A hospice patient stable on a 75 microgram per hour transdermal fentanyl patch develops influenza with a fever of 39 degrees Celsius. Over the next day she becomes increasingly sedated with a respiratory rate of 8 per minute. What is the mechanism?

• A Fever accelerates hepatic metabolism of fentanyl to the toxic metabolite norfentanyl
• B Dehydration reduces renal clearance of fentanyl, causing accumulation
• C Fever enhances mu receptor expression, sensitising the patient to fentanyl
• D Raised skin temperature increases fentanyl absorption from the patch reservoir ✓

Explanation

Systemic absorption of fentanyl from a transdermal matrix or reservoir patch is driven partly by skin temperature. Fever, hot baths, heating pads, and sun exposure raise delivery rates substantially, producing supra-therapeutic serum levels with respiratory depression. Fentanyl is cleared hepatically with negligible renal excretion of parent drug, so reduced renal clearance does not explain toxicity, which eliminates option B. Patients must be counselled to avoid external heat sources.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.