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.

AN SGLT2 INHIBITOR TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS

FARXIGA as Add-On to Insulin ± Oral Antidiabetic(s)

A1C Reductions

 

REDUCED A1C LEVELS WHEN ADDED TO INSULIN ± ORAL ANTIDIABETIC(S)1

Primary end point: FARXIGA achieved significant reduction in A1C levels when added to insulin ± up to 2 oral antidiabetic agents (OADs) at 24 weeks1,2

Primary end point: FARXIGA® (dapagliflozin) achieved significant reduction in A1C levels when added to insulin ± up to 2 oral antidiabetic agents (OADs) at 24 weeks Primary end point: FARXIGA® (dapagliflozin) achieved significant reduction in A1C levels when added to insulin ± up to 2 oral antidiabetic agents (OADs) at 24 weeks

aP<0.0001 vs placebo + insulin.

BL=baseline; OAD=oral antidiabetic.

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

Rates of hypoglycemia

  • At 24 weeks, there were 2 episodes of severe hypoglycemia§ reported in the FARXIGA 5 mg and 10 mg plus insulin groups and 1 episode in the insulin plus placebo group. Glucose <54 mg/dL were reported in 25.9%, 23.0% and 21.8% of patients in the FARXIGA 5 mg or 10 mg plus insulin and the insulin plus placebo groups, respectively1

Up to 2 OADs.

§Severe episodes of hypoglycemia were defined as episodes of severe impairment in consciousness or behavior, requiring external (third party) assistance, and with prompt recovery after intervention regardless of glucose level.

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.

Weight Reductions >

Weight Reductions*

 

REDUCED WEIGHT WHEN ADDED TO INSULIN1,*

A secondary end point: Significant weight reduction with FARXIGA when added to insulin ± up to 2 OADs at 24 weeks1,2

Secondary end point: significant weight reductions with FARXIGA when added to insulin ± up to 2 OADs at 24 weeks Secondary end point: significant weight reductions with FARXIGA when added to insulin ± up to 2 OADs at 24 weeks

bP<0.0001 + insulin ± up to 2 OADs.

BL=baseline; OAD=oral antidiabetic.

± up to 2 OADs.

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.

*Weight reduction was a secondary end point.

Insulin Dose Reductions >

Insulin Dose Reduction†

 

INSULIN DOSE REDUCTIONS1,†

-5.7 IU/DAY PLACEBO-ADJUSTED REDUCTION IN REQUIRED MEAN DOSE OF INSULIN WITH FARXIGA 5 MG AT WEEK 24 (P<0.0001; BASELINE DOSES WERE 77.0 IU AND 73.7 IU FOR FARXIGA 5 MG AND PLACEBO, RESPECTIVELY)1,2

-6.2 IU/DAY PLACEBO-ADJUSTED REDUCTION IN REQUIRED MEAN DOSE OF INSULIN WITH FARXIGA 10 MG AT WEEK 24 (P<0.0001; BASELINE DOSES WERE 78.0 IU AND 73.7 IU FOR FARXIGA 10 MG AND PLACEBO, RESPECTIVELY)1,2

 

± up to 2 OADs.

A secondary end point: Mean daily insulin dose reductions at 24 weeks1

FARXIGA 10 mg

+ insulin ± ≤2 OADs

Placebo

+ insulin ± ≤2 OADs

19.6%c 11.0%

cP<0.05 vs placebo.

Values are last observation (after rescue) carried forward.

Insulin dose reduction was a secondary end point.

Study Design >

Study Design

 

STUDY DESIGN1,2

FARXIGA as Add-On to Insulin ± Oral Antidiabetic(s)

24-week, randomized, double-blind, placebo-controlled, parallel-group, international, multicenter trial

Randomization with FARXIGA 5 mg + insulin regimen ± ≤2 OAD(s) (n=211), FARXIGA 10 mg + insulin regimen ± ≤2 OAD(s) (n=194), Dapagliflozin 2.5 mg + insulin regimen ± ≤2 OAD(s) (n=202), Placebo + insulin regimen ± ≤2 OAD(s) (n=193)

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 in adult patients with type 2 diabetes inadequately controlled with insulin and up to 2 oral antidiabetic agents (OADs).

 

Study Length

24 weeks

 

 

Key Inclusion Criteria

Men and women 18 to 80 years of age were enrolled if they had type 2 diabetes mellitus, inadequate glycemic control (A1C ≥7.5% and ≤10.5%), and a BMI of 45 kg/m2 or less. Participants had to have received a stable insulin regimen with a mean daily insulin dose of 30 IU or more for at least 8 weeks, with daily insulin requirements varying by more than 10% on no more than one occasion in the 7 days before randomization. Additional treatment with stable doses of up to 2 OADs was allowed. Patients were stratified into 2 strata (with and without OADs).

 

 

Study Dosing

Patients were randomized 1:1:1:1 to dapagliflozin 2.5 mg,# FARXIGA 5 mg, FARXIGA 10 mg, or placebo once daily in addition to open-label therapy with their usual daily dose of insulin and existing OADs. Mean dose of insulin was ≥30 IU of injectable insulin per day, in addition to current regimen of up to 2 OADs (if applicable).

#Dapagliflozin 2.5 mg is not an FDA-approved dose.

FARXIGA tablets shown are not actual sizes.

