Side Effects of Amoxicillin in Children
Amoxicillin causes diarrhea and rash in approximately 5% more children compared to placebo, with even higher rates when viral illness is present. 1
Common Adverse Events
Gastrointestinal Effects
- Diarrhea is the most frequent side effect, occurring in approximately 15% of children treated with amoxicillin compared to 11% with placebo 2
- When amoxicillin-clavulanate is used instead of amoxicillin alone, diarrhea rates are substantially higher—44% versus 14% in placebo groups 1
- Mild gastrointestinal disturbances are the most frequently reported adverse events in pediatric patients 3
Dermatologic Reactions
- Rash occurs in approximately 5% more children treated with amoxicillin versus placebo 1
- Maculopapular rash is the most common presentation (36% of amoxicillin-associated reactions) 4
- Critical distinction: Over 90% of children with reported amoxicillin rashes tolerate the drug on re-exposure, indicating most rashes are not true allergies 4
- In children with viral infections (especially Epstein-Barr virus), 30-100% develop rashes when given amoxicillin—this represents a virus-drug interaction, NOT a true drug allergy 4
Serious but Rare Adverse Events
Severe Cutaneous Reactions
- Stevens-Johnson syndrome can occur but is rare 1
- Severe reactions requiring permanent avoidance include: blistering, skin exfoliation, and mucosal involvement 4
Allergic Reactions
- Anaphylaxis is possible but uncommon 1
- True IgE-mediated allergies are characterized by immediate-onset reactions (within 1 hour) with urticaria, angioedema, or anaphylaxis 4
- Urticaria accounts for 44% of amoxicillin-associated reactions presenting to emergency settings 4
Other Serious Effects
- Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage 5
- Crystalluria, in some cases leading to renal failure, has been reported after amoxicillin overdosage 5
- Clostridioides difficile colitis incidence in hospitalized children has increased substantially, with recent antibiotic exposure as an important risk factor 1
Long-Term and Systemic Effects
Microbiome Disruption
- Antibiotic exposures early in life may disrupt the microbial balance of the intestines, potentially contributing to long-term adverse health effects including inflammatory bowel disease, obesity, eczema, and asthma 1
Antimicrobial Resistance
- Individual patient exposure contributes to development of antibiotic resistance 1
- The relationship between antibiotic exposure and resistance at both individual and community levels is well established 1
Other Systemic Effects
- Amoxicillin may lead to sensitization of infants when used by nursing mothers 5
- Thrush (oral candidiasis) can occur as a secondary effect 6
Drug Interactions Causing Adverse Effects
- Concurrent allopurinol administration increases the incidence of rashes in patients receiving both drugs compared to amoxicillin alone 5
- Amoxicillin may reduce efficacy of combined oral estrogen/progesterone contraceptives by affecting intestinal flora 5
- Abnormal prolongation of prothrombin time has been reported with concurrent oral anticoagulant use 5
Clinical Context and Risk Mitigation
Overall Safety Profile
- A large pediatric postmarketing study reported a low total incidence of adverse events (3.6%) with no serious events 3
- The safety and effectiveness of amoxicillin for treatment of upper respiratory tract infections, genitourinary tract infections, skin and skin structure infections, and lower respiratory tract infections have been established in pediatric patients 5
Special Populations
- In neonates and young infants (≤12 weeks), elimination of amoxicillin may be delayed due to incompletely developed renal function, requiring dosing modifications 5