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

FARXIGA: A Well-Established Safety Profile

FARXIGA Side Effects

SETTING EXPECTATIONS FOR YOUR PATIENTS MAY HELP THEM HAVE CONFIDENCE IN FARXIGA

WELL-ESTABLISHED SAFETY PROFILE

Pooled Safety Analysis

Adverse reactions in 12 placebo-controlled studies reported in ≥2% of patients treated with FARXIGA1,a,b FARXIGA 5 mg FARXIGA 10 mg Placebo
Female genital mycotic infectionsc 8.4% 6.9% 1.5%
Nasopharyngitis 6.6% 6.3% 6.2%
Urinary tract infectionsd 5.7% 4.3% 3.7%
Back pain 3.1% 4.2% 3.2%
Increased urinatione 2.9% 3.8% 1.7%
Male genital mycotic infectionsf 2.8% 2.7% 0.3%
Nausea 2.8% 2.5% 2.4%
Influenza 2.7% 2.3% 2.3%
Dyslipidemia 2.1% 2.5% 1.5%
Constipation 2.2% 1.9% 1.5%
Discomfort with urination 1.6% 2.1% 0.7%
Pain in extremity 2.0% 1.7% 1.4%
  (N=1145) (N=1193) (N=1393)

aAdverse events were evaluated with FARXIGA 5 mg and 10 mg in 12 placebo-controlled studies ranging from 12 to 24 weeks.

bFARXIGA was studied as monotherapy in 4 studies, and in 8 studies as add-on to background antidiabetic therapy or as combination with metformin.

cGenital mycotic infections include the following adverse reactions, listed in order of frequency reported for females: vulvovaginal mycotic infection, vaginal infection, vulvovaginal candidiasis, vulvovaginitis, genital infection, genital candidiasis, fungal genital infection, vulvitis, genitourinary tract infection, vulval abscess, and vaginitis bacterial (N for females: FARXIGA 5 mg=581, FARXIGA 10 mg=598, placebo=677).

dUrinary tract infections include the following adverse reactions, listed in order of frequency reported: urinary tract infection, cystitis, Escherichia urinary tract infection, genitourinary tract infection, pyelonephritis, trigonitis, urethritis, kidney infection, and prostatitis.

eIncreased urination includes the following adverse reactions, listed in order of frequency reported: pollakiuria, polyuria, and increased urine output.

fGenital mycotic infections include the following adverse reactions, listed in order of frequency reported for males: balanitis, fungal genital infection, balanitis candida, genital candidiasis, genital infection male, penile infection, balanoposthitis, balanoposthitis infective, genital infection, posthitis (N for males: FARXIGA 5 mg=564, FARXIGA 10 mg=595, placebo=716).

Volume depletion1

  • Volume depletion includes reports of dehydration, hypovolemia, orthostatic hypotension, or hypotension
  • In a pool of 12 short-term, placebo-controlled studies, these rates were 0.6% with FARXIGA 5 mg, 0.8% with FARXIGA 10 mg, and 0.4% with placebo
  • In a pool of 13 short-term, placebo-controlled studies, these rates were 1.1% with FARXIGA 10 mg vs 0.7% with placebo

Genital mycotic infections1

  • Genital mycotic infections (GMIs) were reported in 5.7% of patients with FARXIGA 5 mg, 4.8% with FARXIGA 10 mg, and 0.9% with placebo, in the 12-study placebo-controlled pool
  • Discontinuation from study due to GMI occurred in 0% of placebo-treated patients and 0.2% of patients treated with FARXIGA 10 mg
  • Rates of GMI were higher among patients with a history of GMI than in those without
Clinical Results

Hypoglycemic Events

Rates of Hypoglycemia

INCIDENCE OF MAJORa AND MINORb HYPOGLYCEMIA

IN PLACEBO-CONTROLLED STUDIES1

 

FARXIGA 5 mg

FARXIGA 10 mg

Placebo/Active Control

Monotherapya (24 weeks)

Major [n (%)]

Minor [n (%)]

N=64

0

0

N=70

0

0

N=75

0

0

Add-on to metformina (24 weeks)

Major [n (%)]

Minor [n (%)]

N=137

0

2 (1.5%)

N=135

0

1 (0.7%)

N=137

0

0

Active control add-on to metformin vs glipizide (52 weeks)

