What is the maximum recommended dose of Paracetamol (Acetaminophen) intravenous (IV)?

Maximum Dose of Paracetamol IV

For healthy adults, administer 1000 mg IV every 6 hours with a maximum daily dose of 4000 mg in 24 hours, ensuring a minimum 4-hour interval between doses and not exceeding 6 doses per day. 1

Standard IV Dosing Parameters

• Single dose maximum: 1000 mg administered over 15 minutes 1
• Dosing interval: Every 6 hours (minimum 4-hour interval between doses) 1
• Maximum daily dose: 4000 mg in 24 hours for healthy adults 1
• Maximum number of doses: 6 doses per 24 hours 1

A loading dose approach can be used with 15-20 mg/kg initially, followed by maintenance doses of 10-15 mg/kg every 6-8 hours 1. However, the single dose should still not exceed 1000 mg in standard adult practice.

Conservative Dosing for Prolonged Use

For use beyond acute postoperative care, limit the maximum daily dose to 3000 mg to minimize hepatotoxicity risk. 1, 2 This recommendation is critical because:

• Even therapeutic doses of 4000 mg/day for 14 days cause ALT elevations >3× normal in 31-41% of healthy adults 3, 4
• Repeated supratherapeutic ingestions (just above therapeutic range) carry a worse prognosis than acute single overdoses and account for approximately 30% of acetaminophen overdose admissions 1, 3

High-Risk Populations Requiring Dose Reduction

Patients with Liver Disease

• Maximum daily dose: 2000-3000 mg for patients with cirrhosis or chronic liver disease 1, 3, 4
• Paracetamol is contraindicated in hepatic insufficiency 5

Elderly Patients (≥60 years)

• Maximum daily dose: 3000 mg per day 1, 2
• Single dose remains 1000 mg, but reduce total daily exposure 2

Chronic Alcohol Users

• Maximum daily dose: 2000-3000 mg per day 1, 3
• Counsel patients to avoid concurrent alcohol use 1
• Hepatotoxicity can occur at doses ≤4000 mg in this population, with case series showing severe hepatotoxicity at doses as low as 5-8.75 g/day 3

Pediatric IV Dosing

• Loading dose: 15-20 mg/kg IV 1
• Maintenance: 10-15 mg/kg every 6-8 hours 1
• Maximum daily dose: 60 mg/kg 1
• For infants <10 kg: Loading dose of 15 mg/kg 1

Critical Safety Warnings

Hemodynamic Effects

IV paracetamol may cause hypotension in up to 50% of critically ill patients, which may preclude use in hemodynamically unstable patients 1, 3. Monitor blood pressure closely during and after infusion.

Avoiding Unintentional Overdose

Explicitly counsel patients to avoid all other paracetamol-containing products when prescribed IV paracetamol, including: 1, 4

• Over-the-counter cold remedies
• Sleep aids
• Opioid combination products (e.g., hydrocodone/acetaminophen, oxycodone/acetaminophen)

This is a common pitfall—failing to recognize paracetamol in combination products leads to unintentional overdose 1, 4.

Multimodal Analgesia Approach

When paracetamol alone provides insufficient pain control, add adjuvant therapies rather than exceeding the 3000 mg daily maximum. 1 Consider:

• NSAIDs once renal function is confirmed normal and bleeding risk has passed 1
• Regional nerve blocks (TAP blocks, epidural analgesia, rectus sheath blocks) 2
• Low-dose ketamine as an adjuvant in ICU patients 1

Regular dosing of paracetamol up to 15 mg/kg every 6 hours provides a good analgesic base in multimodal regimens 1.

Common Pitfalls to Avoid

• Do not assume low or absent paracetamol levels rule out toxicity if ingestion was remote, occurred over several days, or timing is uncertain 1
• Very high aminotransferase levels (AST >1000 IU/L) should raise suspicion of paracetamol poisoning even without clear overdose history 1, 3
• Verify the patient is not receiving additional paracetamol sources from other routes (oral, rectal) or combination products 1, 4
• Do not exceed the recommended dosing frequency—maintain at least 4-hour intervals between doses 1

Research Context on Higher Dosing

One study in healthy volunteers demonstrated that a 2-g IV starting dose followed by 1-g doses every 6 hours (total 5 g in 24 hours) resulted in plasma concentrations far below the toxic threshold with no hepatotoxicity 6. However, this regimen is not FDA-approved or guideline-recommended and should not be used in routine clinical practice. The standard 4000 mg/24-hour maximum remains the appropriate limit for patient safety 1.