What is Amoxicillin used for and what are its typical dosages and side effects?

Amoxicillin: Clinical Uses, Dosing, and Adverse Effects

Primary Clinical Indications

Amoxicillin is a first-line penicillin-class antibiotic indicated for treating bacterial infections of the upper respiratory tract (otitis media, sinusitis, pharyngitis), lower respiratory tract (pneumonia, bronchitis), genitourinary tract, and skin/soft tissue infections caused by susceptible organisms. 1

Respiratory Tract Infections

• Acute otitis media: High-dose amoxicillin (80-90 mg/kg/day in children, 500-1000 mg three times daily in adults) is the recommended first-line treatment 2, 3
• Acute bacterial sinusitis: Standard dose is 500 mg three times daily for 5-7 days in adults, or high-dose (80-90 mg/kg/day) in children with risk factors 2, 3
• Community-acquired pneumonia: 500 mg three times daily for 7-10 days in mild-to-moderate cases 3
• Streptococcal pharyngitis: 500 mg twice daily for 10 days 3

Genitourinary Infections

• Uncomplicated urinary tract infections: Single 3-gram dose is effective in adults 4
• Complicated UTIs: Standard dosing of 500 mg three times daily for 7-10 days 1

Other Indications

• Helicobacter pylori eradication: 1 gram twice daily with clarithromycin and lansoprazole for 14 days (triple therapy) 1
• Lyme disease (erythema migrans): 500 mg three times daily for 14-21 days 3
• Gonorrhea: Effective as single-dose therapy 5

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Standard Dosing Regimens

Adult Dosing

• Mild-to-moderate infections: 500 mg orally three times daily or 250 mg every 8 hours 2, 3, 1
• Severe infections or resistant organisms: 1000 mg three times daily 3
• High-risk patients (age >65, recent antibiotic use, areas with >10% penicillin-resistant S. pneumoniae): 2000 mg twice daily 3
• Maximum adult dose: 1750 mg/day in divided doses 1

Pediatric Dosing (>3 months)

• Standard dose: 20-45 mg/kg/day divided every 8-12 hours 1
• High-dose regimen (for resistant organisms): 80-90 mg/kg/day divided twice daily 2, 6
• Neonates and infants ≤3 months: Maximum 30 mg/kg/day divided every 12 hours 1
• Children <40 kg with mild-moderate skin infections: 25 mg/kg/day every 12 hours or 20 mg/kg/day every 8 hours 2
• Children ≥40 kg: 500 mg every 12 hours or 250 mg every 8 hours 2

When to Use High-Dose Amoxicillin

High-dose therapy is indicated when there are risk factors for resistant organisms 2, 3:

• Recent antibiotic use within 30 days
• Daycare attendance (children)
• Age <2 years or >65 years
• Geographic areas with >10% penicillin-resistant S. pneumoniae
• Treatment failure with standard dosing
• Severe or complicated infections

Renal Dosing Adjustments

• GFR <30 mL/min: Reduce dose or extend dosing interval 2, 1

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When to Use Amoxicillin-Clavulanate Instead

Switch to amoxicillin-clavulanate when β-lactamase-producing organisms are suspected or confirmed, including H. influenzae, M. catarrhalis, or S. aureus. 3, 7

Specific Indications for Amoxicillin-Clavulanate

• Recent antibiotic use within 30 days 2, 8
• Concurrent purulent conjunctivitis (otitis-conjunctivitis syndrome) 2, 6
• Treatment failure with amoxicillin alone 2, 3
• Animal or human bite wounds 3
• β-lactamase-producing pathogens documented or suspected 2, 7

Dosing for Amoxicillin-Clavulanate

• Adults: 875/125 mg twice daily or 500/125 mg three times daily; high-dose is 2000/125 mg twice daily 2, 8
• Children: High-dose is 90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate in 2 divided doses (14:1 ratio) 2, 8, 6
• The 14:1 ratio formulation causes less diarrhea than other amoxicillin-clavulanate preparations 2, 6

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Common Adverse Effects

Gastrointestinal (Most Common)

• Diarrhea: Occurs in approximately 5% more patients than placebo 2
• Nausea and vomiting: Common, generally mild 2, 1
• Abdominal pain: Reported in clinical trials 2
• Clostridioides difficile-associated diarrhea: Can range from mild diarrhea to fatal colitis; evaluate if diarrhea occurs 1
• Oral candidiasis: Secondary fungal overgrowth 2