Primary End Point

Change in A1C from baseline at Week 24

Select Secondary End Points

  • Change in total body weight from baseline at Week 24
  • Change in mean daily insulin dose from baseline at Week 24
  • Change in the percent of patients who reduced their insulin dose by >10% at Week 24

Important Safety Information For Farxiga

INDICATIONS AND LIMITATIONS OF USE

Contraindications

  • Prior serious hypersensitivity reaction to FARXIGA
  • Patients with severe renal impairment (eGFR <30 mL/min/1.73 m2) being treated for glycemic control without established CV disease or multiple CV risk factors
  • Patients on dialysis

Warnings and Precautions

  • Volume Depletion: FARXIGA can cause intravascular volume depletion which may manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including FARXIGA. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating FARXIGA in these patients, assess volume status and renal function. After initiating therapy, monitor for signs and symptoms of hypotension and renal function
  • Ketoacidosis in Diabetes Mellitus 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
  • 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 with diabetes mellitus 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

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

INDICATIONS AND LIMITATIONS OF USE FOR FARXIGA

FARXIGA is indicated:

  • to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction
  • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors
  • 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.

DOSING

  • To reduce the risk of CV death and hospitalization for heart failure in patients with HFrEF, the recommended dose of FARXIGA is 10 mg orally once daily
  • To reduce the risk of hospitalization for heart failure in patients with T2D and established CV disease or multiple CV risk factors, the recommended dose of FARXIGA is 10 mg orally once daily
  • To improve glycemic control in patients with T2D, the recommended starting dose of FARXIGA is 5 mg orally once daily, taken in the morning. In patients tolerating FARXIGA 5 mg once daily who require additional glycemic control, the dose can be increased to 10 mg once daily

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

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

FARXIGA is indicated:

  • to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction
  • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors
  • 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.

DOSING

  • To reduce the risk of CV death and hospitalization for heart failure in patients with HFrEF, the recommended dose of FARXIGA is 10 mg orally once daily
  • To reduce the risk of hospitalization for heart failure in patients with T2D and established CV disease or multiple CV risk factors, the recommended dose of FARXIGA is 10 mg orally once daily
  • To improve glycemic control in patients with T2D, the recommended starting dose of FARXIGA is 5 mg orally once daily, taken in the morning. In patients tolerating FARXIGA 5 mg once daily who require additional glycemic control, the dose can be increased to 10 mg once daily

References:

Reference:

  1. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  2. Invokana® (canagliflozin) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2020.
  3. Jardiance® (empagliflozin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2020.
  4. Steglatro (ertugliflozin) [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc; 2020.
  5. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  6. Invokana® (canagliflozin) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2020.
  7. Jardiance® (empagliflozin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2020.
  8. Steglatro (ertugliflozin) [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc; 2020.
  9. Cannon CP, McGuire DK, Pratley R, et al. Design and baseline characteristics of the evaluation of Ertugliflozin efficacy and Safety Cardiovascular outcomes trial (VERTIS-CV). Am Heart J. 2018;206:11-23.
  10. 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.
  11. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  12. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  13. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  14. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  15. 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.
  16. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  17. 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.
  18. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  19. 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.
  20. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  21. 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.
  22. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  23. 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.
  24. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  25. 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.
  26. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  27. 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.
  28. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  29. 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.
  30. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  31. 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.
  32. Data on File. REF-4920; AstraZeneca Pharmaceuticals LP.
  33. 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.
  34. FARXIGA® [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  35. 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.
  36. 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.
  37. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  38. Invokana® (canagliflozin) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2020.
  39. Jardiance® (empagliflozin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2020.
  40. Cefalu WT, Kaul S, Gerstein HC, et al. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a Diabetes Care editors' expert forum. Diabetes Care. 2018;41(1):14-31.
  41. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657.
  42. Steglatro (ertugliflozin) [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc; 2020.
  43. Cannon CP, McGuire DK, Pratley R, et al. Design and baseline characteristics of the evaluation of Ertugliflozin efficacy and Safety Cardiovascular outcomes trial (VERTIS-CV). Am Heart J. 2018;206:11-23.
  44. 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.
  45. Data on File, REF-62129; AstraZeneca Pharmaceuticals LP.
  46. Supplementary appendix to: 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.
  47. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  48. Sattar N, McLaren J, Kristensen SL, Preiss D, McMurray JJ. SGLT2 inhibition and cardiovascular events: why did EMPA-REG outcomes surprise and what were the likely mechanisms? Diabetologia. 2016;59(7):1333-1339.
  49. Verma S, McMurray JJV, Cherney DZI. The metabolodiuretic promise of sodium-dependent glucose cotransporter 2 inhibition: the search for the sweet spot in heart failure. JAMA Cardiol. 2017;2(9):939-940.
  50. Formulary data are provided by Fingertip Formulary® and are current as of September 1, 2020.

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
  • History of drug-induced, immune-mediated thrombocytopenia from exenatide products

WARNINGS AND PRECAUTIONS

  • Never share a BYDUREON pen or needle with anyone else Sharing poses a risk for transmission of blood-borne pathogens
  • 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
  • Drug-induced, immune-mediated thrombocytopenia and associated bleeding has been reported with exenatide. Serious bleeding, which may be fatal, has been reported. Discontinue promptly if suspected and avoid re-exposure to exenatide
  • 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%), and 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 mellitus 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.

References:

  1. FARXIGA® (dapagliflozin) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  2. BYDUREON® ([exenatide extended-release] injectable suspension) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.
  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.

Important Safety Information For Farxiga

INDICATIONS AND LIMITATIONS OF USE

Contraindications

  • Prior serious hypersensitivity reaction to FARXIGA
  • Patients with severe renal impairment (eGFR <30 mL/min/1.73 m2) being treated for glycemic control without established CV disease or multiple CV risk factors
  • Patients on dialysis

FARXIGA is indicated:

  • to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction
  • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors
  • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
  • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors
  • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors
  • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
  • to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction
  • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors