BLACK BOX WARNING
- addiction, abuse, and misuse; respiratory depression; neonatal opioid withdrawal syndrome; concurrent CNS depressants; patch — accidental exposure and child deaths; transmucosal products — only for opioid-tolerant cancer patients
fentanyl
Brand: Duragesic (patch), Sublimaze (IV), Actiq (lozenge), Abstral, Lazanda
⚠ BBW ISMP High Alert Prototype: morphine
Drug Class: opioid analgesic
Drug Family: opioid
Subclass: full mu-opioid agonist / phenylpiperidine
Organ Systems: cns
Mechanism of Action
Highly lipophilic full mu-opioid agonist; 100 times more potent than morphine; rapid CNS penetration due to lipophilicity; inactive metabolites make it preferred in renal failure.
mu-opioid receptors (MOR)
Indications
- anesthesia induction/maintenance
- procedural/breakthrough pain
- chronic cancer pain (transdermal patch)
- ICU analgesia/sedation
Contraindications
- respiratory depression without resuscitation
- paralytic ileus
- acute/intermittent pain not requiring continuous opioid therapy (for patch)
Adverse Effects
Common
- respiratory depression
- sedation
- constipation
- nausea
- bradycardia
- hypotension
Serious
- chest wall rigidity (high-dose IV: 'wooden chest syndrome')
- respiratory arrest
- physical dependence
- adrenal insufficiency (chronic use)
Pharmacokinetics (ADME)
| Absorption | IV: 100%; transdermal patch: ~92% over 72 hours (significant lag 12–24h before effect) |
| Distribution | Highly lipophilic; Vd ~6 L/kg; protein binding ~80–85%; rapid CNS penetration |
| Metabolism | CYP3A4 to inactive norfentanyl — no active metabolites; safe in renal failure |
| Excretion | Renal (~75%) as metabolites; <8% unchanged |
| Half-life | 2–4 hours (IV); effective half-life 17 hours (patch due to subcutaneous depot) |
| Onset | IV: 1–2 minutes; transdermal: 12–24 hours (lag time) |
| Peak | IV: 5 minutes; transdermal: 24–72 hours |
| Duration | IV: 30–60 minutes; patch: 72 hours |
| Protein Binding | 80–85% |
| Vd | ~6 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CYP3A4 inhibitors (ketoconazole, ritonavir, grapefruit) | reduce fentanyl clearance; dramatically increase levels | major |
| CNS depressants | additive respiratory depression | major |
| serotonergic drugs | fentanyl has weak serotonergic activity; serotonin syndrome risk | moderate |
Nursing Considerations
- Transdermal patch: apply to clean, dry, non-irritated skin; rotate sites; temperature elevations (fever, heating pad) increase absorption by up to 26% — remove patch with fever
- Patch lag time: when initiating transdermal fentanyl, continue short-acting opioids for 12–24 hours during onset; when discontinuing, residual drug persists in skin depot for 17–24 hours
- Dispose of used patches by folding sticky sides together and flushing; even used patches contain enough fentanyl to be fatal to a child
- IV fentanyl: monitor for chest wall rigidity (wooden chest) at high doses during rapid administration — requires neuromuscular blockade, not naloxone, to treat
Clinical Pearls
- Fentanyl is preferred in renal failure over morphine because its metabolites are inactive — morphine-6-glucuronide accumulates in CKD and causes prolonged respiratory depression
- The transdermal fentanyl patch is only appropriate for opioid-tolerant patients with stable, chronic pain — it is NOT for acute pain, opioid-naive patients, or intermittent/PRN use
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.