Can Zofran (ondansetron) be used to treat opioid-induced pruritus?

Ondansetron (Zofran) for Opioid-Induced Pruritus

Ondansetron is not recommended as a first-line treatment for opioid-induced pruritus as it does not reduce the incidence of pruritus compared to placebo, though it may reduce severity in some cases. 1

Efficacy of Ondansetron for Opioid-Induced Pruritus

• Opioid-induced pruritus is common, affecting 2-10% of patients receiving oral opioids, 10-50% receiving intravenous opioids, and 20-100% receiving epidural or intrathecal opioids 1
• According to the British Association of Dermatologists' guidelines, ondansetron and other 5-HT3 receptor antagonists do not reduce the incidence of opioid-induced pruritus or time to onset when compared with placebo 1
• While some evidence suggests ondansetron 4 mg or 8 mg may reduce the severity or need for treatment of pruritus secondary to opiates, this has been refuted in more recent studies 1

Recommended Treatment Algorithm for Opioid-Induced Pruritus

First-line options:

• Antihistamines such as diphenhydramine or promethazine are recommended as initial treatment 1
• Assess for other causes of pruritus, as pruritus is more likely to occur early in the course of opioid treatment 1

Second-line options (if antihistamines fail):

• Opioid antagonists have proven useful when antihistamines fail 1
• Mixed agonist/antagonists (e.g., nalbuphine) can be used to treat opioid-induced pruritus 1, 2
• μ-opioid receptor antagonists (e.g., naloxone, naltrexone) can be used with careful dose titration to produce relief without reversing analgesic efficacy 1, 3
• Methylnaltrexone (a peripheral opioid antagonist with reduced ability to cross the blood-brain barrier) can be considered 1, 3

Third-line options:

• Consider opioid rotation if pruritus persists despite symptomatic management 1
• Diclofenac 100 mg rectally has shown efficacy in reducing postoperative pruritus 1, 3
• Mirtazapine 30 mg daily orally or gabapentin 1200 mg daily in divided doses have shown efficacy in preventing morphine-induced pruritus in surgical settings 1, 3

Important Clinical Considerations

• The use of opioid antagonists in treating opioid-induced pruritus risks inducing significant pain by reversing analgesia, requiring careful dose titration 1
• Pruritus is particularly common with neuraxial (epidural and intrathecal) opioid administration 4
• While some small studies have reported success with ondansetron for opioid-induced pruritus 5, 6, the highest quality evidence from guidelines does not support its routine use 1
• Intranasal butorphanol has shown promise in small studies for treating opioid-induced pruritus unresponsive to antihistamines 2

Common Pitfalls to Avoid

• Do not rely on ondansetron as a first-line treatment for opioid-induced pruritus despite its efficacy for opioid-induced nausea 1
• Avoid using full doses of opioid antagonists in opioid-dependent patients as this may precipitate withdrawal 1
• Don't overlook other causes of pruritus in patients receiving opioids, such as other medications or underlying skin conditions 1
• Remember that pruritus can be so severe that it may require modification or abandonment of opioid therapy if unresponsive to treatment 2, 7