What is the appropriate dosing of Augmentin (amoxicillin-clavulanate) in a patient with impaired renal function, specifically stage 4 chronic kidney disease (CKD)?

From the FDA Drug Label

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate of <30 mL/min should not receive the 875 mg/125 mg dose Patients with a glomerular filtration rate of 10 to 30 mL/min should receive 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on the severity of the infection. Patients with a glomerular filtration rate less than 10 mL/min should receive 500 mg/125 mg or 250 mg/125 mg every 24 hours, depending on severity of the infection

For a patient with stage 4 kidney disease, the glomerular filtration rate is typically between 15-29 mL/min.

• The recommended dose for a patient with a glomerular filtration rate of 15-29 mL/min is 500 mg/125 mg or 250 mg/125 mg every 12 hours, depending on the severity of the infection 1.
• The dose may need to be adjusted based on the severity of the infection and the patient's individual response to treatment.
• It is essential to monitor the patient's renal function and adjust the dose accordingly.

From the Research

For patients with stage 4 kidney disease (eGFR 15-29 mL/min), Augmentin (amoxicillin-clavulanate) dosing should be reduced to 250-500 mg every 12 hours, depending on the severity of infection, as recommended by the most recent and highest quality study 2. The standard 875/125 mg formulation should be avoided due to the increased risk of toxicity associated with impaired renal function.

Key Considerations

• For severe infections, consider 500 mg every 12 hours initially, while for mild to moderate infections, 250 mg every 12 hours is appropriate.
• Monitoring for side effects is essential, including gastrointestinal symptoms, rash, and signs of neurotoxicity, as both amoxicillin and clavulanic acid are eliminated primarily by the kidneys and impaired renal function can lead to drug accumulation 3.
• Regular assessment of renal function during treatment is recommended, as kidney function may fluctuate, and treatment duration should follow standard guidelines for the specific infection being treated, typically 7-14 days depending on the infection site and severity 4.
• If the patient's renal function worsens during treatment, further dose adjustment may be necessary, and therapeutic drug monitoring should occur when possible along with careful monitoring for antibiotic efficacy and safety 2.

Supporting Evidence

• A study published in 2020 provides an evidence-based update of infectious disease recommendations to health professionals managing patients with chronic kidney disease, emphasizing the importance of dose adjustment for antibiotics in patients with renal failure 3.
• Another study from 2019 highlights the challenges of antibiotic dosing in chronic kidney disease and end-stage renal disease, emphasizing the need for careful evaluation of renal function and the influence of renal replacement therapy on antibiotic clearance 2.
• The definition and classification of chronic kidney disease have evolved over time, with current international guidelines defining this condition as decreased kidney function shown by estimated glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m2, or markers of kidney damage, or both, of at least 3 months duration 4.