Major [n (%)]

Minor [n (%)]

-

-

-

N=406

0

7 (1.7%)

N=408

3 (0.7%)

147 (36.0%)

Add-on to glimepiridea (24 weeks)

Major [n (%)]

Minor [n (%)]

N=145

0

8 (5.5%)

N=151

0

9 (6.0%)

N=146

0

3 (2.1%)

Add-on to pioglitazonea(24 weeks)

Major [n (%)]

Minor [n (%)]

N=141

0

3 (2.1%)

N=140

0

0

N=139

0

0

Add-on to DPP-4 inhibitor (24 weeks)

Major [n (%)]

Minor [n (%)]

-

-

-

N=225

1 (0.4%)

4 (1.8%)

N=226

0

3 (1.3%)

Add-on to insulin with or without other OADs (24 weeks)

Major [n (%)]

Minor [n (%)]

N=212

1 (0.5%)

92 (43.4%)

N=196

1 (0.5%)

79 (40.3%)

N=197

1 (0.5%)

67 (34.0%)

Monotherapya (24 weeks)
  Major [n (%)] Minor [n (%)]
FARXIGA 5 mg(N=64) 0 0
FARXIGA 10 mg (N=70) 0 0
Placebo/Active Control(N=75) 0 0
Add-on to metformina (24 weeks)
  Major [n (%)] Minor [n (%)]
FARXIGA 5 mg(N=137) 0 2 (1.5%)
FARXIGA 10 mg (N=135) 0 1 (0.7%)
Placebo/Active Control(N=137) 0 0
Active control add-on to metformin vs glipizide (52 weeks)
  Major [n (%)] Minor [n (%)]
FARXIGA 5 mg -
-
-
FARXIGA 10 mg (N=406) 0
7 (1.7%)
Placebo/Active Control(N=408) 3 (0.7%)
147 (36.0%)
Add-on to glimepiridea (24 weeks)
  Major [n (%)] Minor [n (%)]
FARXIGA 5 mg (N=145)
0
8 (5.5%)
FARXIGA 10 mg (N=151) 0
9 (6.0%)
Placebo/Active Control(N=146) 0
3 (2.1%)
Add-on to pioglitazonea (24 weeks)
  Major [n (%)] Minor [n (%)]
FARXIGA 5 mg (N=141)
0
3 (2.1%)
FARXIGA 10 mg (N=140) 0
0
Placebo/Active Control(N=139) 0
0
Add-on to DPP-4 inhibitor (24 weeks)
  Major [n (%)] Minor [n (%)]
FARXIGA 5 mg -
-
-
FARXIGA 10 mg (N=225) 1 (0.4%)
4 (1.8%)
Placebo/Active Control(N=226) 0
3 (1.3%)
Add-on to insulin with or without other OADs (24 weeks)
  Major [n (%)] Minor [n (%)]
FARXIGA 5 mg (N=212)
1 (0.5%)
92 (43.4%)
FARXIGA 10 mg (N=196) 1 (0.5%)
79 (40.3%)
Placebo/Active Control(N=197) 1 (0.5%)
67 (34.0%)

aMajor 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.

bMinor 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.

OAD=oral antidiabetic therapy.

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.

Hypersensitivity reactions1

  • Hypersensitivity reactions (eg, angioedema, urticaria, hypersensitivity) were reported with FARXIGA treatment
  • Across the clinical program, serious anaphylactic reactions and severe cutaneous adverse reactions and angioedema were reported in 0.2% of comparator-treated patients and 0.3% of FARXIGA-treated patients
Clinical Results

Safety Data From the DECLARE Trial

SAFETY DATA FROM THE DECLARE TRIAL1

Select adverse events of interest, n (%) FARXIGA 10 mg (n=8574) Placebo (n=8569)
Bladder cancer 26 (0.3) 45 (0.5)
Amputation 123 (1.4) 113 (1.3)
Acute kidney injury 125 (1.5) 175 (2.0)
Fracture 457 (5.3) 440 (5.1)
Major hypoglycemia 58 (0.7) 83 (1.0)
Symptoms of volume depletion 213 (2.5) 207 (2.4)
Urinary tract infection 127 (1.5) 133 (1.6)
Genital infectiona 76 (0.9) 9 (0.1)
Diabetic ketoacidosis 27 (0.3) 12 (0.1)
Fournier’s gangrene 1 (0.01) 5 (0.06)

aLeading to discontinuation of the trial regimen or considered to be serious adverse events.

