Skip to Content

Dapagliflozin

Medically reviewed by Drugs.com. Last updated on Jul 27, 2020.

Pronunciation

(dap a gli FLOE zin)

Index Terms

  • BMS-512148
  • Dapagliflozin Propanediol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Farxiga: 5 mg, 10 mg

Brand Names: U.S.

  • Farxiga

Pharmacologic Category

  • Antidiabetic Agent, Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
  • Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

Pharmacology

By inhibiting sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, dapagliflozin reduces reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose (RTG). SGLT2 is the main site of filtered glucose reabsorption; reduction of filtered glucose reabsorption and lowering of RTG result in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations. Dapagliflozin also reduces sodium reabsorption and increases sodium delivery to the distal tubule, which may decrease cardiac preload/afterload and downregulate sympathetic activity.

Metabolism

Primarily mediated by UGT1A9 to an inactive metabolite (dapagliflozin 3-O-glucuronide); CYP-mediated metabolism (minor)

Excretion

Urine (75%; < 2% as parent drug); feces (21%; ~15% as parent drug)

Time to Peak

2 hours

Duration of Action

Following discontinuation, urinary glucose excretion returns to baseline within ~3 days for the 10 mg dose.

Half-Life Elimination

~12.9 hours

Protein Binding

~91%

Special Populations: Renal Function Impairment

Patients with mild, moderate, or severe impairment had higher systemic exposure compared to patients with normal renal function.

Special Populations: Hepatic Function Impairment

In patients with severe impairment (Child-Pugh class C), mean Cmax and AUC were increased up to 40% and 67%, respectively.

Use: Labeled Indications

Diabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; risk reduction of hospitalization for heart failure in patients with type 2 diabetes mellitus and established cardiovascular disease or multiple cardiovascular risk factors.

Heart failure with reduced ejection fraction: To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction (NYHA class II to IV).

Contraindications

History of serious hypersensitivity to dapagliflozin or any component of the formulation; severe renal impairment (eGFR <30 mL/minute/1.73 m2) when used for glycemic control in patients without established cardiovascular disease or multiple cardiovascular risk factors; patients on dialysis.

Canadian labeling: Additional contraindications (not in US labeling): eGFR <30 mL/minute/1.73 m2 (independent of indication).

Dosing: Adult

Note: Hypovolemia, if present, should be corrected prior to initiating therapy. May require a gradual dose reduction of insulin and/or insulin secretagogues to avoid hypoglycemia.

Diabetes mellitus, type 2, treatment:

Note: May be used as an adjunctive agent or alternative monotherapy for patients who fail initial therapy with lifestyle intervention and metformin or who cannot take metformin. May be preferred in patients with heart failure or chronic kidney disease given demonstrated cardiovascular and renal benefits (ADA 2020; DeSantis 2020; McMurray 2019; Wiviott 2019).

Management of hyperglycemia: Oral: Initial: 5 mg once daily; may increase to 10 mg once daily after 4 to 12 weeks if needed to achieve glycemic goals (DeSantis 2020).

Use in patients with heart failure and/or patients with or at risk for atherosclerotic cardiovascular disease: Oral: 10 mg once daily. Note: Risk reduction for heart failure hospitalization is demonstrated in patients with established atherosclerotic cardiovascular disease or multiple cardiovascular risk factors (Wiviott 2019) and in patients with established heart failure with reduced ejection fraction (McMurray 2019).

Use in patients with diabetic kidney disease (off-label use): Oral: 5 mg once daily in patients with urinary albumin excretion >300 mg/day; it is unknown if higher doses result in better kidney protection. Note: Some experts also use this regimen in patients without severely increased albuminuria (eg, urinary albumin excretion ≤300 mg/day); benefits and harms may be more closely balanced due to smaller absolute benefit (Perkovic 2020; Neuen 2019; Wiviott 2019). Because SGLT2 inhibitors have less glycemic benefit as eGFR declines, another agent may be needed to achieve glycemic goals (Wexler 2020).

Heart failure with reduced ejection fraction (adjunctive agent):

Note: May be used as a secondary agent in persistently symptomatic patients with elevated N-terminal pro-B-type natriuretic peptide despite optimized therapy (including other evidence-based drug and device therapy, as indicated). Benefits were consistently demonstrated in patients with or without type 2 diabetes (McMurray 2019).

Oral: 10 mg once daily. Temporary discontinuation or dose reduction to 5 mg once daily may be necessary in the setting of acute renal dysfunction, volume depletion, or hypotension (McMurray 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: Administer in the morning with or without food.

