Amoxicillin-Clavulanate Dosing in Neonates
For neonates, the recommended dose of amoxicillin-clavulanate is 30 mg/kg/day (based on the amoxicillin component) divided every 12 hours. 1
FDA-Approved Neonatal Dosing
- Neonates and infants aged <12 weeks (<3 months) should receive 30 mg/kg/day divided every 12 hours, based on the amoxicillin component 1
- The 125 mg/5 mL oral suspension formulation is specifically recommended for this age group, as experience with the 200 mg/5 mL formulation is limited 1
- The medication may be taken without regard to meals, though absorption of clavulanate is enhanced when administered at the start of a meal 1
Age-Specific Considerations for Dosing Intervals
Gestational age and postnatal age significantly affect amoxicillin clearance, which is critical for optimizing dosing:
- In neonates born after 30 weeks' gestation, clearance increases with postnatal age: 1.25-fold by day 10 and 1.43-fold by day 20 compared to day 3 2
- Current weight, postnatal age, and gestational age are all significant covariates affecting amoxicillin pharmacokinetics 3
- Twice-daily dosing (50 mg/kg/day in two divided doses) is superior to three or four times daily schedules in the first week of life for achieving pharmacodynamic targets 2
Clinical Context and Efficacy Data
The twice-daily regimen achieves adequate therapeutic levels:
- For early-onset sepsis using 25 mg/kg twice daily, 99.0% of premature neonates and 87.3% of term neonates achieve the pharmacodynamic target (time above MIC) at a MIC breakpoint of 1 mg/L 3
- For late-onset sepsis, 25 mg/kg three times daily in premature neonates and 25 mg/kg four times daily in term neonates achieves targets at MIC breakpoint of 2 mg/L 3
- Oral bioavailability is 87%, making oral administration a viable alternative to intravenous therapy 2
Important Caveats
Do not substitute different formulations or strengths, as they contain varying amounts of clavulanic acid:
- The 250 mg/125 mg tablet contains 125 mg clavulanic acid, while the 250 mg/62.5 mg chewable tablet contains only 62.5 mg 1
- Two 250 mg/125 mg tablets are not equivalent to one 500 mg/125 mg tablet due to the fixed clavulanate content 1
Twice-daily dosing reduces diarrhea compared to three-times-daily administration, improving tolerability without compromising efficacy 1, 4