Can a patient with impaired renal function take 300 mg of Invokana (Canagliflozin)?

Canagliflozin (Invokana) Use in a Patient with GFR of 33 mL/min/1.73m²

Canagliflozin 300 mg is not recommended for patients with eGFR <45 mL/min/1.73m² due to reduced efficacy and increased risk of adverse effects. 1

Dosing Recommendations Based on Renal Function

The FDA label for Invokana (canagliflozin) provides clear guidance for patients with impaired renal function:

• For patients with eGFR 30-45 mL/min/1.73m²:

  • Maximum dose should be limited to 100 mg once daily
  • 300 mg dose is not recommended

• For patients with eGFR <30 mL/min/1.73m²:

  • Canagliflozin should not be initiated
  • Treatment should be discontinued if eGFR falls persistently below 30 mL/min/1.73m²

Rationale for Dose Limitation

1. Reduced Efficacy: The glucose-lowering effect of canagliflozin is significantly diminished in patients with moderate to severe renal impairment 1, 2

2. Safety Concerns:

   • Increased risk of volume depletion (hypotension, postural dizziness, orthostatic hypotension)
   • Higher risk of acute kidney injury
   • Potential for electrolyte abnormalities, particularly hyperkalemia with the 300 mg dose 3

Pharmacokinetic Considerations

In patients with moderate renal impairment (eGFR 30-50 mL/min/1.73m²), canagliflozin exposure is increased by approximately 63% compared to those with normal renal function 4. This increased exposure contributes to the higher risk of adverse effects without proportionally increasing efficacy.

Mechanism of Reduced Efficacy

Canagliflozin works by inhibiting SGLT2 transporters in the proximal renal tubules, reducing glucose reabsorption and increasing urinary glucose excretion. As renal function declines, there is:

• Decreased filtered glucose load
• Reduced urinary glucose excretion (UGE)
• Less suppression of renal threshold for glucose (RTG) 4

These factors collectively diminish the glucose-lowering effect of canagliflozin in patients with reduced renal function.

Alternative Medication Options

For patients with eGFR 30-45 mL/min/1.73m², consider:

1. Canagliflozin 100 mg (if specifically indicated for cardiovascular or renal protection)
2. GLP-1 receptor agonists (preferred in patients with CKD) 5
3. DPP-4 inhibitors (dose adjustment may be needed)
4. Insulin (with appropriate dose adjustment)

Monitoring Recommendations

If canagliflozin 100 mg is used in a patient with eGFR 33 mL/min/1.73m²:

• Monitor renal function regularly
• Assess for signs of volume depletion
• Monitor serum potassium levels
• Evaluate for urinary tract infections and genital mycotic infections
• Consider temporary discontinuation during acute illness or procedures with risk of volume depletion

Common Pitfalls to Avoid

1. Inappropriate dosing: Using 300 mg dose in patients with eGFR <45 mL/min/1.73m²
2. Failure to monitor: Not regularly assessing renal function in at-risk patients
3. Continuing therapy: Not discontinuing canagliflozin when eGFR falls below 30 mL/min/1.73m²
4. Dehydration risk: Not educating patients about maintaining adequate hydration

In conclusion, for a patient with eGFR of 33 mL/min/1.73m², canagliflozin 300 mg is not recommended. The maximum dose should be limited to 100 mg daily, with careful monitoring of renal function and potential adverse effects.