Clarithromycin Has Superior GI Tolerability Compared to Clavulin in Infants
Clarithromycin demonstrates significantly better gastrointestinal tolerability than amoxicillin-clavulanate (Clavulin) in pediatric patients, with diarrhea occurring in only 12% of clarithromycin-treated children versus 32% with amoxicillin-clavulanate. 1
Direct Comparative Evidence
The most definitive evidence comes from a head-to-head randomized trial in 338 children aged 6 months to 12 years with acute otitis media:
- Diarrhea rates were nearly 3 times higher with Clavulin (32%) compared to clarithromycin (12%), a statistically significant difference (P < 0.001). 1
- Both medications showed comparable clinical efficacy (90% vs 92% success rates), making tolerability the key differentiating factor. 1
- Gastrointestinal adverse events were the most commonly reported side effects in both groups, but the frequency was markedly lower with clarithromycin. 1
Why Clavulanate Causes More GI Problems
The clavulanic acid component in Clavulin is the primary culprit for gastrointestinal side effects:
- Diarrhea becomes especially problematic when clavulanate doses exceed approximately 10 mg/kg per day. 2
- The American Academy of Otolaryngology-Head and Neck Surgery identifies GI side effects, particularly diarrhea, as the most common and problematic adverse effect of clavulanate. 2
- Three-times-daily dosing of amoxicillin-clavulanate is associated with significantly higher GI side effects compared to twice-daily dosing. 2
Additional Supporting Evidence
Multiple studies confirm this pattern across different pediatric populations:
- In adult comparative studies, amoxicillin/clavulanate showed 25% adverse event rates versus only 12.4% with other antibiotics (p=0.012), with GI events being the most common complaints. 3
- A study in children with urinary tract infections found GI disorders occurred in 12% of cases with amoxicillin-clavulanate, which required dosing adjustment from 12-hour to 8-hour intervals to manage symptoms. 4
- Clarithromycin maintains excellent tolerability even at higher-than-recommended doses (up to 30 mg/kg/day), with only 17.5% reporting adverse reactions (mainly GI), and no significant difference in tolerability between standard and high-dose groups. 5
Clinical Implications
When choosing between these antibiotics for infants:
- If both medications are clinically appropriate for the infection, clarithromycin should be preferred when GI tolerability is a concern. 1
- The newer 14:1 ratio formulation of high-dose amoxicillin-clavulanate (90/6.4 mg/kg/day) causes less diarrhea than older formulations, but this still doesn't match clarithromycin's tolerability profile. 6
- For infants requiring amoxicillin-clavulanate, using twice-daily dosing rather than three-times-daily reduces GI side effects. 2
Important Caveats
- Antibiotic selection should ultimately be based on the specific pathogen and infection type, not solely on tolerability. 1
- Clarithromycin may not provide adequate coverage for β-lactamase-producing organisms that require clavulanate for eradication. 7
- Most upper respiratory infections in children are viral and don't require antibiotics at all. 6