Side Effects of Amoxicillin
Amoxicillin commonly causes gastrointestinal side effects, skin reactions, and can lead to serious adverse events including hypersensitivity reactions and Clostridioides difficile-associated diarrhea. 1
Common Side Effects
- Gastrointestinal effects: Diarrhea, nausea, and vomiting are the most frequently reported adverse reactions (>1%) in clinical trials 1
- Skin reactions: Rash is among the most common side effects observed in clinical trials 1
- Oral candidiasis: Mucocutaneous candidiasis can develop due to disruption of normal flora 1
- Diarrhea: Particularly common with amoxicillin-clavulanate combinations, with studies showing a number needed to harm of 10 (95% CI 6-17) 2
Serious Adverse Effects
- Hypersensitivity reactions: Can range from mild rashes to severe anaphylactic/anaphylactoid reactions including shock, angioedema, and serum sickness-like reactions 1
- Severe cutaneous adverse reactions (SCAR): Including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis 1
- Clostridioides difficile-associated diarrhea (CDAD): Can range from mild diarrhea to fatal colitis and may occur up to 2 months after antibiotic use 1
Other Reported Adverse Effects
- Hepatic effects: Moderate rises in AST/ALT, cholestatic jaundice, hepatic cholestasis, and acute cytolytic hepatitis 1
- Hematologic effects: Anemia (including hemolytic anemia), thrombocytopenia, eosinophilia, leukopenia, and agranulocytosis 1
- Central nervous system effects: Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, aseptic meningitis, and dizziness 1
- Renal effects: Crystalluria has been reported 1
Special Populations
Pediatric Patients
- Tooth discoloration (brown, yellow, or gray staining) has been reported primarily in pediatric patients 1
- Antibiotics are responsible for the largest number of unplanned medical visits for medication-related adverse events among children, exceeding 150,000 per year 3
- Growing evidence suggests early-life antibiotic exposures may disrupt microbial balance, potentially contributing to inflammatory bowel disease, obesity, eczema, and asthma 3
Patients with Mononucleosis
- A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash; therefore, amoxicillin should not be administered to these patients 1
Risk-Benefit Considerations
- When treating acute bacterial rhinosinusitis, adverse events are more common in antibiotic-treated patients (odds ratio 1.87 to 2.10; number needed to harm 8.1) 4
- For sinusitis treatment, adverse events (rash, diarrhea, vomiting, and abdominal pain) occurred in 44% of patients treated with high-dose amoxicillin-clavulanate compared with 14% in placebo groups 3
- Shorter courses of antibiotics (5-7 days) may be equally effective as 10-day courses for treating acute bacterial rhinosinusitis, with fewer side effects 4
Clinical Pearls
- Always inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens before initiating therapy 1
- Monitor patients for skin rashes and discontinue amoxicillin if lesions progress 1
- Consider the risk of C. difficile infection when patients present with diarrhea following antibiotic use, even up to 2 months after treatment 1
- Amoxicillin-clavulanate combinations have higher rates of gastrointestinal side effects than amoxicillin alone 2, 5
- Carefully weigh benefits against potential harms, especially for upper respiratory tract infections where benefits may be limited 3