Can Invokana (canagliflozin) be used in a patient with a history of pancreatitis or diabetic ketoacidosis?

Invokana (Canagliflozin) Use in Patients with History of Pancreatitis or Diabetic Ketoacidosis

Invokana (canagliflozin) should not be used in patients with a history of diabetic ketoacidosis (DKA) and should be used with caution in patients with a history of pancreatitis. 1, 2

Diabetic Ketoacidosis Considerations

Contraindication for DKA History

• Invokana has been associated with an increased risk of euglycemic ketoacidosis, which can be life-threatening 1
• The American College of Cardiology guidelines specifically list "euglycemic ketoacidosis in vulnerable patients" as a caution for SGLT2 inhibitors 1
• Patients with a history of DKA are at higher risk for recurrence when using SGLT2 inhibitors 1
• Case reports have documented severe ketoacidosis associated with canagliflozin use 2

Risk Mitigation

• If Invokana must be used in patients at risk for DKA:
  • Monitor ketone levels regularly
  • Educate patients about symptoms of DKA
  • Discontinue medication immediately if DKA is suspected
  • Consider temporary discontinuation during acute illness or surgical procedures

Pancreatitis Considerations

Risk Assessment

• While acute pancreatitis is a very rare side effect of canagliflozin with an incidence <1% 3, caution is warranted
• A case report has documented acute pancreatitis in a patient after 4 days of canagliflozin treatment 3
• Unlike GLP-1 receptor agonists, which have more established pancreatitis concerns, SGLT2 inhibitors are generally not contraindicated specifically for pancreatitis history 1, 4

Alternative Options for Patients with Pancreatitis History

If avoiding Invokana in a patient with pancreatitis history:

• Metformin is a safe first-line option with no pancreatitis risk 4
• Insulin therapy is a safe option without pancreatitis risk that can be used at any level of renal function 1, 4
• Other SGLT2 inhibitors (empagliflozin, dapagliflozin) may be considered, though class effects should be monitored 4
• Sulfonylureas can be used with caution regarding hypoglycemia risk 4

Important Monitoring Parameters

For All Patients on Invokana

• Regular monitoring of renal function (contraindicated if eGFR <30 mL/min/1.73m²) 1
• Monitor for signs of volume depletion and hypotension 1
• Watch for genital mycotic infections, which are common adverse effects 5
• Monitor for signs of ketoacidosis, even with normal blood glucose levels 1

Additional Precautions

• Invokana has been associated with increased risk of lower limb amputations (particularly in patients with cardiovascular disease) 1
• Bone fracture risk may be increased with canagliflozin 1
• Discontinue medication if acute kidney injury occurs 1

Clinical Decision Algorithm

1. For patients with history of DKA:

   • Avoid Invokana and all SGLT2 inhibitors
   • Consider alternative agents: metformin, GLP-1 receptor agonists (if no pancreatitis history), insulin, or sulfonylureas

2. For patients with history of pancreatitis:

   • Consider risk-benefit ratio carefully
   • If using Invokana, monitor closely for abdominal pain and elevated pancreatic enzymes
   • Consider alternative agents with lower pancreatitis risk (metformin, insulin)

3. For patients with both conditions:

   • Avoid Invokana completely
   • Use insulin as primary therapy, with metformin if renal function permits

In summary, while Invokana offers cardiovascular and renal benefits for many patients with type 2 diabetes, the risk of recurrent DKA in patients with prior DKA history outweighs these benefits. For patients with pancreatitis history, careful consideration and monitoring are required if Invokana is used.