Is Farxiga (dapagliflozin) contraindicated in Chronic Kidney Disease (CKD) stage 4, characterized by Impaired Renal Function?

From the Guidelines

Farxiga (dapagliflozin) is not contraindicated in CKD stage 4, and can actually be beneficial for these patients. According to the most recent evidence from Galindo et al 1, dapagliflozin is expected to be effective in patients with eGFR as low as 30 mL/min/1.73m², and the labeling recommends avoiding initiation if eGFR < 60 mL/min/1.73 m², but does not contraindicate its use in CKD stage 4. The typical dose is 10 mg once daily. However, it should not be initiated in patients with eGFR below 25 mL/min/1.73m² (which would be late stage 4 or stage 5 CKD). For patients already on dapagliflozin who progress to an eGFR below 25, the medication can be continued. The renal benefits of dapagliflozin in CKD patients include slowing kidney function decline and reducing the risk of kidney failure, regardless of diabetes status. These benefits are thought to occur through multiple mechanisms including reduced intraglomerular pressure, decreased hyperfiltration, anti-inflammatory effects, and metabolic improvements. Patients should be monitored for potential side effects such as volume depletion, urinary tract infections, and genital mycotic infections.

Some key points to consider when using dapagliflozin in CKD stage 4 patients include:

• Monitoring eGFR and adjusting the dose as needed
• Being aware of the potential for adverse effects such as volume depletion and urinary tract infections
• Considering the benefits of combination therapy with other medications, such as GLP-1 RAs, to provide additional cardiovascular and kidney outcomes benefit, as suggested by recent guidelines 1
• Keeping in mind that the use of dapagliflozin in CKD stage 4 patients is supported by recent studies and guidelines, including those from the American Diabetes Association and the Kidney Disease: Improving Global Outcomes 1

From the FDA Drug Label

Dapagliflozin was evaluated in 4304 adult patients with chronic kidney disease (eGFR 25 to 75 mL/min/1.73 m2) in the DAPA-CKD trial. Efficacy and safety trials with dapagliflozin did not enroll patients with an eGFR less than 25 mL/min/1.73 m2 or on dialysis. Once enrolled in the DAPA-CKD and DELIVER trials, adult patients were not required to discontinue therapy if eGFR fell below 25 mL/min/1. 73 m2 or if dialysis was initiated.

Contraindication in CKD Stage 4:

• The FDA drug label does not explicitly state that dapagliflozin (Farxiga) is contraindicated in CKD stage 4.
• However, it is noted that efficacy and safety trials with dapagliflozin did not enroll patients with an eGFR less than 25 mL/min/1.73 m2, which corresponds to CKD stage 4 or higher.
• The DAPA-CKD trial included patients with eGFR between 25 and 75 mL/min/1.73 m2, but the label does not provide specific guidance on the use of dapagliflozin in patients with CKD stage 4.
• Key Points:
  • No explicit contraindication in CKD stage 4
  • Limited data available for patients with eGFR < 25 mL/min/1.73 m2
  • Use with caution and consider individual patient factors 2, 2

From the Research

Farxiga Contraindication in CKD Stage 4

• The use of Farxiga (dapagliflozin) in patients with chronic kidney disease (CKD) stage 4 is not entirely contraindicated, as evidenced by the DAPA-CKD trial 3.
• In fact, the study found that dapagliflozin significantly reduced the risk of kidney failure and prolonged survival in patients with CKD stage 4, with a 27% reduction in the primary composite endpoint 3.
• The effects of dapagliflozin in patients with stage 4 CKD were consistent with those observed in the overall DAPA-CKD trial, with no evidence of increased risks 3.
• However, an earlier review of dapagliflozin noted that it is not recommended in patients with moderate or severe renal impairment 4, which may include some patients with CKD stage 4.
• Nevertheless, the more recent study 3 suggests that dapagliflozin may be beneficial in patients with CKD stage 4, and its use is approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with CKD with or without type 2 diabetes 5.

Key Findings

• Dapagliflozin reduced the risk of kidney failure and prolonged survival in patients with CKD stage 4 3.
• The effects of dapagliflozin in patients with stage 4 CKD were consistent with those observed in the overall DAPA-CKD trial 3.
• Dapagliflozin is not recommended in patients with moderate or severe renal impairment, but its use may be beneficial in patients with CKD stage 4 3, 4.
• The use of dapagliflozin in patients with CKD stage 4 should be carefully considered, taking into account the individual patient's characteristics and medical history 3.