19.3 Pediatric Pharmacology & Prescribing/Dosing
Key Takeaways
- Pediatric drugs are dosed by weight (mg/kg) rather than fixed adult doses because body water, protein binding, enzyme maturity, and renal clearance all change dramatically from the neonatal period through adolescence.
- Neonates have immature hepatic CYP450/glucuronidation pathways and a low glomerular filtration rate (GFR), so many drugs are cleared more slowly and require reduced doses or longer dosing intervals.
- For a 12 kg child receiving paracetamol at 15 mg/kg/dose, the correct single dose is 180 mg, and the total daily dose must also be checked against the roughly 75 mg/kg/day maximum.
- Prescribing errors classically arise from missing or extra decimal points, mg-versus-mcg confusion, and using a child's weight in pounds instead of kilograms.
- Aspirin is linked to Reye syndrome in children with viral illness, tetracyclines stain developing teeth in children under 8 years, and fluoroquinolones carry a theoretical cartilage-toxicity risk in growing children.
Pediatric Pharmacology & Prescribing/Dosing
Why Weight-Based (mg/kg) Dosing
Children are not simply small adults: body composition, organ function, and enzyme maturity change continuously from the newborn period through adolescence. Because a fixed adult dose could be dangerously wrong for a 3 kg neonate or a 40 kg adolescent, nearly all pediatric drug doses are calculated per kilogram of body weight (mg/kg/dose or mg/kg/day). A small number of high-risk drugs, such as chemotherapy agents, are instead dosed by body surface area (BSA, in m²), because BSA correlates better with metabolic rate and organ size across a wide weight range.
Key Pharmacokinetic Differences From Adults
| Pharmacokinetic phase | Pediatric difference | Clinical consequence |
|---|---|---|
| Absorption | Higher (less acidic) gastric pH in neonates; irregular gastric emptying; thin skin and high surface-area-to-weight ratio in infants | Altered absorption of acid-labile drugs; increased risk of toxicity from topical or percutaneous agents in infants |
| Distribution | Higher total body water (about 75–80% of body weight in neonates vs. 55–60% in adults); lower plasma albumin | Larger volume of distribution for water-soluble drugs (e.g., aminoglycosides), needing higher mg/kg doses than adults; more free (unbound) drug for highly protein-bound agents |
| Metabolism | Immature hepatic cytochrome P450 (CYP450) and glucuronidation pathways at birth, maturing over months to years | Neonates metabolize many drugs slowly (toxicity risk, e.g., chloramphenicol causing gray baby syndrome); children aged 1–10 years sometimes metabolize certain drugs (e.g., theophylline, phenytoin) faster per kg than adults, needing higher mg/kg doses |
| Excretion | Glomerular filtration rate (GFR) is only about 30% of the adult (BSA-corrected) value at birth, reaching adult levels by 6–12 months of age | Renally cleared drugs (aminoglycosides, penicillins, vancomycin) need reduced doses or extended dosing intervals in neonates, especially if born preterm |
Worked Weight-Based Dosing Example
Paracetamol (acetaminophen) is dosed at 15 mg/kg/dose every 4–6 hours, up to a maximum daily dose of about 75 mg/kg/day (or 4 g, whichever is lower).
For a child weighing 12 kg:
- Single dose = 15 mg/kg × 12 kg = 180 mg per dose
- If dosed every 6 hours (4 doses per day): daily total = 180 mg × 4 = 720 mg/day
- Maximum allowed for this child = 75 mg/kg × 12 kg = 900 mg/day, so 720 mg/day is safely below the ceiling.
Exam Alert: Always calculate BOTH the single dose AND the total daily dose, and check the daily total against the weight-based maximum — a single dose can look correct while the prescribed frequency pushes the child over the daily ceiling.
Body Surface Area Dosing
For drugs where BSA is a better predictor of exposure than weight alone (classically chemotherapy, and some drugs in oncology or transplant protocols), the Mosteller formula is the version most often quoted on exams:
BSA (m²) = √[(height in cm × weight in kg) ÷ 3600]
Because BSA changes less steeply with weight than a simple mg/kg calculation, BSA-based dosing helps avoid relative overdosing in very small infants and relative underdosing in larger children for these specific drug classes.
