What are the recommended oral medications for pain management?

Recommended Oral Pain Medications

For mild pain, start with paracetamol (acetaminophen) 500-1000 mg every 4-6 hours (maximum 4-6 grams daily) or an NSAID such as ibuprofen 400-600 mg every 6 hours; for moderate pain, add a weak opioid like codeine or tramadol in combination with the non-opioid, or use low-dose strong opioids; for severe pain, use oral morphine as the first-line strong opioid, with the oral route being the preferred method of administration. 1, 2

Mild Pain (WHO Level I)

Non-opioid analgesics form the foundation of pain management:

• Paracetamol (Acetaminophen) is recommended at 500-1000 mg every 4-6 hours with a maximum daily dose of 4000-6000 mg, with caution in hepatotoxicity risk 1, 2

• NSAIDs are particularly effective for inflammatory and bone pain 1, 2:

  • Ibuprofen 400-600 mg every 6 hours (maximum 2400 mg daily) 1
  • Naproxen 250-500 mg twice daily (maximum 1000 mg daily) 1
  • Diclofenac 50 mg four times daily or 100 mg twice daily (retarded formulation) 1

• Combination therapy with paracetamol plus ibuprofen provides superior pain relief compared to either drug alone, with an NNT of 1.5-1.6 for at least 50% pain relief 3

• When using NSAIDs long-term, gastroprotection is recommended due to gastrointestinal, renal, and cardiovascular risks 1, 2

Moderate Pain (WHO Level II)

Weak opioids or low-dose strong opioids should be added when non-opioids are insufficient:

• Codeine 30-60 mg combined with paracetamol or NSAIDs, with maximum codeine dose of 240 mg daily 1, 2

• Tramadol is effective for moderate pain 2, 4:

  • Initial dosing: 50-100 mg every 4-6 hours as needed (maximum 400 mg daily) 4
  • For improved tolerability, titrate gradually: start with 50 mg and increase by 50 mg every 3 days to reach 200 mg/day, then adjust to 50-100 mg every 4-6 hours 4
  • Use with caution in patients with seizure risk or those taking antidepressants 2

• Low-dose strong opioids (morphine or oxycodone) are reasonable alternatives to weak opioids, especially when progressive pain is expected 1, 2

• Do not combine weak opioids with strong opioids 1

Severe Pain (WHO Level III)

Strong opioids are indicated when pain is not controlled with lower-level analgesics:

• Oral morphine is the first-line choice for moderate to severe pain 1, 2:

  • Available in immediate-release and sustained-release formulations 2
  • Oral to parenteral conversion ratio is 1:2 to 1:3 1

• Oxycodone is an effective alternative, approximately 1.5-2 times as potent as oral morphine 5, 2

• Hydromorphone is another effective alternative to morphine 2

• Transdermal fentanyl is best reserved for patients with stable opioid requirements (equivalent to ≥60 mg/day morphine), those unable to swallow, or those with poor morphine tolerance 1

• Strong opioids may be combined with ongoing WHO Level I agents for enhanced analgesia 1

Critical Implementation Principles

Scheduling and administration:

• Prescribe analgesics on a regular schedule, not "as needed," for chronic pain 1, 2

• The oral route should be the first choice for medication administration 1, 2

• Provide rescue doses (immediate-release formulations) for breakthrough pain at approximately 10-15% of the total daily opioid dose 1, 5, 2

• If more than four breakthrough doses are needed daily, increase the baseline sustained-release opioid dose 1

Opioid titration:

• Titrate opioid doses rapidly to effect using immediate-release formulations 1

• Once pain is controlled, convert to sustained-release formulations based on total daily rescue medication use 1

Special populations:

• In renal impairment (creatinine clearance <30 mL/min), increase tramadol dosing interval to every 12 hours with maximum 200 mg daily 4

• In advanced chronic kidney disease (stages 4-5), fentanyl and buprenorphine are the safest opioid choices 1, 2

• For elderly patients over 75 years, limit tramadol to maximum 300 mg daily 4

• In cirrhosis, reduce tramadol to 50 mg every 12 hours 4

Managing Opioid Side Effects

Prophylactic and therapeutic measures are essential:

• Laxatives must be routinely prescribed for both prophylaxis and management of opioid-induced constipation 1

• Metoclopramide or antidopaminergic drugs should be used for opioid-related nausea/vomiting 1

• Consider opioid rotation if side effects are refractory despite dose adjustment 1

Common Pitfalls to Avoid

• Do not underdose: Inadequate pain control negatively impacts quality of life and treatment adherence 5

• Do not use tramadol as sole therapy for severe cancer pain previously requiring strong opioids 5

• Do not forget individual variability: Monitor closely when converting between opioids, as metabolism varies 5

• Do not overlook renal/hepatic function: Adjust doses appropriately to prevent metabolite accumulation 1, 5

• Avoid acetaminophen/paracetamol alone for moderate-severe pain requiring opioid therapy 5