Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ALFENTANIL vs UPTRAVI
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Uptravi (selexipag) is a prostacyclin receptor (IP receptor) agonist. Selexipag and its active metabolite, ACT-333679, selectively bind to the IP receptor, leading to vasodilation, inhibition of platelet aggregation, and antiproliferative effects on smooth muscle cells.
Analgesic adjunct during general anesthesia,Induction of anesthesia,Maintenance of anesthesia for short surgical procedures,Off-label: Procedural sedation in monitored settings
Treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization,Off-label: None established
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.
Initial dose 200 mcg orally twice daily, titrated in increments of 200 mcg twice daily at weekly intervals to a maximum of 1600 mcg twice daily.
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.
Terminal elimination half-life is approximately 7–9 hours in healthy subjects, but prolonged in patients with hepatic impairment (Child-Pugh class A: ~11 hours; class B: ~16 hours). Steady-state is reached within 2–4 days of twice-daily dosing.
Alfentanil is primarily metabolized by hepatic cytochrome P450 enzymes, mainly CYP3A4, through oxidative N-dealkylation and O-demethylation to inactive metabolites.
Selexipag is hydrolyzed by carboxylesterases (mainly CES1 and CES2) to its active metabolite, ACT-333679. Both are further metabolized by CYP3A4 and CYP2C8. ACT-333679 is also a substrate for UGT1A3 and UGT2B7.
Primarily hepatic metabolism via CYP3A4; <1% excreted unchanged in urine; metabolites (mainly noralfentanil) excreted renally. Biliary/fecal excretion of metabolites accounts for ~30%.
Primarily hepatic metabolism; renal excretion of unchanged drug is <1%. Fecal excretion accounts for approximately 70% of total elimination, mainly as metabolites. Biliary excretion contributes to fecal elimination.
~92% bound primarily to alpha-1-acid glycoprotein (AAG) and albumin.
99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein.
Vd: 0.4–1.0 L/kg (mean ~0.75 L/kg). Moderate Vd reflecting rapid distribution to tissues, especially brain and muscle.
Approximately 0.3 L/kg in healthy subjects, indicating distribution primarily within the vascular space and well-perfused tissues.
IV: 100%. IM: ~90%. Epidural: ~30–50% due to local uptake and redistribution. No significant oral bioavailability.
Oral bioavailability is approximately 50–60% due to first-pass metabolism. Food does not significantly affect absorption.
GFR 10-50 m L/min: administer with caution, consider dose reduction of 25-50%; GFR <10 m L/min: reduce dose by 50% and extend dosing interval.
No dose adjustment required for mild to moderate renal impairment (e GFR ≥15 m L/min/1.73 m²). Not studied in severe renal impairment (e GFR <15 m L/min/1.73 m²) or on dialysis; use caution.
Child-Pugh class A: no adjustment needed; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: reduce dose by 75%.
Mild hepatic impairment (Child-Pugh A): No dose adjustment. Moderate hepatic impairment (Child-Pugh B): Initial dose 200 mcg once daily, titrate cautiously. Severe hepatic impairment (Child-Pugh C): Not recommended.
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.
Not indicated for pediatric patients; safety and efficacy not established in patients <18 years.
Reduce initial IV bolus by 30-50% to 3-10 mcg/kg; titrate carefully; monitor for prolonged sedation and respiratory depression.
No specific dose adjustment recommended; elderly patients may have increased sensitivity, monitor closely.
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.
None.
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.
Pulmonary edema may occur; consider the possibility of pulmonary veno-occlusive disease (PVOD) if symptoms develop,Hepatic impairment: Avoid use in severe hepatic impairment (Child-Pugh Class C),Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil) increases exposure; reduce dose or consider alternative,Concomitant use with strong CYP3A4 inducers (e.g., rifampin) may reduce efficacy; monitor for loss of effect
Hypersensitivity to alfentanil, fentanyl, or any opioid,Significant respiratory depression (e.g., acute asthma, COPD in acute exacerbation),Acute or severe bronchial asthma,Suspected or known paralytic ileus,MAO inhibitor use within 14 days (serotonin syndrome risk),Myasthenia gravis (relative contraindication due to risk of respiratory muscle weakness),Morbid obesity with sleep apnea (relative contraindication; increased risk of respiratory depression)
Severe hepatic impairment (Child-Pugh Class C),Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil)
No significant food interactions known. Avoid grapefruit and grapefruit juice as they may inhibit CYP3A4 metabolism, potentially prolonging effects.
Avoid grapefruit juice as it may increase systemic exposure to UPTRAVI. Take with or without food, but consistent timing with meals is recommended to maintain stable drug levels.
