Can the extended-release formulation of Augmentin (amoxicillin/clavulanic acid) be prescribed to a patient with impaired renal function?

Augmentin Extended-Release in Renal Impairment

The extended-release formulation of Augmentin (amoxicillin/clavulanate 875 mg/125 mg) should NOT be prescribed to patients with severe renal impairment (GFR <30 mL/min). 1

Dosing Recommendations Based on Renal Function

Severe Renal Impairment (GFR <30 mL/min)

• Patients with GFR <30 mL/min should NOT receive the 875 mg/125 mg formulation (which includes extended-release preparations) 1
• This is an absolute contraindication per FDA labeling, as both amoxicillin and clavulanic acid accumulate significantly when renal clearance is severely compromised 1, 2

Moderate Renal Impairment (GFR 10-30 mL/min)

• Use standard-release formulations only: 500 mg/125 mg or 250 mg/125 mg every 12 hours 1
• Dose selection depends on infection severity 1
• The extended-release formulation is inappropriate because the fixed dosing interval cannot accommodate the prolonged half-life in this population 2

Severe Renal Impairment (GFR <10 mL/min)

• Use standard-release formulations: 500 mg/125 mg or 250 mg/125 mg every 24 hours 1
• Dose based on infection severity 1

Hemodialysis Patients

• Administer 500 mg/125 mg or 250 mg/125 mg every 24 hours (standard-release only) 1
• Give an additional dose both during and at the end of dialysis to compensate for drug removal 1
• The extended-release formulation is contraindicated because dialysis timing cannot be synchronized with the prolonged absorption profile 1

Pharmacokinetic Rationale

The prohibition against extended-release formulations in renal impairment is based on several factors:

• Amoxicillin clearance decreases proportionally with creatinine clearance, with a linear relationship between elimination rate and renal function 2
• Both amoxicillin and clavulanic acid are primarily renally eliminated, leading to significant accumulation when GFR falls below 30 mL/min 1, 2
• Extended-release formulations provide sustained drug delivery that cannot be adjusted for the already-prolonged half-life in renal insufficiency, risking toxic accumulation 1, 2

Clinical Evidence in Renal Impairment

Standard-release Augmentin has been studied in patients with chronic renal insufficiency (GFR 55-70 mL/min) and demonstrated acceptable safety when dosed appropriately 3. However, this evidence applies only to standard-release formulations with appropriate dose adjustments 3.

Common Pitfalls to Avoid

• Do not substitute two 250 mg/125 mg tablets for one 500 mg/125 mg tablet, as both contain the same amount of clavulanic acid (125 mg), leading to clavulanate overdosing 1
• Do not assume mild-to-moderate renal impairment requires no adjustment—patients with GFR 30-50 mL/min still need careful monitoring even though they may not require dose reduction 1
• Always calculate estimated GFR or creatinine clearance before prescribing, as serum creatinine alone is unreliable, especially in elderly patients with reduced muscle mass 4, 5

Monitoring Requirements

• Hepatic function should be monitored at regular intervals in all patients receiving Augmentin, as hepatically impaired patients require cautious dosing 1
• Renal function monitoring is essential throughout therapy in patients with any degree of renal impairment to detect further deterioration 5, 6