Dapagliflozin Contraindications
Absolute Contraindications
Dapagliflozin is absolutely contraindicated in patients with a history of serious hypersensitivity reactions (including anaphylaxis or angioedema) to dapagliflozin or any excipient in the formulation 1.
- Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with dapagliflozin use 1.
- Known hypersensitivity to the drug is listed as a contraindication across multiple guideline sources 2.
Clinical Contraindications Based on Indication
For Glycemic Control in Type 2 Diabetes
- Dapagliflozin is not recommended for glycemic control when eGFR is <45 mL/min/1.73 m², as it is likely ineffective due to its mechanism of action 1.
- The drug is contraindicated for glycemic control in patients on dialysis 2.
- Dapagliflozin is not approved for use in patients with type 1 diabetes due to markedly increased risk of diabetic ketoacidosis 2, 1.
For Cardiovascular and Renal Protection
- Initiation is not recommended when eGFR is <25 mL/min/1.73 m² for heart failure or chronic kidney disease indications 1.
- However, if eGFR falls below 25 mL/min/1.73 m² during treatment, dapagliflozin 10 mg daily may be continued until dialysis is required 1.
- Patients already on dialysis should not receive dapagliflozin 2.
Important Cautions and Warnings (Not Absolute Contraindications)
Ketoacidosis Risk
- Type 2 diabetes with pancreatic disorders (history of pancreatitis or pancreatic surgery) significantly increases ketoacidosis risk 1.
- Dapagliflozin markedly increases the risk of diabetic ketoacidosis in type 1 diabetes patients, which led to European withdrawal of authorization for this indication 3.
- Euglycemic diabetic ketoacidosis can occur even with normal blood glucose levels 2, 1.
Volume Depletion and Renal Function
- Use caution in patients with intravascular volume depletion, particularly those with renal impairment, low systolic blood pressure (<100 mm Hg), elderly patients, or those on diuretics 2.
- May cause volume contraction, especially in patients with severe renal impairment 2.
Pregnancy and Lactation
- Pregnancy is listed as a caution in heart failure guidelines 2.
- Lactation has no available data and is listed as a caution 2.
Temporary Withholding Required
- Withhold dapagliflozin at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 2, 1.
- Temporarily discontinue during acute illness with reduced oral intake, fever, vomiting, or diarrhea 2.
Additional Safety Considerations
- Increased risk of mycotic genital infections (approximately 6% vs 1% with placebo) 2.
- Rare but serious risk of necrotizing fasciitis of the perineum (Fournier's gangrene) 2.
- Assess for ketoacidosis in patients presenting with signs of metabolic acidosis regardless of blood glucose level 2, 1.
- Urosepsis and pyelonephritis require prompt evaluation and treatment 2.
Key Clinical Pitfall to Avoid
Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal protective benefits persist even when glucose-lowering efficacy is lost 2, 4, 5.