What are the recommended medications for managing cancer pain?

Pain Medications for Cancer Pain

For cancer pain management, follow the WHO analgesic ladder: start with acetaminophen or NSAIDs for mild pain, add weak opioids (tramadol, codeine) or low-dose strong opioids for moderate pain, and use strong opioids (morphine as first-line) for severe pain, with all opioids prescribed around-the-clock plus breakthrough doses rather than as-needed. 1

Pain Assessment Framework

• Evaluate pain at every clinical visit using standardized tools: visual analog scales (VAS), numerical rating scales (NRS), or verbal rating scales (VRS) 1, 2
• Characterize pain type (nociceptive vs. neuropathic), location, intensity (mild 1-4, moderate 5-7, severe 8-10), duration, and temporal patterns 2
• Over 80% of advanced cancer patients experience pain from direct tumor infiltration, while 20% have treatment-related pain from surgery, radiotherapy, or chemotherapy 1, 2

Stepwise Pharmacological Approach

Mild Pain (NRS 1-4): WHO Level I

Start with non-opioid analgesics as monotherapy:

• Acetaminophen/Paracetamol: 500-1000 mg every 6 hours, maximum 4000-6000 mg/day; monitor for hepatotoxicity 1, 2
• NSAIDs (if no contraindications):
  • Ibuprofen: 200-600 mg every 6-8 hours, maximum 2400 mg/day 1
  • Naproxen: 250-500 mg twice daily, maximum 1000 mg/day 1
  • Diclofenac: topical gel three times daily or patch 180 mg once-twice daily 1

Critical caveat: Monitor NSAIDs closely for GI bleeding, platelet dysfunction, renal failure, and cardiovascular thrombotic events with COX-2 inhibitors; provide gastroprotection for prolonged use 1, 2

Moderate Pain (NRS 5-7): WHO Level II

Add weak opioids to non-opioids, OR use low-dose strong opioids:

• Tramadol: Start 50-100 mg every 6 hours, maximum 400 mg/day; modified-release 100-200 mg every 12 hours 1
• Codeine combinations: Start with codeine 30-60 mg every 4-6 hours 1
• Dihydrocodeine: Modified-release 60-120 mg every 12 hours, maximum 240 mg/day 1
• Alternative approach: Low-dose morphine 20-40 mg/day oral or oxycodone 20 mg/day oral instead of weak opioids 1

Important note: Evidence for weak opioids is controversial—no clear superiority over non-opioids alone has been definitively proven, and they cause more side effects than tramadol 1

Severe Pain (NRS 8-10): WHO Level III

Use strong opioids as first-line therapy:

• Oral morphine (preferred first choice): Start 20-40 mg/day in divided doses; titrate every 3-5 days based on breakthrough dose requirements 1
• Oral oxycodone: Start 20 mg/day; twice as potent as oral morphine 1
• Transdermal fentanyl: Reserve for stable pain ≥60 mg/day oral morphine equivalent; start 25 mcg/hr patch every 72 hours 1, 3
• Hydromorphone: Alternative to morphine with similar efficacy 1
• Methadone: 10 mg starting dose but complicated dosing due to variable half-life; conversion ratio varies (4:1 to 12:1 depending on baseline morphine dose) 1

Conversion ratios to remember:

• Oral to IV/SC morphine: 2:1 to 3:1 1
• Oral morphine to oral oxycodone: 1:2 1
• Oral morphine to transdermal fentanyl: 60-134 mg/day = 25 mcg/hr patch 3

Critical Opioid Prescribing Principles

• Schedule around-the-clock dosing for persistent pain, not "as needed" 1, 2
• Provide breakthrough doses: 10-15% of total daily dose for transient pain exacerbations, available up to hourly 1, 2
• Titrate rapidly: If >4 breakthrough doses needed daily, increase baseline long-acting opioid 1, 2
• Oral route preferred as first choice unless contraindicated by vomiting, obstruction, dysphagia, or need for rapid escalation 1
• Initial fentanyl transdermal dose is conservative: 50% of patients require dose increase after 3 days; wait 24 hours to assess maximum effect, increase no sooner than every 3 days initially or every 6 days thereafter 3

Adjuvant Analgesics for Neuropathic Pain

Neuropathic pain responds poorly to opioids alone—add co-analgesics:

Antidepressants

• Nortriptyline or desipramine (better tolerated): Start 10-25 mg nightly, increase to 50-150 mg nightly 1
• Duloxetine: Start 30-60 mg daily, increase to 60-120 mg daily 1
• Venlafaxine: Start 50-75 mg daily, increase to 75-225 mg daily 1

Anticonvulsants

• Gabapentin: Start 100-300 mg nightly, titrate to 900-3600 mg/day in 2-3 divided doses; increase by 50-100% every few days; adjust for renal insufficiency 1
• Pregabalin: Start 50 mg three times daily, increase to 100 mg three times daily, maximum 600 mg/day; more efficiently absorbed than gabapentin; adjust for renal insufficiency 1

Topical Agents

• Lidocaine 5% patch: Apply daily to painful site with minimal systemic absorption 1
• Diclofenac gel/patch: Apply three times daily or 180 mg patch once-twice daily 1

Managing Opioid Side Effects

Prophylactic management is mandatory:

• Constipation (universal): Prescribe laxatives routinely for all patients on opioids 1
• Nausea/vomiting: Metoclopramide or antidopaminergic drugs 1
• Sedation: Consider psychostimulants 1
• Confusion/hallucinations: Major tranquilizers 1
• Refractory side effects: Consider opioid rotation to different agent or route 1

For renal impairment (eGFR <30 ml/min): Fentanyl and buprenorphine (transdermal or IV) are safest; use all other opioids with caution at reduced doses and frequency 1

Non-Pharmacological Interventions

• Radiation therapy: Single 8-Gy dose for painful bone metastases 1
• Surgical stabilization: For impending or evident fractures 1
• Nerve blocks: Celiac plexus block for pancreatic cancer visceral pain; superior hypogastric plexus block for pelvic pain 1
• Ketamine (subanesthetic doses): NMDA antagonist for intractable refractory pain 1

Common Pitfalls to Avoid

• Starting too low with strong opioids: The recommended initial fentanyl transdermal dose is too low for 50% of patients 3
• Inadequate breakthrough medication: Patients need immediate-release opioids available even when on long-acting formulations 1
• Delaying opioid escalation: Waiting too long between dose adjustments (should be every 3 days initially) 1, 3
• Using conversion tables backwards: Tables for converting TO fentanyl are conservative and will overestimate doses when converting FROM fentanyl to other opioids 3
• Ignoring psychosocial components: Pain has emotional dimensions requiring team support including psychologists, social workers, and spiritual counselors 1
• Underestimating pain in cognitively impaired patients: Observe pain-related behaviors and discomfort 1, 2