How should I calculate and prescribe weight‑based medication doses, considering the patient’s age, renal and hepatic function, obesity, and other comorbidities?

Weight-Based Medication Dosing in Clinical Practice

Calculate pediatric doses using mg/kg based on actual body weight in kilograms for children under 40 kg, then transition to body surface area (BSA) normalization after age 6 months for most drugs, with critical exceptions for specific drug classes and patient populations requiring adjusted body weight calculations. 1

Core Dosing Principles by Age and Development

Infants and Young Children (Birth to 2 Years)

• For hydrophilic drugs with high volume of distribution (Vd) in adults, normalize doses to actual body weight (kg) in children under 2 years of age. 1
• For hydrophilic drugs with low Vd in adults, normalize doses to BSA in this age group. 1
• Drugs primarily metabolized by the liver require extreme caution until 2 months of age; base dosing on therapeutic drug monitoring and clinical response rather than standard weight-based calculations. 1
• Between 2-6 months of age, use body weight (kg) as the primary dosing metric for most medications. 1
• Documenting weight in kilograms (not pounds) significantly reduces dosing errors, particularly in infants where error rates drop from 53% to 33% when weight is properly documented. 2

Children 6 Months to 2 Years

• After 6 months of age, BSA becomes the preferred metric for most medications, providing more accurate dosing than weight alone. 1
• Critical exception: Drugs metabolized by CYP2D6 or UGT (uridine diphosphate glucuronosyltransferase) should continue to be dosed by body weight (kg) even after 6 months. 1
• For renally excreted drugs in the first 2 years of life, determine dosing based on actual renal function markers (serum creatinine, p-aminohippuric acid clearance) rather than age-based estimates. 1

Children Over 2 Years and Adolescents

• After renal and hepatic maturation is complete (approximately 2 years), normalize doses to BSA for most medications. 1
• Transition to adult dosing protocols when patients exceed 40 kg, but never exceed maximum adult doses regardless of weight. 3, 4

Obesity-Specific Dosing Adjustments

Determining Which Body Weight to Use

• For lipophilic drugs in obese children, expect higher Vd and use total body weight (TBW) for initial dosing of antineoplastics, cefazolin, and succinylcholine. 5
• For hydrophilic drugs in obese children, expect lower Vd relative to TBW; consider using ideal body weight (IBW) or adjusted body weight. 5
• For aminoglycosides (e.g., tobramycin) in obese patients, calculate initial doses using adjusted body weight: IBW + 0.4 × (TBW - IBW), then monitor serum concentrations. 5
• For fluoroquinolones (e.g., levofloxacin) in severely obese patients (BMI ≥40 kg/m²), estimate creatinine clearance using the Cockcroft-Gault equation with IBW, not TBW, to avoid underdosing. 6

Practical Obesity Dosing Algorithm

1. Calculate IBW using height-based formulas appropriate for age and sex. 5
2. Determine if the drug is lipophilic (distributes to fat) or hydrophilic (distributes to water compartments). 5
3. For lipophilic drugs: use TBW for dosing calculations. 5
4. For hydrophilic drugs: use IBW or adjusted body weight [IBW + 0.4 × (TBW - IBW)]. 5, 6
5. Apply therapeutic drug monitoring when available, especially for narrow therapeutic index drugs. 6

Renal and Hepatic Impairment Considerations

Renal Dosing Adjustments

• In the first 2 years of life, calculate renal function using measured serum creatinine and validated pediatric formulas, not adult equations. 1
• For renally cleared drugs after age 2, adjust doses based on estimated glomerular filtration rate (eGFR) normalized to BSA. 1
• In obese patients with renal impairment, use IBW-based creatinine clearance estimates (Cockcroft-Gault with IBW) to avoid overestimating renal function. 6
• Specific example: Reduce oseltamivir dose to 30-75 mg (based on weight) once daily when creatinine clearance is <30 mL/min. 7

Hepatic Dosing Adjustments

• Drugs primarily metabolized by immature enzyme systems (CYP2D6, UGT) in infants <2 months require individualized dosing based on therapeutic monitoring, not standard calculations. 1
• For patients with severe hepatic dysfunction, reduce doses of hepatically cleared drugs (e.g., rimantadine to 100 mg/day) and monitor closely for adverse effects. 7
• Most anticancer drugs require empiric dose reductions in hepatic impairment due to altered pharmacokinetics and narrow therapeutic indices. 8

