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 when the eGFR is <45 mL/min/1.732
  • 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

Head-to-Head vs Glipizide (a Sulfonylurea) + Metformin: 1-Year Data

Back to Clinical Results

A1C Reductions

 

COMPARABLE REDUCTION IN A1C LEVELS AT 1 YEAR

Primary end point: With FARXIGA + metformin, reductions in A1C levels were noninferior to glipizide + metformin at 1 year1,2,a

Primary end point: With FARXIGA® (dapagliflozin) + metformin, reductions in A1C were noninferior to glipizide + metformin at 1 year Primary end point: With FARXIGA® (dapagliflozin) + metformin, reductions in A1C were noninferior to glipizide + metformin at 1 year

aPatients on metformin ≥1500 mg per day were randomized following a 2-week placebo lead-in period to glipizide 5 mg or dapagliflozin 2.5 mg and were up-titrated over 18 weeks to optimal glycemic effect (FPG <110 mg/dL, <6.1 mmol/L) or to the highest dose level (up to glipizide 20 mg and FARXIGA 10 mg) as tolerated by patients. At the end of the titration period, 87% of patients treated with FARXIGA had been titrated to the maximum study dose (10 mg) vs 73% treated with glipizide (20 mg). Dapagliflozin 2.5 mg is not an FDA-approved dose.

BL=baseline.

Values are last observation carried forward and represent adjusted mean change from baseline.

Weight Reductions >

Weight Reductions*

 

SIGNIFICANT WEIGHT REDUCTION AT 1 YEAR*

Secondary end point: Significant mean weight reduction from baseline with FARXIGA + metformin vs glipizide + metformin at 1 year1,2

Secondary end point: significant weight reductions with FARXIGA vs glipizide at 1 year Secondary end point: significant weight reductions with FARXIGA vs glipizide at 1 year
  • • FARXIGA + metformin (n=400) (BL=194.9 lb)
  • • Glipizide + metformin (n=401) (BL=193.1 lb)

bP<0.0001.

BL=baseline.

Values are last observation carried forward and represent adjusted mean change from baseline.

FARXIGA is not indicated for weight loss.

*Weight reduction was a secondary end point.

Blood Pressure Reductions >

Blood Pressure Reductions

 

SIGNIFICANT BLOOD PRESSURE REDUCTION AT 1 YEAR†

A secondary end point: Significant mean change from baseline in systolic BP with FARXIGA + metformin relative to glipizide + metformin at 1 year1-3

Secondary end point: Significant mean change from baseline in systolic BP with FARXIGA + metformin relative to glipizide + metformin at 1 year Secondary end point: Significant mean change from baseline in systolic BP with FARXIGA + metformin relative to glipizide + metformin at 1 year

cP<0.0001 vs glipizide + metformin.

BL=baseline.

Values are last observation carried forward.

FARXIGA is not indicated for the treatment of hypertension.

†Blood pressure reduction was a secondary end point.

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.

Lower Rate of Hypoglycemia

  • 1.7% (n=7) OF PATIENTS TAKING FARXIGA EXPERIENCED MINOR‡ HYPOGLYCEMIA VS 36.0% (n=147) WITH GLIPIZIDE OVER 52 WEEKS. 0% OF PATIENTS TAKING FARXIGA EXPERIENCED MAJOR§ HYPOGLYCEMIA VS 0.7% (n=3) WITH GLIPIZIDE OVER 52 WEEKS1

‡Minor episodes of hypoglycemia were defined as either a symptomatic episode with a capillary or plasma glucose measurement <63 mg/dL regardless of need for external assistance, or an asymptomatic capillary or plasma glucose measurement <63 mg/dL that does not qualify as a major episode.

§Major episodes of hypoglycemia were defined as symptomatic episodes requiring external (third-party) assistance due to severe impairment in consciousness or behavior with a capillary or plasma glucose value <54 mg/dL and prompt recovery after glucose or glucagon administration.

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.

