What are the side effects of Syjardy (empagliflozin and linagliptin)?

Side Effects of Syjardy (Empagliflozin and Linagliptin)

The most common side effects of Syjardy include genital mycotic infections (especially in women), urinary tract infections, gastrointestinal effects, and potential volume depletion, while serious but rare side effects include diabetic ketoacidosis and necrotizing fasciitis of the perineum (Fournier's gangrene). 1, 2

Common Side Effects

SGLT2 Inhibitor Component (Empagliflozin)

• Genital mycotic infections:

  • More common in women than men
  • Symptoms include vaginal odor, white/yellowish discharge, and vaginal itching
  • In men: redness, itching, swelling of penis, rash, foul-smelling discharge 1

• Urinary tract infections:

  • More frequent in women
  • Higher risk in those with history of chronic/recurrent UTIs 1

• Volume depletion effects:

  • Dizziness, fainting, light-headedness, weakness (especially when standing)
  • Higher risk in elderly patients, those on diuretics, or with low blood pressure 1, 3

• Laboratory changes:

  • Increased LDL cholesterol (2.3-6.5%)
  • Increased hematocrit 1

DPP-4 Inhibitor Component (Linagliptin)

• Gastrointestinal effects: Less pronounced than with other antidiabetic medications 4
• Joint pain 4
• Potential risk of pancreatitis (rare, causality not established) 5

Serious Side Effects

• Diabetic ketoacidosis (DKA):

  • Can occur with normal blood glucose levels (euglycemic DKA)
  • Higher risk in insulin-deficient patients
  • Symptoms include difficulty breathing, nausea, vomiting, abdominal pain 1

• Necrotizing fasciitis of the perineum (Fournier's gangrene):

  • Rare but serious infection requiring prompt treatment 1

• Heart failure risk:

  • Linagliptin has shown neutral effect on heart failure hospitalization
  • Unlike saxagliptin (another DPP-4 inhibitor), which has increased risk 5

Special Populations and Considerations

Renal Function

• Empagliflozin's glucose-lowering effect diminishes with eGFR <45 mL/min/1.73 m²
• Linagliptin requires no dose adjustment for renal impairment 5

Risk of Hypoglycemia

• Low risk when used as monotherapy
• Increased risk when combined with insulin or sulfonylureas 1, 2

Monitoring Recommendations

• Before starting treatment:

  • Assess renal function
  • Consider reducing doses of insulin or sulfonylureas by 20-50% if patient is on these medications 5

• During treatment:

  • Monitor for signs of genital infections and UTIs
  • Watch for symptoms of volume depletion, especially in elderly patients
  • Be alert for symptoms of DKA, even with normal blood glucose levels 1

Practical Advice for Patients

1. Maintain good genital hygiene to reduce risk of infections
2. Stay well-hydrated, especially during illness or hot weather
3. Temporarily discontinue medication during severe illness, fasting, or before scheduled surgery
4. Seek medical attention promptly for:
   • Symptoms of genital infections that don't improve with over-the-counter treatment
   • Signs of urinary tract infection
   • Symptoms of ketoacidosis (nausea, vomiting, abdominal pain, difficulty breathing)
   • Unusual skin reactions 1

Comparative Safety Profile

Pooled analysis from five randomized clinical trials showed that the combination of empagliflozin and linagliptin has a safety profile similar to the individual components, with no new safety signals identified 2. The fixed-dose combination provides the advantage of improved compliance with a favorable safety profile 6.