Opioid analgesic – synthetic μ-opioid receptor agonist
ATC code: N02AB03 (Fentanyl)
A highly selective full μ-opioid agonist with 50–100× the affinity of morphine. Analgesia from 100 mcg fentanyl matches 10 mg morphine. High lipophilicity gives rapid CNS entry (IV onset 1–2 minutes) and enables transdermal and sublingual use. CYP3A4-metabolized to inactive metabolites. IV half-life is short (1–2 hours); after patch removal, half-life reaches 17 hours (skin depot).
Second line
Transdermal fentanyl is used in stable chronic pain in opioid-tolerant patients who do not manage on oral opioids or have intake problems. NCCN Adult Cancer Pain 2024 and 2018 do not prescribe the patch to opioid-naive patients or for acute pain. Starting dose 25 mcg/h with patch change every 72 hours. Peak concentration is reached at 17–48 hours after the first patch – a short-acting opioid is needed in this window for breakthrough pain.
Only in opioid-tolerant patients with stable chronic pain.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Transdermal fentanyl is not used in acute pain – unsuitable pharmacokinetics (slow onset, long elimination), disproportionate risk of fatal respiratory depression in opioid-naive patients. Sublingual and buccal forms (Abstral, Effentora) are approved only for breakthrough pain in cancer patients on stable baseline opioid therapy – not for general acute pain. Per TIRF REMS data, a million off-label prescriptions led to hundreds of deaths in the US.
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Boxed warning
FDA boxed warning: high addiction and abuse risk; fatal respiratory depression in opioid-naive patients on the patch; accidental exposure in children has been fatal; combination with benzodiazepines or other CNS depressants carries risk of profound sedation, respiratory depression, coma, and death; CYP3A4 interactions can dangerously raise fentanyl levels.
Long-term T3 use causes neonatal abstinence syndrome. In pregnant patients with severe chronic pain, decisions are made with the obstetrician; non-opioid alternatives are first-line.
Fentanyl passes into milk. Lactation use is possible in patients on stable opioid therapy under monitoring of infant sedation, weight gain, and activity.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Fentanyl is evaluated for the following indications with varying evidence strength: Moderate-to-severe chronic pain (evidence tier A), Acute mild-to-moderate pain (evidence tier D). See the full indication matrix with dosing and citations above on this page.
Common side effects of Fentanyl (≥ 1 in 100): Nausea and vomiting, Constipation, Drowsiness, Confusion, Itching, Dry mouth. See the Safety section for uncommon and serious reactions.
FDA category C. Long-term T3 use causes neonatal abstinence syndrome. In pregnant patients with severe chronic pain, decisions are made with the obstetrician; non-opioid alternatives are first-line.
Fentanyl passes into milk. Lactation use is possible in patients on stable opioid therapy under monitoring of infant sedation, weight gain, and activity.
Fentanyl is contraindicated in: Fentanyl hypersensitivity; Opioid-naive patients (transdermal); Acute pain, postoperative pain with available alternatives; Severe respiratory failure; Acute bronchospasm. Full list in the Safety section.
FDA boxed warning: high addiction and abuse risk; fatal respiratory depression in opioid-naive patients on the patch; accidental exposure in children has been fatal; combination with benzodiazepines or other CNS depressants carries risk of profound sedation, respiratory depression, coma, and death; CYP3A4 interactions can dangerously raise fentanyl levels.