(dap a gli FLOE zin)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Farxiga: 5 mg, 10 mg
Brand Names: U.S.
- Antidiabetic Agent, Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
- Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
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.
Primarily mediated by UGT1A9 to an inactive metabolite (dapagliflozin 3-O-glucuronide); CYP-mediated metabolism (minor)
Urine (75%; < 2% as parent drug); feces (21%; ~15% as parent drug)
Time to Peak
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: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
History of serious hypersensitivity to dapagliflozin or any component of the formulation; severe renal impairment (eGFR <30 mL/minute/1.73 m2), end-stage renal disease (ESRD), or patients on dialysis
Canadian labeling: Additional contraindications (not in US labeling): Moderate renal impairment (eGFR <60 mL/minute/1.73 m2)
Note: If present, correct volume depletion prior to initiation.
Diabetes mellitus, type 2: Oral: Initial: 5 mg once daily; may increase to 10 mg once daily
Refer to adult dosing.
Dosing: Renal Impairment
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute/1.73 m2: Use is not recommended for initiation of therapy or when eGFR is persistently between 30 and <60 mL/minute/1.73 m2.
eGFR <30 mL/minute/1.73 m2: Use is contraindicated.
ESRD: Use is contraindicated.
Hemodialysis: Use is contraindicated.
Dosing: Hepatic Impairment
No dosage adjustment necessary; use caution if initiating in severe impairment (has not been studied).
Administer in the morning with or without food.
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
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).
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. 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
Insulin: SGLT2 Inhibitors may enhance the hypoglycemic effect of Insulin. 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
MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Sulfonylureas: 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
Positive test for glucosuria; may interfere with 1,5-anhydroglucitol (1,5-AG) assay; use alternative methods to monitor glycemic control.
Frequency not always defined.
Endocrine & metabolic: Mild hypoglycemia (plus insulin or other oral antidiabetic therapy: 40% to 43%), dyslipidemia (3%), hyperphosphatemia (2%), hypovolemia (1%), increased LDL cholesterol, increased serum phosphate
Gastrointestinal: Nausea (3%)
Genitourinary: Fungal vaginosis (7% to 8%; includes [in order of frequency] vulvovaginal mycotic infection, vaginal infection, vulvovaginal candidiasis, vulvovaginitis, genital infection, genital candidiasis, fungal genital infection, vulvitis, genitourinary tract infection, vulval abscess, vaginitis bacterial), urinary tract infection (6%), increased urine output (3% to 4%: includes [in order of frequency] pollakiuria, polyuria, and urine output increased), genitourinary fungal infections (mycotic; in males: 3%; includes [in order of frequency] balanitis, fungal genital infection, balanitis candida, genital candidiasis, genital infection, penile infection, balanoposthitis, balanoposthitis infective, genital infection, posthitis), dysuria (2%)
Hematologic & oncologic: Increased hematocrit (1%, hematocrit >55%)
Hypersensitivity: Hypersensitivity reaction
Infection: Influenza (2% to 3%)
Neuromuscular & skeletal: Back pain (4%), limb pain (2%), bone fracture (in patients with moderate renal impairment)
Renal: Decreased estimated GFR, increased serum creatinine
Respiratory: Nasopharyngitis (7%)
<1% (Limited to important or life-threatening): Acute renal failure, bladder neoplasm, ketoacidosis (FDA Safety Communication, December 4, 2015), pyelonephritis (FDA Safety Communication, December 4, 2015), urosepsis (FDA Safety Communication, December 4, 2015)
Concerns related to adverse effects:
• Bone fractures: May cause increased risk of bone fractures. According to the American Diabetes Association guidelines, sodium glucose co-transporter-2 (SGLT2) inhibitors should be avoided in patients with fracture risk factors (ADA 2016a).
• 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.
• Hematologic effects: An increase in mean hemoglobin/hematocrit was observed in clinical trials; hematocrit >55% was observed in ~1% of patients by week 24. Use with caution in patients with an elevated hematocrit.
