What is the indication for paracetamol (acetaminophen)?

Paracetamol Indications

Paracetamol (acetaminophen) is indicated as first-line therapy for mild to moderate pain and fever in adults and children, with specific applications in osteoarthritis, cancer pain, headache, and musculoskeletal conditions. 1, 2

Primary Indications

Pain Management

• Mild pain (pain score 1-4): Paracetamol is the recommended first-line oral analgesic, with doses up to 4000-6000 mg daily in adults 1
• Moderate pain (pain score 5-7): Can be used alone or in combination with weak opioids (codeine, tramadol) or low-dose strong opioids 1
• Severe pain: Provides significant additive analgesic effect when combined with opiates, recommended at all steps of the WHO analgesic ladder for cancer pain 1, 3

Specific Pain Conditions

• Osteoarthritis: Recommended as the oral analgesic to try first and the preferred long-term option for knee, hip, and hand OA 1
• Cancer pain: Used as part of stepwise escalation following the WHO pain ladder for mild cancer pain 1
• Musculoskeletal pain: First-line choice for noninflammatory musculoskeletal conditions 4
• Headache: Indicated for simple headaches 4

Fever Reduction

• Antipyretic use: Standard indication for fever management in adults and children, though fever alone without discomfort may not require treatment 2, 5, 6
• Pediatric fever: Considered first-line therapy at 15 mg/kg doses, as effective as NSAIDs with superior safety profile 6

Dosing Parameters

Adult Dosing

• Standard dose: 500-1000 mg every 4-6 hours 1, 3
• Maximum daily dose: 4000 mg per 24 hours (some sources suggest 4000-6000 mg) 1, 7, 2
• Time to onset: 15-30 minutes 1
• Duration of effect: Varies by formulation, typically 4-6 hours for immediate-release 1

Special Population Considerations

• Liver disease: Use with caution; 2-3 g daily generally recommended for cirrhotic patients due to prolonged half-life 7
• Chronic use: Consider limiting to 3000 mg or less per day to reduce hepatotoxicity risk 7
• Elderly patients: No routine dose reduction required; standard adult dosing appropriate with normal liver function 7, 8
• Kidney disease: Suitable first-line option; no routine dose adjustment needed for mild-moderate renal impairment 8

Pediatric Dosing

• Recommended dose: 15 mg/kg every 4-6 hours 5, 6
• Maximum daily dose: 60 mg/kg/day (up to 5 doses in 24 hours) 2, 5
• Age considerations: Indicated for children of all ages, unlike NSAIDs 6

Clinical Advantages Supporting Use

Safety Profile

• Gastrointestinal: Minimal GI toxicity at recommended doses; no more GI upset than placebo (RR = 0.80,95% CI 0.27 to 2.37) 1
• Cardiovascular: Safer than NSAIDs in patients with cardiovascular disease 1, 3
• Renal: Lower renal toxicity risk compared to NSAIDs 1, 3
• Respiratory: Safe in aspirin-sensitive asthmatics where NSAIDs are contraindicated 4, 8

Comparative Efficacy

• Versus placebo: Effect size for pain relief 0.21 (95% CI 0.02 to 0.41), NNT = 4 for moderate to excellent pain relief 1
• Versus NSAIDs: Less effective than NSAIDs for pain relief but significantly safer, making it preferred first-line therapy 1
• Cost-effectiveness: Superior to NSAIDs, NSAIDs plus gastroprotection, and COX-2 inhibitors for cost per GI adverse event avoided 1

Important Safety Warnings

Hepatotoxicity Risk

• Overdose threshold: Single ingestions >10 times recommended dose (>4000 mg in adults) are potentially toxic 2, 5
• Chronic overdose: Exposures >140 mg/kg/day for several days carry risk of serious toxicity in children 5
• Severe liver damage warning: May occur if adult takes >6 doses in 24 hours or >4000 mg total daily 2
• Alcohol interaction: Risk increased when taken with ≥3 alcoholic drinks daily 2

Critical Contraindications and Precautions

• Combination products: Do not use with other acetaminophen-containing drugs (prescription or nonprescription) 2
• Warfarin interaction: Consult physician before use in patients taking warfarin 2
• Severe skin reactions: Rare but serious; symptoms include skin reddening, blisters, rash—stop use immediately if occurs 2
• Duration limits: Do not use >10 days for pain or >3 days for fever unless directed by physician 2

Common Clinical Pitfalls

• Assuming always safer long-term: While generally well-tolerated, some evidence suggests long-term renal toxicity with high doses over many years 1, 3
• Inadequate dosing: Older studies using subtherapeutic doses ≤10 mg/kg show inferior efficacy; use 15 mg/kg in children for optimal effect 6
• Overlooking hidden sources: Many combination products contain acetaminophen; total daily intake from all sources must not exceed maximum 2, 9
• Delayed treatment of overdose: Quick medical attention is critical even without symptoms; N-acetylcysteine is effective antidote when given early 2, 5, 4