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 Compared to that in healthy adult subjects, the pharmacokinetics of ceftriaxone were only minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction (Table 4); therefore, dosage adjustments are not necessary for these patients with ceftriaxone dosages up to 2 grams per day
Dose Adjustment in CKD 4:
- No dose adjustment is necessary for patients with renal impairment, including those with CKD 4, when administering usual doses of ceftriaxone up to 2 grams per day 1, 1.
- The pharmacokinetics of ceftriaxone are minimally altered in patients with renal impairment 1.
- 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 1, 1.
From the Research
Ceftriaxone may require dose adjustment in CKD stage 4, with a recommended decrease of approximately 50% in moderate to severe renal disease to provide comparable exposure to the healthy population. This is based on a physiologically-based pharmacokinetic modeling study published in 2023 2, which suggested that decreasing the dose by approximately 25% in mild and 50% in moderate to severe renal disease provided a comparable exposure to the healthy population.
The study used a physiologically-based pharmacokinetic (PBPK) modeling approach to predict the biological exposure of ceftriaxone in a virtually-constructed healthy and chronic kidney disease patient populations, with subsequent dosing optimizations. The results showed that the developed PBPK model was able to precisely describe the pharmacokinetic behavior of ceftriaxone in adult healthy population and in mild, moderate, and severe CKD patient populations.
Some key points to consider when dosing ceftriaxone in patients with CKD stage 4 include:
- Monitoring patients closely for signs of toxicity, particularly when using higher doses or in patients with both renal and hepatic impairment
- Serum levels of ceftriaxone may be monitored in critically ill patients with severe renal dysfunction if there are concerns about drug accumulation
- The maximum daily dose should not exceed 2 grams in these patients to minimize the risk of adverse effects
- Alternative methods for quantifying kidney function, such as the Cockcroft-Gault formula or direct measures of glomerular filtration rate using exogenous isotope compounds, may be considered in certain patient subsets 3.
It's worth noting that other studies have suggested that ceftriaxone does not require dose adjustment in CKD stage 4, but these studies are older and may not reflect the most recent evidence 4, 5. Additionally, a 2024 review on the care of adults with advanced chronic kidney disease highlighted the importance of considering health equity and person-centered care when managing patients with CKD 6.