What is the recommended renal dose of co-amoxiclav (amoxicillin/clavulanic acid) for a patient with Chronic Kidney Disease (CKD)?

Co-Amoxiclav Dosing in Chronic Kidney Disease

Co-amoxiclav 625 mg TID for 7 days is NOT appropriate for patients with CKD without dose adjustment; the standard dose must be reduced based on creatinine clearance, particularly when GFR is <30 mL/min. 1

Renal Dose Adjustment Requirements

Amoxicillin (the primary component of co-amoxiclav) is primarily eliminated by the kidney, and dosage adjustment is required in patients with severe renal impairment (GFR <30 mL/min). 1 The FDA label explicitly states that the risk of adverse reactions is greater in patients with impaired renal function, and elderly patients with decreased renal function require particular attention to dose selection. 1

Specific Dosing Recommendations by Renal Function:

• GFR ≥30 mL/min: Standard dosing (625 mg TID) can generally be used without adjustment 1

• GFR <30 mL/min (severe renal impairment): Dose reduction is mandatory 1

  • Reduce frequency to twice daily (BID) rather than three times daily
  • Consider reducing individual dose strength
  • The pharmacokinetics show significant decreases in elimination and total body clearance in renal failure 2

• Hemodialysis patients: Additional dose after dialysis sessions is recommended, as amoxicillin is removed during hemodialysis (half-life during dialysis is 2.3 hours) 2

Clinical Approach to Dosing

Calculate creatinine clearance before prescribing using validated formulas (Cockcroft-Gault, CKD-EPI, or aMDRD), as drug dosing errors are common in patients with renal impairment and can cause adverse effects. 3, 4

Practical Dosing Algorithm:

1. Assess baseline renal function using creatinine clearance calculation 4

2. For CrCl >30 mL/min: Use standard 625 mg TID dosing 1

3. For CrCl <30 mL/min:

   • Reduce to 625 mg BID (twice daily) OR
   • Use 375 mg TID if available
   • Monitor for drug accumulation 1, 2

4. For dialysis patients: Give supplemental dose post-dialysis 2

Important Clinical Caveats

• Acute kidney injury (AKI) considerations: If the patient has AKI superimposed on CKD, the renal function may improve within 48 hours in over 57% of cases. 5 However, initial dosing should still be based on the presenting creatinine clearance to avoid early drug accumulation. 5

• Wide therapeutic index: Amoxicillin has a relatively wide therapeutic index, but clavulanic acid accumulation in severe renal impairment can increase risk of adverse effects, making dose adjustment essential. 1

• Monitoring: Renal function should be monitored during treatment, particularly in patients with borderline renal function (CrCl 30-50 mL/min), as further deterioration may necessitate additional dose reduction. 4, 6

• Drug interactions: Avoid nephrotoxic drug combinations in CKD patients to prevent further kidney damage. 7

Pharmacokinetic Rationale

The elimination half-life of amoxicillin increases significantly in renal impairment, with a linear relationship between the elimination rate constant (beta) and creatinine clearance. 2 This relationship allows for precise dosage regimen adjustment based on measured renal function. 2 Without adjustment, drug accumulation occurs due to decreased total body clearance and reduced renal elimination. 2