What is the recommended intravenous dosage of amoxicillin (amoxicillin-clavulanic acid) for a patient with impaired renal function and a history of allergy to penicillins?

Amoxicillin-Clavulanic Acid IV Dosing in Renal Impairment with Penicillin Allergy

Critical Contraindication

A history of penicillin allergy is an absolute contraindication to amoxicillin-clavulanic acid administration, regardless of renal function, as amoxicillin is a penicillin-class antibiotic. 1

Alternative Antibiotic Selection for Penicillin-Allergic Patients

For Beta-Lactam Allergic Patients

• Vancomycin 30 mg/kg/day IV in 2 divided doses is the recommended alternative for patients with true penicillin allergy requiring IV therapy 2
• Serum vancomycin trough concentrations should be maintained at 10-15 mg/L, with monitoring required in renal impairment 2
• For patients with immediate-type penicillin allergy (anaphylaxis, urticaria), cephalosporins carry approximately 10% cross-reactivity risk and should be avoided 3

Renal Dose Adjustments for Vancomycin

• In patients with impaired renal function, vancomycin dosing intervals must be extended based on creatinine clearance to prevent nephrotoxicity 2
• Loading doses remain unchanged, but maintenance doses require adjustment 2
• Hemodialysis patients require supplemental dosing after dialysis sessions 1

If Amoxicillin-Clavulanic Acid Were Appropriate (No Allergy)

Standard IV Dosing with Normal Renal Function

• The new European formulation provides amoxicillin 2 g/clavulanic acid 125 mg IV every 12 hours for resistant strains (MIC 4-8 mg/L) 2
• Standard dosing: amoxicillin 100-200 mg/kg/day IV in 4-6 divided doses 2

Renal Impairment Dosing Adjustments

For GFR 10-30 mL/min:

• Reduce to 500 mg or 250 mg every 12 hours depending on infection severity 1
• Total body clearance decreases significantly with declining renal function 4, 5

For GFR <10 mL/min:

• Reduce to 500 mg or 250 mg every 24 hours 1
• Serum half-life increases from 71 minutes (normal function) to 16 hours in anephric patients 4

Hemodialysis patients:

• Administer 500 mg or 250 mg every 24 hours 1
• Provide supplemental dose both during and at the end of dialysis 1
• Dialysis clearance is 77.1 mL/min for amoxicillin with 64% fractional drug removal during 4-hour sessions 6
• Half-life during dialysis decreases to 2.3-3.6 hours 4, 6

Critical Pharmacokinetic Considerations

• Clavulanic acid clearance is less affected by renal impairment than amoxicillin clearance 7
• The ratio of amoxicillin to clavulanic acid AUC increases dramatically with declining GFR: from 4.9 at GFR 75 mL/min to 14.7 in hemodialysis patients 7
• Non-renal clearance is reduced in end-stage renal disease, suggesting hepatic impairment 6

Common Pitfalls

• Never administer amoxicillin-clavulanic acid to patients reporting penicillin allergy without formal allergy testing and desensitization 2
• Avoid the 875 mg tablet formulation in patients with GFR <30 mL/min 1
• Do not use aminoglycosides or tetracyclines as alternatives in renal failure due to nephrotoxicity 2
• Failure to provide supplemental dosing after hemodialysis results in subtherapeutic levels 1, 6