Coamoxiclav Dosing in Adults with Renal Impairment
For adults with impaired renal function, coamoxiclav (amoxicillin/clavulanic acid) requires dose reduction or interval extension based on creatinine clearance, with specific adjustments recommended at CrCl thresholds of 10-30 mL/min and <10 mL/min, including post-dialysis dosing for hemodialysis patients.
Standard Dosing in Normal Renal Function
For adults with normal renal function, the typical dosing regimens include:
- 625 mg (500/125 mg) three times daily for most community-acquired infections 1, 2, 3
- 1750/250 mg (two 1g tablets) every 4-6 hours for severe infections requiring higher amoxicillin concentrations 4
- 2000/125 mg twice daily for respiratory tract infections requiring enhanced pharmacokinetics 5
Dose Adjustment Algorithm for Renal Impairment
Creatinine Clearance 30-50 mL/min
- Reduce the dose by one-half or double the dosing interval 1
- For standard 625 mg dosing: give 312.5 mg three times daily OR 625 mg every 12 hours 1
Creatinine Clearance 10-30 mL/min (Moderate-Severe Impairment)
- Reduce dose to half the standard dose 1
- Typical adjustment: 312.5 mg twice daily or 625 mg once daily 1
Creatinine Clearance <10 mL/min (Severe Impairment)
- Further dose reduction to half the adjusted dose or use alternative dosing 1
- Consider 312.5 mg once daily or less frequent dosing 1
Hemodialysis Patients
- Administer the full dose after each dialysis session 1
- Both amoxicillin and clavulanate are removed by hemodialysis, necessitating post-dialysis supplementation 1
- Standard approach: give 625 mg after each dialysis session 1
Critical Pharmacokinetic Considerations
Time above MIC (T>MIC) is the critical pharmacodynamic parameter for beta-lactam antibiotics like amoxicillin:
- For optimal bactericidal activity, maintain T>MIC ≥50% of the dosing interval as a minimum target 4
- For maximal efficacy, achieve T>MIC ≥90% of the dosing interval 4
- In severe infections with organisms having higher MICs, dosing intervals should not exceed 6 hours even with enhanced formulations 4
Common Pitfalls and Safety Considerations
Avoid Underdosing in Serious Infections
- In renal impairment with serious infections, do not reduce the individual dose below therapeutic levels—instead, extend the dosing interval 4
- For infections requiring high amoxicillin concentrations, maintain adequate individual doses (e.g., 1000 mg amoxicillin component) but space them further apart 4
Monitor for Drug Accumulation
- Clavulanic acid accumulation can occur in severe renal impairment, though it has a favorable safety profile 6
- Both components are renally eliminated, requiring parallel dose adjustments 1
Nephrotoxic Drug Interactions
- Avoid concomitant nephrotoxic agents (aminoglycosides, NSAIDs) in patients with baseline renal impairment 1, 7
- Aminoglycosides should be avoided entirely in advanced chronic kidney disease 1
Consultation Recommendations
- Consult nephrology before prescribing in patients on dialysis or with CrCl <30 mL/min to optimize dosing and minimize toxicity 1
- Consider therapeutic drug monitoring in critically ill patients with fluctuating renal function 8
Special Population Considerations
For patients on continuous renal replacement therapy (CRRT), dosing principles differ from intermittent hemodialysis, though specific coamoxiclav data is limited—extrapolating from similar beta-lactams suggests maintaining higher individual doses with extended intervals 8.