Dermatologic

• Rash: Occurs in >1% of patients, approximately 5% more than placebo 2, 1
• Urticaria and pruritus: Common allergic manifestations 2
• Severe cutaneous adverse reactions (SCAR): Including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme; discontinue immediately if rash progresses 2, 1
• Acute generalized exanthematous pustulosis: Rare but serious 2

Hypersensitivity Reactions

• Anaphylaxis: Serious and occasionally fatal reactions have been reported; discontinue immediately if occurs 1
• Serum sickness: Delayed hypersensitivity reaction 2
• Angioedema: Potentially life-threatening 2

Hematologic

• Eosinophilia, thrombocytopenia, anemia: Rare but documented 2
• Hemolytic anemia, agranulocytosis: Very rare 2

Neurologic

• Headache, dizziness: Common, generally mild 2, 1
• Seizures: Rare, more likely with high doses or renal impairment 2
• Behavioral changes, agitation, anxiety: Particularly in children 2

Hepatic

• Elevated liver enzymes (AST/ALT): Monitor in prolonged therapy 2
• Cholestatic jaundice, hepatitis: Rare but serious 2

Other

• Superinfection: Including vaginal candidiasis 2
• Crystalluria: With very high doses 1

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Important Drug Interactions

Contraindicated or Not Recommended

• Probenecid: Coadministration not recommended; increases amoxicillin levels by decreasing renal excretion 1

Requires Monitoring

• Oral anticoagulants (warfarin): May increase prothrombin time; monitor INR closely 2, 1
• Allopurinol: Increases risk of rash; use combination cautiously 2, 1
• Oral contraceptives: Amoxicillin may reduce efficacy; advise backup contraception 1
• Methotrexate: Amoxicillin may decrease methotrexate clearance 2

Other Interactions

• Tetracyclines: May antagonize bactericidal effects of amoxicillin 2
• Antacids (aluminum/magnesium): May decrease absorption 2

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Critical Warnings and Contraindications

Absolute Contraindications

• History of serious hypersensitivity reaction (anaphylaxis, Stevens-Johnson syndrome) to amoxicillin or other β-lactams (penicillins or cephalosporins) 1

Penicillin Allergy Considerations

Cross-reactivity between penicillins and cephalosporins is lower than historically reported (<10%), and cephalosporins with distinct chemical structures (cefdinir, cefuroxime, cefpodoxime, ceftriaxone) are highly unlikely to cross-react. 2

• Differentiate immediate Type I hypersensitivity reactions from other less dangerous side effects 2
• Patients with non-immediate reactions may tolerate specific β-lactams 2
• For true penicillin allergy, alternatives include doxycycline, respiratory fluoroquinolones, or TMP-SMX depending on indication 2

Special Populations

• Pregnancy Category B: Generally safe; minimal risk to fetus 2
• Breastfeeding: Distributed into milk but minimal risk to infant; compatible with breastfeeding 2
• Renal impairment: Requires dose adjustment when GFR <30 mL/min 2, 1

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Common Pitfalls to Avoid

Inappropriate Use

• Viral upper respiratory infections: The vast majority of URTIs are viral and do not benefit from antibiotics; prescribing antibiotics for viral URTIs increases adverse effects without benefit and promotes resistance 2, 6
• Nonspecific URI and common cold: Antibiotics provide no benefit and only expose patients to potential harm 2
• Monotherapy should be avoided in certain settings where combination therapy is indicated 2

Dosing Errors

• Underdosing in children: Using subtherapeutic doses (e.g., 80 mg for a 5-year-old) fails to achieve adequate concentrations and promotes resistance 6
• Not using high-dose regimen when indicated: Standard doses lead to treatment failure with resistant organisms 2, 6
• Incorrect suspension concentration: Verify 125/31 vs 250/62 formulation before calculating volume 6

Treatment Failure

• Failure to respond after 72 hours: Should prompt either a switch to alternative antimicrobial therapy or reevaluation with imaging, endoscopy, or culture 2, 8
• Not considering β-lactamase producers: Switch to amoxicillin-clavulanate if H. influenzae or M. catarrhalis suspected 2, 3

Resistance Concerns

• Antibiotic exposure early in life: May disrupt intestinal microbiota and contribute to long-term adverse health effects including inflammatory bowel disease, obesity, eczema, and asthma 2
• Promoting resistance: Use only when bacterial infection is proven or strongly suspected 1
• Antibiotics are responsible for >150,000 unplanned medical visits annually for medication-related adverse events in children 2