What are the side effects of dapagliflozin (Forxiga)?

Side Effects of Dapagliflozin (Forxiga)

Dapagliflozin commonly causes genital mycotic infections, urinary tract infections, and volume depletion-related side effects, while more serious but rare complications include diabetic ketoacidosis and necrotizing fasciitis of the perineum. 1, 2

Common Side Effects

Genitourinary Side Effects

• Genital mycotic infections: Most common side effect, particularly in women
  • Symptoms include vaginal odor, white/yellowish discharge, vaginal itching 1
  • In men: redness, itching, swelling of the penis, foul-smelling discharge 1
• Urinary tract infections: Can be serious and lead to hospitalization 1
  • Signs include burning during urination, frequent urination, pelvic pain, blood in urine 1
• Increased urination: Due to osmotic diuresis mechanism 2

Volume Depletion Effects

• Hypotension: Especially when standing up (orthostatic hypotension) 1
• Dehydration: Loss of body water and salt 1
• Dizziness/lightheadedness: Particularly in elderly patients or those on diuretics 1

Metabolic Effects

• Elevated LDL cholesterol: May require monitoring 2
• Weight loss: Generally considered beneficial but can be significant 2

Serious Side Effects

Diabetic Ketoacidosis (DKA)

• Can occur with normal or only slightly elevated blood glucose (euglycemic DKA) 1
• Higher risk during illness, reduced food intake, surgery, or alcohol consumption 1
• Symptoms: nausea, vomiting, abdominal pain, tiredness, trouble breathing 1
• Requires immediate medical attention and ketone monitoring 1

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)

• Rare but serious bacterial infection affecting the area between genitals and rectum 1
• Symptoms include pain, tenderness, redness, swelling in the genital/perianal area, fever, malaise 1
• Requires urgent medical attention, may need surgical intervention 1

Renal Effects

• Acute kidney injury: Risk increases with volume depletion 2
• Not recommended if eGFR <60 mL/min/1.73m² due to reduced glycemic efficacy 2
• May cause initial small decrease in eGFR that typically stabilizes 3

Other Serious Side Effects

• Hypersensitivity reactions: Including urticaria, anaphylactic reactions, and angioedema 1
• Hypoglycemia: Risk increases when used with insulin or sulfonylureas 1

Special Populations

Elderly Patients

• Higher risk of volume depletion and hypotension 2
• More likely to experience renal adverse events 3

Patients with Renal Impairment

• Increased risk of adverse renal events 3
• Reduced glycemic efficacy with declining renal function 2

Perioperative Considerations

• Should be discontinued before scheduled surgery due to DKA risk 1
• Temporary discontinuation recommended during acute illness 1

Monitoring Recommendations

1. Renal function: Monitor eGFR, especially at initiation of therapy 3
2. Signs of volume depletion: Monitor for dizziness, hypotension, especially in elderly 1
3. Genital and urinary symptoms: Watch for signs of infection 1
4. Ketones: Check if symptoms of DKA occur, even with normal blood glucose 1

Practical Management of Side Effects

• For genital mycotic infections: Over-the-counter antifungal medications may help; seek medical attention if symptoms persist 1
• For volume depletion: Ensure adequate fluid intake, consider temporary dose reduction in vulnerable patients 1
• For DKA prevention: Temporarily stop medication during illness, surgery, or prolonged fasting 1

Despite these side effects, dapagliflozin has shown significant cardiovascular and renal benefits in multiple trials, including reduced risk of heart failure hospitalization and cardiovascular death in the DAPA-HF trial 2.