What is the recommended dosing of Augmentin (amoxicillin/clavulanic acid) for a patient with severe renal impairment, specifically a Glomerular Filtration Rate (GFR) of 17?

Renal Dosing for Augmentin (Amoxicillin/Clavulanic Acid) with GFR 17

For a patient with GFR 17 mL/min, administer Augmentin 500 mg or 250 mg every 24 hours (depending on infection severity), with an additional dose both during and at the end of hemodialysis if the patient is on dialysis. 1

Dosing Recommendations Based on Renal Function

The FDA-approved dosing for severe renal impairment is clear and should be followed:

• GFR 10-30 mL/min (which includes your patient with GFR 17): 500 mg or 250 mg every 12 hours, depending on infection severity 1
• GFR <10 mL/min: 500 mg or 250 mg every 24 hours, depending on infection severity 1
• Hemodialysis patients: 500 mg or 250 mg every 24 hours, with an additional dose both during and at the end of dialysis 1

Critical contraindication: The 875 mg dose formulation should NOT be used in patients with GFR <30 mL/min 1

Pharmacokinetic Rationale

The differential elimination of amoxicillin versus clavulanic acid becomes clinically significant in severe renal impairment:

• Amoxicillin clearance decreases more dramatically than clavulanic acid clearance as GFR declines 2
• At GFR 10-35 mL/min, the ratio of amoxicillin to clavulanic acid exposure increases to approximately 11.9-13.4 (compared to 4.9 in normal renal function) 2
• Total body clearance of amoxicillin in end-stage renal disease is reduced to approximately 14.4 mL/min (compared to normal values of 200-300 mL/min) 3
• The terminal half-life of amoxicillin extends to approximately 13.6 hours in non-dialysis ESRD patients (versus 1-1.5 hours normally) 3

Practical Dosing Algorithm

Step 1: Determine infection severity

• Mild-to-moderate infections (uncomplicated UTI, mild skin infections): Use 250 mg every 12 hours 1
• Severe infections (pneumonia, complicated skin infections): Use 500 mg every 12 hours 1

Step 2: Assess dialysis status

• If on hemodialysis: Switch to once-daily dosing (250 mg or 500 mg every 24 hours) and administer supplemental doses during and after each dialysis session 1
• If not on dialysis: Continue every 12-hour dosing as above 1

Step 3: Monitor for accumulation

• Treatment should continue for minimum 48-72 hours beyond symptom resolution 1
• Watch for signs of amoxicillin toxicity (neurological symptoms, seizures in severe cases) given the prolonged half-life 4

Critical Clinical Pitfalls

Avoid these common errors:

• Do not use standard dosing intervals – the every 8-hour regimens used in normal renal function will cause dangerous drug accumulation 5
• Do not prescribe 875 mg tablets – this formulation is explicitly contraindicated at GFR <30 mL/min 1
• Do not forget post-dialysis dosing – approximately 64% of amoxicillin is removed during a 4-hour hemodialysis session, necessitating replacement doses 3
• Do not assume clavulanic acid requires the same adjustment – clavulanic acid has higher nonrenal clearance (43.6 mL/min in ESRD) and shorter half-life (3.05 hours), meaning it clears more efficiently than amoxicillin even in severe renal impairment 3

Special Considerations for GFR 17

Your patient sits in the borderline zone between moderate-severe (GFR 10-30) and severe (<10) renal impairment:

• Start with the every 12-hour regimen (500 mg or 250 mg) as recommended for GFR 10-30 mL/min 1
• Monitor closely for signs of drug accumulation, particularly if renal function deteriorates further 5
• Consider switching to every 24-hour dosing if the patient develops symptoms suggesting drug accumulation or if GFR drops below 10 mL/min 1
• Reassess renal function during treatment, as acute illness may further compromise kidney function 6

Duration of Therapy

• Continue treatment for at least 48-72 hours after the patient becomes asymptomatic or bacterial eradication is documented 1
• For streptococcal infections, maintain at least 10 days of therapy to prevent acute rheumatic fever 1
• Some infections may require several weeks of treatment with ongoing clinical and bacteriological monitoring 1