Dietary Considerations

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Exceptions: Danazol. Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulins: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors may enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Sulfonylureas: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Test Interactions

Positive test for glucosuria; may interfere with 1,5-anhydroglucitol (1,5-AG) assay; use alternative methods to monitor glycemic control.

Adverse Reactions

Incidences may include dapagliflozin used as add-on therapy.

1% to 10%:

Endocrine & metabolic: Dyslipidemia (3%), hypovolemia (1% to 3%)

Gastrointestinal: Nausea (3%)

Genitourinary: Dysuria (2%), increased urine output (3% to 4%), urinary tract infection (6%)

Hematologic & oncologic: Increased hematocrit (1%)

Infection: Genitourinary fungal infection (3% to 8%), influenza (3%)

Neuromuscular & skeletal: Back pain (4%), limb pain (2%)

Respiratory: Nasopharyngitis (7%)

Frequency not defined:

Genitourinary: Decreased estimated GFR (eGFR)

Hypersensitivity: Hypersensitivity reaction

Neuromuscular & skeletal: Bone fracture

Renal: Increased serum creatinine

<1%, postmarketing, and/or case reports: Acute renal failure, anaphylaxis (severe), angioedema, increased LDL cholesterol, ketoacidosis, necrotizing fasciitis (perineum), pyelonephritis, severe dermatological reaction, skin rash, urinary tract infection with sepsis

Warnings/Precautions

Concerns related to adverse effects:

• Bone fractures: An increased incidence of bone fractures occurred in patients with type 2 diabetes mellitus and moderate renal impairment (eGFR 30 to 60 mL/minute/1.73 m2) in 1 randomized controlled trial (Kohan 2014); however, a second randomized controlled trial did not confirm a similar increased risk in patients with type 2 diabetes mellitus and eGFR 45 to 60 mL/minute/1.73 m2 (Fioretto 2018). In the overall population, dapagliflozin does not appear to increase risk of fractures, though longer-term data may be necessary to clarify risk (Jabbour 2018; Ruanpeng 2017; Tang 2016).

• Genital mycotic infections: May increase the risk of genital mycotic infections (eg, vulvovaginal mycotic infection, vulvovaginal candidiasis, vulvovaginitis, candida balanitis, balanoposthitis). Patients with a history of these infections or uncircumcised males are at greater risk.

• Hypersensitivity reactions: Patients may experience hypersensitivity reactions (eg, angioedema, urticaria), with some being severe. Discontinue dapagliflozin if hypersensitivity occurs and treat as appropriate.

• Hypotension: May cause symptomatic hypotension due to intravascular volume depletion, especially in patients with renal impairment (ie, eGFR <60 mL/minute/1.73 m2), elderly, patients on other antihypertensives (eg, diuretics, angiotensin-converting enzyme [ACE] inhibitors, or angiotensin receptor blockers), or those with low systolic blood pressure. Assess volume status prior to initiation in patients at risk of hypotension and correct if depleted; monitor for signs and symptoms of hypotension after initiation.

• Ketoacidosis: Cases of ketoacidosis (some fatal) have been reported in patients with type 1 and type 2 diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors; in some cases, patients have presented with normal or only modestly elevated blood glucose (<250 mg/dL). Before initiating treatment, consider risk factors that may predispose to ketoacidosis (eg, pancreatic insulin deficiency, dose decreases of insulin, caloric restriction, alcohol abuse, acute febrile illness, surgery, any other extreme stress event). Consider temporary discontinuation of therapy at least 3 days prior to surgery or any event that may precipitate ketoacidosis; ensure risk factors are resolved prior to reinitiating therapy. Patients presenting with nausea/vomiting, abdominal pain, generalized malaise, and/or shortness of breath should be assessed immediately for ketoacidosis; discontinue therapy and treat promptly if ketoacidosis is suspected.

• Lower limb amputation: There are conflicting data involving the risk of lower limb amputations with SGLT2 inhibitor therapy. Canagliflozin was associated with almost a 2-fold increased risk of lower limb amputations compared to placebo in the CANVAS and CANVAS-R trials, which included patients with type 2 diabetes at high cardiovascular risk (Neal 2017). Trials involving dapagliflozin have not consistently shown an increased risk of lower limb amputation associated with its use (Khouri 2018; McMurray 2019; Wiviott 2019). The following FDA guidance (developed specifically for canagliflozin) may reasonably apply to use of other SGLT2 inhibitors: Prior to initiation, consider risk factors for amputation including prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients about the importance of preventative foot care. Discontinue therapy if any of the following occur: signs and symptoms of new infection (including osteomyelitis), new pain or tenderness, or sores/ulcers involving the lower limbs (FDA Drug Safety Communication 2017).