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.
In animal studies, UPTRAVI (selexipag) and its active metabolite showed developmental toxicity including reduced fetal weights and increased skeletal variations at maternal toxic doses. No adequate and well-controlled studies in pregnant women. Risk cannot be ruled out. First trimester: potential teratogenicity based on animal data. Second and third trimesters: may cause fetal harm due to pharmacological action (IP receptor agonist) potentially affecting uterine blood flow.
Alfentanil is excreted into breast milk in very low concentrations; estimated relative infant dose is low (<2% of maternal weight-adjusted dose). M/P ratio not determined in humans. Compatible with breastfeeding with caution; monitor infant for drowsiness, feeding difficulties.
No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio is unknown. The active metabolite is potentially excreted in animal milk. Due to potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least 2 days after final dose.
Pregnancy can alter alfentanil pharmacokinetics: increased volume of distribution, decreased plasma clearance, prolonged elimination half-life. Dose reduction may be needed for prolonged use; titrate to effect. During labor, use smallest effective dose.
No pharmacokinetic studies in pregnant women. Pregnancy may alter drug metabolism (e.g., increased clearance, Vd). No specific dose adjustment recommendations; use only if benefit outweighs risk. Close clinical monitoring for efficacy and tolerability.
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.
Titrate to maximum tolerated dose up to 1600 mg twice daily. Monitor for signs of pulmonary edema (PPH with veno-occlusive disease). Co-administration with strong CYP2C8 inhibitors (e.g., gemfibrozil) reduces UPTRAVI clearance; decrease dose by 50% during co-administration. Avoid abrupt discontinuation; taper if possible. May cause orthostatic hypotension; assess blood pressure regularly. UPTRAVI is a prodrug of the active metabolite ACT-333679, a selective prostacyclin receptor (IP receptor) agonist.
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.
Take exactly as prescribed; do not crush or split tablets.,Do not stop taking this medication suddenly; consult your doctor if you need to discontinue.,Avoid grapefruit juice as it may increase drug exposure.,Report any severe headaches, jaw pain, or flushing to your healthcare provider.,Use caution when driving or operating machinery until you know how this medication affects you.,Store at room temperature away from moisture and heat.
"Propantheline, an anticholinergic agent, can competitively antagonize muscarinic acetylcholine receptors, potentially reducing gastrointestinal motility and secretion. Alfentanil, a mu-opioid receptor agonist, also decreases gastrointestinal motility through central and peripheral opioid receptors. Concomitant use may synergistically inhibit peristalsis, leading to severe constipation, paralytic ileus, or delayed gastric emptying, which can increase the risk of aspiration and complicate anesthesia recovery."
"Alfentanil, a potent opioid analgesic, can cause significant hypotension and respiratory depression. When combined with furosemide, a loop diuretic that reduces blood volume and vascular resistance, there is a synergistic decrease in blood pressure, which may precipitate cardiovascular collapse, especially in patients with compromised circulatory reserves. Additionally, furosemide may enhance the sedative and respiratory depressant effects of alfentanil, leading to increased risk of respiratory acidosis and altered mental status."
"Alfentanil, a potent mu-opioid receptor agonist, can enhance the bradycardic effects of nebivolol, a beta-1 selective blocker with additional nitric oxide-mediated vasodilation. The combination may lead to excessive slowing of heart rate, reduced cardiac output, and potential hemodynamic instability, particularly in patients with underlying cardiac conduction abnormalities or hypovolemia."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ALFENTANIL vs UPTRAVI, answered by our medical review team.
ALFENTANIL is a Opioid Analgesic that works by 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.. UPTRAVI is a Prostacyclin Receptor Agonist that works by Uptravi (selexipag) is a prostacyclin receptor (IP receptor) agonist. Selexipag and its active metabolite, ACT-333679, selectively bind to the IP receptor, leading to vasodilation, inhibition of platelet aggregation, and antiproliferative effects on smooth muscle cells.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ALFENTANIL and UPTRAVI depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ALFENTANIL is: 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.. The standard adult dose of UPTRAVI is: Initial dose 200 mcg orally twice daily, titrated in increments of 200 mcg twice daily at weekly intervals to a maximum of 1600 mcg twice daily.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between ALFENTANIL and UPTRAVI in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. ALFENTANIL is classified as Category C. 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. UPTRAVI is classified as Category C. In animal studies, UPTRAVI (selexipag) and its active metabolite showed developmental toxicity including reduced fetal weights and increased skeletal variations at maternal toxic d. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.