What are the potential side effects of amoxicillin (amoxicillin) in children?

Amoxicillin Side Effects in Children

Amoxicillin causes adverse events in approximately 5% more children compared to placebo, with the most common side effects being diarrhea and rash, though serious reactions including anaphylaxis and Stevens-Johnson syndrome can occur. 1, 2

Common Side Effects

Gastrointestinal Effects:

• Diarrhea is the most frequently reported adverse event, occurring in approximately 7-8% of children treated with amoxicillin 1, 3
• Nausea and vomiting occur in more than 1% of treated children 3
• Black hairy tongue and mucocutaneous candidiasis can develop during treatment 3

Dermatologic Reactions:

• Rash occurs in approximately 5% more children receiving amoxicillin compared to placebo 1, 2
• Maculopapular exanthem (36% of reactions), urticaria (44% of reactions), and pruritus are common presentations 4
• Most rashes appear on days 7-10 of treatment 4

Serious Adverse Reactions

Life-Threatening Hypersensitivity:

• Anaphylaxis and anaphylactoid reactions (including shock) can occur, though they are rare 5, 3
• Angioedema and serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever) affect approximately 11% of children presenting to emergency departments with amoxicillin-associated reactions 4, 6
• True allergic reactions including urticaria and angioedema are potentially life-threatening 5

Severe Cutaneous Adverse Reactions:

• Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported 1, 3
• Erythema multiforme and exfoliative dermatitis can occur 3

Systemic and Organ-Specific Effects

Hematologic:

• Reversible reactions including anemia (including hemolytic anemia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported 3
• These reactions are usually reversible upon discontinuation and are believed to be hypersensitivity phenomena 3

Hepatic:

• Moderate rise in AST and/or ALT has been noted 3
• Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis have been reported 3

Central Nervous System:

• Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, aseptic meningitis, and dizziness have been reported 3

Renal:

• Crystalluria has been reported 3

Long-Term Health Concerns

Microbiome Disruption:

• Growing evidence indicates that early-life antibiotic exposures may disrupt microbial balance in the intestines and other body sites 1, 2
• This disruption may contribute to long-term adverse health effects including inflammatory bowel disease, obesity, eczema, and asthma 1, 2

Clostridioides difficile:

• The incidence of C. difficile colitis in hospitalized children has increased substantially, with recent antibiotic exposure as an important risk factor 1
• Hemorrhagic/pseudomembranous colitis can occur during or after antibacterial treatment 3

Clinical Considerations and Pitfalls

"Worrisome" Features:

• Fever, angioedema, or gastrointestinal symptoms occur in 73% of children with serum sickness-like reactions 4
• Delayed-onset systemic symptoms are identified frequently across all reaction phenotypes 4
• Emergency department reutilization is unexpectedly high, with 10% of children returning for re-evaluation 4

Dosing-Related Adverse Events:

• High-dose amoxicillin-clavulanate (used for resistant pathogens) shows adverse event rates of 44% compared to 14% with placebo, including rash, diarrhea, vomiting, and abdominal pain 1
• Children receiving higher doses should be carefully monitored for side effects from long-term treatment 1

Important Caveats:

• Over 90% of children with amoxicillin-associated rashes tolerate amoxicillin on re-exposure, suggesting many reactions are not true allergies 4
• Most adverse events occur relatively frequently but are relatively mild in most cases 1
• Tooth discoloration (brown, yellow, or gray staining) has been reported, mostly in pediatric patients, but is usually reduced or eliminated with brushing or dental cleaning 3