How to manage opioid-induced pruritus in a hospice patient?

Treatment of Opioid-Induced Itching in Hospice Patients

Start with antihistamines as first-line therapy: diphenhydramine 25-50 mg IV, PO, or subcutaneously every 6 hours, or promethazine 12.5-25 mg PO every 6 hours. 1

First-Line Treatment: Antihistamines

• Diphenhydramine 25-50 mg every 6 hours is the National Comprehensive Cancer Network's recommended first-line treatment and can be administered IV, PO, or subcutaneously 1
• Subcutaneous administration of diphenhydramine is particularly valuable in hospice patients who cannot swallow and lack IV access, with demonstrated safety in 648 injections across 109 hospice patients without any adverse cutaneous reactions 2
• Promethazine 12.5-25 mg PO every 6 hours is an alternative sedating antihistamine 1
• Cetirizine may be used as a non-sedating alternative if sedation is problematic 1
• Important caveat: Sedating antihistamines may compound opioid-induced sedation, requiring close monitoring 1

Second-Line Treatment: Opioid Rotation

• If antihistamines fail, rotate to a different opioid (e.g., from morphine to oxycodone or fentanyl), as different opioids have varying propensities to cause pruritus 1, 3
• Opioid-induced pruritus is more likely early in treatment and affects 10-50% of patients receiving opioids 1

Third-Line Treatment: Mixed Agonist-Antagonists

• Nalbuphine 0.5-1 mg IV every 6 hours as needed is superior to placebo, diphenhydramine, and naloxone for treating opioid-induced pruritus without attenuating analgesia 1, 4
• Use 25-50% of the analgesic dose (2.5-5 mg versus 10 mg) to avoid reversing pain control 4
• Nalbuphine provides relief without increasing sedation and may actually reduce nausea/vomiting 4
• Intranasal butorphanol 2 mg every 4-6 hours is an alternative mixed agonist-antagonist that showed significant relief within 15-60 minutes in patients unresponsive to antihistamines 5

Fourth-Line Treatment: Low-Dose Opioid Antagonists

• Continuous naloxone infusion starting at 0.25 mcg/kg/hour can be titrated carefully to relieve pruritus without reversing analgesia 1, 3
• Critical warning: Careful dose titration is essential to avoid precipitating withdrawal and reversing pain control 1, 6
• Naltrexone is effective when opioid cessation is impossible but is contraindicated in hospice patients requiring opioids for pain control as it will reverse analgesia 1, 7
• Methylnaltrexone (a peripheral opioid antagonist) may be considered as it has reduced ability to cross the blood-brain barrier 1, 6

Alternative Agents (Limited Evidence)

• Mirtazapine or gabapentin may be considered as alternative antipruritic agents 1
• Droperidol for refractory cases 1
• Do NOT use ondansetron routinely, as recent evidence shows it does not reduce incidence or severity of opioid-induced pruritus despite its efficacy for opioid-induced nausea 7, 6

Key Clinical Pitfalls to Avoid

• Never use full opioid antagonists (naltrexone, high-dose naloxone) in hospice patients requiring pain control, as this will precipitate withdrawal and reverse analgesia 7, 6
• Always assess for other causes of pruritus (other medications, liver disease, skin conditions) before attributing symptoms solely to opioids 1, 6
• Be aware that subcutaneous diphenhydramine is safe and practical in hospice settings when oral and IV routes are unavailable 2
• Monitor closely for compounded sedation when combining sedating antihistamines with opioids 1