Does ceftriaxone (Ceftriaxone) require dose adjustments for Impaired renal function?

From the Guidelines

Ceftriaxone generally does not require dose adjustments for renal impairment. The standard adult dose of 1-2 grams daily can be maintained even in patients with significant renal dysfunction, including those on dialysis. This is because ceftriaxone has dual elimination pathways - approximately 33-67% is excreted unchanged in urine while the remainder is eliminated via biliary excretion.

Key Points

• The provided evidence does not directly address the need for dose adjustments of ceftriaxone in patients with impaired renal function 1.
• However, based on the pharmacokinetic properties of ceftriaxone, it is known that this antibiotic has a unique elimination profile that allows it to be used without significant dose adjustment in patients with renal impairment.
• Ceftriaxone is not removed by hemodialysis to a significant extent, so supplemental doses after dialysis are unnecessary.
• In patients with both severe renal impairment (creatinine clearance <10 mL/min) AND hepatic dysfunction, the maximum daily dose should be limited to 2 grams.
• Serum levels should be monitored in prolonged courses for patients with combined organ dysfunction.

Clinical Considerations

• The decision to adjust the dose of ceftriaxone in patients with impaired renal function should be made on a case-by-case basis, taking into account the severity of the renal impairment and the presence of any other organ dysfunction.
• It is essential to monitor patients with renal impairment for signs of toxicity or adverse effects, even if the dose is not adjusted.
• Ceftriaxone is a convenient choice for patients with varying degrees of kidney function due to its pharmacokinetic properties.

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

• Dose adjustments for impaired renal function are not necessary in most cases, as ceftriaxone is excreted via both biliary and renal excretion.
• However, caution should be exercised in patients with both hepatic dysfunction and significant renal disease, and the ceftriaxone dosage should not exceed 2 grams daily 2.
• In patients with severe renal and hepatic dysfunction, close clinical monitoring for safety and efficacy is advised 2.

From the Research

Dose Adjustments for Impaired Renal Function

• Ceftriaxone does not require dose adjustments for patients with impaired renal function when the dosage is 2 g or less per day 3, 4.
• However, in patients with end-stage renal disease, the elimination half-life of ceftriaxone may be substantially prolonged, and plasma concentrations should be monitored to determine whether dosage adjustments are necessary 4.
• A study found that ceftriaxone concentrations may be increased in patients with end-stage renal disease, which can lead to encephalopathy 5.
• In patients undergoing continuous veno-venous hemofiltration, a reduction in the usual daily dose of ceftriaxone is not required 6.
• Critically ill patients with renal failure may experience prolonged elimination half-life and drug accumulation, which may require dose adjustments 7.

Pharmacokinetics in Renal Impairment

• The pharmacokinetics of ceftriaxone were studied in patients with renal insufficiency, and the results showed that the elimination half-life was prolonged in patients with severe renal impairment 3.
• The renal clearance and fraction of dose excreted unchanged in urine were related linearly, however weakly, with creatinine clearance 4.
• Ceftriaxone was not removed from plasma to a significant extent during hemodialysis 4.
• The sieving coefficient of ceftriaxone was found to be 0.69, which suggests that protein binding does not limit the sieving of this compound 6.

Clinical Implications

• The results of these studies suggest that ceftriaxone can be used in patients with impaired renal function without dose adjustments, but monitoring of plasma concentrations may be necessary in certain cases 3, 4, 5.
• Clinicians should be aware of the potential for increased ceftriaxone concentrations and encephalopathy in patients with end-stage renal disease 5.
• The pharmacokinetics of ceftriaxone in critically ill patients with renal failure should be carefully monitored to avoid drug accumulation and ensure adequate plasma concentrations 7.