From the Guidelines
Amoxicillin dosage adjustments are necessary for patients with impaired renal function to prevent drug accumulation and potential toxicity. According to the study published in the International Journal of Oral Science in 2017 1, patients with impaired renal function, especially those on hemodialysis, require careful consideration of antibiotic dosing to avoid excessive accumulation of drugs. The study highlights that many drugs, including amoxicillin, are excreted by the kidney, and diminished renal function can alter their volume of distribution, metabolism, rate of elimination, and bioavailability.
For patients with impaired renal function, the dose adjustment of amoxicillin is associated with the residual kidney function, as suggested by the American Heart Association (AHA) 2007 recommendations 1. Typically, for patients not allergic to penicillin, 2 g of amoxicillin is administered orally 1 hour before dental treatment. However, for patients with severe renal impairment, the dose may need to be reduced, and the dosing interval extended to prevent toxicity.
Key considerations for amoxicillin dosing in patients with impaired renal function include:
- Extending the standard dosing interval from every 8 hours to every 12-24 hours
- Reducing the dose by 50-75% while maintaining the usual frequency
- Reducing the dose to 250-500 mg every 24 hours in severe renal impairment
- Supplemental doses may be needed after hemodialysis sessions, as hemodialysis can remove amoxicillin.
It is essential to consult with the patient's nephrologist to determine the appropriate dose adjustment and to avoid nephrotoxic drugs, such as aminoglycoside antibiotics and tetracyclines, which should be avoided in patients with chronic kidney disease (CKD) due to their potential to exacerbate renal impairment 1.
From the FDA Drug Label
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. 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). High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin
Key Points:
- Amoxicillin is substantially excreted by the kidney.
- Patients with impaired renal function are at a greater risk of toxic reactions.
- Dosage adjustment is required in patients with severe renal impairment.
- Decreased renal clearance of amoxicillin can lead to high blood levels in patients with impaired renal function.
Amoxicillin affects renal clearance in patients with impaired renal function, as it is primarily eliminated by the kidney and decreased renal clearance can lead to high blood levels 2.
From the Research
Amoxicillin and Renal Clearance
- Amoxicillin clearance is affected by renal function, with studies showing a correlation between creatinine clearance and amoxicillin half-life 3, 4, 5.
- In patients with impaired renal function, amoxicillin clearance is decreased, leading to increased half-life and potentially subtherapeutic drug concentrations 3, 4, 5.
- Dosage nomograms have been developed to guide amoxicillin dosing in patients with impaired renal function, taking into account factors such as creatinine clearance and body weight 4.
- However, there is inconsistency between guidelines on recommended dose reduction of renally cleared antibiotics, including amoxicillin, in patients with impaired renal function 6.
Pharmacokinetics of Amoxicillin
- Amoxicillin pharmacokinetics follow an open two-compartment model, with renal clearance being a significant factor in determining drug exposure 5.
- The half-life of amoxicillin is increased in patients with renal impairment, with a linear relationship between beta (elimination rate constant) and creatinine clearance 5.
- Hemodialysis can affect amoxicillin clearance, with studies showing a reduced half-life during dialysis 4, 5.
Clinical Implications
- Recommended dose reductions for amoxicillin in patients with impaired renal function may lead to subtherapeutic drug concentrations, particularly when targeting less susceptible pathogens 3.
- Careful consideration of antibiotic dose and frequency is required in critically ill patients receiving renal replacement therapy, with therapeutic drug monitoring recommended to ensure adequate drug exposure 7.