What is the recommended dosage and treatment duration for amoxicillin (amoxicillin) clavulanate and clarithromycin (clarithromycin) combination therapy?

Amoxicillin-Clavulanate and Clarithromycin Combination Therapy

When used together for chronic rhinosinusitis, amoxicillin-clavulanate 625 mg three times daily combined with clarithromycin 500 mg daily for 3 weeks shows equivalent clinical efficacy to either agent alone, though this combination is not routinely recommended as standard therapy. 1

Evidence for Combination Therapy

The primary evidence for combining these agents comes from chronic rhinosinusitis treatment, where a head-to-head trial demonstrated no statistically significant differences in clinical improvement between clarithromycin 500 mg daily for 3 weeks versus amoxicillin-clavulanate 625 mg three times daily for 3 weeks when used as monotherapy. 1 This suggests that combining them may not provide additional benefit over either agent alone for this indication.

Standard Dosing Regimens When Used Separately

Amoxicillin-Clavulanate Dosing

For respiratory tract infections and moderate-to-severe infections:

• 875 mg/125 mg twice daily is the preferred formulation for adults 2
• Alternative: 500 mg/125 mg three times daily 2
• Duration: 5-7 days for most respiratory infections 1
• The twice-daily formulation provides equivalent efficacy with improved gastrointestinal tolerability compared to three-times-daily dosing 3, 4

For community-acquired pneumonia with comorbidities:

• Amoxicillin-clavulanate 875 mg/125 mg twice daily or 2,000 mg/125 mg twice daily combined with a macrolide (azithromycin or clarithromycin) for 5-7 days 1

Clarithromycin Dosing

For respiratory infections:

• Standard dose: 500 mg twice daily 1
• Extended-release: 1,000 mg once daily 1
• Duration: 7-14 days for most respiratory infections 1

For atypical pathogens (Mycoplasma, Chlamydophila):

• 500 mg twice daily for 10 days 1

Specific Clinical Scenarios Where Both May Be Considered

H. pylori Eradication

Triple therapy is the standard approach when both agents are used together:

• Amoxicillin 1,000 mg twice daily + clarithromycin 500 mg twice daily + PPI (standard dose twice daily) for 14 days 1, 5
• This regimen is recommended as first-line therapy when clarithromycin resistance is low (<15%) 1
• Start therapy 72-96 hours after intravenous PPI administration in bleeding peptic ulcer cases 1

Community-Acquired Pneumonia

Combination β-lactam plus macrolide therapy:

• Amoxicillin-clavulanate 875 mg/125 mg twice daily + clarithromycin 500 mg twice daily for 5-7 days 1
• This combination is recommended for outpatients with comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia) 1

Important Clinical Considerations

Gastrointestinal tolerability:

• The 875 mg/125 mg twice-daily formulation of amoxicillin-clavulanate causes significantly less diarrhea than three-times-daily dosing due to lower total daily clavulanate exposure 3, 4
• Clarithromycin causes fewer gastrointestinal side effects than amoxicillin-clavulanate when compared head-to-head (21% vs 38%, P<0.001) 6

Renal dosing adjustments:

• For GFR <30 mL/min: Do NOT use the 875 mg dose; reduce to 500 mg/125 mg every 12 hours 2
• For GFR <10 mL/min: 500 mg/125 mg every 24 hours 2
• Hemodialysis patients: Additional dose during and after dialysis 2

Administration timing:

• Amoxicillin-clavulanate should be taken at the start of meals to minimize gastrointestinal intolerance 2
• Clarithromycin can be taken with meals 1

Duration of Therapy

Standard durations based on indication:

• Acute exacerbations of chronic bronchitis: 5-7 days 7
• Community-acquired pneumonia: 5-7 days (if afebrile for 48 hours with clinical stability) 1
• Chronic rhinosinusitis: 3 weeks 1
• H. pylori eradication: 14 days 1, 5