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

Side Effects of Augmentin (Amoxicillin-Clavulanic Acid)

Augmentin is generally well tolerated, but gastrointestinal side effects—particularly diarrhea (9%), nausea (3-9%), and vomiting (1%)—are the most common adverse events, with higher doses increasing the incidence of these effects. 1

Most Common Side Effects

The FDA-approved drug label identifies the following most frequent adverse reactions 1:

• Diarrhea/loose stools: 9% - This is the most common side effect and increases with higher doses 1
• Nausea: 3-9% - Reported consistently across clinical trials 1, 2, 3
• Skin rashes and urticaria: 3% 1
• Vomiting: 1% 1
• Vaginitis: 1% 1
• Abdominal discomfort, flatulence, and headache - Less frequently reported 1

Pediatric-Specific Adverse Events

In children, adverse events occur at significantly higher rates with high-dose formulations, with 44% experiencing side effects (rash, diarrhea, vomiting, abdominal pain) compared to 14% in placebo groups. 4

• Meta-analyses show approximately 5% increased rate of adverse events (particularly diarrhea and rash) when comparing antibiotic treatment to placebo for acute otitis media 4
• The 14:1 ratio formulation (high-dose amoxicillin-clavulanate) is less likely to cause diarrhea than other amoxicillin-clavulanate preparations 5
• Antibiotics are responsible for over 150,000 unplanned medical visits annually for medication-related adverse events in children 4
• Tooth discoloration (brown, yellow, or gray staining) has been rarely reported, mostly in pediatric patients, but is usually reversible with brushing or dental cleaning 1

Serious Gastrointestinal Reactions

• Pseudomembranous colitis and Clostridium difficile-associated diarrhea can occur during or after treatment 1
• Other gastrointestinal effects include gastritis, stomatitis, glossitis, black "hairy" tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic colitis 1

Hypersensitivity Reactions

Serious and occasionally fatal anaphylactic reactions can occur with oral penicillin, requiring immediate discontinuation. 1

• Skin reactions: pruritus, urticaria, angioedema 1
• Serum sickness-like reactions (urticaria or skin rash with arthritis, arthralgia, myalgia, and frequently fever) 1
• Erythema multiforme (rarely Stevens-Johnson syndrome) 1
• Acute generalized exanthematous pustulosis 1
• Hypersensitivity vasculitis 1
• Exfoliative dermatitis (including toxic epidermal necrolysis) - rare but serious 1

These reactions may be controlled with antihistamines and systemic corticosteroids if necessary, but the drug should be discontinued unless the physician determines otherwise 1.

Hepatic (Liver) Adverse Events

Hepatic dysfunction, including hepatitis and cholestatic jaundice, has been reported and can be severe, though usually reversible. 1

• Moderate rise in liver enzymes (AST/ALT) noted in patients treated with ampicillin-class antibiotics 1
• Increases in serum transaminases, bilirubin, and/or alkaline phosphatase reported infrequently 1
• More common in elderly patients, males, and those on prolonged treatment 1
• Focal destructive cholangiopathy - a distinctive pattern of bile duct destruction has been reported, with symptoms appearing within 8 weeks of treatment 6
• Histologic findings show predominantly cholestatic, hepatocellular, or mixed changes 1
• Onset may occur during or several weeks after therapy discontinuation 1
• Rare deaths reported (less than 1 per 4 million prescriptions), generally in cases with serious underlying diseases or concomitant medications 1
• Chronic liver disease with persistent cholestatic abnormalities has been documented in at least one case 6

Hematologic (Blood) Reactions

• Anemia, including hemolytic anemia 1
• Thrombocytopenia and thrombocytopenic purpura 1
• Eosinophilia 1
• Leukopenia and agranulocytosis 1
• Slight thrombocytosis noted in less than 1% of patients 1
• Increased prothrombin time in patients receiving concurrent anticoagulant therapy 1

These reactions are usually reversible upon discontinuation and are believed to be hypersensitivity phenomena 1.

Renal (Kidney) Effects

• Interstitial nephritis - reported rarely 1
• Hematuria 1
• Crystalluria 1

Central Nervous System Effects

Rarely reported reactions include 1:

• Agitation and anxiety
• Behavioral changes
• Confusion
• Convulsions
• Dizziness
• Insomnia
• Reversible hyperactivity

Long-Term Health Concerns in Children

Growing evidence suggests early-life antibiotic exposures may disrupt microbial balance, potentially contributing to inflammatory bowel disease, obesity, eczema, and asthma. 4

Discontinuation Rates

• Less than 3% of patients discontinued therapy due to drug-related side effects in clinical trials 1
• A large pediatric postmarketing study reported a low total incidence of adverse events (3.6%) with no serious events 7

Dosing-Related Considerations

The overall incidence of side effects, particularly diarrhea, increases with higher recommended doses. 1 Twice-daily dosing generally results in less frequent diarrhea compared to three-times-daily treatment 7.