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
  • 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

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 may report side effects related to AstraZeneca products by clicking here.

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

FARXIGA 10 mg as Add-On Therapy to Metformin XR

Back to Clinical Results

A1C Reductions

 

REDUCTION IN A1C LEVELS WITH 10 MG DOSE AS ADD-ON TO METFORMIN XR1

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

Reduction in A1C levels with 10 mg dose as add-on to metformin XR at 24 weeks Reduction in A1C levels with 10 mg dose as add-on to metformin XR at 24 weeks

Saxagliptin 5 mg + metformin XRa demonstrated a mean A1C reduction from baseline of 0.9% (n=175; BL=9.0%) at 24 weeks.1

Study not designed to compare treatment arms.

aBackground metformin XR dose was ≥1500 mg per day.

BL=baseline.

Recommended starting dose for patients taking FARXIGA is one 5 mg tablet QD.

Weight Reductions >

Weight Reductions*

 

WEIGHT REDUCTION WITH 10 MG DOSE AS ADD-ON THERAPY TO METFORMIN XR1,*

Secondary end point: Weight reduction at 24 weeks1

Weight reduction with 10 mg dose as add-on therapy to metformin XR at 24 weeks Weight reduction with 10 mg dose as add-on therapy to metformin XR at 24 weeks

Saxagliptin 5 mg + metformin XR demonstrated no weight reduction from baseline (n=175; BL=194.0 lb) at 24 weeks.1

Study not designed to compare treatment arms.

bBackground metformin XR dose was ≥1500 mg per day.

BL=baseline.

FARXIGA is not indicated for weight loss.

*Weight reduction was a secondary end point.

Study Design >

Study Design

 

STUDY DESIGN1

FARXIGA as Add-On Therapy to Metformin XR or Saxagliptin as Add-On Therapy to Metformin XR

A 24-week, phase 3, multicenter, randomized, double-blind, active-controlled trial in patients with type 2 diabetes. Adult patients with inadequate glycemic control (A1C 8.0% to 12.0%) on metformin were randomized to dapagliflozin 10 mg or saxagliptin 5 mg added on to metformin XR. These are two control arms of a multi-arm trial. This study was not designed to compare these arms.

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
  • 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

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 may report side effects related to AstraZeneca products by clicking here.

References:

Reference:

  1. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  2. 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.
  3. Rosenstock J, Mathieu C, Chen H, Garcia-Sanchez R, Saraiva GL. Dapagliflozin versus saxagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin. Arch Endocrinol Metab. 2018;62(4):424-430.
  4. 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.
  5. European Medicines Agency. EPAR summary for the public: Forxiga (dapagliflozin). October 2012.
  6. IQVIA database, MIDAS July 2017 – January 2018 (extracted April 10, 2018).
  7. ClinicalTrials.gov. Search results, search term “Dapagliflozin + phase 2 + phase 3.” Last accessed August 27, 2018.
  8. ClinicalTrials.gov. https://www.clinicaltrials.gov. Accessed August 27, 2018.
  9. Wiviott S, Raz I, Bonaca M, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes [published online ahead of print]. N Engl J Med. 2018.
  10. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  11. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  12. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  13. 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.
  14. 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.
  15. 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.
  16. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  17. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  18. 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.
  19. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  20. 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.
  21. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  22. 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: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010;33(10):2217-2224.
  23. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  24. 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.
  25. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  26. 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.
  27. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  28. 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.
  29. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  30. 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.
  31. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  32. 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.
  33. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  34. 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.
  35. Data on File. REF-4920; AstraZeneca Pharmaceuticals LP.
  36. 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.
  37. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  38. 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.
  39. Rosenstock J, Mathieu C, Chen H, Garcia-Sanchez R, Saraiva GL. Dapagliflozin versus saxagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin. Arch Endocrinol Metab. 2018;62(4):424-430.

IMPORTANT SAFETY INFORMATION FOR BYDUREON® (exenatide extended-release) injectable suspension 2 mg

WARNING: RISK OF THYROID C-CELL TUMORS

  • Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of exenatide extended-release-induced rodent thyroid C-cell tumors has not been determined
  • BYDUREON is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with the use of BYDUREON and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for detection of MTC in patients treated with BYDUREON

CONTRAINDICATIONS

  • Personal or family history of MTC, patients with MEN 2
  • Prior serious hypersensitivity reactions to exenatide or product components

WARNINGS AND PRECAUTIONS

  • Acute Pancreatitis including fatal and non-fatal hemorrhagic or necrotizing pancreatitis has been reported. After initiation, observe patients carefully for symptoms of pancreatitis. If suspected, discontinue promptly and do not restart if confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis
  • Hypoglycemia Risk of hypoglycemia is increased when exenatide is coadministered with insulin or insulin secretagogues. Consider lowering the dose of these agents when coadministered with BYDUREON
  • Acute Kidney Injury and Impairment of Renal Function Altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation have been reported. Not recommended in patients with severe renal impairment or end-stage renal disease. Use caution in patients with renal transplantation or moderate renal impairment
  • Gastrointestinal Disease Because exenatide is commonly associated with gastrointestinal adverse reactions, not recommended in patients with severe gastrointestinal disease (eg, gastroparesis)
  • Immunogenicity Patients may develop antibodies to exenatide. Patients with higher titer antibodies may have an attenuated HbA1c response. In clinical trials, attenuated glycemic response was associated with BYDUREON-treated patients. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy
  • Hypersensitivity Reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON and promptly seek medical advice
  • Injection-Site Reactions Serious reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, have been reported
  • Macrovascular Outcomes No clinical studies establishing conclusive evidence of macrovascular risk reduction with exenatide

ADVERSE REACTIONS

Most common (≥5%) and occurring more frequently than comparator in clinical trials: nausea (16.9%), diarrhea (12.7%), headache (8.0%), vomiting (6.8%), constipation (5.9%), injection-site pruritus (5.9%), injection-site nodule (5.3%), dyspepsia (5.1%).

DRUG INTERACTIONS

  • Oral Medications BYDUREON slows gastric emptying and may reduce the rate of absorption of orally administered drugs
  • Warfarin Increased international normalized ratio (INR) sometimes associated with bleeding has been reported with concomitant use of exenatide with warfarin. Monitor INR frequently until stable upon initiation of BYDUREON

PREGNANCY

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

INDICATION AND LIMITATIONS OF USE

BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

  • Not recommended as first-line therapy for patients inadequately controlled on diet and exercise
  • Not a substitute for insulin. Should not be used to treat type 1 diabetes or diabetic ketoacidosis
  • Use with prandial insulin has not been studied
  • Do not coadminister with other exenatide-containing products
  • Not studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis

Please read US Full Prescribing Information and Medication Guide for BYDUREON, including Boxed WARNING.

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References:

  1. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018.
  2. Exenatide [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017.
  3. Frías JP, Guja C, Hardy E, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016;4(12):1004-1016.