FENTANYL-62
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.
| Metabolism | Hepatic metabolism primarily via CYP3A4 to norfentanyl and other inactive metabolites; also undergoes N-dealkylation and hydroxylation. |
| Excretion | Renal (primarily as metabolites, <10% unchanged; ~75% total metabolites in urine), fecal (~9% total metabolites). |
| Half-life | 3–7 hours (terminal elimination half-life; prolonged in elderly, hepatic impairment, or with continuous infusion due to redistribution). |
| Protein binding | ~80–85% (primarily to alpha-1-acid glycoprotein, also albumin). |
| Volume of Distribution | 3–6 L/kg (large Vd due to high lipophilicity; distributes extensively to tissues and fat). |
| Bioavailability | Transdermal: ~92%; Buccal: ~50%; Intranasal: ~50–70%; Oral: <30% (extensive first-pass metabolism). |
| Onset of Action | IV: 30–60 seconds; IM: 7–15 minutes; Transdermal: 12–24 hours (initial); Buccal/Intranasal: 5–15 minutes. |
| Duration of Action | IV: 30–60 minutes (analgesic effect; respiratory depression may persist longer); IM: 1–2 hours; Transdermal: 72 hours (steady-state levels maintained). |
For analgesia: 50-100 mcg IV/IM every 1-2 hours as needed. For anesthesia: 2-50 mcg/kg IV. For PCA: 10-20 mcg IV with 5-10 min lockout. Transdermal: 12-100 mcg/h patch every 72 hours; start at 25 mcg/h in opioid-naive patients.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | GFR 30-60 mL/min: no adjustment for single doses; use with caution for chronic therapy. GFR 15-29 mL/min: consider dose reduction by 25-50% and monitor for CNS toxicity. GFR <15 mL/min: avoid transdermal formulations; reduce IV/oral doses by 50-75% and monitor closely. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce starting dose by 50% and titrate slowly. Child-Pugh Class C: avoid use or reduce dose by 75% with extended dosing intervals; monitor for respiratory depression. |
| Pediatric use | For procedural sedation: 0.5-2 mcg/kg IV/IM; for analgesia: 0.5-1 mcg/kg IV every 1-2 hours. For anesthesia: 2-5 mcg/kg IV for induction; maintenance 0.5-2 mcg/kg/h IV infusion. Transdermal not recommended for opioid-naive children. |
| Geriatric use | Reduce initial dose by 50-75% due to increased sensitivity; titrate slowly. Avoid transdermal patches in frail elderly; use lowest effective dose. Monitor for respiratory depression and constipation. PCA may require lower bolus doses (5-10 mcg) and longer lockout intervals. |
| 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 concentrations; the M/P ratio is approximately 0.4. Use with caution due to potential for infant sedation and respiratory depression; lowest effective dose for shortest duration. Risk of withdrawal in breastfed infants if maternal use is prolonged. |
| Teratogenic Risk |
■ FDA Black Box Warning
Risk of respiratory depression, particularly in non-opioid-tolerant patients; risk of abuse, addiction, and diversion; concomitant use with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma, and death; neonatal opioid withdrawal syndrome with prolonged use during pregnancy.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to fentanyl or any component; significant respiratory depression; acute or severe bronchial asthma; paralytic ileus; suspected or known GI obstruction; concurrent use with MAOIs or within 14 days of discontinuation; non-opioid-tolerant patients for transmucosal immediate-release formulations.
| Precautions | Respiratory depression, risk of serotonin syndrome with serotonergic drugs, adrenal insufficiency, hypotension, bradycardia, seizures, serotonin syndrome, severe hypotension, and risk of misuse/abuse. Caution in patients with COPD, sleep apnea, head injury, increased intracranial pressure, biliary tract disease, and elderly/debilitated patients. |
Loading safety data…
| First trimester: Limited data; no clear evidence of major malformations in humans, but opioid exposure may be associated with neural tube defects in some studies. Second trimester: Risk of miscarriage or fetal growth restriction with prolonged use; no specific teratogenic effects identified. Third trimester: Risk of neonatal opioid withdrawal syndrome (NOWS) if used near term; respiratory depression at birth. |
| Fetal Monitoring | Maternal: Vital signs (respiratory rate, oxygen saturation, sedation level), pain assessment, signs of opioid dependence. Fetal: Heart rate monitoring during labor if used for analgesia; ultrasound for growth if prolonged use. Neonatal: Monitor for signs of withdrawal for at least 48 hours after delivery. |
| Fertility Effects | May suppress gonadotropin-releasing hormone (GnRH) leading to hypogonadism, oligomenorrhea, or anovulation with chronic use; reversible upon discontinuation. |