From Wiviott, et al.

“The rates of amputation, fracture, volume depletion, and hypersensitivity were balanced between the groups. Diabetic ketoacidosis was more common in the dapagliflozin group than in the placebo group... more than 80% of patients with diabetic ketoacidosis were using insulin at baseline.”1

Warnings and Precautions

  • 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

ADDITIONAL POOLED SAFETY DATA ACROSS CLINICAL STUDIES (PHASE 2b/3a)1,3-6

Select adverse events of interest, n (%) FARXIGA Placebo/Control
Bladder cancerb 10 (0.17) 1 (0.03)
Amputationc 8 (0.1) 7 (0.2)
Renal SAEsd 9 (0.2) 5 (0.1)
Fracturee 79 (1.3) 53 (1.6)
Major hypoglycemiaf 3 (0.1) 2 (0.1)
Symptoms of volume depletionf,g 27 (1.1) 17 (0.7)
Urinary tract infectionf 110 (4.7) 81 (3.5)
Pyelonephritish 7 (0.1) 7 (0.2)
Genital infectionf 130 (5.5) 14 (0.6)
Diabetic ketoacidosisi 1 (0.02) 0 (0)

bAcross 22 clinical studies, newly diagnosed cases of bladder cancer were reported in 10/6045 patients treated with FARXIGA and 1/3512 patients treated with placebo/comparator.1

cPool of 30 placebo-/active-comparator-controlled trials of ≥12 weeks was used to assess lower limb amputation. Patients were randomized to dapagliflozin (n=9195) or placebo-/active-comparator (n=4629). As surgical procedures were not specifically collected as adverse events during the clinical trial program, a manual free-text search was used to determine the occurrence of amputation.3

dPool of 21 phase 2b/3 trials was used to assess renal safety. For all pooled phase 2b and 3 studies at baseline, patients were randomized to dapagliflozin (n=5936) or placebo (n=3403). Renal SAEs included impairment or failure.4

eFracture data were assessed from a pool of 21 phase 2b/3 studies of up to 208 weeks in duration (dapagliflozin n=5936; comparator n=3403).5

fPooled data from 13 placebo-controlled, double-blind, phase 2b/3 studies of up to 24 weeks’ duration, in which patients with T2D were randomized to receive dapagliflozin 10 mg (n=2360) or placebo (n=2295).3

gVolume depletion AEs included hypotension/hypovolemia/dehydration.3

hPool of 21 phase 2b/3 trials was used to assess pyelonephritis (dapagliflozin n=5936; control n=3403).6

iPool of 21 placebo-/active-comparator-controlled trials of ≤208 weeks’ duration was used to assess SAEs of DKA. Patients with T2D were randomized to receive dapagliflozin (n=5936) or placebo-/active-comparator (n=3403).3

AE=adverse event; DKA=diabetic ketoacidosis; SAEs=serious adverse events; T2D=type 2 diabetes.

Post-marketing reports leading to class label updates

  • Fournier’s Gangrene: In October 2018, the FDA issued a class label update for all SGLT2is based on a review of medical literature and the FDA Adverse Event Reporting System (FAERS) post-marketing database from March 2013 to May 2018, which identified 12 cases of Fournier’s gangrene reported with SGLT2i class7
  • Renal Safety: In June 2016, the FDA issued a safety communication based on a review of the FAERS post-marketing database from March 2013 to October 2015, which identified 101 total cases of acute kidney injury reported with SGLT2i use; 28 cases were associated with use of dapagliflozin8
  • Ketoacidosis: In December 2015, the FDA issued a safety communication based on a review of the FAERS post-marketing database from March 2013 to May 2015, which identified 73 cases of ketoacidosis reported with SGLT2i use; 21 of these cases were in patients treated with dapagliflozin9
  • Urosepsis and Pyelonephritis: In December 2015, the FDA issued a safety communication based on a review of the FAERS post-marketing database from March 2013 to October 2014, which identified 19 cases of urosepsis reported with SGLT2i use; 9 of these cases were in patients treated with dapagliflozin9

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.
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  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.
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  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.
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  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.
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  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.

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.

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