ALFENTANIL
Clinical safety rating
cautionComprehensive clinical and safety monograph for ALFENTANIL (ALFENTANIL).
Alfentanil is a potent, short-acting synthetic opioid analgesic that primarily acts as a mu-opioid receptor agonist. It binds to mu-opioid receptors in the central nervous system, leading to G-protein coupled activation of inwardly rectifying potassium channels and inhibition of voltage-gated calcium channels, resulting in hyperpolarization and reduced neurotransmitter release. This produces analgesia, sedation, and respiratory depression.
| Metabolism | Alfentanil is primarily metabolized by hepatic cytochrome P450 enzymes, mainly CYP3A4, through oxidative N-dealkylation and O-demethylation to inactive metabolites. |
| Excretion | Primarily hepatic metabolism via CYP3A4; <1% excreted unchanged in urine; metabolites (mainly noralfentanil) excreted renally. Biliary/fecal excretion of metabolites accounts for ~30%. |
| Half-life | Terminal elimination half-life: 90–111 minutes (1.5–1.85 hours). Clinically, context-sensitive half-time is short (~40 min after 3-hour infusion) due to rapid redistribution and metabolism. |
| Protein binding | ~92% bound primarily to alpha-1-acid glycoprotein (AAG) and albumin. |
| Volume of Distribution | Vd: 0.4–1.0 L/kg (mean ~0.75 L/kg). Moderate Vd reflecting rapid distribution to tissues, especially brain and muscle. |
| Bioavailability | IV: 100%. IM: ~90%. Epidural: ~30–50% due to local uptake and redistribution. No significant oral bioavailability. |
| Onset of Action | IV: 30–60 seconds (rapid onset). IM: 10–15 minutes. Epidural: 10–15 minutes. |
| Duration of Action | IV: 5–10 minutes after single bolus (analgesic effect); dose-dependent. Context-sensitive half-time increases with infusion duration but remains short vs. fentanyl. Epidural: 30–60 minutes. |
| Molecular Weight | 416.5 |
Initial IV bolus of 5-20 mcg/kg; maintenance infusion of 0.5-1.5 mcg/kg/min; incremental boluses of 5-10 mcg/kg as needed. Induction of anesthesia: 50-100 mcg/kg IV.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: administer with caution, consider dose reduction of 25-50%; GFR <10 mL/min: reduce dose by 50% and extend dosing interval. |
| Liver impairment | Child-Pugh class A: no adjustment needed; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: reduce dose by 75%. |
| Pediatric use | Initial IV bolus of 5-20 mcg/kg; maintenance infusion of 0.5-2 mcg/kg/min. For neonates, reduce dose by 30-50% due to immature clearance. |
| Geriatric use | Reduce initial IV bolus by 30-50% to 3-10 mcg/kg; titrate carefully; monitor for prolonged sedation and respiratory depression. |
| 1st trimester | Alfentanil crosses the placenta. Animal studies show no teratogenicity, but human data are limited. Use only if clearly needed. |
| 2nd trimester | Similar to first trimester; consider risk-benefit. May cause fetal respiratory depression if used near term. |
| 3rd trimester | Use near term may cause neonatal respiratory depression and withdrawal. Avoid prolonged use or high doses. |
Clinical note
Comprehensive clinical and safety monograph for ALFENTANIL (ALFENTANIL).
| Placental transfer | Rapidly crosses placenta; maternal-fetal equilibration occurs within minutes. Fetal concentrations approximately 50-100% of maternal levels. |
| Breastfeeding | Alfentanil is excreted into breast milk in low concentrations. After a single dose, the relative infant dose is estimated at <1% of maternal weight-adjusted dose. Short half-life minimizes accumulation. Consider waiting 4 hours after dose before breastfeeding. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Alfentanil is an opioid analgesic; limited human data. No clear evidence of major malformations, but third trimester use may cause neonatal opioid withdrawal syndrome (NOWS). Avoid prolonged use or high doses near term; use during labor may cause respiratory depression in neonate. |
| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, sedation level, and pain control. Fetal heart rate monitoring during labor; neonate observation for respiratory depression, sedation, and withdrawal symptoms if used chronically. |
| Fertility Effects | No human data on fertility effects. Animal studies show no significant impairment of fertility. Opioids may affect hypothalamic-pituitary-gonadal axis; chronic use may cause hormonal changes but clinical significance unknown. |
■ FDA Black Box Warning
Risk of respiratory depression: Alfentanil can cause severe, life-threatening, or fatal respiratory depression. Monitor for respiratory depression, especially during initiation or following dose increases. Accidental ingestion of even one dose can be fatal. Concomitant use with central nervous system depressants (e.g., benzodiazepines, alcohol) may increase risk. Alfentanil is an opioid agonist and a Schedule II controlled substance with high potential for abuse and addiction.
| Serious Effects |
Hypersensitivity to alfentanil or any opioidAcute or severe bronchial asthmaRespiratory depressionObstructive airway diseaseConcurrent MAO inhibitor therapy or within 14 daysMyasthenia gravisIncreased intracranial pressure (except during anesthesia)
| Precautions | Respiratory depression: Potentially fatal; monitor oxygenation and ventilation., Abuse potential: Schedule II controlled substance; risk of addiction, abuse, and diversion., Concomitant use with CNS depressants: Increases risk of profound sedation, respiratory depression, coma, and death; limit use or monitor closely., Geriatric and cachectic patients: Increased sensitivity; reduce initial dose., Hepatic impairment: Alfentanil clearance is reduced in patients with cirrhosis; consider dose adjustment., Bradycardia and hypotension: Use with caution in patients with hypovolemia or reduced cardiac reserve., Serotonin syndrome: Risk with concurrent serotonergic drugs (e.g., MAOIs, SSRIs, triptans); monitor for symptoms., Withdrawal: Prolonged use may lead to physical dependence; taper dose gradually. |
| Food/Dietary | No significant food interactions known. Avoid grapefruit and grapefruit juice as they may inhibit CYP3A4 metabolism, potentially prolonging effects. |
| Clinical Pearls | Alfentanil is a potent, short-acting synthetic opioid (4-5 times more potent than fentanyl) with rapid onset (1-2 min) and brief duration (5-10 min). Primarily used for induction and maintenance of anesthesia, especially in short procedures. Requires careful monitoring of respiratory depression and chest wall rigidity, particularly during rapid IV administration. Hepatic metabolism (CYP3A4) affected by liver disease; reduce dose. Decrease dose in elderly and hypovolemic patients. Not recommended for chronic pain due to short half-life. |
| Patient Advice | This medication causes drowsiness and dizziness; avoid driving or operating machinery for at least 24 hours after administration. · Report any difficulty breathing, chest tightness, or feeling faint immediately. · Alfentanil is used only in hospital settings under direct supervision of healthcare professionals. · Inform your doctor if you have a history of liver disease, lung disease, or drug/alcohol abuse. · Do not consume alcohol or other sedatives while under the effects of alfentanil. |
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