What are the contraindications for taking amoxicillin (amoxicillin-clavulanate)?

Contraindications for Amoxicillin-Clavulanate

Amoxicillin-clavulanate is absolutely contraindicated in patients with a history of serious hypersensitivity reactions to amoxicillin, clavulanate, or other beta-lactam antibiotics, and in those with prior cholestatic jaundice or hepatic dysfunction associated with this medication. 1

Absolute Contraindications

Hypersensitivity Reactions

• Patients with a history of anaphylaxis, Stevens-Johnson syndrome, or other serious hypersensitivity reactions to amoxicillin, clavulanate, penicillins, or cephalosporins must not receive amoxicillin-clavulanate. 1
• This includes any beta-lactam antibacterial drug hypersensitivity that was severe or life-threatening. 1

Hepatic Contraindications

• Patients with previous cholestatic jaundice or hepatic dysfunction specifically associated with amoxicillin-clavulanate use are absolutely contraindicated from receiving this medication again. 1
• Drug-induced cholestatic hepatitis has been documented in 208 reported cases, with a mean reaction time of 25.2 days after starting therapy and normalization of liver enzymes taking an average of 11.5 weeks. 2
• Three deaths have been reported among 153 evaluable patients who developed amoxicillin-clavulanate-induced liver injury. 2

Alternative Therapies for Contraindicated Patients

Adults with Penicillin Allergy

• For adults who cannot take amoxicillin-clavulanate due to penicillin allergy, use doxycycline or respiratory fluoroquinolones (levofloxacin or moxifloxacin) as alternatives. 3
• These alternatives provide adequate coverage for respiratory tract infections without cross-reactivity risk. 4

Children with Penicillin Allergy

• For children with non-type I penicillin allergy, use clindamycin plus a third-generation oral cephalosporin as an alternative. 3
• For acute otitis media in penicillin-allergic children, cefdinir (14 mg/kg/day), cefuroxime (30 mg/kg/day), or cefpodoxime (10 mg/kg/day) are appropriate alternatives. 4
• Third-generation cephalosporins (cefdinir, cefuroxime, cefpodoxime, ceftriaxone) are highly unlikely to cross-react with penicillin allergy due to their distinct chemical structures. 4

Important Clinical Caveats

Hepatotoxicity Monitoring

• If amoxicillin-clavulanate must be prescribed despite risk factors, obtain baseline transaminase, alkaline phosphatase, and bilirubin tests within the first two weeks and again at four to five weeks after starting treatment. 2
• Liver injury can be hepatocellular (35 patients), cholestatic (24 patients), or mixed (83 patients) in pattern. 2
• The mean treatment duration before adverse hepatic events was 13.9 days, with most cases occurring in patients treated for respiratory tract infections or sinusitis. 2

Gastrointestinal Limitations

• The clavulanate component limits maximum daily dosing due to gastrointestinal adverse effects, particularly diarrhea. 3
• The 14:1 ratio formulation (high-dose amoxicillin-clavulanate with 90 mg/kg/day amoxicillin and 6.4 mg/kg/day clavulanate) causes less diarrhea than other ratios. 4

Patient Populations Requiring Careful Consideration

• Patients on multidrug regimens are at higher risk for severe adverse effects. 2
• Older patients (mean age 60 years in reported hepatotoxicity cases) may be at increased risk, though adverse events occur across all age groups. 2
• Many authors recommend carefully reconsidering whether amoxicillin-clavulanate is truly necessary for localized or uncomplicated infections given the potential for severe adverse effects. 2