What is the preferred treatment between ibuprofen (nonsteroidal anti-inflammatory drug) and paracetamol (acetaminophen) for pain and fever in adults?

Ibuprofen vs Paracetamol for Pain and Fever in Adults

For pain and fever in adults, ibuprofen is generally more effective than paracetamol and should be considered the preferred first-line agent in patients without contraindications, though paracetamol remains the safer option for those with gastrointestinal, cardiovascular, or renal disease. 1

Efficacy Comparison

Pain Management

• Ibuprofen demonstrates superior analgesic efficacy across multiple pain conditions including acute post-operative pain, dysmenorrhea, migraine, and osteoarthritis compared to paracetamol at standard doses 1
• Direct head-to-head comparisons consistently favor ibuprofen for producing more patients with clinically meaningful pain relief (≥50% pain intensity reduction) 1
• In acute sore throat, ibuprofen provides significantly better pain relief than paracetamol, particularly after the first 2 hours 2, 3
• For bacterial fever-associated symptoms in emergency settings, the combination paracetamol/ibuprofen (500/150 mg) was more effective than paracetamol 1000 mg alone at 1 hour (48.6% vs 33.6% achieving primary endpoint) 4

Fever Reduction

• Ibuprofen is marginally more effective than paracetamol for fever reduction, particularly after the first 2 hours of administration 3
• Both IV ibuprofen 400 mg and IV paracetamol 1000 mg provide equivalent fever control within 30 minutes, with no significant difference in efficacy 5
• In emergency department settings, paracetamol 1000 mg and paracetamol/ibuprofen combination (500/150 mg) achieved similar efficacy at 2 hours (90.5% vs 91.9%) 4

Safety Profile: Critical Differences

Paracetamol Safety Advantages

• Paracetamol has significantly fewer adverse events compared to NSAIDs, particularly regarding gastrointestinal, cardiovascular, and renal complications 3, 6
• Minimal gastrointestinal toxicity at recommended doses (≤4 g/24 hours) 2, 6
• No increased risk of cardiovascular events or renal dysfunction at therapeutic doses 6
• Hepatotoxicity is rare when used as directed, even in patients with compensated cirrhotic liver disease 6

Ibuprofen Safety Concerns

• Dose-dependent gastrointestinal bleeding risk increases with higher doses and prolonged use 2
• Cardiovascular adverse events show dose-response relationship 3
• Renal adverse events with significant risk in vulnerable populations 2
• NSAIDs implicated in 23.5% of adverse drug reaction hospitalizations in older adults 2

Clinical Decision Algorithm

First-Line Selection

Choose Paracetamol (1000 mg every 6 hours, max 4 g/24 hours) if patient has: 2, 3

• Chronic kidney disease or reduced creatinine clearance 2
• History of gastrointestinal bleeding or peptic ulcer disease 2
• Cardiovascular disease or heart failure 2, 3
• Concurrent anticoagulation or antiplatelet therapy 2
• Age >65 years with multiple comorbidities 2

Choose Ibuprofen (400-600 mg every 6-8 hours, max 2.4 g/24 hours) if patient has: 7, 3

• No contraindications listed above 1
• Inflammatory pain conditions (e.g., acute musculoskeletal injury) 2
• Moderate-to-severe pain requiring superior efficacy 7, 1
• Failed adequate trial of paracetamol 3

Escalation Strategy

If paracetamol alone provides inadequate relief: 3

1. Ensure maximum dose (4 g/24 hours) has been tried 2, 3
2. Add ibuprofen 400 mg every 6-8 hours if no contraindications 3
3. Use both medications together: paracetamol up to 4 g daily plus ibuprofen up to 2.4 g daily 3

If ibuprofen alone causes gastrointestinal symptoms:

• Add proton pump inhibitor for gastroprotection in high-risk patients 3
• Consider switching to paracetamol if symptoms persist 2

Special Population Considerations

Older Adults

• Paracetamol is recommended as first-line therapy due to superior safety profile 2
• No evidence supports routine dose reduction in older adults without organ dysfunction 6
• If NSAIDs required, use lowest effective dose for shortest duration with gastroprotection 2
• Particular caution with NSAIDs due to age-related decline in renal function 2

Patients with Liver Disease

• Paracetamol is safe at standard doses in compensated cirrhosis 6
• Individualize dosing in decompensated cirrhosis in consultation with physician 6
• NSAIDs should be avoided in cirrhosis due to renal and bleeding risks 2

Cancer Pain

• Both paracetamol and NSAIDs are recommended at all steps of WHO analgesic ladder 2
• Evidence for paracetamol efficacy in cancer pain is limited but it remains widely recommended 2
• NSAIDs show benefit in 26-51% of patients with moderate-to-severe cancer pain 2
• Monitor long-term NSAID use closely for gastrointestinal, renal, and cardiovascular toxicity 2

Common Pitfalls to Avoid

• Do not assume paracetamol is always safer long-term: while generally well-tolerated, some evidence suggests long-term renal toxicity with high doses over many years 2
• Do not exceed maximum daily doses: paracetamol >4 g/24 hours risks hepatotoxicity; ibuprofen >2.4 g/24 hours increases adverse events 2, 7
• Do not overlook combination products: patients may inadvertently exceed maximum paracetamol dose from multiple sources 2
• Do not use NSAIDs without assessing renal function: particularly critical in older adults and those with heart failure 2
• Do not continue NSAIDs indefinitely without reassessment: monitor for gastrointestinal, cardiovascular, and renal complications 2