What is the recommended treatment for opioid-induced pruritus?

Management of Opioid-Induced Pruritus

The first-line treatment for opioid-induced pruritus includes antihistamines such as diphenhydramine (25-50 mg IV or PO every 6 hours) or promethazine (12.5-25 mg PO every 6 hours). 1

Stepwise Treatment Algorithm

Step 1: Assessment and First-Line Treatment

• Assess for other causes of pruritus (other medications, underlying conditions) before attributing symptoms solely to opioids 1
• Begin with antihistamines:
  • Diphenhydramine 25-50 mg IV or PO every 6 hours (sedating) 1
  • Promethazine 12.5-25 mg PO every 6 hours (sedating) 1
  • Cetirizine (non-sedating option) may also be beneficial 1

Step 2: If Pruritus Persists Despite Antihistamines

• Consider opioid rotation (changing to a different opioid) if symptomatic management has failed 1
• This approach is particularly important as different opioids have varying propensities to cause pruritus 2

Step 3: Opioid Receptor Antagonists and Mixed Agonist-Antagonists

• Consider adding small doses of mixed agonist-antagonist:
  • Nalbuphine 0.5-1 mg IV every 6 hours as needed 1
  • Butorphanol (intranasal) has shown effectiveness for antihistamine-resistant opioid-induced pruritus 3
• Consider continuous infusion of naloxone:
  • Start at 0.25 mcg/kg/h and titrate up as needed 1
  • Careful titration can relieve pruritus without reversing analgesic efficacy 1
• Naltrexone is effective for treating opioid-induced pruritus when cessation of opioid therapy is impossible (first-choice recommendation in this situation) 1
• Methylnaltrexone may be an alternative 1

Step 4: Additional Pharmacologic Options

• Consider ondansetron (serotonin antagonist) 1
• Consider mirtazapine or gabapentin as alternative antipruritic agents 1
• Consider droperidol for refractory cases 1

Mechanism and Considerations

• Opioid-induced pruritus occurs in 10-50% of patients receiving opioids 1
• The mechanism is complex, involving both peripheral and central pathways 2
• Mu-opioid receptor antagonists and kappa-opioid agonists are particularly effective in relieving opioid-induced pruritus 2, 4
• Pruritus is more likely to occur early in the course of opioid treatment 1
• Opioid-induced pruritus often does not respond to regular antipruritic treatments, making it challenging to manage 2

Important Caveats and Pitfalls

• Antihistamines alone may not be sufficient for opioid-induced pruritus, as the mechanism differs from histamine-mediated pruritus 2, 4
• When using naloxone or other opioid antagonists, careful dose titration is essential to avoid reversing analgesic effects 1
• Sedating antihistamines may compound opioid-induced sedation, so monitor patients closely 1
• If multiple treatments fail, consider neuraxial analgesics or neuroablative techniques to potentially reduce the opioid dose 1
• A multimodal analgesic approach that reduces overall opioid requirements may help prevent or minimize pruritus 2