What is the recommended paracetamol dose, contraindications, and alternative therapy for children of all ages, including infants under two months?

Paracetamol Dosing and Management in Pediatrics

Recommended Dosing by Age and Route

For children 2 years and older, use 10-15 mg/kg per dose every 4-6 hours (maximum 60 mg/kg/day), with 15 mg/kg being the preferred dose for optimal efficacy in fever and pain management. 1, 2

Oral Dosing

• Children ≥12 years: 650 mg (20.3 mL of liquid) every 4-6 hours, not exceeding 6 doses in 24 hours 3
• Children 6 to <12 years: 325 mg (10.15 mL) every 4 hours, not exceeding 5 doses in 24 hours 3
• Children 4 to <6 years: 240 mg (7.5 mL) every 4 hours, not exceeding 5 doses in 24 hours 3
• Children 2 to <4 years: 160 mg (5 mL) every 4 hours, not exceeding 5 doses in 24 hours 3
• Children <2 years: Requires physician consultation per FDA labeling 3

Intravenous Dosing

• Loading dose: 15-20 mg/kg (using 10 mg/mL preparation) 1
• Maintenance: 10-15 mg/kg every 6-8 hours 1
• Maximum daily dose: 60 mg/kg/day 1
• Preparation: Can be diluted in 0.9% normal saline or 5% dextrose for smaller volumes in neonates 4
• Example calculation: For a 5 kg infant receiving 7.5 mg/kg = 37.5 mg = 3.75 mL of 10 mg/mL solution 4

Rectal Dosing

• Loading dose: 20-40 mg/kg (15 mg/kg if <10 kg) as single dose with anesthesia 1
• Note: Higher rectal loading dose compensates for poor bioavailability from rectal route 1

Special Populations: Infants Under 2 Months

Paracetamol dosing in neonates and young infants requires extreme caution due to immature hepatic metabolism and risk of cumulative toxicity. 5, 6

Neonates (0-4 weeks)

• Recommended dose: 30 mg/kg/day divided into doses achieves therapeutic concentrations 6
• Dosing interval: Every 8-12 hours due to prolonged elimination half-life (55-90 hours vs 30 hours in adults) 5
• Critical consideration: Neonates have reduced glucuronide conjugation but enhanced sulphation pathways, which is protective but still requires dose reduction 5
• Maximum daily dose: Do not exceed 60 mg/kg/day 6

Infants 1-3 Months

• Recommended dose: 60-65 mg/kg/day divided every 6-8 hours 6
• Alternative approach: 10-15 mg/kg per dose every 6-8 hours 5
• Important caveat: Rectal bioavailability is higher in very young infants than older patients, requiring dose adjustment if switching routes 5

Critical Safety Points for Young Infants

• Avoid cumulative toxicity: Doses exceeding 90-140 mg/kg/day for multiple consecutive days carry risk of hepatotoxicity 7, 6
• Therapeutic plasma concentration: Target 10-20 mg/mL for antipyretic and analgesic effects 5
• Monitoring: Close observation for signs of hepatotoxicity with repeated dosing, particularly in preterm infants with reduced clearance 5

Contraindications and Precautions

Absolute contraindications include known hypersensitivity to paracetamol and severe hepatic impairment. 7

Relative Contraindications

• Hepatic disease: Use with extreme caution; consider dose reduction or alternative therapy 7
• Renal impairment: Paracetamol can cause renal damage with cumulative toxicity; adjust dosing interval 6
• Chronic malnutrition: Depleted glutathione stores increase hepatotoxicity risk 7
• Concurrent hepatotoxic medications: Avoid or use with enhanced monitoring 7

Dosing Errors to Avoid

• Subtherapeutic dosing: Doses ≤10 mg/kg are less effective than NSAIDs; use 15 mg/kg for optimal efficacy 2
• Excessive daily dosing: Never exceed 90-95 mg/kg/day to prevent cumulative hepatotoxicity 7, 6
• Premature infant extrapolation: Do not extrapolate term infant dosing to premature infants due to immature renal function and drug accumulation risk 5
• Rapid IV administration: Avoid bolus injection; infuse over 15 minutes 1

Alternative Therapies

NSAIDs (Second-Line)

Ibuprofen is the preferred alternative when paracetamol is contraindicated or ineffective, but carries higher risk of adverse events with repeated use. 2, 7

• Ibuprofen dosing: 10 mg/kg every 8 hours (oral or rectal) 1
• Age restriction: Unlike paracetamol, ibuprofen is not indicated for all ages; avoid in infants <6 months 2
• Comparative efficacy: At paracetamol 15 mg/kg, both drugs show equivalent efficacy for fever and pain 2
• Safety profile: Paracetamol shows lower risk of adverse events with consecutive-day dosing compared to NSAIDs 2

Other NSAID Options

• Diclofenac: 0.5-1 mg/kg rectal every 8 hours; 1 mg/kg oral every 8 hours 1
• Naproxen: 5-7.5 mg/kg every 12 hours 1
• Ketorolac (IV): 0.5-1 mg/kg (max 30 mg) single intraoperative dose; 0.15-0.2 mg/kg (max 10 mg) every 6 hours for maximum 48 hours 1

Opioids (For Severe Pain)

• Tramadol: 1-1.5 mg/kg IV/oral every 4-6 hours for breakthrough pain 1
• Morphine: 25-100 mcg/kg IV titrated to effect, depending on age 1
• Fentanyl: 0.5-1 mcg/kg IV for breakthrough pain 1
• Important note: Paracetamol provides significant additive analgesic effect when combined with opioids, even in severe pain 7

Metamizole (Where Available)

• Dosing: 10-15 mg/kg IV every 8 hours 1
• Restriction: Recommended for short-term postoperative use in hospital setting only due to agranulocytosis risk with long-term use 1

Clinical Pearls

• Optimal dose selection: Use 15 mg/kg rather than 10 mg/kg for superior efficacy while maintaining safety profile equivalent to placebo 2
• Route considerations: Oral absorption is faster and more reliable than rectal, except in very young infants where rectal bioavailability is paradoxically higher 5
• Combination therapy: Paracetamol can be safely combined with NSAIDs or opioids for enhanced analgesia 1, 7
• First-line status: Paracetamol remains the first-choice over-the-counter treatment for analgesia and antipyresis in children of all ages 7
• Toxicity threshold: Single ingestions >10 times the recommended dose (>150 mg/kg) are potentially hepatotoxic and require immediate antidote treatment 7