What is the recommended dose and route of administration for Paracetamol (acetaminophen)?

Paracetamol (Acetaminophen) Dosing and Route

For adults, administer paracetamol 650-1000 mg orally every 4-6 hours, not exceeding 4000 mg per day in healthy individuals, though a more conservative maximum of 3000 mg daily is increasingly recommended for chronic use to reduce hepatotoxicity risk. 1, 2, 3

Adult Dosing by Route

Oral Route (First-Line)

• Standard dose: 650-1000 mg every 4-6 hours 2, 3
• Maximum single dose: 1000 mg 3
• Maximum daily dose: 4000 mg in 24 hours for healthy adults 1, 2, 3
• Conservative daily maximum: 3000-3250 mg for chronic use or to minimize hepatotoxicity risk 1, 2, 3

Intravenous Route

• Loading dose (pediatric): 15-20 mg/kg 2
• Maintenance dose (pediatric): 10-15 mg/kg every 6-8 hours 2
• Maximum daily dose (adults): 4000 mg 3

Rectal Route

• Loading dose (pediatric): 20-40 mg/kg (15 mg/kg if <10 kg) due to poor bioavailability 2
• Note: Rectal absorption is slow and irregular compared to oral route 4

Pediatric Dosing

For children, administer 10-15 mg/kg orally every 4-6 hours, with a maximum daily dose of 60 mg/kg/day. 2, 5

Age-Based Oral Dosing (FDA-Approved)

• Ages 12+ years: 650 mg (20.3 mL) every 4-6 hours, maximum 6 doses/24 hours 6
• Ages 6 to <12 years: 325 mg (10.15 mL) every 4 hours, maximum 5 doses/24 hours 6
• Ages 4 to <6 years: 240 mg (7.5 mL) every 4 hours, maximum 5 doses/24 hours 6
• Ages 2 to <4 years: 160 mg (5 mL) every 4 hours, maximum 5 doses/24 hours 6
• Under 2 years: Consult physician 6

Weight-Based Dosing (Preferred)

• Dose: 15 mg/kg every 4 hours 4
• Maximum daily: 60 mg/kg/day 2, 5, 4
• WHO recommendation: 10-15 mg/kg every 4-6 hours 2

Special Population Adjustments

Liver Disease or Chronic Alcohol Use

• Maximum daily dose: 2000-3000 mg 1, 2, 3
• This reduced dose applies to patients with cirrhosis or chronic liver disease 1, 2

Elderly Patients (≥60 years)

• Starting dose: 650 mg every 4-6 hours (rather than 1000 mg) 2
• Maximum daily dose: 3000 mg 3
• No routine dose reduction is required based solely on age, but individualize based on comorbidities 7

Renal Insufficiency

• No routine dose reduction necessary in chronic renal insufficiency, even though clearance is reduced 4

Critical Safety Considerations

Maximum Daily Dose Warnings

The most dangerous scenario is repeated supratherapeutic ingestions (doses just above therapeutic range), which carry a worse prognosis than acute single overdoses and account for approximately 30% of acetaminophen overdose admissions. 1, 2

• Doses ranging from just over 4 g/day to >15 g/day have been associated with liver damage 1
• Chronic exposures >140 mg/kg/day for several days carry risk of serious toxicity in children 5
• Single ingestions of more than 10 times the recommended dose are potentially toxic 5

Common Pitfalls to Avoid

• Combination products: Failing to recognize paracetamol in cold medicines, sleep aids, and opioid combinations leads to unintentional overdose 1, 2
• Multiple products simultaneously: Using several acetaminophen-containing products without tracking total daily intake 1, 2, 3
• Fixed-dose combinations: Prescription combinations should be limited to ≤325 mg acetaminophen per dosage unit 1, 3
• Exceeding dosing frequency: Taking doses too close together (e.g., every 3 hours instead of 4-6 hours) 2

Patient Counseling Requirements

When prescribing paracetamol up to 4000 mg/day, explicitly counsel patients to avoid ALL other acetaminophen-containing products, including OTC cold remedies and opioid combination products. 1, 2, 3

Chronic Use Monitoring

Duration and Monitoring

• Conservative chronic dosing: Limit to 3000 mg/day rather than 4000 mg maximum for long-term management 1, 3
• Liver enzyme monitoring: Monitor AST/ALT regularly when using chronically, especially at doses approaching 4000 mg/day 1, 3
• Reassessment: Frequently reassess need for continued paracetamol and reduce dose when appropriate 1

Multimodal Approach

• If inadequate pain relief at 3000 mg/day, add adjuvant analgesics or consider multimodal approach rather than increasing to 4000 mg/day 1
• Paracetamol provides significant additive analgesic effect when combined with opioids for severe pain 2, 5

Clinical Context by Pain Severity

Mild Pain (WHO Level I)

• First-line: Paracetamol alone 2
• Onset of action: 15-30 minutes 2

Moderate Pain (WHO Level II)

• Combination therapy: Paracetamol with weak opioids (codeine, tramadol) 2

Severe Pain (WHO Level III)

• Adjunct therapy: Continue paracetamol with strong opioids for significant additive analgesic effect 2, 5