FENTANYL-50
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Fentanyl is a synthetic opioid agonist primarily acting on mu-opioid receptors in the central nervous system, leading to analgesia, sedation, and respiratory depression. It also interacts with kappa and delta receptors to a lesser extent.
| Metabolism | Primarily metabolized via CYP3A4 in the liver to norfentanyl (inactive) and other metabolites; minor contributions from CYP3A5. Less than 10% excreted unchanged in urine. |
| Excretion | Renal: 75% (primarily as metabolites, <10% unchanged); Fecal: 9%; Biliary: minor contribution. |
| Half-life | Terminal elimination half-life: 3-12 hours (mean 7 hours); context: prolonged with continuous infusion or in elderly, hepatic impairment, or obesity due to accumulation in adipose tissue. |
| Protein binding | 80-85% bound, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 3-8 L/kg (mean 4 L/kg); high Vd indicates extensive distribution into tissues including skeletal muscle and fat. |
| Bioavailability | IV: 100%; Transdermal: 92% (relative to IV, absolute bioavailability ~92%); Transmucosal (buccal, sublingual): 50-70%; Intranasal: 70-90%; Oral: low (<50% due to first-pass metabolism). |
| Onset of Action | IV: almost immediate (30-60 seconds); IM: 7-15 minutes; Transdermal: 12-18 hours (steady state achieved in 24-72 hours); Intranasal: 5-15 minutes. |
| Duration of Action | IV: 30-60 minutes (single dose); IM: 1-2 hours; Transdermal: 72 hours (patch removal continues analgesia for 12-24 hours due to dermal depot); Intranasal: 1-2 hours. |
50 mcg intravenously every 5-10 minutes as needed for breakthrough pain or for induction of anesthesia; for transdermal, 12-100 mcg/hour applied every 72 hours.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 25-50%; GFR <30 mL/min: avoid or reduce dose by 50-75% and monitor closely. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: reduce dose by 75% or avoid use. |
| Pediatric use | Intravenous: 0.5-2 mcg/kg per dose every 5-10 minutes as needed; transdermal: not recommended for children under 2 years; for children >2 years, start at 12 mcg/hour based on prior opioid exposure. |
| Geriatric use | Starting dose should be 50-75% lower than in younger adults; titrate slowly; transdermal patch starting dose no higher than 25 mcg/hour; monitor for respiratory depression and cognitive impairment. |
| 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 in low amounts (M/P ratio ~0.4-0.5). Single doses are unlikely to harm infant, but chronic use may cause sedation or respiratory depression in the neonate. Monitor for drowsiness, poor feeding. Benefit-risk assessment recommended. |
| Teratogenic Risk |
■ FDA Black Box Warning
Black Box Warning: Risk of respiratory depression, addiction, abuse, and misuse; life-threatening respiratory depression and death can occur at any dose, especially with initial use or dose escalation. Concomitant use with CNS depressants (e.g., benzodiazepines, alcohol) may cause profound sedation, respiratory depression, coma, and death. Accidental exposure (especially in children) can be fatal.
| Common Effects | Constipation |
| Serious Effects |
["Hypersensitivity to fentanyl or any component","Acute or severe bronchial asthma in unmonitored settings","Significant respiratory depression (without resuscitative equipment)","Paralytic ileus or known gastrointestinal obstruction","Concurrent use with MAOIs (within 14 days) for immediate-release forms (dose adjustment may be considered for transdermal under strict monitoring)"]
| Precautions | ["Risk of respiratory depression requires monitoring; use with caution in COPD, decreased respiratory reserve, or hypoxia","Serotonin syndrome risk with concomitant serotonergic drugs","Adrenal insufficiency and androgen deficiency with prolonged use","Neonatal opioid withdrawal syndrome with prolonged maternal use during pregnancy","Severe hypotension, especially in hypovolemic patients","QT prolongation (high doses, especially IV)","Risks of tolerance, physical dependence, and withdrawal upon abrupt discontinuation"] |
Loading safety data…
| First trimester: Limited data, but animal studies show no structural teratogenicity at clinically relevant doses. Second/third trimester: Chronic exposure may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery. Avoid prolonged use. |
| Fetal Monitoring | Maternal: heart rate, blood pressure, respiratory rate, oxygen saturation, sedation level. Fetal: heart rate monitoring (especially during labor), growth ultrasound if prolonged use, neonatal monitoring for withdrawal after delivery. |
| Fertility Effects | Animal studies show no impairment of fertility at therapeutic doses. In humans, chronic opioid use may disrupt menstrual cycles and reduce libido due to hormonal changes (e.g., hypothalamic-pituitary-gonadal axis suppression). Reversible upon discontinuation. |