From the Guidelines
Amoxicillin can be used in patients with CKD stage 4, but dose adjustment is necessary to minimize the risk of toxicity. The dose adjustment is crucial because amoxicillin is primarily eliminated by the kidneys, and reduced kidney function leads to drug accumulation, potentially causing toxicity 1. For patients with CKD stage 4, the recommended dosing is typically reduced to 250-500 mg every 12-24 hours, depending on the severity of infection.
- Key considerations for using amoxicillin in CKD stage 4 patients include:
- Monitoring for signs of adverse effects such as rash, diarrhea, or nausea
- Reassessing renal function during treatment, especially if prolonged therapy is required
- Consulting with a nephrologist or infectious disease specialist in severe infections where higher antibiotic concentrations are needed It is also important to note that certain antibiotics, such as aminoglycoside antibiotics and tetracyclines, should be avoided in CKD patients due to their nephrotoxicity 1. Additionally, nitrofurantoin can produce a toxic metabolite that can cause peripheral neuritis, and its use should be cautious in patients with CKD.
- Alternative antibiotics, such as cephalexin and clindamycin, can be used in patients allergic to amoxicillin, but the choice of antibiotic and dose adjustment should be made based on comments from the patient’s nephrologist before the treatment 1.
From the FDA Drug Label
Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR less than 30 mL/min). See Dosing in Renal Impairment (2. 5) for specific recommendations in patients with renal impairment. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Key Points:
- Amoxicillin is primarily eliminated by the kidney.
- Dosage adjustment is required in patients with severe renal impairment.
- The risk of toxic reactions may be greater in patients with impaired renal function.
- Care should be taken in dose selection for patients with decreased renal function.
Amoxicillin may not be safe to use in patients with Chronic Kidney Disease (CKD) stage 4 without proper dosage adjustment and monitoring, as the drug is primarily eliminated by the kidney and the risk of toxic reactions may be greater in patients with impaired renal function 2.
From the Research
Amoxicillin Safety in Stage 4 CKD
- The safety of amoxicillin in patients with stage 4 Chronic Kidney Disease (CKD) is a concern due to the potential for reduced renal clearance and increased risk of toxicity 3, 4.
- A study published in 2022 found that recommended dose reductions for amoxicillin in patients with impaired kidney function could lead to suboptimal treatments and subtherapeutic drug exposure 5.
- Another study published in 2024 found that almost one-third of antibiotics used in patients with CKD, including those with stage 4 CKD, did not have dose adjustments, which generates a significant risk of toxicity 3.
- The use of antibiotics in patients with CKD requires careful consideration of the dose adjustment according to the glomerular filtration rate (GFR) to avoid accumulation and toxicity 3, 6.
- A review published in 2019 suggested that deferred renal dose reduction of wide therapeutic index antibiotics, such as amoxicillin, could improve outcomes in patients with infectious diseases 7.
- The pharmacokinetics of amoxicillin in patients with impaired renal function have been studied, and a linear relationship between the elimination rate constant of amoxicillin and creatinine clearance was found, allowing for dosage regimen adjustment for patients with renal impairment 4.
Key Findings
- Amoxicillin dose reductions in patients with stage 4 CKD may lead to subtherapeutic drug exposure 5.
- Dose adjustments according to GFR are crucial to avoid toxicity in patients with CKD 3, 6.
- Deferred renal dose reduction of amoxicillin may improve outcomes in patients with infectious diseases 7.
- The pharmacokinetics of amoxicillin can be adjusted based on creatinine clearance to ensure safe and effective use in patients with renal impairment 4.