How should intravenous paracetamol (acetaminophen) be dosed and administered in adults and children, and what are the contraindications and dose adjustments for hepatic impairment?

Intravenous Paracetamol (Acetaminophen) Administration Guidelines

Dosing for Adults and Adolescents

For adults and adolescents weighing ≥50 kg, administer 1000 mg IV every 6 hours OR 650 mg every 4 hours, with a maximum daily dose of 4000 mg and a minimum dosing interval of 4 hours. 1

• For adults and adolescents weighing <50 kg, use 15 mg/kg every 6 hours OR 12.5 mg/kg every 4 hours, with a maximum of 75 mg/kg per day and minimum 4-hour intervals 1
• Each dose must be administered as a 15-minute intravenous infusion only—never as a bolus 1
• Regular dosing up to 15 mg/kg every 6 hours (maximum 4 g per 24 hours) provides effective analgesia as part of multimodal pain management 2

Dosing for Pediatric Patients

Children aged 2-12 years: 15 mg/kg every 6 hours OR 12.5 mg/kg every 4 hours, maximum 75 mg/kg per day, minimum 4-hour intervals 1

Infants (29 days to 2 years): 15 mg/kg every 6 hours, maximum 60 mg/kg per day, minimum 6-hour intervals 1

Neonates (≥32 weeks gestational age to 28 days): 12.5 mg/kg every 6 hours, maximum 50 mg/kg per day, minimum 6-hour intervals 1

• The effectiveness of IV acetaminophen for acute pain in children <2 years has not been established 1
• IV administration provides more rapid onset of action compared to rectal formulations, though rectal dosing may control fever and pain for longer duration 3

Critical Contraindications

IV paracetamol is absolutely contraindicated in patients with severe hepatic impairment or severe active liver disease. 1

• Known hypersensitivity to acetaminophen or any excipients in the IV formulation is an absolute contraindication 1
• Discontinue immediately at the first appearance of skin rash or symptoms of allergy/hypersensitivity 1

Dose Adjustments for Hepatic Impairment

For patients with mild to moderate hepatic impairment or chronic stable liver disease (including compensated cirrhosis), a conservative daily dose of 2-3 grams is recommended rather than the standard 4 gram maximum. 4, 5

• Patients with existing cirrhosis can safely use 2-3 g/day long-term without causing decompensation 4
• Paracetamol is actually the preferred analgesic in cirrhotic patients because NSAIDs carry higher risks of renal failure, hepatorenal syndrome, and GI bleeding 4
• For chronic use in any patient, limit to ≤3000 mg/day to reduce hepatotoxicity risk 4, 5

Dose Adjustments for Renal Impairment

In severe renal impairment (creatinine clearance ≤30 mL/min), use longer dosing intervals and reduce the total daily dose. 1

• Use caution in cases of severe hypovolemia or severe renal impairment 1
• Paracetamol is generally the non-opioid analgesic of choice in chronic renal insufficiency, and dosage reduction is usually not necessary in mild to moderate impairment 6

Special Population Considerations

Elderly patients (≥60 years): For chronic administration, limit to ≤3000 mg per day due to increased hepatotoxicity risk 5

• No routine dose reduction is required for acute use in older adults 7
• The single dose maximum of 1000 mg remains unchanged 4

Chronic alcohol users: Can consume up to 3 g daily without increased risk of decompensation, though chronic alcohol use may increase acute hepatotoxicity risk 4

Pregnancy and lactation: Paracetamol can be used safely 6

Critical Safety Warnings

Hepatotoxicity Risk

Administration of doses higher than recommended (from all routes and all acetaminophen-containing products) may result in hepatic injury, including liver failure and death. 1

• Repeated supratherapeutic ingestions (doses just above therapeutic range) carry worse prognosis than acute single overdoses, with approximately 30% of overdose admissions involving this pattern 5
• Hepatotoxicity can occur with doses ranging from just over 4 g per day to >15 g per day 2, 5
• Most acute liver failure cases occur with ingestions exceeding 10 grams per day 5

Cardiovascular Risk

Severe hypotension and cardiac arrest have been reported with IV paracetamol infusion, though extremely rare. 8

• Monitor hemodynamics during infusion, particularly in pediatric patients 8

Essential Patient Counseling

When prescribing paracetamol up to 4000 mg/day, explicitly counsel patients to avoid ALL other acetaminophen-containing products, including:

• Over-the-counter cold/flu remedies 5
• Sleep aids and combination analgesics 5
• Prescription opioid-acetaminophen combination products 5

Common Prescribing Pitfalls to Avoid

• Do not prescribe combination opioid-acetaminophen products without accounting for their acetaminophen content toward the daily maximum 5
• Take care when prescribing, preparing, and administering to avoid dosing errors that could result in accidental overdose and death 1
• Never administer as an IV bolus—must be given as 15-minute infusion 1
• Do not use NSAIDs in cirrhotic patients with ascites due to risk of acute renal failure and hepatorenal syndrome 4

Drug Interactions

Substances that induce hepatic cytochrome enzyme CYP2E1 may alter acetaminophen metabolism and increase hepatotoxic potential. 1

• Chronic oral acetaminophen at 4000 mg/day can increase INR in patients stabilized on warfarin 1
• Very low plasma protein binding results in minimal drug interactions 6

Monitoring Requirements

For chronic use beyond 7-10 days, monitor liver enzymes (AST/ALT), especially when dosing approaches 3000 mg daily. 5

• Hepatotoxicity is defined as any AST increase; severe hepatotoxicity as AST >1000 IU/L 5
• Serum aminotransferase levels >3500 IU/L are highly correlated with acetaminophen toxicity 5

Clinical Efficacy Context

IV paracetamol is indicated for management of mild to moderate pain in adults and pediatric patients ≥2 years, moderate to severe pain with adjunctive opioid analgesics, and reduction of fever. 1

• The optimum single dose in adults is 1 g, with maximum daily dosage of 4 g consistent with analgesic activity duration of approximately 6 hours 6
• When added to NSAIDs, paracetamol enhances analgesic effect or allows lower NSAID doses 6
• As part of multimodal analgesia in emergency laparotomy, regular dosing provides superior analgesia and decreases reliance on perioperative opioids 2