Dapagliflozin

Dapagliflozin
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]

Disclaimer

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Black Box Warning

ConditionName: See full prescribing information for complete Boxed Warning. ConditionName: Content

Overview

Dapagliflozin is a {{{drugClass}}} that is FDA approved for the treatment of type 2 diabetes mellitus. There is a Black Box Warning for this drug as shown here. Common adverse reactions include female genital mycotic infections, nasopharyngitis, and urinary tract infections.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Type 2 diabetes mellitus

• FARXIGA (dapagliflozin) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Limitation of Use

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

• Dosing Information

• 2.1 Recommended Dosing

The recommended starting dose of FARXIGA is 5 mg once daily, taken in the morning, with or without food. In patients tolerating FARXIGA 5 mg once daily who require additional glycemic control, the dose can be increased to 10 mg once daily.

In patients with volume depletion, correcting this condition prior to initiation of FARXIGA is recommended [see Warnings and Precautions (5.1), Use in Specific Populations (8.5, 8.6), and Patient Counseling Information (17)].

2.2 Patients with Renal Impairment

Assessment of renal function is recommended prior to initiation of FARXIGA therapy and periodically thereafter.

FARXIGA should not be initiated in patients with an eGFR less than 60 mL/min/1.73 m2.

No dose adjustment is needed in patients with mild renal impairment (eGFR of 60 mL/min/1.73 m2 or greater).

FARXIGA should be discontinued when eGFR is persistently less than 60 mL/min/1.73 m2 [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)].

Condition2

• Dosing Information

• Dosage

Condition3

• Dosing Information

• Dosage

Condition4

• Dosing Information

• Dosage

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Dapagliflozin in adult patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Dapagliflozin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding FDA-Labeled Use of Dapagliflozin in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1

• Developed by:

• Class of Recommendation:

• Strength of Evidence:

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Dapagliflozin in pediatric patients.

Non–Guideline-Supported Use

Condition1

• Dosing Information

• Dosage

Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Dapagliflozin in pediatric patients.

Contraindications

History of a serious hypersensitivity reaction to FARXIGA [see Adverse Reactions (6.1)].

   Severe renal impairment, end-stage renal disease (ESRD), or patients on dialysis [see Use in Specific Populations (8.6)].

Warnings

ConditionName: See full prescribing information for complete Boxed Warning. ConditionName: Content

5.1 Hypotension

FARXIGA causes intravascular volume contraction. Symptomatic hypotension can occur after initiating FARXIGA [see Adverse Reactions (6.1)] particularly in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics. Before initiating FARXIGA in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms of hypotension after initiating therapy.

5.2 Impairment in Renal Function

FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Adverse reactions related to renal function can occur after initiating FARXIGA [see Adverse Reactions (6.1)]. Renal function should be evaluated prior to initiation of FARXIGA and monitored periodically thereafter.

5.3 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues

Insulin and insulin secretagogues are known to cause hypoglycemia. FARXIGA can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue [see Adverse Reactions (6.1)]. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when these agents are used in combination with FARXIGA.

5.4 Genital Mycotic Infections

FARXIGA increases the risk of genital mycotic infections. Patients with a history of genital mycotic infections were more likely to develop genital mycotic infections [see Adverse Reactions (6.1)]. Monitor and treat appropriately.

5.5 Increases in Low-Density Lipoprotein Cholesterol (LDL-C)

Increases in LDL‑C occur with FARXIGA [see Adverse Reactions (6.1)]. Monitor LDL‑C and treat per standard of care after initiating FARXIGA.

5.6 Bladder Cancer

Across 22 clinical studies, newly diagnosed cases of bladder cancer were reported in 10/6045 patients (0.17%) treated with FARXIGA and 1/3512 patient (0.03%) treated with placebo/comparator. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were 4 cases with FARXIGA and no cases with placebo/comparator. Bladder cancer risk factors and hematuria (a potential indicator of pre-existing tumors) were balanced between treatment arms at baseline. There were too few cases to determine whether the emergence of these events is related to FARXIGA.

There are insufficient data to determine whether FARXIGA has an effect on pre-existing bladder tumors. Consequently, FARXIGA should not be used in patients with active bladder cancer. In patients with prior history of bladder cancer, the benefits of glycemic control versus unknown risks for cancer recurrence with FARXIGA should be considered.

5.7 Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with FARXIGA or any other antidiabetic drug.

