What are the side effects of Augmentin (amoxicillin and clavulanic acid)?

Side Effects of Augmentin (Amoxicillin and Clavulanic Acid)

Gastrointestinal side effects are the most common adverse reactions to Augmentin, with diarrhea occurring in approximately 9% of patients, followed by nausea (3%), vomiting (1%), and abdominal discomfort.

Common Side Effects

Gastrointestinal Effects

• Diarrhea/loose stools (9%) - most frequent adverse effect 1
• Nausea (3%) 1
• Vomiting (1%) 1
• Abdominal discomfort and flatulence 1
• Higher incidence of diarrhea with higher doses of amoxicillin-clavulanate 2
• Gastrointestinal side effects are more strongly associated with the clavulanic acid component 3
• Pseudomembranous colitis (Clostridioides difficile infection) 1, 3

Dermatologic Reactions

• Skin rashes and urticaria (3%) 1
• Pruritus 1

Other Common Side Effects

• Headache 1
• Vaginitis (1%) 1

Serious Side Effects (Less Common)

Hypersensitivity Reactions

• Serum sickness-like reactions (urticaria with arthritis, arthralgia, myalgia, fever) 1
• Erythema multiforme (rarely Stevens-Johnson syndrome) 1
• Acute generalized exanthematous pustulosis 1
• Hypersensitivity vasculitis 1
• Exfoliative dermatitis (including toxic epidermal necrolysis) 1
• Anaphylactic reactions (rare but potentially fatal) 1

Hepatic Effects

• Moderate rise in liver enzymes (AST/SGOT and ALT/SGPT) 1
• Hepatic dysfunction, including hepatitis and cholestatic jaundice 1
• More common in elderly patients, males, or those on prolonged treatment 1
• Usually reversible but rare fatal cases have been reported 1

Hematologic Effects

• Anemia, including hemolytic anemia 1
• Thrombocytopenia and thrombocytopenic purpura 1
• Eosinophilia, leukopenia, and agranulocytosis 1
• Increased prothrombin time in patients on anticoagulant therapy 1

Renal Effects

• Interstitial nephritis (rare) 1
• Hematuria (rare) 1
• Crystalluria 1

Neurological Effects

• Agitation, anxiety, behavioral changes 1
• Confusion, convulsions, dizziness 1
• Insomnia and reversible hyperactivity (rare) 1

Risk Factors for Side Effects

• Higher doses of amoxicillin-clavulanate increase the risk of adverse events 2
• In a sinusitis study, adverse events occurred in 44% of patients treated with high-dose amoxicillin-clavulanate compared with 14% in the placebo group 2
• Clavulanate doses exceeding 10 mg/kg/day increase the risk of diarrhea 4
• Formulations with higher amoxicillin:clavulanate ratios (14:1 or 16:1) have lower incidence of gastrointestinal effects 4, 3

Special Considerations

Pediatric Patients

• Tooth discoloration (brown, yellow, or gray staining) has been rarely reported, mostly in pediatric patients 1
• Diarrhea is generally less frequent with twice-daily than with three-times-daily treatment in children 5

Overdose Management

• Primarily results in gastrointestinal symptoms 1
• May require supportive care, adequate fluid intake, and diuresis 1
• Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients 1
• Crystalluria can occur and may lead to renal failure 1

Clinical Implications

When prescribing Augmentin, clinicians should:

• Consider using amoxicillin alone when appropriate, as it has fewer gastrointestinal side effects 3
• Reserve amoxicillin-clavulanate for infections where beta-lactamase-producing bacteria are suspected 4
• Monitor patients for signs of hepatic dysfunction, especially elderly patients and those on prolonged treatment 1
• Be aware of potential drug interactions, particularly with anticoagulants 1
• Discontinue treatment if serious hypersensitivity reactions occur 1

Understanding these side effects helps in appropriate patient selection, monitoring, and management when using Augmentin for bacterial infections.