What is the stepwise approach to pain medication in cancer patients, including doses and equivalent conversions for opioids and patches?

Stepwise Approach to Pain Medication in Cancer Patients

The stepwise approach to pain management in cancer patients should follow the WHO analgesic ladder, beginning with non-opioid analgesics for mild pain, adding weak opioids for moderate pain, and using strong opioids for severe pain, with appropriate dose titration and management of side effects. 1

Step 1: Mild Pain (Pain Score 1-3)

• Non-opioid analgesics are the foundation for treating mild cancer pain 1
• Options include:
  • Acetaminophen/paracetamol: 500-1000 mg every 4-6 hours (maximum 4000 mg/day) 1
  • Acetylsalicylic acid: 500-1000 mg every 4-6 hours (maximum 3000 mg/day) 1
  • Ibuprofen: 400-600 mg every 6 hours (maximum 2400 mg/day) or 800 mg modified release (maximum 2400 mg/day) 1
  • Diclofenac: 50 mg every 8 hours (maximum 200 mg/day) or 100 mg modified release twice daily 1
  • Naproxen: 250-500 mg twice daily (maximum 1000 mg/day) 1

Step 2: Moderate Pain (Pain Score 4-6)

• For moderate pain, weak opioids should be added to non-opioids 1
• Alternatively, low doses of strong opioids may be used in combination with non-opioid analgesics 1
• Options include:
  • Dihydrocodeine: Modified-release tablets 60-120 mg every 12 hours (maximum 240 mg/day) 1
  • Tramadol: 50-100 mg every 4-6 hours (maximum 400 mg/day) or 100-200 mg modified release every 12 hours 1
  • Low-dose formulations of transdermal fentanyl or buprenorphine may be considered 1

Step 3: Severe Pain (Pain Score 7-10)

• Strong opioids are the mainstay for moderate to severe cancer pain 1
• Oral morphine is the first-choice opioid for moderate to severe cancer pain 1
• Starting doses for opioid-naïve patients:
  • Oral morphine: 5-15 mg of short-acting morphine every 4 hours 1
  • Intravenous morphine: 2-5 mg (one-third of oral dose) 1
• Other strong opioid options include:
  • Oxycodone: Oral starting dose 20 mg/day (1.5-2 times more potent than oral morphine) 1
  • Hydromorphone: Oral starting dose 8-17 mg/day (7.5 times more potent than oral morphine) 1
  • Fentanyl transdermal: Only for opioid-tolerant patients with stable pain, starting at 25 mcg/hour (equivalent to 60-134 mg oral morphine/day) 1, 2
  • Methadone: Oral starting dose 10 mg/day (complex conversion, 4-12 times more potent than oral morphine depending on prior morphine dose) 1

Opioid Titration and Breakthrough Pain Management

• Titrate opioid doses rapidly to achieve pain control 1
• All patients should receive around-the-clock dosing with provision for breakthrough pain 1
• Breakthrough dose should be 10-20% of the total daily opioid dose 1
• If more than four breakthrough doses are needed per day, increase the baseline opioid dose 1
• For breakthrough pain, use short-acting opioids with rapid onset 1
• Transmucosal fentanyl may be considered for breakthrough pain in opioid-tolerant patients 1

Opioid Conversion Guidelines

• When converting from oral to parenteral morphine, divide by 3 (parenteral dose = 1/3 oral dose) 1
• When converting to transdermal fentanyl, use conversion tables 2:
  • 60-134 mg oral morphine/day = 25 mcg/hour fentanyl patch
  • 135-224 mg oral morphine/day = 50 mcg/hour fentanyl patch
  • 225-314 mg oral morphine/day = 75 mcg/hour fentanyl patch
  • 315-404 mg oral morphine/day = 100 mcg/hour fentanyl patch

Management of Opioid Side Effects

• Common side effects include constipation, nausea, vomiting, drowsiness, and cognitive impairment 1
• Preventive strategies:
  • Constipation: Prophylactic laxatives for all patients on opioids 1
  • Nausea/vomiting: Antiemetics as needed 1
  • CNS effects: Consider dose reduction, opioid rotation, or adjuvant medications 1
• For severe CNS toxicity (confusion, hallucinations, myoclonus), consider opioid rotation 1
• Naloxone is available for reversal of severe opioid overdose 1

Adjuvant Therapies for Refractory or Neuropathic Pain

• For neuropathic pain, consider adding:
  • Anticonvulsants (e.g., gabapentin, pregabalin) 3
  • Antidepressants (e.g., amitriptyline, duloxetine) 3
• For bone pain:
  • Radiotherapy is highly effective 1
  • Bisphosphonates or denosumab may be beneficial 3
• For refractory pain:
  • Consider interventional approaches (nerve blocks, neuraxial analgesia) 1
  • Ketamine at subanesthetic doses may help with intractable pain 1

Common Pitfalls and Caveats

• Avoid using mixed agonist-antagonists in patients already on opioid agonists as this may precipitate withdrawal 1
• Monitor for safe limits of acetaminophen or NSAIDs when using combination products 1
• Avoid codeine or morphine in patients with renal failure due to accumulation of metabolites 1
• When converting between opioids, it's safer to underestimate the equianalgesic dose and provide rescue medication than to overestimate 2
• Never use conversion tables meant for converting to fentanyl when converting from fentanyl to other opioids, as this can lead to fatal overdose 2