FENTANYL-75
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 and sedation by activating G-protein coupled opioid receptors in the central nervous system, leading to decreased neurotransmitter release and hyperpolarization of neurons.
| Metabolism | Primarily hepatic via CYP3A4 to norfentanyl (inactive), with minor contributions from CYP3A5; also undergoes N-dealkylation and hydroxylation. |
| Excretion | Renal: ~75% as metabolites (primarily norfentanyl) and ~10% unchanged; fecal: ~9%; biliary: minor. |
| Half-life | Terminal elimination half-life: 3-12 hours (mean ~7 hours); prolonged in elderly, hepatic impairment, or continuous infusion. |
| Protein binding | ~80-85% bound, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Vd: 3-8 L/kg (mean ~6 L/kg); large Vd indicates extensive tissue distribution. |
| Bioavailability | Transdermal: ~92%; transmucosal (oral): ~50%; buccal: ~65%; intranasal: ~70%; IM: ~100%. |
| Onset of Action | IV: almost immediate (30 seconds); IM: 7-15 minutes; transdermal: 12-24 hours to steady state. |
| Duration of Action | IV: 30-60 minutes (single dose); transdermal: 72 hours per patch; duration increases with accumulation. |
Apply 75 mcg/h transdermally every 72 hours for opioid-tolerant patients; not for acute pain. Rotate application site.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | GFR <30 mL/min: reduce dose by 50% or use alternative; monitor for respiratory depression. Not recommended in GFR <15 mL/min. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Transdermal fentanyl is not recommended for pediatric patients under 2 years. For opioid-tolerant children 2-12 years: initiate at 25 mcg/h, titrate based on 24-hour opioid requirement. Monitor closely. |
| Geriatric use | Initiate at lowest dose (12.5 or 25 mcg/h) and titrate slowly; monitor for respiratory depression, hypotension, and constipation. Avoid in frail elderly. |
| 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 0.49. Low oral bioavailability reduces infant exposure, but monitor for sedation and respiratory depression in the infant. Contraindicated in breastfeeding with high maternal doses or long-term use. |
| Teratogenic Risk | First trimester: Limited data; potential for neural tube defects based on animal studies. Second/third trimester: Fetal dependence and withdrawal syndrome with chronic use; risk of preterm labor, intrauterine growth restriction. Transplacental transfer occurs. Avoid in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Risk of respiratory depression, especially during initiation or dose escalation; risk of opioid addiction, abuse, and misuse; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risk of fatal overdose from accidental exposure; risk of interaction with CYP3A4 inhibitors; risk of serotonin syndrome with serotonergic drugs.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to fentanyl, opioid non-tolerant patients, significant respiratory depression, acute or severe bronchial asthma, paralytic ileus, known or suspected gastrointestinal obstruction, concurrent use of MAOIs or within 14 days.
| Precautions | Respiratory depression, abuse potential, interactions with CNS depressants, serotonin syndrome, adrenal insufficiency, hypotension, seizure risk, biliary tract spasm, and increased intracranial pressure. |
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| Fetal Monitoring | Maternal: Sedation level, respiratory rate, oxygen saturation, blood pressure, heart rate. Fetal: Heart rate monitoring (non-stress test, biophysical profile) for growth restriction or distress. Neonatal: Withdrawal symptoms (Neonatal Abstinence Syndrome) after delivery. |
| Fertility Effects | Animal studies suggest potential for reduced fertility and embryo-fetal toxicity. In humans, no conclusive evidence; however, chronic opioid use may disrupt menstrual cycles and hypothalamic-pituitary-gonadal axis, potentially impairing fertility. |