If hydromorphone is not available, should morphine or fentanyl be used as an alternative for pain management?

Alternative to Hydromorphone: Morphine Should Be Used First

When hydromorphone is unavailable, morphine should be the first-line alternative for pain management, as it is the established opioid of first choice for moderate to severe pain and has the most extensive evidence base. 1

Primary Recommendation

• Oral morphine is the gold standard opioid recommended by ESMO (European Society for Medical Oncology) guidelines for moderate to severe pain management 1
• Morphine provides effective pain relief, is widely tolerated, simple to administer, and is the only opioid on the WHO essential drug list 1
• There is no high-quality evidence demonstrating that hydromorphone is superior to morphine in terms of efficacy, adverse effects, or patient preference 2, 3

When to Consider Fentanyl Instead

Fentanyl should be reserved for specific clinical scenarios rather than as a routine hydromorphone substitute:

Renal Impairment (Primary Indication for Fentanyl)

• Fentanyl (transdermal or IV) is the safest opioid choice in patients with chronic kidney disease stages 4-5 (eGFR <30 mL/min) 1
• Morphine accumulates toxic metabolites (morphine-3-glucuronide and morphine-6-glucuronide) in renal failure, increasing risk of neurotoxicity 1
• All opioids should be used with caution and at reduced doses in renal impairment, but fentanyl requires the least adjustment 1

Stable Opioid Requirements

• Transdermal fentanyl is best reserved for patients whose opioid requirements are stable and predictable 1
• The 72-hour patch duration complicates management in patients with fluctuating pain or during dose titration 1
• Fentanyl takes 8-16 hours to achieve analgesic effects and 72 hours to reach steady state, making it unsuitable for acute pain titration 1

Patients Unable to Take Oral Medications

• Transdermal fentanyl is appropriate for patients who cannot swallow or have poor oral tolerance 1
• However, subcutaneous morphine infusion remains the preferred first-choice alternative route when oral administration is not possible 1

Practical Dosing Considerations

Morphine Conversion from Hydromorphone

• Hydromorphone is approximately 5-10 times more potent than morphine 1, 4
• When switching from hydromorphone to morphine, multiply the hydromorphone dose by 5-7 to estimate the equivalent morphine dose 4
• Start with immediate-release morphine every 4 hours plus rescue doses for breakthrough pain 1

Route-Specific Conversions

• Oral to parenteral morphine: divide oral dose by 2-3 to achieve equianalgesic effect 1
• The average relative potency ratio of oral to IV/subcutaneous morphine is 1:2 to 1:3 1
• Subcutaneous route is simpler and less painful than intramuscular for chronic pain 1

Starting Doses for Opioid-Naïve Patients

• Oral morphine: 20-40 mg daily in divided doses 1
• Elderly patients: 10-12 mg daily divided into 5-6 doses 4
• Provide rescue doses of 10-30% of the 4-hourly dose for breakthrough pain 4

Common Pitfalls to Avoid

Don't Use Fentanyl for Dose Titration

• Fentanyl's delayed onset (8-16 hours) and prolonged steady-state achievement (72 hours) make it inappropriate for patients requiring rapid dose adjustments 1
• The 16-hour half-life after patch removal complicates management of adverse effects 1

Don't Assume Equivalent Adverse Effect Profiles

• While hydromorphone and morphine have similar side effect profiles at equianalgesic doses 2, 3, fentanyl may cause less constipation than morphine 1
• All opioids require prophylactic laxatives 1

Don't Forget Alternative Strong Opioids

• Oxycodone (1.5-2 times more potent than morphine) is also an effective alternative to hydromorphone 1
• Methadone is valid but requires specialist expertise due to variable half-life and complex dose conversions 1

Algorithm for Selection

1. First choice: Morphine (oral immediate-release for titration, then convert to modified-release) 1
2. If renal impairment (eGFR <30): Fentanyl transdermal or IV 1
3. If unable to take oral medications: Subcutaneous morphine infusion 1
4. If stable pain and oral route unavailable: Consider transdermal fentanyl 1
5. If morphine intolerance develops: Consider opioid rotation to oxycodone or methadone (specialist consultation) 1