Is Jardiance (Empagliflozin) contraindicated in patients with impaired renal function, hypercreatininemia, and hyperkalemia?

From the Guidelines

Jardiance (empagliflozin) is not absolutely contraindicated in patients with impaired renal function, hypercreatininemia, or hyperkalemia, but its use requires careful consideration based on the degree of renal impairment, as evidenced by the 2022 consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1. The medication should not be initiated in patients with an eGFR below 30 mL/min/1.73m², and it should be discontinued if eGFR persistently falls below 30 mL/min/1.73m². For patients with eGFR between 30-45 mL/min/1.73m², caution is advised as the glycemic efficacy may be reduced, and the dose should be adjusted to 10 mg daily, as recommended in the package insert and supported by the ADA and KDIGO consensus report 1. Regarding hyperkalemia, empagliflozin does not typically worsen this condition and may actually have a mild potassium-lowering effect through its diuretic action, which is beneficial in patients with hyperkalemia. For patients with elevated creatinine, the underlying cause and degree of renal function impairment should guide decision-making rather than the creatinine level alone. The mechanism of action of empagliflozin involves inhibiting sodium-glucose cotransporter-2 (SGLT2) in the proximal renal tubules, which reduces glucose reabsorption and increases urinary glucose excretion, and this mechanism becomes less effective with declining kidney function, which is why the medication has limitations in advanced renal impairment, as discussed in the 2021 standards of medical care in diabetes 1. Key considerations for the use of empagliflozin in patients with impaired renal function include:

• Monitoring eGFR regularly to assess the progression of kidney disease
• Adjusting the dose of empagliflozin based on eGFR, as recommended in the package insert and supported by the ADA and KDIGO consensus report 1
• Carefully evaluating the risks and benefits of continuing empagliflozin in patients with declining kidney function, taking into account the potential benefits of reduced risk of CKD progression, CVD events, and hypoglycemia, as demonstrated in large cardiovascular outcomes trials, including EMPA-REG OUTCOME 1.

From the FDA Drug Label

CONTRAINDICATIONS Severe renal impairment, end-stage renal disease, or dialysis (4)

• Contraindication: Jardiance (Empagliflozin) is contraindicated in patients with severe renal impairment.
• The FDA drug label does not provide a specific eGFR threshold or creatinine level for contraindication, but it does mention severe renal impairment as a contraindication.
• Hyperkalemia is not explicitly listed as a contraindication, but renal impairment can increase the risk of hyperkalemia.
• Given the patient's decreasing eGFR, increasing creatinine, and slightly increasing potassium, Jardiance may be contraindicated due to the risk of worsening renal function 2. The FDA drug label does not answer the question.

From the Research

Jardiance (Empagliflozin) Contraindications

• Jardiance is not explicitly contraindicated in patients with impaired renal function, hypercreatininemia, and hyperkalemia, but its use requires careful consideration of the patient's renal function and potential risks 3.
• The EMPA-KIDNEY trial demonstrated that empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo in patients with chronic kidney disease 3.

Renal Impairment Considerations

• Empagliflozin exposure increases with increasing renal impairment, but the maximum plasma concentrations remain similar among all renal function groups 4.
• Decreases in renal clearance of empagliflozin correlate with estimated glomerular filtration rate (eGFR) 4.
• Urinary glucose excretion decreases with increasing renal impairment and correlates with eGFR 4.

Hyperkalemia and Creatinine Level Considerations

• Patients with chronic renal insufficiency who receive therapy with ACE inhibitors have a higher risk of developing hyperkalemia than those with normal renal function 5.
• A rise in serum creatinine level is common after initiation of ACE inhibitor or ARB therapy, but this rise is often moderate and temporary 5.
• Initial increases in creatinine level of at least 30% were associated with mortality in the total cohort, but this effect was only independent for diuretics and not for RAASIs 6.

Clinical Implications

• The use of Jardiance in patients with impaired renal function, hypercreatininemia, and hyperkalemia requires careful monitoring of renal function, serum creatinine, and potassium levels 3, 4.
• The benefits and risks of Jardiance therapy should be weighed individually for each patient, taking into account their specific clinical characteristics and renal function 3.