What is the appropriate amoxicillin dosage, administration schedule, contraindications, and common adverse effects for an adult without a known penicillin allergy?

Amoxicillin Dosing and Administration for Adults

For most adult bacterial infections, amoxicillin should be dosed at 500 mg three times daily or 875 mg twice daily, with treatment duration typically 7-10 days depending on the infection type. 1

Standard Adult Dosing Regimens

The FDA-approved dosing range for adults is 750 to 1750 mg/day divided every 8 to 12 hours. 1

• For uncomplicated respiratory tract infections: 500 mg every 8 hours or 875 mg every 12 hours 1
• For more severe infections or those requiring higher tissue penetration: 875 mg every 12 hours or 500 mg every 8 hours 1
• For skin and soft tissue infections: Standard dosing of 500 mg three times daily is appropriate 1

Specific Clinical Scenarios

Respiratory Infections

Amoxicillin is the first-line agent for acute bacterial rhinosinusitis and community-acquired pneumonia in adults without risk factors for resistant organisms. 2

• For sinusitis: Standard-dose amoxicillin (500 mg three times daily) is recommended for most patients 2
• For pneumonia: Dosing should be 500 mg three times daily for 7-10 days 2

Helicobacter pylori Infection

For H. pylori eradication, amoxicillin 1 gram is given twice daily (every 12 hours) with clarithromycin 500 mg and lansoprazole 30 mg for 14 days (triple therapy). 1

• Alternative dual therapy: 1 gram amoxicillin with 30 mg lansoprazole, both given three times daily (every 8 hours) for 14 days 1

Skin and Soft Tissue Infections

For cellulitis and erysipelas, penicillin is the treatment of choice, but when broader coverage is needed, amoxicillin can be used at standard doses. 2

• For animal or human bite wounds: Amoxicillin-clavulanate is preferred over amoxicillin alone due to beta-lactamase-producing organisms 2

Renal Dose Adjustments

Patients with severe renal impairment (GFR <30 mL/min) require dose reduction. 1

• For GFR 10-30 mL/min: Reduce frequency to every 12 hours or decrease dose by 50% 3
• For GFR <10 mL/min: Reduce frequency to every 24 hours or decrease dose by 75% 3
• Hemodialysis patients: Require supplemental dosing after each dialysis session 3

Absolute Contraindications

Amoxicillin is absolutely contraindicated in patients with a history of serious hypersensitivity reactions (anaphylaxis or Stevens-Johnson syndrome) to amoxicillin or other beta-lactams. 1

• Cross-reactivity with cephalosporins: Historically cited at 10%, but recent data suggest this is an overestimate, with actual rates being much lower 2
• For true penicillin allergy: Alternative agents include doxycycline, fluoroquinolones (levofloxacin, moxifloxacin), or macrolides depending on the infection 2

Common Adverse Effects

The most common adverse reactions (>1%) are diarrhea, rash, vomiting, and nausea. 1

Gastrointestinal Effects

• Diarrhea: Most frequent adverse effect, occurring in 15-40% of patients 3
• Nausea and vomiting: Common but rarely require discontinuation 1

Dermatologic Reactions

• Maculopapular rash: Occurs in a small percentage of patients 1
• Severe cutaneous adverse reactions (SCAR): Rare but serious; discontinue immediately if rash progresses 1

Serious Adverse Effects

• Clostridioides difficile-associated diarrhea (CDAD): Can range from mild diarrhea to fatal colitis; evaluate if diarrhea develops during or after treatment 1
• Anaphylaxis: Serious and occasionally fatal reactions have been reported; discontinue immediately if suspected 1

Important Drug Interactions

Probenecid coadministration is not recommended as it increases amoxicillin serum levels by decreasing renal tubular secretion. 1

• Oral anticoagulants: Concomitant use may increase prothrombin time prolongation; monitor INR closely 1
• Allopurinol: Increases risk of rash; use caution with coadministration 1
• Oral contraceptives: Amoxicillin may reduce efficacy; advise patients to use backup contraception 1

Treatment Duration by Infection Type

Duration varies by infection severity and location:

• Acute bacterial sinusitis: 5-7 days is as effective as 10 days for uncomplicated cases 2, 3
• Community-acquired pneumonia: 7-10 days, may extend to 14 days based on clinical response 2, 3
• Skin and soft tissue infections: 7-10 days typically 2
• Urinary tract infections: 3-7 days for uncomplicated cases 3

Critical Clinical Considerations

Reassess patients who fail to improve or worsen after 48-72 hours of therapy. 2

• Treatment failure indicators: Progression of symptoms, onset of new symptoms, or lack of improvement by day 3 2
• When to escalate therapy: Consider amoxicillin-clavulanate or alternative agents if no improvement by 72 hours 2
• Risk factors for resistant organisms: Recent antibiotic use (within 30 days), daycare attendance, age >65 years, comorbidities, or immunocompromised status warrant consideration of higher doses or alternative agents 2, 3

Administration Guidance

Amoxicillin can be taken with or without food, which improves compliance. 1

• Suspension formulation: Shake well before each use; refrigeration improves palatability but is not required 1
• Adherence counseling: Emphasize completing the full course even if symptoms improve 2