What are the contraindications for Augmentin (amoxicillin and clavulanic acid) in patients with a history of hypersensitivity, impaired renal function, hepatic dysfunction, or other comorbidities?

Augmentin Contraindications

Absolute Contraindications

Augmentin (amoxicillin/clavulanic acid) is absolutely contraindicated in patients with a history of allergic reactions to any penicillin or other beta-lactam antibiotics, and in patients with previous cholestatic jaundice or hepatic dysfunction associated with amoxicillin/clavulanate. 1, 2

Specific Contraindications:

• Hypersensitivity reactions: Any history of serious hypersensitivity reaction (anaphylaxis, Stevens-Johnson syndrome) to amoxicillin, clavulanic acid, or other beta-lactams including penicillins or cephalosporins 1, 2

• Previous hepatic dysfunction: Prior cholestatic jaundice or hepatic dysfunction specifically associated with amoxicillin/clavulanate use 1

Critical Warnings for High-Risk Populations

Hepatic Dysfunction Considerations

Use extreme caution in patients with underlying liver disease or elderly patients, as hepatotoxicity can be severe, delayed, and protracted. 3, 4

• Hepatic dysfunction may develop several weeks after completing therapy (up to 6 weeks post-treatment), making diagnosis challenging 3, 4, 5
• The mechanism is likely immunological hypersensitivity to clavulanic acid 4
• Cholestatic jaundice is the predominant pattern, though mixed cholestatic/hepatocellular injury occurs 5
• While usually reversible upon discontinuation, cases of progressive hepatic failure leading to death have been reported 5
• Elderly patients are at higher risk for severe hepatotoxicity 3

Renal Impairment Considerations

Dose adjustment is required in patients with severe renal impairment, as both amoxicillin and clavulanic acid clearance are significantly reduced. 6

• In end-stage renal disease (ESRD), total serum clearance is markedly reduced for both components 6
• Non-renal clearance is lower than normal subjects, suggesting some degree of hepatic impairment in ESRD patients 6
• During hemodialysis, approximately 64% of amoxicillin and 65% of clavulanic acid are removed 6
• Dosing should be adjusted based on creatinine clearance, with supplemental doses given after dialysis 6

Common Pitfalls and Clinical Pearls

Delayed Hepatotoxicity Recognition

• Do not dismiss jaundice, pruritus, or rash developing weeks after stopping Augmentin 3, 4
• The delayed onset (up to 6 weeks post-therapy) frequently leads to missed diagnosis 3
• If hepatic dysfunction occurs with rash, consider early systemic steroids or liver transplantation referral to prevent progression to Stevens-Johnson syndrome or hepatic failure 5

Cross-Reactivity Concerns

• Patients with penicillin allergy have potential cross-reactivity with cephalosporins and other beta-lactams 2
• History of serious hypersensitivity (not just mild rash) is an absolute contraindication 1, 2

Pregnancy and Pediatric Use

• Generally considered safe in pregnancy and pediatrics when indicated 7
• Well-tolerated in children with low adverse event rates (3.6% in large postmarketing studies) 7
• Most common pediatric adverse events are mild gastrointestinal disturbances, with diarrhea less frequent with twice-daily versus three-times-daily dosing 7