FENTANYL-87
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Fentanyl is a synthetic opioid that primarily acts as a mu-opioid receptor agonist, inhibiting adenylate cyclase, decreasing cAMP production, and modulating ion channels (calcium, potassium) to reduce neurotransmitter release and neuronal excitability.
| Metabolism | Fentanyl undergoes extensive hepatic metabolism via CYP3A4-mediated N-dealkylation to norfentanyl, along with other minor pathways; elimination is primarily renal. |
| Excretion | Primarily hepatic metabolism (>90%) to norfentanyl and other inactive metabolites; renal excretion of metabolites accounts for approximately 75% of total elimination, with about 9% excreted unchanged in urine. Fecal excretion is minimal (<9%). |
| Half-life | Terminal elimination half-life is approximately 3–12 hours (mean 7 hours) in adults; prolonged to up to 20–30 hours in elderly, critically ill, or patients with hepatic impairment. Context-sensitive half-life increases with infusion duration. |
| Protein binding | Approximately 80–85% bound to plasma proteins (primarily alpha-1-acid glycoprotein and albumin). Increased free fraction in hypoalbuminemia. |
| Volume of Distribution | 4–6 L/kg (large, extensive tissue distribution). High Vd reflects rapid redistribution from blood to tissues (muscle, fat). |
| Bioavailability | Intravenous: 100%; intramuscular: ~90%; oral transmucosal: ~50% (range 25–70%, first-pass hepatic metabolism); intranasal: ~50–90%; transdermal: ~30–50% (variable, rate-limited by skin barrier). |
| Onset of Action | Intravenous: nearly immediate (30–60 seconds); intramuscular: 7–15 minutes; transdermal: delayed onset (~12–24 hours for initial effect, requires 24–72 hours for steady state); intranasal: 5–15 minutes; oral transmucosal: 5–15 minutes. |
| Duration of Action | Intravenous/Intramuscular: 30–60 minutes (analgesic effect); transdermal: 72 hours per patch (analgesic) but respiratory depression may persist longer; oral transmucosal: 1–2 hours. Duration is dose-dependent and affected by redistribution. |
IV: 0.5-2 mcg/kg as a bolus; continuous infusion: 0.7-10 mcg/kg/hr. Transdermal: 25-100 mcg/h every 72 hours. Transmucosal (buccal or lozenge): 200-1600 mcg as a single dose.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | No specific dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, consider dose reduction by 50% or increase dosing interval. Caution in renal impairment due to potential accumulation of metabolites. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Use with caution; consider 75% dose reduction. Monitor for prolonged effect. |
| Pediatric use | IV bolus: 1-2 mcg/kg for analgesia; for sedation/analgesia: 1-2 mcg/kg followed by infusion 0.5-2 mcg/kg/hr. Transdermal: Not recommended for opioid-naive pediatric patients. Transmucosal: Not recommended for children under 2 years. |
| Geriatric use | Reduce initial dose by 50% compared to younger adults. Titrate slowly; monitor for respiratory depression and constipation. Consider using lower strength transdermal patches (12 mcg/h or 25 mcg/h). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Breastfeeding | Fentanyl is excreted in breast milk; M/P ratio approximately 0.4. Low concentrations in milk; use with caution in neonates due to potential respiratory depression or withdrawal. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show increased risk of neural tube defects at high doses. Second/third trimester: Chronic use may cause fetal opioid dependence and neonatal abstinence syndrome; avoid prolonged high-dose use. |
■ FDA Black Box Warning
Fentanyl carries a risk of respiratory depression, abuse, misuse, addiction, and diversion. Concomitant use with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma, and death. Neonatal opioid withdrawal syndrome may occur with prolonged use during pregnancy.
| Common Effects | Constipation |
| Serious Effects |
Significant respiratory depression; acute or severe bronchial asthma; known or suspected gastrointestinal obstruction; concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy; hypersensitivity to fentanyl.
| Precautions | Life-threatening respiratory depression; risk of serotonin syndrome with concurrent serotonergic drugs; adrenal insufficiency; severe hypotension; bradycardia; use in patients with head injuries or increased intracranial pressure; opioid-induced hyperalgesia; withdrawal if abruptly discontinued. |
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| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, and sedation level. For fetal monitoring, assess fetal heart rate during labor; watch for neonatal respiratory depression after delivery. |
| Fertility Effects | May impair fertility in both sexes by altering gamete function and hormonal regulation; data from opioid class suggest decreased libido and menstrual irregularities. |