Is a 2g IV dose of ceftriaxone (Ceftriaxone) okay in a patient with acute kidney injury (AKI) and an estimated glomerular filtration rate (eGFR) of 27?

From the Guidelines

A 2g IV dose of ceftriaxone is generally acceptable for a patient with acute kidney injury (AKI) and an eGFR of 27, as ceftriaxone does not typically require dose adjustment in renal impairment due to its dual elimination pathways. Ceftriaxone has dual elimination pathways, with approximately 33-67% excreted unchanged in urine and the remainder eliminated via biliary excretion 1. This unique pharmacokinetic profile means that when kidney function is reduced, the biliary pathway can compensate. For most indications, the standard adult dose of 1-2g IV daily can be maintained even with severe renal impairment or patients on dialysis. However, it's essential to monitor the patient closely for signs of toxicity, particularly if they have concurrent hepatic dysfunction, as this could impair the compensatory elimination pathway. Additionally, serum levels of ceftriaxone may be slightly higher in patients with renal impairment, but this rarely leads to clinical consequences at standard dosing. The medication should be administered as an IV infusion over 30 minutes to minimize vascular irritation. Some key points to consider:

• Ceftriaxone's dual elimination pathways allow for maintained efficacy in renal impairment
• Monitoring for signs of toxicity is crucial, especially with concurrent hepatic dysfunction
• Standard dosing is usually safe, but serum levels may be slightly elevated in renal impairment
• Administration as an IV infusion over 30 minutes can help minimize vascular irritation, as recommended in guidelines such as those from the Infectious Diseases Society of America 1.

From the FDA Drug Label

Patients with Renal or Hepatic Impairment Ceftriaxone is excreted via both biliary and renal excretion (see CLINICAL PHARMACOLOGY). Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of ceftriaxone are administered Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the ceftriaxone dosage should not exceed 2 grams daily.

Ceftriaxone dosing in patients with AKI and eGFR of 27:

• The FDA drug label states that dosage adjustments are not necessary in patients with renal impairment, but caution should be exercised in patients with both hepatic dysfunction and significant renal disease.
• Since the patient has an eGFR of 27, which indicates significant renal impairment, but there is no mention of hepatic dysfunction, a 2g IV dose of ceftriaxone may be acceptable.
• However, close clinical monitoring for safety and efficacy is advised 2.

From the Research

Ceftriaxone Dosage in Acute Kidney Injury (AKI)

• The use of ceftriaxone in patients with AKI requires careful consideration of the drug's pharmacokinetics and potential risks 3, 4, 5.
• Studies have shown that ceftriaxone is eliminated primarily by the kidneys, and its clearance is closely dependent on creatinine clearance 5.
• In patients with severe renal insufficiency, the half-life of ceftriaxone is prolonged, and the total body clearance is reduced 3, 4.
• The recommended dose of ceftriaxone in patients with renal insufficiency is 1 g every 24 hours 3.
• However, there is limited information available on the safety and efficacy of a 2 g IV dose of ceftriaxone in patients with AKI and an eGFR of 27.

Risks of Ceftriaxone-Associated Renal Toxicity

• Ceftriaxone has been associated with renal toxicity, including urolithiasis and post-renal acute renal failure (PARF) 6, 7.
• The risk of ceftriaxone-associated renal toxicity is increased in patients with pre-existing renal impairment 6.
• The use of high doses of ceftriaxone, such as 2 g IV, may increase the risk of renal toxicity 6.

Considerations for Dosing in AKI

• In patients with AKI, the dose of ceftriaxone should be adjusted based on the degree of renal impairment 5.
• The use of a 2 g IV dose of ceftriaxone in a patient with an eGFR of 27 may be excessive and increase the risk of renal toxicity.
• A dose reduction to 1 g every 24 hours may be more appropriate in this patient population 3.