• 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, ACE inhibitors, or angiotensin receptor blockers [ARBs]), or those with low systolic blood pressure. Assess volume status prior to initiation in patients at risk of hypotension and correct if depleted; monitor signs and symptoms of hypotension after initiation. If volume depletion occurs during therapy consider temporary interruption of therapy until depletion can be corrected.
• Ketoacidosis: Cases of ketoacidosis, a serious and life-threatening condition resulting in urgent hospitalization, 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) (Bobart 2016; FDA 2015; Handelsman 2016). Before initiating treatment, consider risk factors that may predispose to ketoacidosis (eg, pancreatic insulin deficiency, dose decreases or discontinuation of insulin, caloric restriction, alcohol abuse, extensive exercise, myocardial infarction, stroke, severe infection, surgery, any other extreme stress event) (Handelsman 2016). The American Association of Clinical Endocrinologists and American College of Endocrinology recommend considering withholding of SGLT2 inhibitors for at least 24 hours prior to events that may precipitate diabetic ketoacidosis (DKA) (Handelsman 2016), while others have suggested withholding for 3 to 5 days (Bobart 2016). Patients presenting with nausea/vomiting, abdominal pain, generalized malaise, and/or shortness of breath should be assessed immediately for ketoacidosis; if indicated, consider interruption or discontinuation of therapy.
• Lipid abnormality: May cause LDL-cholesterol (C) elevation; monitor LDL-C and treat as needed.
• Renal effects: Acute kidney injury has been reported and may require hospitalization and dialysis; has occurred in patients <65 years of age. Prior to initiation, consider risk factors for acute kidney injury (eg, hypovolemia, chronic renal insufficiency, heart failure, use of concomitant medications [eg, diuretics, ACE inhibitors, angiotensin receptor blockers, or NSAIDs]). Temporarily discontinue use with reduced oral intake or fluid losses; discontinue use if acute kidney injury occurs. Additional abnormalities in renal function (decreased eGFR, increased serum creatinine) and adverse effects related to renal function may occur; elderly patients and patients with preexisting renal impairment may be at greater risk. Assess 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.
• Bladder cancer: Newly diagnosed bladder cancer occurred more frequently in dapagliflozin patients; causal relationship could not be established. Do not use in patients with active bladder cancer; weigh the benefits of glycemic control versus the unknown risks for cancer recurrence in patients with a history of bladder cancer.
• Hepatic impairment: Weigh benefits versus risk in patients with severe hepatic impairment (has not been studied).
• Renal impairment: Glycemic efficacy may be less and adverse reactions (eg, renal-related adverse reactions, bone fractures) may be higher with moderate renal impairment (eGFR 30 to <60 mL/minute/1.73 m2); dapagliflozin should not be initiated in this population and/or when eGFR is persistently <60 mL/minute/1.73 m2. Use is contraindicated in severe renal impairment (eGFR <30 mL/minute/1.73 m2, ESRD, and in patients receiving dialysis.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• 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.
• Appropriate use: Not for use in patients with DKA or patients with type 1 diabetes mellitus (insulin-dependent, IDDM).
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 2016b); renal function (baseline and periodically during treatment); LDL-C; monitor for genital mycotic infections and UTI; hypersensitivity reactions; volume status (eg, blood pressure, hematocrit, electrolytes); signs and symptoms of metabolic acidosis
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Based on animal data, adverse fetal effects on renal development may occur in humans following in utero exposure during the second and third trimesters.
In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2016d; Kitzmiller 2008; Metzger 2007). 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 (ACOG 2013; ADA 2016d; Blumer 2013; Kitzmiller 2008). Agents other than dapagliflozin are currently recommended to treat diabetes in pregnant women (ACOG 2013; Blumer 2013).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience rhinitis, rhinorrhea, or pharyngitis. Have patient report immediately to prescriber signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, tachycardia, increased thirst, seizures, loss of strength and energy, lack of appetite, urinary retention or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of lactic acidosis (fast breathing, tachycardia, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), vaginal yeast infection, or penile yeast infection (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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Other brands: Farxiga