What intravenous (IV) opioids can be given to a patient with a known allergy to codeine and morphine?

IV Opioid Options for Patients with Codeine and Morphine Allergy

For patients with codeine and morphine allergies, intravenous fentanyl and hydromorphone are the safest and most effective IV opioid alternatives. 1

Primary IV Opioid Alternatives

Fentanyl (First-line)

• Highly lipid-soluble mu-opioid receptor agonist that can be safely administered intravenously 2
• Recommended as first-line for patients with morphine and codeine allergies due to:
  • Different chemical structure (synthetic phenylpiperidine) compared to morphine/codeine (natural phenanthrenes)
  • Lower risk of cross-reactivity with morphine/codeine allergies 1
  • Faster onset of action and lower incidence of side effects in emergency settings 1
• Initial IV dosing: 25-50 mcg (0.5-1 mcg/kg) IV every 30-60 minutes as needed 3

Hydromorphone (Alternative first-line)

• Semi-synthetic opioid that is 7.5 times more potent than oral morphine 1
• Excellent alternative for patients with morphine/codeine allergies because:
  • Different metabolic pathway than morphine and codeine
  • Less likely to accumulate in renal impairment compared to morphine 2, 1
• Initial IV dosing: 0.2-0.6 mg IV every 2-3 hours as needed (approximately 1.5 mg IV hydromorphone = 10 mg IV morphine) 2, 3

Clinical Decision-Making Algorithm

1. Assess allergy history:

   • Determine if true allergy (urticaria, anaphylaxis) or intolerance (nausea, vomiting)
   • True allergies to both morphine and codeine suggest possible cross-reactivity with other phenanthrene opioids

2. Select appropriate alternative:

   • First choice: Fentanyl IV - synthetic opioid with minimal cross-reactivity
   • Second choice: Hydromorphone IV - semi-synthetic with different metabolic pathway
   • Third choice: Oxymorphone IV (if available) - less commonly used but effective alternative

3. Consider clinical context:

   • For acute severe pain: Fentanyl IV (faster onset)
   • For moderate-severe pain requiring longer duration: Hydromorphone IV
   • For patients with renal impairment: Fentanyl or hydromorphone preferred 2, 1

Important Considerations

Pharmacological Differences

• Fentanyl and hydromorphone have different metabolic pathways than morphine/codeine, making cross-reactivity less likely 1, 4
• Morphine and codeine are natural opioids (phenanthrenes), while fentanyl is synthetic (phenylpiperidine) and hydromorphone is semi-synthetic 5, 4
• Codeine is a prodrug requiring CYP2D6 to be metabolized to morphine, so patients allergic to codeine may actually be reacting to morphine metabolites 1, 6

Monitoring and Side Effects

• Monitor all patients receiving IV opioids for:
  • Respiratory depression (most serious adverse effect)
  • Sedation
  • Hypotension
  • Nausea and vomiting 1
• Fentanyl has a shorter duration of action (30-60 minutes) compared to hydromorphone (2-3 hours) when given IV 2
• Constipation is less common with fentanyl compared to other opioids 7

Conversion Considerations

When switching between opioids due to allergies, use equianalgesic dosing tables but reduce the calculated dose by 25-50% to account for incomplete cross-tolerance 2:

• 10 mg IV morphine ≈ 1.5 mg IV hydromorphone ≈ 100 mcg IV fentanyl 2, 3

Pitfalls to Avoid

• Do not use mixed agonist-antagonists (like nalbuphine, butorphanol) in opioid-dependent patients as they may precipitate withdrawal 2
• Do not use meperidine (Demerol) due to toxic metabolites and poor safety profile 2
• Avoid assuming that allergy to morphine/codeine means allergy to all opioids - synthetic and semi-synthetic opioids often remain safe options 1
• Never administer an opioid without appropriate monitoring for respiratory depression, especially in opioid-naïve patients 2, 1