What are the contraindications for dapagliflozin?

Contraindications for Dapagliflozin

Dapagliflozin is absolutely contraindicated only in patients with a history of serious hypersensitivity reactions (including anaphylaxis or angioedema) to dapagliflozin or any of its excipients, and it is not approved for use in patients with type 1 diabetes mellitus due to markedly increased risk of diabetic ketoacidosis. 1, 2

Absolute Contraindications

• Known hypersensitivity: Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with dapagliflozin 1, 2
• Type 1 diabetes mellitus: Dapagliflozin significantly increases the risk of diabetic ketoacidosis beyond the background rate in type 1 diabetes and is not indicated for glycemic control in this population 1, 2, 3

Clinical Contraindications Based on Indication

For Glycemic Control

• Chronic dialysis: Dapagliflozin should not be used for glycemic control in patients receiving chronic dialysis 1, 2
• eGFR <45 mL/min/1.73 m²: Not recommended for glycemic control when eGFR is below this threshold, as it is likely ineffective due to its mechanism of action 4, 2

For Cardiovascular and Renal Protection

• Chronic dialysis: Patients already on chronic dialysis should not be prescribed dapagliflozin for heart failure or chronic kidney disease benefits 1
• eGFR <25 mL/min/1.73 m²: Initiation is not recommended below this threshold, though continuation may be appropriate if eGFR falls during treatment 4, 2

Situations Requiring Temporary Discontinuation

• Major surgery or prolonged fasting: Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis 5, 1, 2
• Acute illness: Temporarily discontinue during acute illnesses with reduced oral intake, fever, vomiting, or diarrhea 4, 1
• Intercurrent illness requiring hospitalization: Hold during any acute illness that significantly reduces food and fluid intake 4

Important Warnings and Precautions (Not Absolute Contraindications)

Ketoacidosis Risk

• Euglycemic diabetic ketoacidosis can occur even with normal blood glucose levels; this risk is markedly elevated in type 1 diabetes but also present in type 2 diabetes, particularly with precipitating factors such as insulin dose reduction, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse 5, 1, 2, 6
• Patients with history of pancreatitis or pancreatic surgery are at increased risk for ketoacidosis 2

Volume Depletion and Hemodynamic Concerns

• Use caution in patients with intravascular volume depletion, renal impairment (eGFR 25-45 mL/min/1.73 m²), systolic blood pressure <100 mmHg, elderly patients (especially ≥75 years), or those on concurrent diuretic therapy 5, 1
• Assess volume status before initiation and correct any depletion; consider reducing concurrent diuretic doses 4, 7

Pregnancy and Lactation

• Pregnancy and lactation are listed as precautions, with no specific safety data available for dapagliflozin use during these periods 1

Adverse Effects Requiring Monitoring

• Genital mycotic infections occur in approximately 6% of patients versus 1% with placebo 4, 1, 7
• Necrotizing fasciitis of the perineum (Fournier's gangrene) is a rare but serious adverse event requiring prompt treatment 5, 1
• Urinary tract infections and potential progression to urosepsis or pyelonephritis require prompt assessment and treatment 1

Common 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 diminishes 4, 1, 7
• The expected initial eGFR dip of 2-5 mL/min/1.73 m² within the first 2-4 weeks is hemodynamic and reversible, not indicative of kidney injury 4