FENTANYL-37
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Fentanyl is a mu-opioid receptor agonist, producing analgesia, sedation, and respiratory depression by activating G-protein coupled opioid receptors in the CNS, leading to inhibition of adenylate cyclase, decreased cAMP, and reduced neurotransmitter release.
| Metabolism | Primarily metabolized by CYP3A4 to norfentanyl and other inactive metabolites; also undergoes N-dealkylation and hydroxylation. Less than 10% excreted unchanged in urine. |
| Excretion | Renal: ~75% (as metabolites, <10% unchanged); Fecal: ~9%; Biliary: minor. |
| Half-life | Terminal elimination half-life: 3–7 hours (prolonged in elderly, hepatic impairment, or with continuous infusion due to context-sensitive half-life up to 300 min). |
| Protein binding | ~80–85% bound, primarily to α1-acid glycoprotein (AAG) and albumin. |
| Volume of Distribution | 3–8 L/kg (highly lipophilic, rapid redistribution from plasma to tissues). |
| Bioavailability | Transdermal: ~92% (systemic); Buccal/sublingual: 50–65%; Intramuscular: ~100%. |
| Onset of Action | Intravenous: 30–60 seconds; Intramuscular: 7–15 minutes; Transdermal: 12–24 hours (peak effect at 24–72 hours). |
| Duration of Action | Intravenous: 30–60 minutes (single dose); Transdermal: 72 hours per patch; context-sensitive half-life prolongs duration with prolonged infusion. |
| Molecular Weight | 336.47 |
For opioid-naive adults, initial dose 50-100 mcg IV/IM every 1-2 hours as needed for pain; transdermal: 12-25 mcg/h applied every 72 hours for opioid-tolerant patients only. For anesthesia: 2-20 mcg/kg IV as part of balanced anesthesia.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | For GFR 10-50 mL/min: reduce dose by 25-50% and monitor for respiratory depression. For GFR <10 mL/min: reduce dose by 50-75% or use alternative; avoid transdermal in severe impairment. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% and titrate cautiously. Child-Pugh C: reduce dose by 75% or avoid use; monitor for prolonged effects. |
| Pediatric use | For analgesia: 1-2 mcg/kg IV/IM every 1-2 hours as needed; max 4 mcg/kg/dose. For sedation/procedural: 0.5-2 mcg/kg IV, may repeat with 1 mcg/kg after 3-5 min. Use only with resuscitation equipment. |
| Geriatric use | Reduce initial dose by 50-75% (e.g., 25-50 mcg IV/IM for breakthrough pain). Titrate slowly; monitor for respiratory depression and delirium. Avoid transdermal initiation due to increased half-life. |
| 1st trimester | Not recommended; associated with neural tube defects and cardiac malformations in animal studies, limited human data. |
| 2nd trimester | Use with caution; may cause fetal growth restriction and placental abruption with chronic use. |
| 3rd trimester | Avoid; risk of neonatal withdrawal syndrome and respiratory depression at birth. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Placental transfer | Fentanyl crosses the placenta readily; detectable in fetal plasma within minutes after maternal administration. |
| Breastfeeding |
■ FDA Black Box Warning
Risk of respiratory depression, particularly in opioid-naive patients and in the setting of rapid dose escalation; risk of addiction, abuse, and misuse; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risk of fatal respiratory depression when used with benzodiazepines or other CNS depressants.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to fentanyl or any componentConcurrent use or within 14 days of MAO inhibitorsSignificant respiratory depression (in unmonitored settings)Acute or severe bronchial asthmaSuspected or known gastrointestinal obstructionMyasthenia gravis (relative, but considered absolute for some formulations)
| Precautions | Avoid in opioid non-tolerant patients; monitor for respiratory depression; risk of hypotension, bradycardia, and QT prolongation; may cause muscle rigidity (especially with rapid IV administration); tolerance and dependence may develop; avoid abrupt discontinuation; use with caution in elderly, cachectic, or debilitated patients; concomitant use with MAOIs or within 14 days contraindicated. |
Loading safety data…
| Excreted in breast milk in low concentrations; however, due to risk of neonatal respiratory depression and withdrawal, avoid use during breastfeeding unless essential. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Limited data; no clear increase in major malformations. Second/third trimester: Prolonged use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery. Avoid late pregnancy unless essential. |
| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, sedation level, and pain score. Fetal monitoring: Assess fetal heart rate and uterine activity; prolonged use may cause non-reassuring fetal status. Neonatal monitoring post-delivery for signs of opioid withdrawal (e.g., tremors, irritability, poor feeding). |
| Fertility Effects | No specific human data; animal studies do not indicate direct impairment of fertility at therapeutic doses. However, opioid use may disrupt hormonal regulation (hypothalamic-pituitary-gonadal axis) potentially leading to menstrual irregularities and reduced fertility. |
| Food/Dietary | No significant food interactions. Avoid grapefruit juice as it may inhibit CYP3A4 metabolism and increase fentanyl levels. |
| Clinical Pearls | FENTANYL-37 is a high-potency synthetic opioid used primarily for pain management and anesthesia. Due to its high lipophilicity, onset of action is rapid (within 1-2 minutes IV) but redistribution causes short duration. Monitor respiratory depression closely; naloxone may require higher or repeated doses due to potency and long half-life. Avoid in opioid-naive patients without proper monitoring. Use with caution in hepatic impairment due to CYP3A4 metabolism. Transdermal formulation not for acute pain; allow 12-24 hours for steady state. |
| Patient Advice | Do not crush, chew, or break tablets; swallow whole to avoid rapid release and overdose. · Store securely out of reach of children and pets; unused patches should be flushed down toilet. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines) as they increase risk of severe sedation and respiratory depression. · Do not drive or operate heavy machinery until you know how fentanyl affects you. · Seek emergency help if you experience slow heartbeat, severe dizziness, or difficulty breathing. · Do not abruptly stop taking fentanyl; withdrawal symptoms may occur. Consult your healthcare provider for tapering. |