Precautions

• Description

Adverse Reactions

Clinical Trials Experience

The following important adverse reactions are described below and elsewhere in the labeling:

   Hypotension [see Warnings and Precautions (5.1)] 
   Impairment in Renal Function [see Warnings and Precautions (5.2)] 
   Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions (5.3)] 
   Genital Mycotic Infections [see Warnings and Precautions (5.4)] 
   Increases in Low-Density Lipoprotein Cholesterol (LDL‑C) [see Warnings and Precautions (5.5)] 
   Bladder Cancer [see Warnings and Precautions (5.6)] 

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Pool of 12 Placebo-Controlled Studies for FARXIGA 5 and 10 mg

The data in Table 1 is derived from 12 placebo-controlled studies ranging from 12 to 24 weeks. In 4 studies FARXIGA was used as monotherapy, and in 8 studies FARXIGA was used as add-on to background antidiabetic therapy or as combination therapy with metformin [see Clinical Studies (14)].

These data reflect exposure of 2338 patients to FARXIGA with a mean exposure duration of 21 weeks. Patients received placebo (N=1393), FARXIGA 5 mg (N=1145), or FARXIGA 10 mg (N=1193) once daily. The mean age of the population was 55 years and 2% were older than 75 years of age. Fifty percent (50%) of the population were male; 81% were White, 14% were Asian, and 3% were Black or African American. At baseline, the population had diabetes for an average of 6 years, had a mean hemoglobin A1c (HbA1c) of 8.3%, and 21% had established microvascular complications of diabetes. Baseline renal function was normal or mildly impaired in 92% of patients and moderately impaired in 8% of patients (mean eGFR 86 mL/min/1.73 m2).

Table 1 shows common adverse reactions associated with the use of FARXIGA. These adverse reactions were not present at baseline, occurred more commonly on FARXIGA than on placebo, and occurred in at least 2% of patients treated with either FARXIGA 5 mg or FARXIGA 10 mg.

Pool of 13 Placebo-Controlled Studies for FARXIGA 10 mg

The safety and tolerability of FARXIGA 10 mg was also evaluated in a larger placebo-controlled study pool. This pool combined 13 placebo-controlled studies, including 3 monotherapy studies, 9 add-on to background antidiabetic therapy studies, and an initial combination with metformin study. Across these 13 studies, 2360 patients were treated once daily with FARXIGA 10 mg for a mean duration of exposure of 22 weeks. The mean age of the population was 59 years and 4% were older than 75 years. Fifty-eight percent (58%) of the population were male; 84% were White, 9% were Asian, and 3% were Black or African American. At baseline, the population had diabetes for an average of 9 years, had a mean HbA1c of 8.2%, and 30% had established microvascular disease. Baseline renal function was normal or mildly impaired in 88% of patients and moderately impaired in 11% of patients (mean eGFR 82 mL/min/1.73 m2).

Volume Depletion

FARXIGA causes an osmotic diuresis, which may lead to reductions in intravascular volume. Adverse reactions related to volume depletion (including reports of dehydration, hypovolemia, orthostatic hypotension, or hypotension) are shown in Table 2 for the 12-study and 13-study, short-term, placebo-controlled pools [see Warnings and Precautions (5.1)].

Impairment of Renal Function

Use of FARXIGA was associated with increases in serum creatinine and decreases in eGFR (see Table 3). In patients with normal or mildly impaired renal function at baseline, serum creatinine and eGFR returned to baseline values at Week 24. Renal-related adverse reactions, including renal failure and blood creatinine increase, were more frequent in patients treated with FARXIGA (see Table 4). Elderly patients and patients with impaired renal function were more susceptible to these adverse reactions (see Table 4). Sustained decreases in eGFR were seen in patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2).

The safety of FARXIGA was evaluated in a study of patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2) [see Clinical Studies (14)]. In this study 13 patients experienced bone fractures for treatment durations up to 104 weeks. No fractures occurred in the placebo group, 5 occurred in the FARXIGA 5 mg group, and 8 occurred in the FARXIGA 10 mg group. Eight of these 13 fractures were in patients who had a baseline eGFR of 30 to 45 mL/min/1.73 m2. Eleven of the 13 fractures were reported within the first 52 weeks. There was no apparent pattern with respect to the anatomic site of fracture.

Hypoglycemia

The frequency of hypoglycemia by study [see Clinical Studies (14)] is shown in Table 5. Hypoglycemia was more frequent when FARXIGA was added to sulfonylurea or insulin [see Warnings and Precautions (5.3)].

