What is the best pain reliever for mild to moderate pain?

Best Pain Reliever for Mild to Moderate Pain

Acetaminophen (paracetamol) 1000 mg every 4-6 hours is the recommended first-line treatment for mild to moderate pain, with a maximum daily dose of 4000 mg. 1

Primary Recommendation

Acetaminophen should be your initial choice because it provides comparable pain relief to NSAIDs without the gastrointestinal, renal, and cardiovascular risks associated with anti-inflammatory drugs. 1, 2, 3 This recommendation is consistent across multiple international guidelines and has been validated over decades of clinical use. 4

Dosing Specifics

• Standard dose: 1000 mg every 4-6 hours 1
• Maximum daily dose: 4000 mg (some guidelines allow up to 6000 mg, but 4000 mg is safer) 1, 5
• Onset of action: 15-30 minutes 1

Critical Safety Considerations

• Hepatotoxicity risk: Exercise caution in patients with liver failure, malnutrition, or severe alcohol use disorder—consider lower doses in these populations 1, 3
• No dose reduction needed: For older adults without hepatic impairment, standard dosing is appropriate 3
• Overdose threshold: Single ingestions exceeding 10 times the recommended dose (>10 grams) are potentially hepatotoxic 6

Alternative: NSAIDs for Inflammatory Pain

If pain has an inflammatory component (particularly bone pain, musculoskeletal injuries, or arthritis), NSAIDs are the preferred alternative. 1, 2

NSAID Options (in order of consideration):

• Ibuprofen: 400-600 mg every 4-6 hours (maximum 2400 mg/day) 1, 5
• Naproxen: 250-500 mg twice daily (maximum 1000 mg/day) 1
• Diclofenac: 50 mg four times daily or 100 mg modified-release twice daily 1

NSAID Contraindications and Cautions

Avoid NSAIDs in patients with:

• History of gastrointestinal bleeding—requires gastroprotection with proton pump inhibitors if NSAIDs are necessary 1
• Cardiovascular disease—NSAIDs increase cardiovascular risk 2, 3
• Chronic kidney disease—all NSAIDs carry nephrotoxic potential 1, 2
• Concurrent use with methotrexate—absolute contraindication 1
• Concurrent nephrotoxic chemotherapy (e.g., cisplatin) 1

Topical NSAIDs

For localized musculoskeletal pain (excluding low back pain), topical NSAIDs provide effective analgesia with minimal systemic absorption and reduced adverse effects. 2

Combination Therapy

Acetaminophen can be combined with NSAIDs for additive analgesic effect when monotherapy is insufficient. 1 This combination is more effective than either agent alone and allows lower doses of each medication, potentially reducing side effects. 1

When to Escalate Beyond First-Line Agents

If mild to moderate pain remains uncontrolled after optimizing acetaminophen and/or NSAIDs:

• Add weak opioids: Codeine, tramadol, or dihydrocodeine in combination with non-opioid analgesics (WHO Step II) 1
• Alternative approach: Low-dose strong opioids (e.g., morphine 20-40 mg daily) combined with non-opioid analgesics 1

The WHO analgesic ladder remains the standard framework for stepwise pain management, though recent evidence questions whether Step II (weak opioids) offers significant advantages over low-dose Step III opioids. 1

Common Pitfalls to Avoid

• Combining two NSAIDs: Never prescribe two products from the same pharmacological class simultaneously 1
• Exceeding maximum acetaminophen dose: Hepatotoxicity risk increases significantly above 4000 mg/day 1, 5
• Forgetting gastroprotection: When prescribing NSAIDs long-term, always co-prescribe proton pump inhibitors for patients at GI risk 1
• Using NSAIDs in high-risk elderly: Older adults are particularly susceptible to NSAID-related GI, platelet, and renal complications 1