What is the incidence of vomiting in children taking co‑amoxiclav (amoxicillin + clavulanic acid) and how should it be managed?

Co-Amoxiclav in Children: Vomiting Incidence and Management

Co-amoxiclav (amoxicillin-clavulanate) causes gastrointestinal adverse events including vomiting in approximately 22-44% of pediatric patients, significantly higher than amoxicillin alone, and should be managed by continuing therapy if tolerable or switching to alternatives like clindamycin or cephalosporins if symptoms are severe. 1, 2

Incidence of Vomiting and Gastrointestinal Effects

• Gastrointestinal adverse events occur in 22.4% of children treated with co-amoxiclav compared to 11.7% with azithromycin in acute otitis media trials. 3

• High-dose co-amoxiclav (90/6.4 mg/kg/day) causes adverse events in 44% of children compared to 14% in placebo groups, with vomiting, diarrhea, rash, and abdominal pain being the most common. 1, 2

• Diarrhea is the most frequent gastrointestinal complaint, occurring in 32 cases with co-amoxiclav versus only 5 cases with azithromycin in comparative studies. 3

• The clavulanate component specifically causes dose-dependent gastrointestinal toxicity through direct irritation and disruption of normal intestinal flora. 4

Age-Specific Risk Stratification

• Children aged 0-5 years have the highest risk of adverse events with co-amoxiclav (RR 1.23,95% CI 1.10-1.37). 2

• Children aged 6-11 years show intermediate risk (RR 1.19,95% CI 1.04-1.35). 2

• Adolescents aged 12-17 years have the lowest risk (RR 1.04,95% CI 0.95-1.14), though still elevated compared to amoxicillin alone. 2

Management Strategy for Vomiting

Mild to Moderate Vomiting

• Continue co-amoxiclav if clinically necessary while monitoring symptoms, as most gastrointestinal effects are self-limited and do not require discontinuation. 4

• Switch to twice-daily dosing rather than three-times-daily administration, as diarrhea and vomiting are generally less frequent with the twice-daily high-dose formulation (90/6.4 mg/kg/day). 5

• Administer with food to minimize gastrointestinal irritation, though this is not explicitly stated in guidelines, it follows standard clinical practice for reducing GI side effects.

Severe or Persistent Vomiting

• Switch to clindamycin 300 mg twice daily for 10 days (adults/adolescents) as the preferred alternative, which achieves 92.6% clinical cure rates with only 8.6% diarrhea incidence. 4

• Consider cefuroxime or cefaclor as second-line alternatives with lower gastrointestinal side effects than co-amoxiclav. 6, 4

• Avoid azithromycin as first-line replacement due to inadequate coverage for common respiratory pathogens and cardiac risks, despite its lower GI side effect profile. 4

When Vomiting Prevents Oral Absorption

• Switch to intravenous antibiotics when the child cannot absorb oral medications due to vomiting or presents with severe signs and symptoms. 6

• Appropriate IV options include co-amoxiclav 30 mg/kg TDS, cefuroxime 20-30 mg/kg TDS, or cefotaxime for severe infections. 6

Critical Clinical Pitfalls

• Do not discontinue antibiotics prematurely for mild gastrointestinal symptoms, as this increases treatment failure risk without improving outcomes. 4

• Test for C. difficile toxin if diarrhea is moderate to severe, bloody, or accompanied by fever before switching antibiotics. 4

• Avoid commercial wipes on irritated skin if diaper rash develops; use emollient ointment and gentle patting motions instead. 7

• Do not use shorter antibiotic courses (3-5 days) as alternatives, as 7-10 day courses are superior for complete symptom resolution. 4

Dosing Reference for Co-Amoxiclav

• Children <1 year: 2.5 ml/kg of 125/31 suspension TDS 6
• Children 1-6 years: 5 ml of 125/31 suspension TDS 6
• Children 7-12 years: 5 ml of 250/62 suspension TDS 6
• Adolescents 12-18 years: 1 tablet (250/125) TDS 6
• High-dose pediatric formulation: 90 mg/kg/day amoxicillin with 6.4 mg/kg/day clavulanate in two divided doses 6, 1

Balancing Efficacy Against Adverse Events

• Co-amoxiclav shows no superiority over amoxicillin alone for treatment failure rates in acute sinusitis (RR 0.98,95% CI 0.92-1.05), but has significantly higher adverse event rates. 2

• Reserve co-amoxiclav for specific indications: recurrent/persistent infections after amoxicillin failure, suspected β-lactamase-producing organisms, or severe pneumonia requiring broader coverage. 6, 5

• Use amoxicillin alone as first-line when S. pneumoniae is the likely pathogen, as it is better tolerated with equivalent efficacy. 6