What is the best narcotic (opioid) for a patient with end-stage cancer?

Best Narcotic for End-Stage Cancer Pain

Morphine is the first-line opioid of choice for patients with end-stage cancer pain due to its established efficacy, wide availability in various formulations, and extensive clinical experience. 1

Initial Opioid Selection and Administration

• Morphine is generally considered the standard starting drug of choice for patients with cancer pain who have not been previously exposed to opioids 1
• The optimal route of administration for morphine is by mouth, with oral administration being the simplest and most acceptable to patients 1
• Two types of formulations are ideally required: normal release (for dose titration) and modified release (for maintenance treatment) 1
• For opioid-naïve patients, an initial oral dose of 5-15 mg of oral short-acting morphine sulfate is recommended 1
• For patients unable to take oral medications, the subcutaneous route is preferred over intramuscular administration 1
• The average relative potency ratio of oral morphine to subcutaneous morphine is between 1:2 and 1:3 (i.e., 20-30 mg oral morphine equals 10 mg subcutaneous morphine) 1

Dose Titration and Breakthrough Pain Management

• The simplest method of dose titration is with normal release morphine given every 4 hours, with the same dose available for breakthrough pain 1
• Breakthrough doses may be given as often as required (up to hourly) with daily review of the total daily morphine dose 1
• For patients receiving normal release morphine every 4 hours, a double dose at bedtime can effectively prevent nighttime pain awakening 1
• In patients receiving opioids around the clock, immediate-release opioids at 5-20% of the daily regular morphine equivalent daily dose should be prescribed for breakthrough pain 1

Alternative Opioids

While morphine remains first-line, other options may be considered in specific situations:

• Fentanyl (transdermal) is appropriate for patients with stable pain who are unable to swallow, have poor tolerance to morphine, or have compliance issues 1
• Hydromorphone or oxycodone in both immediate-release and modified-release formulations are effective alternatives to oral morphine 1
• Methadone may be considered for patients with renal impairment as it is excreted fecally, but should only be used by clinicians experienced with its use due to its complex pharmacokinetics 1, 2
• Buprenorphine is the safest opioid choice in patients with severe renal impairment (estimated glomerular filtration rate <30 ml/min) 1

Special Considerations

• Morphine, hydromorphone, hydrocodone, oxymorphone, and codeine should be used with caution in patients with fluctuating renal function due to potential accumulation of renally cleared metabolites that may cause neurologic toxicity 1
• For patients with significant renal impairment, fentanyl or methadone may be better options as they are less likely to result in accumulation of active metabolites 1
• Recent evidence suggests that low-dose morphine (starting at 15 mg/day or 10 mg/day in patients >70 years) is effective and well-tolerated in opioid-naïve cancer patients with moderate-to-severe pain 3, 4
• A randomized controlled trial demonstrated that low-dose morphine provided significantly better pain reduction compared to weak opioids (codeine, codeine plus acetaminophen, or tramadol) with similar tolerability 4

Managing Side Effects

• The main continuing adverse effect from morphine is constipation, and prophylactic use of a laxative is almost always required 1
• Daytime drowsiness, dizziness, and mental clouding commonly occur at the start of treatment but usually resolve within a few days when patients are stabilized on a stable dose 1
• Nausea and vomiting occur in up to two-thirds of patients when morphine is started but typically resolve with continued use 1
• For patients who develop intolerable side effects to one opioid, opioid rotation to an alternative agent may improve the balance between analgesia and adverse effects 1

Limitations of Morphine

• The systemic availability of morphine by oral route is poor (20-30%), contributing to unpredictable onset of action and interindividual variability in dose requirements 1
• Active metabolites may contribute to toxicity, particularly in patients with renal impairment 1
• Some types of pain, notably neuropathic pain, may not respond completely to morphine 1
• Despite these limitations, no alternative opioid has demonstrated clear advantages that would make it preferable as the first-line oral opioid for cancer pain 1