DESIGN1,2

FARXIGA 10 mg Initial Combination Therapy With Metformin XR

Randomized, double-blind, active-controlled, multicenter, 24-week, phase 3 trial

Randomization with FARXIGA 5 mg (n=64),  FARXIGA 10 mg (n=70),  Dapagliflozin 2.5mg (n=65), Placebo (n=75) Randomization with FARXIGA 5 mg (n=64),  FARXIGA 10 mg (n=70),  Dapagliflozin 2.5mg (n=65), Placebo (n=75)

Study Objective

Evaluate the efficacy and safety of FARXIGA plus metformin XR in treatment-naïve adult patients whose type 2 diabetes cannot be controlled with diet and exercise alone.

Primary End Point

Change in A1C from baseline at Week 24

Select Secondary End Point

  • Change in total body weight from baseline at Week 24
 

Study Length

24 weeks

 

 

Key Inclusion Criteria

Patients were 18 to 77 years of age with type 2 diabetes who had inadequate glycemic control (A1C ≥7.5% and ≤12.0%) and had a C-peptide ≥1.0 ng/mL and a body mass index (BMI) ≤45 kg/m2.

 

 

Study Dosing

FARXIGA in combination and as monotherapy was dosed at 10 mg. The metformin XR dose was up-titrated weekly in 500-mg increments, as tolerated, up to a maximum of 2000 mg daily. Mean metformin XR dose was 1928.6 mg in the combination group and 1949.7 mg for the metformin XR monotherapy group.

FARXIGA tablet shown is not actual size.

Important Safety Information For Farxiga

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

Warnings and Precautions

  • 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 in patients with an eGFR persistently between 30 and <60 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
  • 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

Adverse Reactions

In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).

Use in Specific Populations

  • Pregnancy: Advise females of potential risk to a fetus especially during the second and third trimesters
  • Lactation: FARXIGA is not recommended when breastfeeding

INDICATION AND LIMITATIONS OF USE

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.

Please read US Full Prescribing Information and Medication Guide for FARXIGA.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-10881-800-FDA-1088.

References:

Reference:

  1. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  2. IQVIA database, MIDAS February-August 2017 (extracted October 20, 2017).
  3. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  4. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  5. Wong ND, Patao C, Wong K, Malik S, Franklin SS, Iloeje U. Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999 to 2010: comparison by prevalent cardiovascular disease status. Diab Vasc Dis Res. 2013;10(6):505-513.
  6. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of diabetes and its burden in the United States, 2014. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. Accessed September 28, 2015.
  7. Centers for Disease Control and Prevention. Age-adjusted percentage of adults aged 18 years or older with diagnosed diabetes who were overweight, United States, 1994–2010. http://www.cdc.gov/diabetes/statistics/comp/fig7_overweight.htm. Accessed September 18, 2015.
  8. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  9. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  10. Henry RR, Murray AV, Marmolejo MH, Hennicken D, Ptaszynska A, List JF. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract. 2012;66(5):446-456.
  11. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  12. Henry RR, Murray AV, Marmolejo MH, Hennicken D, Ptaszynska A, List JF. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract. 2012;66(5):446-456.
  13. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  14. Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise. Diabetes Care. 2010;33(10):2217-2224.
  15. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  16. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9733):2223-2233.
  17. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  18. Jabbour SA, Hardy E, Sugg J, Parikh S; Study 10 Group. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care. 2014;37(3):740-750.
  19. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  20. Strojek K, Yoon KH, Hruba V, Elze M, Langkilde AM, Parikh S. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo controlled trial. Diabetes Obes Metab. 2011;13(10):928-938.
  21. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  22. Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012;35(7):1473-1478.
  23. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  24. Wilding JP, Woo V, Soler NG, et al. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med. 2012;156(6):405-415.
  25. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  26. Nauck MA, Del Prato S, Meier JJ, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011;34(9):2015-2022.
  27. Data on File, REF-4920, AstraZeneca Pharmaceuticals LP.
  28. Del Prato S, Nauck M, Duran-Garcia S, et al. Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes Obes Metab. 2015;17(6):581-590.
  29. FARXIGA [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  30. Nauck MA, Del Prato S, Meier JJ, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care. 2011;34(9):2015-2022.