Complications of Amoxicillin Administration
The most common complications of amoxicillin administration include gastrointestinal disturbances (diarrhea, nausea, vomiting), hypersensitivity reactions (ranging from mild rashes to severe anaphylaxis), and Clostridioides difficile-associated diarrhea (CDAD). 1
Common Adverse Effects
Gastrointestinal Effects
- Diarrhea (most common, >1% of patients)
- Nausea and vomiting
- Black hairy tongue
- Abdominal discomfort
Hypersensitivity Reactions
- Skin rashes (particularly common)
- Urticaria (hives)
- Pruritus (itching)
- Angioedema
- Anaphylactic/anaphylactoid reactions (potentially life-threatening)
Serious Complications
Severe Cutaneous Adverse Reactions (SCAR)
- Stevens-Johnson syndrome (SJS)
- Toxic epidermal necrolysis (TEN)
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Acute generalized exanthematous pustulosis (AGEP)
Clostridioides difficile-Associated Diarrhea (CDAD)
- Can range from mild diarrhea to fatal colitis
- May occur during treatment or up to 2 months after antibiotic use
- Requires prompt recognition and appropriate management 1
Hematologic Complications
- Anemia (including hemolytic anemia)
- Thrombocytopenia
- Thrombocytopenic purpura
- Eosinophilia
- Leukopenia
- Agranulocytosis
Hepatic Effects
- Moderate elevation of AST/ALT
- Cholestatic jaundice
- Hepatic cholestasis
- Acute cytolytic hepatitis
Renal Complications
- Crystalluria (especially with high doses)
- Acute nephrotoxicity (rare, but reported with overdose) 2
Neurological Effects
- Reversible hyperactivity
- Agitation
- Anxiety
- Insomnia
- Confusion
- Convulsions
- Behavioral changes
- Aseptic meningitis
- Dizziness
Special Considerations
Mononucleosis
- High percentage of patients with mononucleosis develop an erythematous skin rash when given amoxicillin
- Amoxicillin should not be administered to patients with known mononucleosis 1
Penicillin Allergy
- Cross-reactivity with cephalosporins may occur in patients with penicillin allergy
- Alternative antibiotics should be considered for patients with known penicillin allergy 3
Risk Mitigation Strategies
Before Prescribing
- Obtain thorough allergy history (especially to penicillins, cephalosporins)
- Consider risk factors for C. difficile infection
- Assess for mononucleosis
During Treatment
- Monitor for skin rashes and discontinue if lesions progress
- Take with food to reduce gastrointestinal irritation
- Consider probiotics (taken 2 hours before or after antibiotics) to help reduce gastrointestinal side effects
Patient Education
- Report any rash, difficulty breathing, or severe diarrhea immediately
- Complete the full course of antibiotics unless instructed otherwise
- Take medication as prescribed (timing and with/without food)
Dosing Considerations to Reduce Complications
- Once or twice daily dosing regimens may improve compliance and have similar efficacy to three-times-daily dosing 4, 5
- Shorter duration therapy (when appropriate) may reduce adverse events while maintaining efficacy 3
- High-dose amoxicillin with clavulanate may be necessary in specific situations but carries increased risk of gastrointestinal side effects 3, 6
By understanding these potential complications and implementing appropriate preventive measures, clinicians can optimize the safety and efficacy of amoxicillin therapy while minimizing adverse outcomes.