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. |
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 | 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 into breast milk in low levels; M/P ratio approximately 0.5-1.0. Use with caution; monitor infant for sedation, respiratory depression, and poor feeding. The American Academy of Pediatrics considers fentanyl compatible with breastfeeding with careful infant monitoring. |
| Teratogenic Risk |
■ 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 component; significant respiratory depression; acute or severe asthma; suspected gastrointestinal obstruction; concurrent use of MAOIs or within 14 days; opioid-naive patients for breakthrough cancer pain (due to high risk of respiratory depression).
| 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…
| 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. |