Study Design >

Study Design

 

STUDY DESIGN1,2

Head-to-Head vs Glipizide (a Sulfonylurea) + Metformin: 1-Year Data

Randomized, 1-year, double-blind, parallel-group, active-controlled, multicenter, noninferiority, phase 3 study

Randomization with Dapagliflozin 2.5 mg to 10 mg + metformin (n=400), Glipizide 5 to 20 mg + metformin (n=401)

ǁPatients received dapagliflozin 2.5 mg or glipizide 5 mg and were up-titrated to optimal glycemic effect (FPG <110 mg/dL) or to the highest dose level (up to FARXIGA 10 mg and glipizide 20 mg) as tolerated by patients. Metformin dose was ≥1500 mg/day. Dapagliflozin 2.5 mg is not an FDA-approved dose; thus, data from this treatment group are not presented.

Study Objective

Evaluate the efficacy and safety of FARXIGA plus metformin vs glipizide plus metformin in adult patients with type 2 diabetes whose A1C is inadequately controlled on metformin monotherapy.

 

Study Length

1 year

 

 

Key Inclusion Criteria

Adult patients with type 2 diabetes who had inadequate glycemic control (A1C >6.5% and ≤10.0%) and had a BMI of ≤45 kg/m2. Patients with systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg were excluded.

 

 

Study Dosing

FARXIGA was up-titrated to a maximum dose of 10 mg. Glipizide was up-titrated to a maximum dose of 20 mg. Up-titration occurred over 18 weeks, after which doses were kept constant unless down-titration was required to prevent hypoglycemia.

FARXIGA tablet shown is not actual size.

Primary End Point

Change in A1C from baseline at 1 year

Select Secondary End Points

  • Change in total body weight from baseline at 1 year
  • Change in seated systolic blood pressure at 1 year

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 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

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; 2019.
  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 NPA Market Dynamics Extracted July 2019 (February 2014–June 2019). Data on File, US-31165; AstraZeneca Pharmaceuticals LP.
  7. ClinicalTrials.gov. Search results, search term “Dapagliflozin + phase 2 + phase 3.” Last accessed August 2, 2019.
  8. ClinicalTrials.gov. https://www.clinicaltrials.gov. Accessed August 2, 2019.
  9. Wiviott S, Raz I, Bonaca M, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357.
  10. Raz I, Mosenzon O, Bonaca MP, et al. DECLARE-TIMI 58: participants’ baseline characteristics. Diabetes Obes Metab. 2018;20(5):1102-1110.
  11. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  12. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  13. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357.
  14. Jabbour S, Seufert J, Scheen A, et al. Dapagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of safety data from phase IIb/III clinical trials. Diabetes Obes Metab. 2017; doi:10.1111/dom.13124.
  15. Ptaszynska A, Mansfield T, Johnsson E, et al. Long-term renal safety with dapagliflozin treatment. Poster presented at: the 74th Scientific Sessions of the American Diabetes Association (ADA); June 13-17, 2014; San Francisco, CA.
  16. Ptaszynska A, Mansfield T, Apanovitch AM, et al. Dapagliflozin, selective SGLT2 inhibitor, does not increase risk of fractures. Poster presented at: the 74th Scientific Sessions of the American Diabetes Association (ADA); June 13-17, 2014; San Francisco, CA.
  17. Data on File, REF-5026; AstraZeneca Pharmaceuticals LP.
  18. FDA Drug Safety Communication: FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. https://www.fda.gov/Drugs/DrugSafety/ucm617360.htm. Accessed March 14, 2019.
  19. FDA. FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (FARXIGA, XIGDUO XR). http://www.fda.gov/Drugs/DrugSafety/ucm505860.htm. Accessed March 14, 2019.
  20. FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. http://www.fda.gov/Drugs/DrugSafety/ucm475463.htm. Accessed March 14, 2019.
  21. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  22. 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.
  23. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of diabetes and its burden in the United States, 2017. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. Accessed April 4, 2019.
  24. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  25. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  26. 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.
  27. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  28. 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.
  29. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  30. 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.
  31. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  32. 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.
  33. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  34. 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.
  35. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  36. 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.
  37. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  38. 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.
  39. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  40. 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.
  41. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  42. 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.
  43. Data on File. REF-4920; AstraZeneca Pharmaceuticals LP.
  44. 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.
  45. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  46. 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.
  47. 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 May induce nausea and vomiting with transient hypovolemia and may worsen renal function. 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 eGFR <45 mL/min/1.73 m2
  • 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
  • Acute Gallbladder Disease has been reported in GLP-1 receptor agonist trials, including exenatide. If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated

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; 2019.
  2. BYDUREON® ([exenatide extended-release] injectable suspension) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  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.