REMIFENTANIL HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REMIFENTANIL HYDROCHLORIDE (REMIFENTANIL HYDROCHLORIDE).
Remifentanil is a μ-opioid receptor agonist with rapid onset and ultra-short duration of action due to esterase metabolism. It produces analgesia by activating G-protein-coupled opioid receptors in the central nervous system, inhibiting nociceptive transmission and altering pain perception.
| Metabolism | Primarily hydrolyzed by nonspecific blood and tissue esterases to remifentanil acid (inactive metabolite). Minimal hepatic metabolism (CYP3A4). |
| Excretion | Remifentanil is rapidly metabolized by non-specific plasma and tissue esterases to essentially inactive carboxylic acid metabolite (GI-90291). Approximately 90% of the dose is excreted renally as this metabolite, with less than 1% excreted unchanged. Fecal excretion is minimal. |
| Half-life | Terminal elimination half-life is 3–10 minutes (mean approximately 6 minutes) in healthy adults. Context-sensitive half-time is 3–5 minutes, independent of infusion duration, due to rapid ester hydrolysis and lack of significant redistribution. In severe hepatic or renal impairment, half-life is not significantly prolonged. |
| Protein binding | Approximately 70% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Steady-state volume of distribution (Vdss) is 0.3–0.5 L/kg (approx. 30–40 L in 70 kg adult), indicating limited tissue distribution due to rapid hydrolysis and low lipophilicity relative to other opioids. |
| Bioavailability | Not orally bioavailable due to extensive first-pass metabolism; only administered intravenously (IV) or by infusion (100% bioavailability for IV route). |
| Onset of Action | Intravenous: Onset of analgesia is 1–2 minutes; maximum respiratory depression occurs within 2–3 minutes. Rapid redistribution leads to short onset for effect-site equilibration (ke0 half-life 1–2 minutes). |
| Duration of Action | Duration of analgesic effect is 5–10 minutes after a single bolus dose. Clinically, continuous infusion is required to maintain effect; recovery of respiratory function occurs within 10–15 minutes after discontinuation. No accumulation with prolonged infusion. |
IV bolus: 0.5–1 mcg/kg over 30–60 sec; continuous IV infusion: 0.05–2 mcg/kg/min, titrated to effect. For induction of anesthesia: 0.5–1 mcg/kg; maintenance: 0.1–0.5 mcg/kg/min; higher doses up to 2 mcg/kg/min for deeper anesthesia.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. Remifentanil pharmacokinetics are not significantly altered by renal function, including in end-stage renal disease. However, monitor for accumulation of the metabolite remifentanil acid (inactive); no clinical effect expected. |
| Liver impairment | No dose adjustment required for hepatic impairment. Pharmacokinetics unchanged in patients with moderate to severe hepatic disease (Child-Pugh class A–C). Dose titration based on clinical response is recommended. |
| Pediatric use | Neonates and infants (<2 years): IV bolus 0.25–1 mcg/kg; continuous infusion 0.025–0.1 mcg/kg/min. Children (2–12 years): IV bolus 0.5–1 mcg/kg; infusion 0.05–0.15 mcg/kg/min. Adolescents: dosing similar to adults. Use weight-based dosing; titrate to effect. |
| Geriatric use | Elderly patients (≥65 years): reduce initial bolus dose by 50% (0.5 mcg/kg) and infusion rate by 50% (start at 0.025 mcg/kg/min) due to increased sensitivity and reduced clearance. Titrate cautiously to avoid hypotension and bradycardia. Monitor for prolonged recovery. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REMIFENTANIL HYDROCHLORIDE (REMIFENTANIL HYDROCHLORIDE).
| Breastfeeding | Remifentanil is excreted into breast milk in low amounts; M/P ratio is 2.5 (based on milk:plasma concentration). Due to rapid metabolism, minimal infant exposure is expected. Use with caution; monitor infant for signs of sedation or respiratory depression. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Chronic use may lead to fetal dependence and neonatal opioid withdrawal syndrome (NOWS). At delivery, may cause neonatal respiratory depression if administered near term. |
■ FDA Black Box Warning
Risk of respiratory depression: Remifentanil can cause life-threatening or fatal respiratory depression. Monitor respiratory function closely, especially during initiation and dose changes. Use with caution in patients with compromised respiratory reserve.
| Common Effects | Nausea Diarrhea Dryness in mouth Fatigue Headache Skin rash Sleepiness Vomiting |
| Serious Effects |
["Hypersensitivity to remifentanil or any component","Use as the sole agent for induction of anesthesia (inadequate loss of consciousness)","Acute or severe bronchial asthma","Known or suspected paralytic ileus","Concomitant use with MAOIs or within 14 days of stopping MAOIs"]
| Precautions | ["Respiratory depression","Muscle rigidity (especially rapid IV administration)","Bradycardia and hypotension","Serotonin syndrome risk with concurrent serotonergic drugs","Adrenal insufficiency with prolonged use","Neonatal opioid withdrawal syndrome with prolonged maternal use","Tolerance and physical dependence with prolonged use"] |
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| Fetal Monitoring | Monitor maternal heart rate, blood pressure, oxygen saturation, and respiratory rate continuously. Fetal heart rate monitoring is recommended during labor. Assess neonatal respiratory status after delivery. Observe for signs of opioid withdrawal in mother and neonate after prolonged use. |
| Fertility Effects | No human studies on fertility effects. Animal studies show no impairment of fertility at clinically relevant doses. Opioid use may cause menstrual cycle irregularities, but data specific to remifentanil are lacking. |