Therapeutic Drug Monitoring
Several pediatric drugs have a narrow therapeutic index — small dose changes produce toxicity or treatment failure. Aminoglycosides (gentamicin, tobramycin) and vancomycin require trough (and sometimes peak) level monitoring because neonatal and infant renal clearance is unpredictable. Phenytoin, theophylline, and some antiepileptics similarly need level checks after dose changes. On the exam, a vignette describing a neonate on gentamicin with rising creatinine or vestibular toxicity should prompt you to check drug levels and extend the dosing interval rather than simply continuing the same mg/kg dose.
Common Prescribing-Error Traps
- Decimal point errors: a misplaced or missing decimal point causes a tenfold dosing error. Always use a leading zero (write
0.5 mg, never.5 mg, which can be misread as 5 mg) and never use a trailing zero (write5 mg, never5.0 mg, which can be misread as 50 mg). - Unit confusion: milligram (mg) versus microgram (mcg) mix-ups cause a thousandfold error and are especially dangerous with drugs dosed in mcg/kg, such as fentanyl and epinephrine; mL is sometimes confused with mg when a drug's concentration is not clearly specified.
- Weight in the wrong unit: always convert pounds to kilograms (kg = lb ÷ 2.2) BEFORE calculating a mg/kg dose — using a child's weight in pounds as if it were kilograms produces a roughly 2.2-fold overdose.
- Forgetting the adult-dose ceiling: once a child's weight approaches adult size, a mg/kg calculation can exceed the standard adult dose; the LOWER of the two values should be used.
- Look-alike/sound-alike drug names, and failure to adjust doses for renal or hepatic impairment, are additional recurring exam traps.
- An independent double-check — a second clinician independently recalculating the dose from the child's weight before a high-risk drug (e.g., insulin, opioids, chemotherapy, concentrated electrolytes) is given — is a standard hospital safety practice specifically because pediatric weight-based calculations are so error-prone.
Classically Tested Pediatric Drug Facts
| Drug/class | Age group affected | Key fact |
|---|---|---|
| Aspirin (salicylates) | Children/adolescents with a viral illness (e.g., varicella, influenza-like illness) | Associated with Reye syndrome (acute encephalopathy with fatty liver); use paracetamol or ibuprofen for fever and pain instead |
| Tetracyclines (including doxycycline) | Children under 8 years, during tooth development | Permanent tooth discoloration (yellow-gray-brown) and enamel hypoplasia; the drug binds calcium in developing teeth and bone |
| Fluoroquinolones (e.g., ciprofloxacin) | Children and adolescents with open growth plates | Cartilage/joint damage (arthropathy) shown in juvenile animal studies; historically reserved for specific indications such as complicated urinary tract infection, cystic fibrosis with pseudomonas, or anthrax exposure |
| Chloramphenicol | Neonates | Gray baby syndrome — cardiovascular collapse from immature hepatic glucuronidation |
| Sulfonamides | Neonates, especially if jaundiced | Displace bilirubin from albumin, raising the risk of kernicterus |
| Codeine | Children, especially after tonsillectomy/adenoidectomy | Ultra-rapid CYP2D6 metabolizers convert codeine to morphine quickly, causing fatal respiratory depression; codeine is now contraindicated in children |
Understanding WHY each rule exists — immature enzymes, calcium binding, cartilage vulnerability, or displacement of bilirubin — makes it far easier to recall the fact under exam pressure than memorizing an isolated list.
Which pharmacokinetic factor explains why neonates require different, often reduced, doses of renally cleared drugs such as aminoglycosides?
A 12 kg child is prescribed paracetamol at 15 mg/kg/dose. What is the correct single dose?
A 6-year-old is being treated for a presumed viral infection with fever. Which analgesic/antipyretic should be AVOIDED because of the risk of Reye syndrome?
A tetracycline antibiotic is prescribed to a 5-year-old child. Which adverse effect is this age group specifically at risk for?