Medication-Specific Examples from Guidelines

Augmentin (Amoxicillin-Clavulanate)

• Standard dosing: 45 mg/kg/day of amoxicillin component divided twice daily for a 25 kg child with normal renal function. 3
• High-dose regimen: 90 mg/kg/day divided twice daily when drug-resistant Streptococcus pneumoniae is suspected or for recent antibiotic exposure within 4-6 weeks. 3
• Never use adult fixed doses for children under 40 kg; always calculate based on mg/kg. 3

Azithromycin

• Standard 5-day course: 10 mg/kg (max 500 mg) on day 1, then 5 mg/kg (max 250 mg) daily on days 2-5 for atypical pneumonia. 9
• Weight-band dosing for children 15-25 kg: 200 mg once daily; 26-35 kg: 300 mg once daily; 36-45 kg: 400 mg once daily; ≥46 kg: 500 mg once daily. 9
• Do not underdose the day 1 loading dose; full 10 mg/kg is essential for therapeutic tissue levels. 9

Influenza Antivirals

• Amantadine/rimantadine: 5 mg/kg/day (max 150 mg/day) in children 1-9 years, divided into two doses. 7
• Oseltamivir dosing by weight: <15 kg = 30 mg twice daily; 15-23 kg = 45 mg twice daily; 23-40 kg = 60 mg twice daily; >40 kg = 75 mg twice daily. 7

IV Paracetamol (Acetaminophen)

• Loading dose: 15-20 mg/kg (max 1000 mg per dose) for adolescents, which equals 600-800 mg for a 40 kg patient. 4
• Maintenance: 10-15 mg/kg every 6-8 hours (400-600 mg every 6-8 hours for a 40 kg patient). 4

Critical Pitfalls to Avoid

Documentation and Calculation Errors

• Always document weight in kilograms, not pounds; conversion errors contribute to 26% of pediatric dosing mistakes versus 22% when kg is used. 2
• Epinephrine and fentanyl have the highest error rates (56% and 31% respectively) when weight is not properly documented. 2
• Double-check that calculated doses do not exceed maximum adult doses, even in large adolescents. 3, 9

Age-Specific Mistakes

• Do not extrapolate adult dosing to children under 40 kg or under 12 years of age without weight-based calculations. 3
• Avoid using standard weight-based formulas for hepatically metabolized drugs in infants <2 months; these require therapeutic drug monitoring. 1
• Do not use TBW for creatinine clearance calculations in obese patients; this overestimates renal function and leads to overdosing of renally cleared drugs. 6

Drug-Specific Errors

• Never use azithromycin as first-line for typical bacterial pneumonia (S. pneumoniae, H. influenzae); amoxicillin 90 mg/kg/day is superior. 9
• Do not prescribe high-dose Augmentin (90 mg/kg/day) for all infections; reserve for drug-resistant pathogens or recent antibiotic exposure. 3
• Avoid administering azithromycin simultaneously with aluminum- or magnesium-containing antacids; separate by at least 2 hours. 9

Practical Dosing Workflow

1. Obtain accurate weight in kilograms using a calibrated scale. 2
2. Assess patient age to determine if maturation affects drug metabolism (critical under 2 years). 1
3. Evaluate renal function using age-appropriate markers (serum creatinine, eGFR). 1
4. Assess hepatic function, particularly for drugs with significant hepatic metabolism. 8, 1
5. Determine if obesity is present (BMI ≥95th percentile for age or BMI ≥40 kg/m² in adults). 5, 6
6. Select appropriate body size descriptor: actual weight (kg), IBW, adjusted body weight, or BSA based on drug properties and patient age. 1, 5
7. Calculate dose using mg/kg or BSA-based formula, applying renal/hepatic adjustments as needed. 7, 3, 9, 4
8. Verify calculated dose does not exceed maximum adult dose. 3, 9
9. Apply therapeutic drug monitoring for narrow therapeutic index drugs when available. 6
10. Reassess clinical response within 48-72 hours and adjust if no improvement. 9