Dapagliflozin (Farxiga) Therapeutic Equivalence and FDA Orange Book Status
Dapagliflozin (Farxiga) is the reference listed drug (RLD) in the FDA Orange Book with no AB-rated generic equivalents currently available, meaning therapeutic substitution requires prescribing the brand-name product for patients with type 2 diabetes and cardiovascular or renal disease. 1
Orange Book Classification
- Farxiga (dapagliflozin) is listed as the innovator/reference drug with New Drug Application (NDA) approval, and as of current FDA records, no generic manufacturers have received AB-rated therapeutic equivalence designations 1
- The brand-name product remains the only FDA-approved formulation for the cardiovascular and renal protection indications established in major outcome trials 2, 3
Clinical Implications for Therapeutic Equivalence
For patients with established cardiovascular disease or impaired renal function, only brand-name Farxiga should be prescribed, as the cardiovascular and renal outcome data establishing mortality and morbidity benefits were generated exclusively with the innovator product. 3, 4, 5
Cardiovascular Disease Population
- Dapagliflozin 10 mg once daily reduces cardiovascular death or heart failure hospitalization by 17-29% in patients with type 2 diabetes and established cardiovascular disease 4, 5
- Heart failure hospitalization is reduced by 27-35% across cardiovascular outcome trials 4
- These benefits are independent of glucose-lowering effects and consistent in patients with and without diabetes 4, 5
Impaired Renal Function Population
- For patients with eGFR 25-75 mL/min/1.73 m² and albuminuria (UACR 200-5000 mg/g), dapagliflozin reduces the composite outcome of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51-0.72) 3, 5
- The renal-specific composite outcome is reduced by 44% (HR 0.56,95% CI 0.45-0.68) 3, 5
- All-cause mortality is reduced by 31% (HR 0.69,95% CI 0.53-0.88) in patients with chronic kidney disease 3
Dosing Considerations by Renal Function
- eGFR ≥45 mL/min/1.73 m²: Initiate dapagliflozin 10 mg once daily for both glycemic control and cardiovascular/renal protection 2
- eGFR 25-44 mL/min/1.73 m²: Initiate dapagliflozin 10 mg once daily for cardiovascular/renal protection only (not for glycemic control, as glucose-lowering efficacy is minimal) 2, 3
- eGFR <25 mL/min/1.73 m²: Do not initiate dapagliflozin, but if already on treatment, may continue 10 mg daily until dialysis 2
Critical Safety Precautions
- Withhold dapagliflozin at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 2
- Temporarily discontinue during acute illness with fever, vomiting, diarrhea, or reduced oral intake to prevent euglycemic diabetic ketoacidosis and volume depletion 2
- Assess volume status before initiation and consider reducing concurrent diuretic doses to prevent excessive intravascular volume contraction, particularly in elderly patients 2
- Monitor for genital mycotic infections (occurring in approximately 6% of patients versus 1% on placebo) and urinary tract infections 2, 6
Common Pitfall to Avoid
Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m² during treatment, as cardiovascular and renal protective benefits persist at lower eGFR levels even when glycemic efficacy is lost. 2, 3 The initial eGFR dip of 3-5 mL/min/1.73 m² within the first 1-4 weeks is transient, reversible, and actually predicts better long-term renal outcomes 2