What are the side effects of dapagliflozin?

Dapagliflozin Side Effects

Dapagliflozin's most common side effects are genital yeast infections (especially in women), urinary tract infections, and increased urination, while serious but rare risks include diabetic ketoacidosis, necrotizing fasciitis of the perineum (Fournier's gangrene), and volume depletion leading to hypotension. 1

Most Common Side Effects

Genitourinary Infections

• Genital mycotic infections are the most frequently reported adverse effect, occurring significantly more often in women than men (P<0.001) 1, 2
• Vaginal yeast infections present with vaginal odor, white or yellowish discharge (may be lumpy), and vaginal itching 1
• Penile yeast infections (balanitis/balanoposthitis) cause redness, itching, swelling, foul-smelling discharge, rash, and pain around the penis 1
• Swelling of uncircumcised penis may make it difficult to pull back foreskin 1

Urinary Tract Infections

• Serious UTIs requiring hospitalization have occurred with dapagliflozin 1
• UTI risk increases with age (P=0.030) and is dose-dependent, with 10 mg causing higher frequency (55% urination frequency) versus 5 mg (25%) 2, 3
• Symptoms include burning with urination, frequent urination, urgency, pelvic pain, blood in urine, and sometimes fever, back pain, nausea, or vomiting 1
• Dapagliflozin was the only SGLT2 inhibitor showing statistically significant increased UTI risk in systematic reviews 4

Changes in Urination

• Urgent need to urinate more often, in larger amounts, or at night 1
• The 10 mg dose causes greater urgency (48%) compared to 5 mg (20%), with statistically significant differences (P<0.01) 3

Upper Respiratory Symptoms

• Stuffy or runny nose and sore throat (nasopharyngitis) 1, 5

Serious Side Effects Requiring Immediate Medical Attention

Diabetic Ketoacidosis (DKA)

• Life-threatening condition that can occur even with blood glucose <250 mg/dL (euglycemic DKA) 1
• Canagliflozin and dapagliflozin were associated with increased DKA risk in systematic reviews 4
• Stop dapagliflozin immediately if symptoms develop: nausea, vomiting, abdominal pain, tiredness, trouble breathing, or ketones in urine/blood 1
• High-risk situations: illness, inability to eat/drink normally, skipped meals, ketogenic diet, reduced insulin doses, excessive alcohol, volume depletion, or surgery 1

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)

• Rare but serious bacterial infection causing tissue damage between anus and genitals 1
• Occurs in both women and men with diabetes, may require hospitalization, multiple surgeries, and can lead to death 1
• Seek immediate medical attention for fever with malaise plus any of: pain/tenderness, swelling, or redness in the genital/perineal area 1

Volume Depletion and Hypotension

• Dapagliflozin causes loss of body water and salt through diuresis and natriuresis 1
• Symptoms: dizziness, faintness, lightheadedness, weakness, especially when standing (orthostatic hypotension) 1
• Sudden kidney injury has been reported in type 2 diabetes patients taking dapagliflozin 1
• Higher risk in patients taking blood pressure medications (including diuretics), on low-salt diets, with kidney problems, or age ≥65 years 1

Hypoglycemia

• Low blood sugar risk increases when combined with sulfonylureas or insulin; dose reduction of these agents may be needed 1
• Symptoms: headache, confusion, hunger, shaking, drowsiness, dizziness, fast heartbeat, weakness, sweating, irritability 1

Serious Allergic Reactions

• Urticaria, anaphylaxis, and angioedema have been reported 1
• Stop dapagliflozin immediately and seek emergency care if allergic reaction symptoms develop 1

Perioperative Considerations

• Discontinue dapagliflozin 3 days before scheduled surgery to prevent postoperative ketoacidosis 6
• Surgical stress and anesthesia increase ketoacidosis risk even with normal glucose levels 6
• Volume depletion from dapagliflozin increases susceptibility to hypotension during anesthesia induction 6

Safety Profile in Clinical Practice

• Overall discontinuation rate is low at approximately 5% in real-world studies 7
• In one real-world analysis, 8.96% discontinued within 3 months, with 49.7% due to side effects and 24.8% due to unexpected causes like increased blood sugar or weight gain 2
• Genital tract infections were the leading cause of discontinuation, particularly in women 2
• The incidence of side effects is generally not as high as initially expected in clinical practice 2

Monitoring and Patient Education

• Healthcare providers should check blood tests before starting and during treatment as needed 1
• Patients will test positive for glucose in urine due to the drug's mechanism 1
• Call provider immediately if reducing food/liquid intake, experiencing vomiting, diarrhea, or prolonged sun exposure 1
• Over-the-counter antifungal medications may be used for yeast infections, but contact provider if symptoms don't resolve 1

Contraindications

• Dialysis, pregnancy, and breastfeeding are absolute contraindications 8
• Type 1 diabetes and end-stage chronic kidney disease are specific contraindications 9