What are the best medications for managing cancer pain?

Best Medications for Cancer Pain Management

Morphine is the standard preferred starting medication for cancer pain management in opioid-naïve patients, with initial oral doses of 5-15 mg or intravenous doses of 2-5 mg recommended. 1

First-Line Opioid Selection

• Pure opioid agonists with short half-lives (morphine, hydromorphone, fentanyl, and oxycodone) are preferred for cancer pain management as they can be more easily titrated than long half-life opioids 1
• In opioid-naïve patients, oral morphine is generally considered the standard first-line medication 1
• Initial dosing should be 5-15 mg oral morphine sulfate or 2-5 mg intravenous morphine sulfate for opioid-naïve patients 1
• Very low starting doses (15 mg/day oral morphine, or 10 mg/day for patients >70 years) have shown effectiveness and good tolerability in opioid-naïve cancer patients 2

Alternative Strong Opioids

• Hydromorphone or oxycodone (both normal release and modified release formulations) are effective alternatives to oral morphine 1
• Oxycodone has a potency ratio to oral morphine of 1.5-2:1 3
• Hydromorphone has a potency ratio to oral morphine of 7.5:1 3
• Fentanyl transdermal patches should only be used after pain is controlled by other opioids, not for rapid titration 1
• Fentanyl transdermal system has been studied in cancer patients at doses ranging from 25 mcg/hr to 600 mcg/hr 4

Special Considerations for Specific Patient Populations

• Morphine should be avoided in patients with renal disease and hepatic insufficiency due to accumulation of morphine-6-glucuronide, an active metabolite 1
• Fentanyl and buprenorphine (transdermal or intravenous) are the safest opioids for patients with severe renal impairment (eGFR <30 ml/min) 1, 3
• Methadone should be used with caution due to its long half-life (8 to >120 hours) and interindividual variations in pharmacokinetics 1
• Methadone should be started at lower-than-anticipated doses and slowly titrated with adequate breakthrough pain medication during titration 1
• Consultation with a pain management specialist is recommended before using methadone 1

Medications to Avoid

• Mixed agonist-antagonists (e.g., butorphanol, pentazocine) have limited efficacy and may precipitate opioid withdrawal in patients on pure opioid agonists 1
• Meperidine and propoxyphene are contraindicated for chronic pain, especially in patients with renal impairment or dehydration 1
• Propoxyphene should be avoided in patients treated with tamoxifen due to CYP2D6 inhibition 1

Dosing Strategies and Administration Routes

• Opioid doses should be titrated to effect as rapidly as possible 1
• All patients should receive around-the-clock dosing with provision of breakthrough doses (usually 10% of total daily dose) for transient pain exacerbations 1
• If more than four breakthrough doses are needed daily, the baseline opioid treatment should be adjusted 1
• Oral administration is the preferred route for chronic opioid therapy 1
• Continuous parenteral infusion (IV or subcutaneous) is recommended for patients who cannot take oral medications 1

Managing Opioid Side Effects

• Common opioid side effects include constipation, nausea, vomiting, drowsiness, cognitive impairment, confusion, hallucinations, and myoclonic jerks 1
• Constipation should be proactively managed with laxatives 1
• Anti-emetics should be used for nausea and vomiting 1
• Major tranquilizers may help manage confusion 1
• Psychostimulants can be considered for excessive drowsiness 1
• Switching to another opioid agonist or changing the administration route may improve analgesia without the same side effects 1

Adjuvant Therapies for Refractory Pain

• For neuropathic pain components, consider adding anticonvulsants (gabapentin, pregabalin) or antidepressants (nortriptyline, duloxetine, venlafaxine) 3
• Non-opioid analgesics (acetaminophen, NSAIDs) can be combined with opioids for enhanced pain control 1
• Radiotherapy is highly effective for pain caused by bone metastases, tumors compressing neural structures, and cerebral metastases 1
• For intractable pain, consider subanesthetic doses of ketamine 1, 3
• Spinal analgesia, nerve blocks, or neurosurgical interventions may be considered for selected patients with refractory pain 3, 5

Opioid Rotation Strategy for Inadequate Pain Control

• When high-dose morphine provides inadequate pain control, rotation to an alternative strong opioid (hydromorphone, oxycodone, or fentanyl) is recommended 3
• Calculate the total 24-hour morphine dose and determine the equianalgesic dose of the new opioid using conversion tables 3
• Reduce the calculated equianalgesic dose by 25-50% to account for incomplete cross-tolerance 3

Common Pitfalls to Avoid

• Inadequate dose reduction when rotating opioids can lead to overdosing 3
• Overlooking adjuvant therapies for specific pain types limits effectiveness 3
• Ignoring non-pharmacological options such as radiation therapy or interventional procedures that may reduce opioid requirements 3
• Using transdermal fentanyl for rapid opioid titration (should only be used after pain is controlled with other opioids) 1
• Failure to provide regular breakthrough pain medication during opioid titration 1