Genital Mycotic Infections

Genital mycotic infections were more frequent with FARXIGA treatment. Genital mycotic infections were reported in 0.9% of patients on placebo, 5.7% on FARXIGA 5 mg, and 4.8% on FARXIGA 10 mg, in the 12-study placebo-controlled pool. Discontinuation from study due to genital infection occurred in 0% of placebo-treated patients and 0.2% of patients treated with FARXIGA 10 mg. Infections were more frequently reported in females than in males (see Table 1). The most frequently reported genital mycotic infections were vulvovaginal mycotic infections in females and balanitis in males. Patients with a history of genital mycotic infections were more likely to have a genital mycotic infection during the study than those with no prior history (10.0%, 23.1%, and 25.0% versus 0.8%, 5.9%, and 5.0% on placebo, FARXIGA 5 mg, and FARXIGA 10 mg, respectively).

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., 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. If hypersensitivity reactions occur, discontinue use of FARXIGA; treat per standard of care and monitor until signs and symptoms resolve.

Laboratory Tests

Increase in Hematocrit

In the pool of 13 placebo-controlled studies, increases from baseline in mean hematocrit values were observed in FARXIGA-treated patients starting at Week 1 and continuing up to Week 16, when the maximum mean difference from baseline was observed. At Week 24, the mean changes from baseline in hematocrit were −0.33% in the placebo group and 2.30% in the FARXIGA 10 mg group. By Week 24, hematocrit values >55% were reported in 0.4% of placebo-treated patients and 1.3% of FARXIGA 10 mg–treated patients.

Increase in Serum Inorganic Phosphorus

In the pool of 13 placebo-controlled studies, increases from baseline in mean serum phosphorus levels were reported at Week 24 in FARXIGA-treated patients compared with placebo-treated patients (mean increase of 0.13 versus −0.04 mg/dL, respectively). Higher proportions of patients with marked laboratory abnormalities of hyperphosphatemia (≥5.6 mg/dL for age 17-65 years or ≥5.1 mg/dL for age ≥66 years) were reported on FARXIGA at Week 24 (0.9% versus 1.7% for placebo and FARXIGA 10 mg, respectively).

Increase in Low-Density Lipoprotein Cholesterol

In the pool of 13 placebo-controlled studies, changes from baseline in mean lipid values were reported in FARXIGA-treated patients compared to placebo-treated patients. Mean percent changes from baseline at Week 24, were 0.0% versus 2.5% for total cholesterol and −1.0% versus 2.9% for LDL cholesterol, in the placebo and FARXIGA 10 mg groups, respectively.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Dapagliflozin in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dapagliflozin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Dapagliflozin during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Dapagliflozin with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Dapagliflozin with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Dapagliflozin with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Dapagliflozin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Dapagliflozin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Dapagliflozin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Dapagliflozin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Dapagliflozin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Dapagliflozin in patients who are immunocompromised.

Administration and Monitoring

Administration

2.1 Recommended Dosing

The recommended starting dose of FARXIGA is 5 mg once daily, taken in the morning, with or without food. In patients tolerating FARXIGA 5 mg once daily who require additional glycemic control, the dose can be increased to 10 mg once daily.

In patients with volume depletion, correcting this condition prior to initiation of FARXIGA is recommended [see Warnings and Precautions (5.1), Use in Specific Populations (8.5, 8.6), and Patient Counseling Information (17)].

2.2 Patients with Renal Impairment

Assessment of renal function is recommended prior to initiation of FARXIGA therapy and periodically thereafter.

FARXIGA should not be initiated in patients with an eGFR less than 60 mL/min/1.73 m2.

No dose adjustment is needed in patients with mild renal impairment (eGFR of 60 mL/min/1.73 m2 or greater).

FARXIGA should be discontinued when eGFR is persistently less than 60 mL/min/1.73 m2 [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)].

DOSAGE FORMS AND STRENGTHS

   FARXIGA 5 mg tablets are yellow, biconvex, round, film-coated tablets with “5” engraved on one side and “1427” engraved on the other side. 
   FARXIGA 10 mg tablets are yellow, biconvex, diamond-shaped, film-coated tablets with “10” engraved on one side and “1428” engraved on the other side.

Monitoring

There is limited information regarding Monitoring of Dapagliflozin in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Dapagliflozin in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Dapagliflozin in the drug label.

Pharmacology

There is limited information regarding Dapagliflozin Pharmacology in the drug label.

Mechanism of Action

Structure

File:Dapagliflozin01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Dapagliflozin in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Dapagliflozin in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Dapagliflozin in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Dapagliflozin in the drug label.

How Supplied

Storage

There is limited information regarding Dapagliflozin Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Dapagliflozin in the drug label.

Precautions with Alcohol

• Alcohol-Dapagliflozin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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