fentanyl
opioid analgesic· Brands: Duragesic, Actiq, Fentora, Sublimaze, Abstral, OnsolisIMINHIVSCSLTOP
Mechanism of action
Fentanyl is a potent synthetic opioid analgesic that primarily acts as an agonist at mu-opioid receptors in the central nervous system. Activation of these receptors inhibits ascending nociceptive pathways, increases descending inhibition, and alters the perception and emotional response to pain, producing analgesia, sedation, and euphoria. It also suppresses respiratory drive at the brainstem, which underlies its potentially fatal respiratory depression.
Pharmacokinetics
Fentanyl is highly lipophilic and crosses the blood-brain barrier rapidly, giving fast onset of action, particularly after parenteral or transmucosal administration. It is metabolised in the liver by CYP3A4 to inactive metabolites, mainly norfentanyl, and about 10% is excreted unchanged in urine. The terminal half-life is roughly 3 to 4 hours after IV injection but is longer after transdermal use (up to 20 hours or more) due to continued absorption. Systemic clearance is reduced in the elderly, in hepatic impairment, and in patients taking CYP3A4 inhibitors.
Indications & dosing
Adjunct to general anaesthesia for analgesia
Titrate to effect; monitor respiratory function.
- adult · IV: 1–2 mcg/kg Single dose or PRN · Titrate to effect; monitor respiratory function.
Acute severe pain in opioid-tolerant patients
Give slow IV injection; monitor for respiratory depression.
- adult · IV: 50–100 mcg Every 30-60 min PRN · Give slow IV injection; monitor for respiratory depression.
Chronic pain in opioid-tolerant patients
Apply to intact skin; not for acute pain or opioid-naive patients.
- adult · TOP: 12–25 mcg/hour Every 72 hours · Apply to intact skin; not for acute pain or opioid-naive patients.
Breakthrough cancer pain in opioid-tolerant patients
Max 4 doses per day; do not use in opioid-naive patients.
- adult · SL: 100–200 mcg PRN · Max 4 doses per day; do not use in opioid-naive patients.
Contraindications & precautions
- Severe respiratory depression · Risk of worsening respiratory failure
- Acute severe asthma · Risk of bronchospasm and respiratory compromise
- Paralytic ileus · Opioids reduce gastrointestinal motility
- Hypersensitivity to fentanyl or other opioids · Risk of anaphylaxis
- Bradyarrhythmias · Fentanyl may cause bradycardia; use with caution
- Monitor respiratory rate and sedation level regularly, especially after dose increases.
- Use with extreme caution in opioid-naive patients; fentanyl is highly potent.
- Avoid concurrent use of CNS depressants and alcohol.
- Have naloxone available to treat respiratory depression.
- Use with caution in patients with bradyarrhythmias.
- Reduce dose in elderly or patients with hepatic impairment, and titrate slowly.
Adverse effects
- Sedation
- Nausea
- Constipation
- Vomiting
- Pruritus
- Respiratory depressionserious
- Bradycardiaserious
- Hypotensionserious
- Chest wall rigidityserious
Renal & hepatic adjustment
- eGFR 30–60: Use with caution. Consider dose reduction or alternative analgesia.
- eGFR 0–30: Avoid or use alternative analgesic. If unavoidable, use lowest effective dose and monitor closely. (avoid)
- Hepatic impairment (mild): No dose adjustment considered necessary.
- Hepatic impairment (moderate): Use with caution; consider dose reduction and monitor for adverse effects.
- Hepatic impairment (severe): Avoid use due to increased risk of toxicity. (avoid)
Monitoring, pregnancy & toxicity
- Respiratory rate · Before and during initiation of therapy, and with dose escalation
- Sedation score · During dose titration and with concurrent sedatives
- Blood pressure and pulse · Before and during dose titration
- Bowel function · Regularly during therapy; monitor for constipation
- Pain score · Before and after dose adjustments
- Pregnancy: Fentanyl should be used during pregnancy only if the benefits outweigh the risks. It crosses the placenta and may cause neonatal respiratory depression and withdrawal. For opioid-dependent women, specialist care is needed. During labour, use only if clearly indicated, with facilities for neonatal resuscitation available.
- Toxicity: Respiratory depression · Administer naloxone; support ventilation. Naloxone may need repeated doses or an infusion because naloxone's duration of action is shorter than fentanyl's.
- Toxicity: Miosis · Typically associated with opioid toxicity; treat the underlying cause.
- Toxicity: Bradycardia and hypotension · Supportive care; atropine for bradycardia; fluids for hypotension.
- Toxicity: Coma or depressed consciousness · Airway management and monitoring; naloxone can reverse opioid-induced coma.
Antidotes & reversal
- Naloxone · Re-dose or infusion often needed; transdermal patches have prolonged effect (remove patch, charcoal).
Clinical notes
Fentanyl has an analgesic potency about 100 times that of morphine. It is used for severe acute pain in perioperative settings and for chronic cancer pain, often via transdermal patches, which are not recommended for opioid-naive patients or acute pain due to the risk of delayed respiratory depression. Careful titration is essential, and routes of administration vary by preparation. Always follow local prescribing guidelines and monitor respiratory function. In the UK, fentanyl is a controlled drug (Schedule 2) and must be prescribed according to local regulations.
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BNF; local formulary