• Necrotizing fasciitis: Cases of necrotizing fasciitis of the perineum (Fournier gangrene), a rare but serious and potentially fatal infection, have been reported in patients with diabetes mellitus receiving dapagliflozin. Assess patients presenting with fever or malaise along with genital or perianal pain, tenderness, erythema, or swelling for necrotizing fasciitis. Discontinue in patients who develop necrotizing fasciitis and initiate treatment immediately.

• Renal effects: Acute kidney injury has been reported in patients with type 2 diabetes mellitus. Risk may be increased in patients with chronic kidney disease (eGFR <60 mL/minute/1.73 m2) or with concomitant use of loop diuretics. Additional abnormalities in renal function (decreased eGFR, increased serum creatinine) may occur within weeks of initiation but typically stabilize. Assess volume status and renal function prior to initiation and periodically during treatment.

• Urinary tract infection: Serious urinary infections including urosepsis and pyelonephritis requiring hospitalization have been reported; treatment with SGLT2 inhibitors increases the risk for urinary tract infections (UTI); monitor for signs and symptoms of UTI and treat as needed.

Disease-related concerns:

• Bariatric surgery:

– Altered absorption: Absorption may be altered given the anatomic and transit changes created by gastric bypass and sleeve gastrectomy surgery (Mechanick 2013; Melissas 2013).

– Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy and closely monitor the patient for the duration of therapy; volume depletion and related adverse events (eg, hypotension, orthostatic hypotension, syncope) have occurred. Fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2013).

– Euglycemic diabetic ketoacidosis: Discontinue therapy 3 to 5 days prior to surgery (Bobart 2016). Postoperatively, assess volume status, caloric intake, and need for diabetes treatment and withhold antidiabetic medication if type 2 diabetes is in remission. Ketoacidosis has been reported in patients with type 1 and type 2 diabetes on SGLT2 inhibitors. In some cases, normal or only modestly elevated blood glucose was present (<250 mg/dL) (van Niekerk 2018). Risk factors include significant reduction in insulin, caloric restriction, stress of surgery, and infection.

• Renal impairment: Glycemic efficacy may be decreased in patients with renal impairment. Assess renal function prior to initiation and as clinically indicated during treatment. The US manufacturer recommends against use for glycemic control in patients with eGFR <45 mL/minute/1.73 m2 and contraindicates use for glycemic control in severe renal impairment (eGFR <30 mL/minute/1.73 m2). Use is contraindicated in all patients on dialysis (regardless of indication).

Special populations:

• Elderly: Elderly patients may be predisposed to symptoms related to intravascular volume depletion (eg, hypotension, orthostatic hypotension, dizziness, syncope, and dehydration) and renal impairment or failure.

Other warnings/precautions:

• Appropriate use: Not for use in patients with diabetic ketoacidosis or patients with type 1 diabetes mellitus.

• Hospitalized patients: Use of SGLT2 inhibitors for glycemic control is not routinely recommended for hospitalized patients (ADA 2020).

• Surgical procedures: In patients with diabetes mellitus, consider temporary discontinuation at least 3 days prior to surgery; ensure risk factors for ketoacidosis are resolved prior to reinitiating therapy.

Monitoring Parameters

Blood glucose, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change (ADA 2020); renal function (baseline and periodically during treatment); monitor for genital mycotic infections and urinary tract infection; hypersensitivity reactions; volume status (eg, weight, blood pressure, hematocrit, electrolytes); if signs/symptoms of ketoacidosis (eg, nausea/vomiting, abdominal pain, malaise, shortness of breath), confirm diagnosis by direct measurement of blood ketones and arterial pH (measurement of serum bicarbonate or urinary ketones may not be adequate) (AACE [Handelsman 2016]).

Pregnancy Considerations

Due to adverse effects on renal development observed in animal studies, the manufacturer does not recommend use of dapagliflozin during the second and third trimesters of pregnancy

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).

Agents other than dapagliflozin are currently recommended to treat diabetes mellitus in pregnancy (ADA 2020).

Patient Education

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

• It is used in certain people to lower the risk of having to go to the hospital for heart failure.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nose irritation

• Throat irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, fast heartbeat, increased thirst, seizures, loss of strength and energy, lack of appetite, unable to pass urine or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Acidosis like confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain

• Pain, swelling, or signs of infection in the genitals or rectum

• Vaginal yeast infection

• Penile yeast infection

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Related questions