Does Fentanyl Cause Itching?
Yes, fentanyl commonly causes itching (pruritus), with incidence rates ranging from 10-50% for intravenous administration and 20-100% for neuraxial (epidural/intrathecal) routes. 1, 2
Incidence and Routes of Administration
- Intravenous fentanyl causes pruritus in 10-50% of patients 1, 2
- Epidural or intrathecal fentanyl has the highest incidence at 20-100% of patients 1, 3
- Oral opioids (including fentanyl formulations) cause pruritus in 2-10% of patients 3
- Pruritus is more likely to occur early in the course of opioid treatment 1, 3
Evidence from Clinical Guidelines
The American Society of Anesthesiologists' practice guidelines specifically document that epidural morphine causes increased frequency of pruritus compared to intramuscular morphine, and this side effect is well-established across all neuraxial opioids including fentanyl 4. Pediatric emergency guidelines note that rapid administration of fentanyl can cause various side effects, though they focus primarily on respiratory complications 4.
Mechanism of Fentanyl-Induced Itching
- The mechanism involves peripheral opioid receptors, as demonstrated by the fact that both naloxone and peripherally-restricted naloxone methiodide suppress fentanyl-induced scratching 5
- Fentanyl-induced itching does NOT respond to antihistamines (diphenhydramine, chlorpheniramine, cetirizine), distinguishing it from morphine-induced itching which is partially histamine-mediated 5
- This suggests fentanyl causes pruritus through a direct opioid receptor mechanism rather than histamine release 5
Treatment Algorithm for Fentanyl-Induced Pruritus
First-Line Treatment
- Start with antihistamines: diphenhydramine 25-50 mg IV or PO every 6 hours, or promethazine 12.5-25 mg PO every 6 hours 1
- Note: These are recommended as first-line despite limited efficacy specifically for fentanyl (they work better for morphine-induced pruritus) 5
Second-Line Treatment (if antihistamines fail)
- Opioid rotation: Switch to a different opioid such as buprenorphine, which may not cause cross-reactivity 1, 6
- Mixed agonist-antagonist: Nalbuphine 0.5-1 mg IV every 6 hours as needed 1
Third-Line Treatment (refractory cases)
- Low-dose naloxone infusion: Start at 0.25 mcg/kg/h and titrate carefully to avoid reversing analgesia 1
- Naltrexone: First-choice when opioid therapy cannot be stopped 1
- Methylnaltrexone: Alternative peripheral opioid antagonist 1
Alternative Agents
- Ondansetron may be considered, though recent evidence shows it does NOT reduce incidence or time to onset of opioid-induced pruritus 3
- Mirtazapine or gabapentin as alternative antipruritic agents 1
- Droperidol for refractory cases 1
Critical Clinical Considerations
- Careful dose titration is essential when using opioid antagonists to avoid reversing analgesic effects 1, 3
- Sedating antihistamines compound opioid-induced sedation, requiring close monitoring 1
- Glucocorticoids are NOT effective for fentanyl-induced pruritus 5
- Transdermal fentanyl patches can cause allergic contact dermatitis (Type IV hypersensitivity) in addition to opioid-induced pruritus, presenting as localized eczema at the application site 6
Common Pitfalls to Avoid
- Do not rely solely on antihistamines for fentanyl-induced pruritus, as they are less effective than for morphine-induced itching 5
- Do not use full doses of opioid antagonists without careful titration, as this will reverse analgesia 1, 3
- Do not overlook the possibility of allergic contact dermatitis with transdermal fentanyl, which requires patch discontinuation rather than antipruritic treatment 6
- Do not expect ondansetron to prevent opioid-induced pruritus despite its efficacy for opioid-induced nausea 3