Why do children require higher amoxicillin (amoxicillin) doses than adults when using weight-based dosing?

From the Guidelines

Children require higher weight-based amoxicillin doses than adults because they metabolize and eliminate the drug more rapidly, with typical doses ranging from 40-90 mg/kg/day, as recommended by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America 1. When prescribing amoxicillin for children, higher mg/kg doses are needed to achieve similar blood concentrations and therapeutic effects as in adults. This difference occurs because children have proportionally larger livers relative to their body size, resulting in faster drug metabolism. Additionally, their kidneys filter blood more efficiently, leading to quicker elimination of medications from the bloodstream. Children also have different body composition with higher water content and lower fat percentage, affecting drug distribution. These physiological differences mean that without higher weight-based dosing, children would have subtherapeutic amoxicillin levels, potentially leading to treatment failure when fighting bacterial infections. Some key considerations for amoxicillin dosing in children include:

• For outpatient treatment of community-acquired pneumonia, amoxicillin is recommended at a dose of 90 mg/kg/day in 2 doses, with a maximum dose of 4 g/day 1.
• The British Thoracic Society guidelines also provide recommendations for amoxicillin dosing in children, with doses ranging from 125 mg to 250 mg or 8 mg/kg, three times a day, depending on the age and severity of the infection 1. As children grow and their metabolic processes mature, their dosing requirements gradually approach adult patterns, typically by adolescence. It's essential to follow the most recent and highest-quality guidelines, such as those from the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America 1, to ensure optimal treatment outcomes and minimize the risk of treatment failure or adverse effects. In clinical practice, the choice of antibiotic and dosing regimen should be individualized based on the specific patient's needs, the suspected or confirmed pathogen, and local resistance patterns, as outlined in the guidelines 1.

From the FDA Drug Label

Table 1 Patients Aged 3 Months (12 Weeks) and Older Infection Severity | Recommended Dosage for Adult and Pediatrics Patients Aged 3 Months and Older and Weight Greater than 40 kg | Recommended Dosage for Pediatric Patient Aged 3 Months and Older and Weight Less than 40 kg Ear/Nose/Throat | 500 mg every 12 hours or 250 mg every 8 hours | 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Skin/Skin Structure | 500 mg every 12 hours or 250 mg every 8 hours | 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours Genitourinary Tract | 500 mg every 12 hours or 250 mg every 8 hours | 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours

Severe | 875 mg every 12 hours or 500 mg every 8 hours | 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

Children may require a higher amoxicillin dose than adults when using weight-based dosing because the recommended dosage for pediatric patients is given in mg/kg/day, which can result in a higher total dose for children due to their smaller body size.

• For example, a child weighing 20 kg with a severe infection would require 45 mg/kg/day in divided doses every 12 hours, which is 900 mg/day.
• In contrast, an adult with a severe infection would require 875 mg every 12 hours, which is 1750 mg/day for a 70 kg adult, but 875 mg is a fixed dose, not dependent on the adult's weight.
• However, when considering the mg/kg dose, children may receive a higher dose per kilogram of body weight compared to adults, which is why they may require a higher dose when using weight-based dosing 2.

From the Research

Amoxicillin Dosing in Children

• Children may require higher amoxicillin doses than adults when using weight-based dosing due to various factors, including the need for effective treatment of infections and the pharmacokinetics of the drug 3, 4.
• The American Academy of Pediatrics recommends high-dose amoxicillin for the treatment of acute uncomplicated otitis media, with a dose of 80 to 90 mg/kg per day, which often exceeds the standard adult dose of 1500 mg/d 4.
• Studies have shown that children weighing 20 kg or less may receive higher mean daily doses of amoxicillin, with a mean daily dose of 74.2 mg/kg per day compared to 40.4 mg/kg per day for children weighing more than 20 kg 4.

Weight-Based Dosing

• Weight-based dosing is recommended for children to ensure that they receive an effective dose of amoxicillin, with dosing instructions based on body weight instead of age 3.
• The Netherlands paediatric formulary recommends a dose of 60 mg/kg/day in two divided doses for the treatment of common uncomplicated infections 3.
• Other studies have used different dosing regimens, such as 90/6.4 mg/kg/d in 2 divided doses for 10 days, which has been shown to be effective in treating bacterial acute otitis media in children 5, 6.

Comparison with Adult Dosing

• The standard adult dose of amoxicillin is often lower than the dose required for children, with a dose of 1500 mg/d compared to 80 to 90 mg/kg per day for children 4.
• Some studies have shown that primary care physicians may prescribe lower-than-recommended doses of amoxicillin for older children and those in higher weight categories 4.
• However, other studies have shown that high-dose amoxicillin can be effective in treating infections in children, with clinical success rates of 90.5% compared to 80.9% for azithromycin 5.