Paediatric Drug Dosing

Introduction

Still vivid in my mind, when comes to paediatric dosing, we should not treat a child as a "mini adult".

  • As children mature physically, their physiological systems develop at varying rates.
  • In general, absorption, plasma protein binding, metabolism and excretion are lower in children. Hence, maintenance dosage (on a mg/kg/day basis) are generally smaller than those of adults.



Difference in Drug Dosing Recommendations

If one is trying to design a paediatric dosing calculator, you will face a scenario: which source of reference should I use to calculate dosing for children.

  • Depending on the reference that you are using, the dosing is different and hence, dosing children is more complicated than adults.
  • Often, the paediatric dosing used could be influenced by your institution practice.

I still remember that few years back, I was arguing with my colleague that desloratadine syrup should be only given to children above 1 years old since the dose is

  • 1.25 mg once a day for 1-5 years
  • 2.5 mg once a day for 6-11 years
  • 5 mg once a day for 12 years and above.

She, on the hand, showed me the Frank Shann Drug Doses 2017, which writes 0.1 mg/kg (adult 5 mg) daily oral.

More examples are listed below.

Cephalexin (oral) for UTI prophylaxis

Folic acid (oral)

  • British National Formulary for Children 2020-2021: Folate-deficiency megaloblastic anaemia
    • Neonate, initially 500 micrograms/kg once daily for up to 4 months
    • Child 1-11 months, initially 500 micrograms/kg once daily (max. per dose 5 mg) for up to 4 months, doses up to 10 mg daily may be required in malabsorption states.
    • Child 1-17 years, 5 mg daily for 4 months (until term in pregnant women), doses up to 15 mg daily be required in malabsorption states.
  • Frank Shann Drug Doses, 2017: NOT/kg. Deficiency: 50 mcg (neonate), 0.1-0.25 mg (<4yr), 0.5-1 mg (>4yr) daily IV, IM, SC or oral.

Loratadine

  • British National Formulary for Children 2020-2021: Symptomatic relief of allergy such as hay fever, chronic idiopathic urticaria
    • Child 2-11 years (body-weight up to 31 kg), 5 mg once daily.
    • Child 2-11 years (body-weight 31 kg and above), 10 mg once daily.
    • Child 12-17 years, 10 mg once daily.
  • Frank Shann Drug Doses, 2017: NOT/kg, 2.5 mg (1 yr-12 kg), 5 mg (12-30 kg), 10 mg (>30 kg) daily oral.

Spironolactone (oral)

  • Paediatric Protocols for Malaysian Hospitals, 2019: 1 mg/kg/dose BD as anti-heart failure medication.
  • Frank Shann Drug Doses, 2017: NOT/kg, 0-10 kg 6.25 mg 12H, 11-20 kg 12.5 mg 12H, 21-40 kg, 25 mg 12H, over 40 kg 25 mg 8H.
  • Neofax, 2020: 1 to 3 mg/kg/dose orally every 24 hours.
  • British National Formulary for Children 2020-2021:
    • Neonate, initially 1-2 mg/kg/daily in 1-2 divided doses; increased if necessary up to 7 mg/kg daily, in resistant ascites.
    • Child 1 month-11 years, initially 1-3 mg/kg daily in 1-2 divided doses; increased if necessary up to 9 mg/kg daily, in resistant ascites.
    • Child 12-17 years, initially 50-100 mg daily in 1-2 divided doses; increased if necessary up to 9 mg/kg daily, in resistant ascites; maximum 400 mg per day.

Paracetamol - rectal route

  • Frank Shann Drug Doses, 2017: 40 mg/kg stat, then 30 mg/kg 6H (max 5 g/day).
  • Lexicomp, 2021: Pain (mild to moderate) or fever
    • Weight-directed dosing: Limited data available: Infants and Children <12 years: 10 to 20 mg/kg/dose every 4 to 6 hours as needed; do not exceed 5 doses in 24 hours; maximum daily dose: 75 mg/kg/day not to exceed 1,625 mg/day.
    • Fixed dosing:
      • Infants 6 to 11 months: 80 mg every 6 hours; maximum daily dose: 320 mg/day.
      • Infants and Children 12 to 36 months: 80 mg every 4 to 6 hours; maximum daily dose: 400 mg/day.
      • Children >3 to 6 years: 120 mg every 4 to 6 hours; maximum daily dose: 600 mg/day.
      • Children >6 up to 12 years: 325 mg every 4 to 6 hours; maximum daily dose: 1,625 mg/day.
      • Children ≥12 years and Adolescents: 650 mg every 4 to 6 hours; maximum daily dose: 3,900 mg/day.
  • British National Formulary for Children 2020-2021: Pain or pyrexia with discomfort
    • Neonate 28 weeks to 32 weeks corrected gestational age: 20 mg/kg for 1 dose, then 10-15 mg/kg every 12 hours as required, maximum daily dose to be given in divided doses; maximum 30 mg/kg per day.
    • Neonate 32 weeks corrected gestational age and above: 30 mg/kg for 1 dose, then 15-20 mg/kg every 8 hours as required, maximum daily dose to be given in divided doses; maximum 60 mg/kg per day.
    • Child 1-2 months: 30-60 mg every 8 hours as required, maximum daily dose to be given in divided doses; maximum 60 mg/kg per day
    • Child 3-11 months: 60-125 mg every 4-6 hours as required; maximum 4 doses per day
    • Child 1-4 years: 125-250 mg every 4-6 hours as required; maximum 4 doses per day
    • Child 5-11 years: 250-500 mg every 4-6 hours as required; maximum 4 doses per day
    • Child 12-17 years: 500 mg every 4-6 hours
  • Two recent clinical trials suggested that single doses of oral (15 mg/kg) and rectal (15 mg/kg or 30-35 mg/kg) acetaminophen all have a similar effect on temperature decline in children.



Key Messages

Paediatric doses are generally based on

  • body-weight (in kg)
  • specific age ranges.
  • and occasionally, body surface area (e.g. cytotoxic drugs)

Sometimes, adult doses are written next to paediatric dosing.

  • This is because for most drugs, the adult maximum dose should not be exceeded.
  • For example, if the dose is stated as 8 mg/kg (max. 300 mg), a child weighing 10 kg should receive 80 mg but a child weighing 40 kg should receive 300 mg (rather than 320 mg).

Of note, the per-kilogram total daily (e.g. mg of medicine per kg of child weight) may differ by age strata, e.g. infants may require a separate dose size +/- frequency due to immaturity of clearance mechanisms.

NOTE: Calculated doses of liquid medicines should be rounded down to the nearest whole number, where appropriate, for ease of measuring.



Can Paediatric Dosing Exceed Adult Doses?

For most drugs, the adult maximum dose should not be exceeded.

However, there are some exceptions to this rule.

  • To achieve therapeutic serum concentrations, larger loading doses (on a mg/kg basis) are needed for some medications. The volume of distribution for these medications is larger in neonates than adults.
    • Aminoglycosides are water-soluble and have a larger volume of distribution because neonates have increased total body water and extracellular fluid volume.
  • The maintenance dose of digoxin is higher in neonates and infants because of the lower affinity of myocardial receptors for digoxin and increased number of digoxin binding sites on neonatal erythrocytes.



Summary

Whenever possible, medicines for children should be prescribed within the terms of marketing authorization (product license). However, in reality, many drugs are used off-label for the neonate and paediatric population.

  • There is a helpful description of what "off-label" means for children and parents on the Medicines For Children website.



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