What to do if a patient develops liver injury while taking Augmentin (amoxicillin/clavulanate)?

Management of Augmentin-Induced Liver Injury

If a patient develops liver injury while taking Augmentin (amoxicillin-clavulanate), immediately discontinue the medication, as hepatic toxicity is usually reversible but deaths have been reported. 1

Immediate Actions Upon Detection

• Stop Augmentin immediately when liver injury is identified, regardless of severity 1
• Discontinue the drug if AST/ALT rises >3× upper limit of normal (ULN) with symptoms, or >5× ULN without symptoms 2
• Discontinue if bilirubin rises above normal range 3

Diagnostic Workup

Perform comprehensive evaluation to exclude other causes of hepatotoxicity:

• Obtain serologic testing for hepatitis A, B, and C viruses (if not done at baseline) 2
• Question the patient carefully about alcohol use and other potential hepatotoxins 2
• Review all concurrent medications for other hepatotoxic agents 2
• Consider liver biopsy if diagnosis remains uncertain or if autoimmune features are present, as amoxicillin-clavulanate can unmask or trigger autoimmune hepatitis 4, 5

Monitoring During Recovery

• Repeat liver function tests (AST, ALT, bilirubin, alkaline phosphatase) within 48-72 hours after initial elevation is detected 2
• Continue monitoring until all abnormalities return to normal or baseline 2
• Follow patients closely as jaundice may develop several weeks after drug completion and illness can be protracted over many weeks 6

Bridging Therapy if Infection Treatment Must Continue

If the patient still requires antibiotic therapy for an ongoing infection:

• Switch to an alternative non-hepatotoxic antibiotic that does not contain clavulanic acid 6
• Avoid amoxicillin-clavulanate permanently in this patient, as the hypersensitivity reaction is likely due to clavulanic acid 6
• Plain amoxicillin may be considered if absolutely necessary, though caution is warranted 6

Critical Clinical Considerations

Augmentin-induced liver injury has distinctive features:

• The hepatotoxicity is primarily attributed to the clavulanic acid component, not amoxicillin 6
• Injury typically presents as cholestatic hepatitis, though mixed patterns occur 1, 5
• Onset can be delayed, occurring weeks after completing the antibiotic course 6
• Histology may show focal destructive cholangiopathy or granulomatous reaction 5
• While usually reversible, rare cases progress to chronic liver disease with persistent cholestatic abnormalities 5
• Deaths have been reported, making this a serious adverse reaction despite its rarity 1

Common Pitfalls to Avoid

• Do not rechallenge with amoxicillin-clavulanate once liver injury has occurred, as this represents a contraindication to future use 1, 6
• Do not delay discontinuation waiting for liver enzymes to reach extremely high levels—act when criteria are met 2
• Do not assume the liver injury will resolve quickly; some patients have protracted courses lasting many weeks 6, 5
• Do not overlook the possibility of drug-induced autoimmune hepatitis, which may require immunosuppressive therapy rather than simple drug withdrawal 4

Long-Term Follow-Up

• Document the adverse reaction prominently in the medical record to prevent future exposure 1
• Counsel the patient to avoid amoxicillin-clavulanate (Augmentin) permanently 6
• Monitor for development of chronic liver disease, particularly if cholestatic pattern persists beyond expected recovery timeframe 5