What are the side effects of amoxicillin?

Side Effects of Amoxicillin

Amoxicillin commonly causes diarrhea, rash, vomiting, and nausea, but can also lead to more serious adverse events including life-threatening allergic reactions, Stevens-Johnson syndrome, and Clostridioides difficile infection. 1

Common Side Effects

• Gastrointestinal effects are among the most frequent adverse reactions:

  • Diarrhea (>1% of patients) 1
  • Nausea (>1% of patients) 1
  • Vomiting (>1% of patients) 1
  • Black hairy tongue 1

• Dermatological reactions:

  • Rash (>1% of patients) 1
  • Pruritus (itching) 1
  • Urticaria (hives) 1

Severe Side Effects

• Allergic reactions:

  • Hypersensitivity reactions ranging from mild to severe 1
  • Anaphylactic/anaphylactoid reactions (including shock) 1
  • Angioedema 1
  • Serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever) 1

• Severe cutaneous adverse reactions (SCAR):

  • Stevens-Johnson syndrome (SJS) 1
  • Toxic epidermal necrolysis (TEN) 1
  • Drug reaction with eosinophilia and systemic symptoms (DRESS) 1
  • Acute generalized exanthematous pustulosis (AGEP) 1
  • Exfoliative dermatitis 1

• Gastrointestinal complications:

  • Clostridioides difficile-associated diarrhea (CDAD), which can range from mild diarrhea to fatal colitis 1
  • Hemorrhagic/pseudomembranous colitis 1

• Hepatic effects:

  • Moderate rise in AST and/or ALT 1
  • Hepatic dysfunction including cholestatic jaundice 1
  • Hepatic cholestasis and acute cytolytic hepatitis 1

• Hematologic abnormalities:

  • Anemia, including hemolytic anemia 1
  • Thrombocytopenia and thrombocytopenic purpura 1
  • Eosinophilia, leukopenia, and agranulocytosis 1

• Renal effects:

  • Crystalluria 1
  • Acute renal failure (rare, especially with overdose) 2

• Central nervous system effects:

  • Reversible hyperactivity, agitation, anxiety, insomnia 1
  • Confusion, convulsions, behavioral changes 1
  • Aseptic meningitis, dizziness 1

Special Considerations

• Patients with mononucleosis:

  • High percentage develop an erythematous skin rash when given amoxicillin 1
  • Amoxicillin should not be administered to patients with mononucleosis 1

• Pediatric patients:

  • Tooth discoloration (brown, yellow, or gray staining) has been reported, primarily in children 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

• Long-term effects:

  • Growing evidence suggests early-life antibiotic exposures may disrupt microbial balance, potentially contributing to inflammatory bowel disease, obesity, eczema, and asthma 3

Risk Factors and Incidence

• Meta-analyses of studies comparing antibiotic treatment to placebo for acute otitis media suggest approximately 5% increased rate of adverse events, particularly diarrhea and rash 3

• In sinusitis treatment trials, adverse events (rash, diarrhea, vomiting, and abdominal pain) occurred in 44% of patients treated with high-dose amoxicillin-clavulanate compared with 14% in the placebo group 3

• The number of courses of antibiotics needed to harm was 27 (95% CI 24-42) for candidiasis with amoxicillin 4

Clinical Implications

• When prescribing amoxicillin, carefully weigh potential benefits against harms, especially for upper respiratory tract infections where benefits may be limited to symptom attenuation 3

• Apply stringent diagnostic criteria before prescribing amoxicillin, as prescribing for nonspecific URI and colds generally provides no benefit while exposing patients to potential harm 3

• Monitor patients for signs of allergic reactions, particularly during the first course of therapy, as severe reactions can occur even without prior history of allergy 5

• Consider checking liver function tests within the first two weeks and after four to five weeks of treatment, especially with amoxicillin-clavulanic acid, to detect hepatic side effects early 6

• Be vigilant for signs of Clostridioides difficile infection, which can occur up to two months after antibiotic administration 1