Pediatric Prescribing

George Rylance · Forfar & Arneil 7th Edition | Pharmacokinetics · Absorption · Distribution · Metabolism · Excretion · Drug interactions · Breast milk · Unlicensed use · Off-label prescribing · Parent information
📌 Key principles: Children are not small adults – pharmacokinetics vary with age (neonates: reduced clearance, longer half-lives). Unlicensed/off-label prescribing common (>30%). Always inform parents, calculate doses by weight, consider therapeutic drug monitoring for narrow therapeutic index drugs.

📖 Pediatric Prescribing: Pharmacokinetics & Safety

💊 Age-related pharmacokinetics
Neonates: reduced gastric acidity, slower gut transit, immature hepatic metabolism (CYP450), reduced renal clearance → longer half-lives. Children 6m-2y: faster clearance than adults.
📐 Volume of distribution
Larger total body water in infants → higher Vd for water-soluble drugs (e.g., aminoglycosides). Loading dose = Vd × desired concentration.
⚖️ Clearance & half-life
Half-life = 0.693 × Vd / Cl. Neonates: longer half-life for renally cleared drugs (e.g., gentamicin) and hepatically cleared (e.g., theophylline).
⚠️ Unlicensed & off-label use
>30% of paediatric prescriptions off-label. Acceptable when supported by responsible professional opinion. Obtain informed consent, especially for novel use.
🤱 Drugs in breast milk
Most drugs safe. Contraindications: cytotoxics, radiopharmaceuticals, amfetamines, cocaine, ergotamine, lithium (caution), phenindione.
📊 Therapeutic drug monitoring (TDM): Indicated for narrow therapeutic index drugs (gentamicin, vancomycin, phenytoin, carbamazepine, ciclosporin). Measure at steady state (5 half-lives).

🔍 Rational approach to prescribing for children

1
Assess patient & indication – Is drug necessary? Consider non-pharmacological options. Identify target condition and desired outcome.
2
Choose appropriate drug & formulation – Use licensed product when possible. Consider liquid vs tablet, taste, dosing frequency, route (oral preferred).
3
Calculate dose by weight (or BSA) – Use current weight (kg). For neonates, gestation and postnatal age important. Check BNF for Children.
4
Consider pharmacokinetic differences – Neonates: reduced clearance → longer dosing interval. Children 1-10y: may need higher mg/kg dose due to faster clearance.
5
Check for drug interactions & allergies – Enzyme inducers (carbamazepine, rifampicin) reduce effect of oral contraceptives, warfarin. Avoid contraindicated combinations.
6
Provide clear information to child/parents – Name, dose, timing, duration, possible side effects, what to do if missed dose. Use written plan.
7
Monitor response & adjust – Therapeutic drug monitoring for narrow index drugs. Review for efficacy and adverse effects.
📌 Clinical pearl: Always write "actual body weight" on prescription. For neonates, record gestation and postnatal age. Use mg/kg/dose, not "ml" alone (concentration varies).

📋 Stepwise prescribing: from calculation to monitoring

1
Calculate loading dose – Loading dose = Vd × target concentration. Example: phenytoin Vd ~0.75 L/kg, target 20 mg/L → load 15 mg/kg IV.
2
Calculate maintenance dose – Maintenance dose = clearance × target concentration × dosing interval. Example: gentamicin Cl ~0.08 L/kg/h, target peak 8-12 mg/L.
3
Adjust for organ dysfunction – Renal impairment: reduce dose or prolong interval (e.g., gentamicin extended interval). Hepatic impairment: reduce dose for highly metabolised drugs.
4
Use therapeutic drug monitoring (TDM) – Measure trough (pre-dose) for gentamicin, vancomycin. Measure phenytoin at steady state (5-7 days).
5
Off-label prescribing – consent & documentation – Explain off-label status, evidence, risks/benefits. Document discussion in notes. Supported by professional opinion.
6
Prescribing in breast-feeding mothers – Avoid cytotoxics, radiopharmaceuticals, amfetamines, cocaine, ergotamine. Most others safe; time medication after breastfeed.
7
Information to give parents/child – Medicine name, what it does, how much (use syringe for liquids), when to take, for how long, possible side effects, who to contact.
⚠️ High-risk drugs requiring TDM: Gentamicin, vancomycin, phenytoin, carbamazepine, ciclosporin, tacrolimus, digoxin, lithium. Check local guidelines.

🧠 Reflex prompts: pediatric prescribing essentials

👶 A 3-day-old neonate requires gentamicin. How does clearance differ from older children?
Neonatal clearance is reduced (immature renal function). Half-life prolonged → extended interval dosing (e.g., 24-36h). Monitor trough levels.
📏 A 6-month-old infant weighs 7kg. Paracetamol dose (oral) is 15 mg/kg/dose. Calculate dose in mg and ml for 120mg/5ml solution.
Dose = 7 × 15 = 105mg. Volume = 105 ÷ 24 = 4.4ml (since 120mg/5ml = 24mg/ml).
💊 A mother is breast-feeding and needs an antidepressant. Which SSRI is generally preferred?
Sertraline or paroxetine have lowest excretion in breast milk. Avoid doxepin. Discuss with specialist.
⚠️ What is the concern with off-label prescribing in children?
Lack of safety and efficacy data, dosing uncertainty, potential for adverse effects. However, necessary for many paediatric conditions. Requires informed consent and documentation.
🧪 A child on phenytoin for epilepsy has breakthrough seizures. What drug level should be measured?
Trough phenytoin level (pre-dose). Therapeutic range 40-80 µmol/L (10-20 mg/L). Free phenytoin if hypoalbuminaemia.
🔄 Which drug is a potent enzyme inducer that reduces efficacy of oral contraceptives?
Carbamazepine, phenytoin, phenobarbital, rifampicin. Alternative contraception needed.
🍼 A 2-month-old with gastro-oesophageal reflux. Metoclopramide – what is the concern?
Extrapyramidal side effects (dystonic reactions) more common in infants. Use for short course only. Avoid if possible.
📊 What is the target vancomycin trough concentration for serious MRSA infection?
10-15 mg/L (or 15-20 for pneumonia/meningitis). Trough measured pre-4th dose.
💉 A child requires IV fluids. Why is 0.18% saline with 4% dextrose commonly used in maintenance?
Provides sodium (30 mmol/L) and glucose to prevent ketosis. Avoids hyponatraemia from hypotonic fluids (risk of cerebral oedema).
📝 What information must be documented when prescribing off-label?
Rationale, evidence base (if any), discussion with parents/child, risks and benefits, consent obtained. Sign and date.