Introduction
Farxiga (dapagliflozin) is an oral medication belonging to the sodium-glucose cotransporter 2 (SGLT2) inhibitor class. Originally approved for type 2 diabetes management, its therapeutic applications have expanded significantly based on cardiovascular and renal outcome trials. This medication represents an important advancement in the management of multiple chronic conditions beyond glycemic control.
Mechanism of Action
Dapagliflozin selectively inhibits SGLT2 receptors in the proximal renal tubules, reducing glucose reabsorption and increasing urinary glucose excretion. This insulin-independent mechanism lowers plasma glucose concentrations by promoting glucosuria. Additionally, Farxiga induces osmotic diuresis and mild natriuresis, contributing to its cardiovascular and renal benefits through hemodynamic effects and potential anti-inflammatory and anti-fibrotic properties.
Indications
- Type 2 diabetes mellitus (as an adjunct to diet and exercise)
- Heart failure with reduced ejection fraction (HFrEF) to reduce risk of cardiovascular death and hospitalization
- Chronic kidney disease (CKD) to reduce risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization
- Heart failure (across the ejection fraction spectrum) to reduce risk of cardiovascular death and hospitalization
Dosage and Administration
Standard dosing: 10 mg orally once daily Initial dose: 5 mg once daily may be used in some patients Administration: Can be taken with or without food Renal impairment: Not recommended when eGFR <25 mL/min/1.73m² for diabetes; no dosage adjustment needed for HF or CKD indications unless eGFR <25 mL/min/1.73m² Hepatic impairment: No dosage adjustment necessaryPharmacokinetics
Absorption: Rapid with absolute bioavailability of 78% Tmax: 1 hour under fasted conditions Distribution: Protein binding approximately 91% Metabolism: Primarily via UGT1A9; major metabolite is dapagliflozin 3-O-glucuronide (inactive) Elimination: Primarily renal (75%) and fecal (21%) Half-life: 12.9 hoursContraindications
- History of serious hypersensitivity reaction to dapagliflozin
- Severe renal impairment (eGFR <30 mL/min/1.73m²) for diabetes indication
- End-stage renal disease requiring dialysis
- Patients with type 1 diabetes mellitus
- Diabetic ketoacidosis
Warnings and Precautions
Ketoacidosis: Reports of ketoacidosis in patients with type 2 diabetes; monitor for signs and symptoms Volume depletion: Can cause intravascular volume contraction; assess volume status in elderly and renal impaired patients Urosepsis and pyelonephritis: Serious urinary tract infections reported Hypoglycemia: Risk increased when used with insulin or insulin secretagogues Necrotizing fasciitis of the perineum (Fournier's gangrene): Rare but serious reports Genital mycotic infections: Higher incidence observed Lower limb amputations: Increased risk observed in some clinical trialsDrug Interactions
Diuretics: Increased risk of volume depletion Insulin and insulin secretagogues: Increased risk of hypoglycemia UGT inducers: Potential decrease in dapagliflozin exposure Lithium: SGLT2 inhibitors may decrease lithium concentrationsAdverse Effects
Common (>5%):- Genital mycotic infections
- Urinary tract infections
- Increased urination
- Thirst
- Nausea
- Ketoacidosis
- Acute kidney injury
- Urosepsis and pyelonephritis
- Hypersensitivity reactions
- Volume depletion
- Fournier's gangrene
Monitoring Parameters
- Renal function (serum creatinine, eGFR) at baseline and periodically
- Volume status and electrolytes
- Blood glucose and HbA1c (for diabetes indication)
- Signs/symptoms of urinary tract and genital infections
- Ketones in patients with signs/symptoms of metabolic acidosis
- Lower limb examinations
- Cardiovascular status
Patient Education
- Take medication as prescribed, typically once daily
- Maintain adequate hydration
- Recognize symptoms of dehydration (dizziness, weakness)
- Monitor for signs of genital itching or discharge
- Report symptoms of urinary tract infection (painful urination, frequency)
- Be aware of symptoms of ketoacidosis (nausea, vomiting, abdominal pain)
- Regular foot examinations recommended
- Inform all healthcare providers about Farxiga use
- Do not use during pregnancy unless potential benefit justifies potential risk
References
1. FDA Prescribing Information: Farxiga (dapagliflozin). 2023 2. Wiviott SD, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357 3. McMurray JJV, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008 4. Heerspink HJL, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446 5. Solomon SD, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):1089-1098 6. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291