FENTANYL-25
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Mu-opioid receptor agonist; produces analgesia by activating G-protein coupled opioid receptors in the CNS, leading to decreased neurotransmitter release and hyperpolarization of neurons.
| Metabolism | Primarily hepatic via CYP3A4; major metabolites include norfentanyl (inactive); minor pathways: CYP3A5, CYP3A7. |
| Excretion | Renal (75% as metabolites, <10% unchanged); Fecal (9%); Biliary (minor). |
| Half-life | Terminal elimination half-life: 2-4 hours in healthy adults; prolonged to 3-12 hours in elderly, hepatic impairment, or critical illness; context: duration of action shorter due to redistribution. |
| Protein binding | 80-85% primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 3-5 L/kg; high Vd indicates extensive tissue distribution, including redistribution to fat and muscle. |
| Bioavailability | Transdermal: 90-100% (but variable); IM: 100%; Oral: <30% (first-pass); Sublingual/Buccal: 50-90%; Intranasal: 70-80%. |
| Onset of Action | IV: 30-60 seconds; IM: 7-15 minutes; Transdermal: 12-24 hours (steady state at 72 hours); Intrathecal/Epidural: 5-10 minutes. |
| Duration of Action | IV: 30-60 minutes (analgesic); IM: 1-2 hours; Transdermal: 72 hours (patch); context: dose-dependent, respiratory depression may outlast analgesia. |
25 mcg/h transdermal patch applied every 72 hours; for opioid-tolerant patients only.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | GFR < 30 mL/min: consider dose reduction by 50% and monitor for respiratory depression; avoid in severe renal impairment (GFR < 15 mL/min) if possible. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use or reduce dose by 75% with close monitoring. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. |
| Geriatric use | Initiate with lowest available dose (12.5 mcg/h) and titrate slowly; monitor for respiratory depression and delirium; reduce dose by 25-50% in patients over 65 years. |
| 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 very low concentrations. M/P ratio not established. Risk of infant sedation and respiratory depression, especially with maternal dose >25 mcg/h. Avoid breastfeeding within 4 hours of drug administration. Generally considered compatible if monitoring infant for drowsiness. |
| Teratogenic Risk |
■ FDA Black Box Warning
Risk of respiratory depression, especially in non-opioid tolerant patients; risk of addiction, abuse, and misuse; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risk of fatal overdose with accidental ingestion; risk of interaction with alcohol and CNS depressants.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to fentanyl or any component; significant respiratory depression; acute or severe bronchial asthma; paralytic ileus; suspected or known gastrointestinal obstruction; use in patients not already tolerant to opioids; concomitant use with MAOIs or within 14 days of discontinuation.
| Precautions | Respiratory depression; hypotension, bradycardia; serotonin syndrome with serotonergic drugs; adrenal insufficiency; severe hypotension; seizures; opioid-induced hyperalgesia; tolerance and physical dependence; withdrawal with abrupt discontinuation; elderly and cachectic patients; renal impairment. |
Loading safety data…
| First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second/third trimester: Chronic use may cause fetal opioid dependence and neonatal abstinence syndrome (NAS). No structural malformations reported. Risk of premature delivery, poor fetal growth. Use only if benefits outweigh risks. |
| Fetal Monitoring | Monitor maternal vital signs (respiratory rate, oxygen saturation, sedation level). Fetal heart rate monitoring during labor. Watch for signs of opioid toxicity in neonate after birth. Consider umbilical cord blood drug levels if indicators of exposure. |
| Fertility Effects | In animal studies, no effects on fertility. In humans, no adequate studies. However, opioid-induced hypogonadism may occur with chronic use, potentially impairing fertility. Withdrawal may normalize function. |