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: 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 SEVERE HYPOGLYCEMIAa AND HYPOGLYCEMIA WITH GLUCOSE <54 mg/dLb IN CONTROLLED CLINICAL STUDIES1

 

FARXIGA 5 mg

FARXIGA 10 mg

Placebo/Active Control

Monotherapy (24 weeks)

Severe [n (%)]

Glucose <54 mg/dL [n (%)]

N=64

0

0

N=70

0

0

N=75

0

0

Add-on to metformin (24 weeks)

Severe [n (%)]

Glucose <54 mg/dL [n (%)]

N=137

0

0

N=135

0

0

N=137

0

0

Add-on to glimepiride (24 weeks)

Severe [n (%)]

Glucose <54 mg/dL [n (%)]

N=145

0

3 (2.1)

N=151

0

5 (3.3)

N=146

0

1 (0.7)

Add-on to metformin and a sulfonylurea (24 weeks)

Severe [n (%)]

Glucose <54 mg/dL [n (%)]

-

-

-

N=109

0

7 (6.4)

N=109

0

3 (2.8)

Add-on to pioglitazone (24 weeks)

Severe [n (%)]

Glucose <54 mg/dL [n (%)]

N=141

0

1 (0.7)

N=140

0

0

N=139

0

0

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

Severe [n (%)]

Glucose <54 mg/dL [n (%)]

-

-

-

N=225

1 (0.4)

1 (0.4)

N=226

0

1 (0.4)

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

Severe [n (%)]

Glucose <54 mg/dL [n (%)]

N=212

2 (0.9)

55 (25.9)

N=196

2 (1.0)

45 (23.0)

N=197

1 (0.5)

43 (21.8)

Monotherapy (24 weeks)
  Severe [n (%)] Glucose <54 mg/dL [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 metformin (24 weeks)
  Severe [n (%)] Glucose <54 mg/dL [n (%)]
FARXIGA 5 mg(N=137) 0 0
FARXIGA 10 mg (N=135) 0 0
Placebo/Active Control(N=137) 0 0
Add-on to glimepiride (24 weeks)
  Severe [n (%)] Glucose <54 mg/dL [n (%)]
FARXIGA 5 mg (N=145)
0
3 (2.1)
FARXIGA 10 mg (N=151) 0
5 (3.3)
Placebo/Active Control(N=146) 0
1 (0.7)
Add-on to metformin and a sulfonylurea (24 weeks)
  Severe [n (%)] Glucose <54 mg/dL [n (%)]
FARXIGA 5 mg -
-
-
FARXIGA 10 mg (N=109) 0
7 (6.4)
Placebo/Active Control(N=109) 0
3 (2.8)
Add-on to pioglitazone (24 weeks)
  Severe [n (%)] Glucose <54 mg/dL [n (%)]
FARXIGA 5 mg (N=141)
0
1 (0.7)
FARXIGA 10 mg (N=140) 0
0
Placebo/Active Control(N=139) 0
0
Add-on to DPP-4 inhibitor (24 weeks)
  Severe [n (%)] Glucose <54 mg/dL [n (%)]
FARXIGA 5 mg -
-
-
FARXIGA 10 mg (N=225) 1 (0.4)
1 (0.4)
Placebo/Active Control(N=226) 0
1 (0.4)
Add-on to insulin with or without other OADsc (24 weeks)
  Severe [n (%)] Glucose <54 mg/dL [n (%)]
FARXIGA 5 mg (N=212)
2 (0.9)
55 (25.9)
FARXIGA 10 mg (N=196) 2 (1.0)
45 (23.0)
Placebo/Active Control(N=197) 1 (0.5)
43 (21.8)

aSevere 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.

bEpisodes of hypoglycemia with glucose <54 mg/dL (3 mmol/L) were defined as reported episodes of hypoglycemia meeting the glucose criteria that did not also qualify as a severe episode.

cOAD=oral antidiabetic therapy.

In the DECLARE study, severe events of hypoglycemia were reported in 58 (0.7%) out of 8574 patients treated with FARXIGA and 83 (1.0%) out of 8569 patients treated with placebo.

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)
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

  • Acute Kidney Injury: FARXIGA causes intravascular volume contraction and can cause acute kidney injury. Reports of acute kidney injury requiring hospitalization and dialysis have occurred with FARXIGA. If acute kidney injury occurs, discontinue and promptly treat

    Increases in serum creatinine and decreases in eGFR may be observed with initiation of FARXIGA. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses

    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

WELL-ESTABLISHED SAFETY PROFILE

Pooled Safety Analysis

Adverse reactions in 12 placebo-controlled studies reported in ≥2% of patients treated with FARXIGA2,b,c FARXIGA 10 mg Placebo
Female genital mycotic infectionsd 6.9% 1.5%
Nasopharyngitis 6.3% 6.2%
Urinary tract infectionse 4.3% 3.7%
Back pain 4.2% 3.2%
Increased urinationf 3.8% 1.7%
Male genital mycotic infectionsg 2.7% 0.3%
Nausea 2.5% 2.4%
Influenza 2.3% 2.3%
Dyslipidemia 2.5% 1.5%
Constipation 1.9% 1.5%
Discomfort with urination 2.1% 0.7%
Pain in extremity 1.7% 1.4%
  (N=1193) (N=1393)

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

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

dGenital 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 10 mg=598, placebo=677).

eUrinary 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.

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

gGenital 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 10 mg=595, placebo=716).

hIn the pool of 21 phase 2b/3 trials, there were 5936 patients in the dapagliflozin group and 3403 patients in the PBO group.

iiIn the pool of 13 phase 2b/3 trials, there were 2360 patients in the dapagliflozin group and 2295 patients in the placebo group.

  • In a pool of 21 phase 2b/3 trials, renal serious adverse events (renal impairment or failure) occurred in 0.2% of patients treated with dapagliflozin and in 0.1% of patients in the placebo group3,h
  • In a pool of 13 phase 2b/3 trials, major hypoglycemia occurred in 0.1% of patients treated with dapagliflozin and in 0.1% of patients in the placebo group4,i
  • In a pool of 13 phase 2b/3 trials, UTI occurred in 4.7% of patients treated with dapagliflozin and in 3.5% of patients in the placebo group4,i
  • 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%)
Clinical Results

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: FARXIGA causes intravascular volume contraction and can cause acute kidney injury. Reports of acute kidney injury requiring hospitalization and dialysis have occurred with FARXIGA. If acute kidney injury occurs, discontinue and promptly treat
  • Increases in serum creatinine and decreases in eGFR may be observed with initiation of FARXIGA. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses

    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

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:

  • 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 disease or multiple cardiovascular risk factors

FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Dosing

To improve glycemic control in patients with T2D, the recommended starting dose of FARXIGA is 5 mg 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.

To reduce the risk of hospitalization for heart failure in patients with T2D, the recommended dose of FARXIGA is 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.

References:

Reference:

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  34. Data on File. REF-4920; AstraZeneca Pharmaceuticals LP.
  35. 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.
  36. FARXIGA® [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
  37. 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.
  38. 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