ULTIVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ULTIVA (ULTIVA).
Selective mu-opioid receptor agonist with rapid onset and short duration of action; produces analgesia without significant histamine release.
| Metabolism | Primarily hydrolyzed by non-specific blood and tissue esterases (not plasma cholinesterase) to a major metabolite (remifentanil acid) with minimal activity (<1/300 potency); CYP450 system not involved. |
| Excretion | Remifentanil is metabolized by non-specific blood and tissue esterases to a virtually inactive metabolite (remifentanil acid, 1/4600 potency). Renal excretion accounts for approximately 90% of the metabolite; fecal elimination is minimal (<5%). |
| Half-life | Terminal elimination half-life is 3-10 minutes (context-sensitive half-time is 3-4 minutes independent of infusion duration due to rapid ester hydrolysis). Clinically, recovery is rapid and predictable even after prolonged infusions, with full recovery within 5-10 minutes of discontinuation. |
| Protein binding | Approximately 70% bound to plasma proteins (primarily alpha-1-acid glycoprotein). |
| Volume of Distribution | Volume of distribution at steady state (Vdss) is 0.2-0.4 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Intravenous: 100% (only approved route). Oral bioavailability is negligible due to extensive first-pass metabolism; not administered orally. |
| Onset of Action | IV: Onset of analgesia occurs within 1-1.5 minutes; peak effect (EEG depression) at 1.5-2 minutes. |
| Duration of Action | IV: Duration of effect is 5-10 minutes after a single bolus; offset is rapid due to metabolic clearance. No accumulation with prolonged infusion due to context-insensitive half-life. |
| Molecular Weight | 376.45 |
IV bolus: 1 mcg/kg over 30-60 seconds, then continuous IV infusion: 0.25-1 mcg/kg/min for intraoperative analgesia. For general anesthesia induction: 0.5-1 mcg/kg IV bolus; maintenance: 0.25-1 mcg/kg/min IV infusion.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >30 mL/min). For severe renal impairment (CrCl ≤30 mL/min), reduce continuous infusion dose by 50% due to decreased clearance and prolonged context-sensitive half-life. |
| Liver impairment | No dose adjustment required for Child-Pugh Class A or B. For Child-Pugh Class C, reduce bolus dose by 50% and continuous infusion rate by 50% due to decreased clearance. |
| Pediatric use | For neonates (≥37 weeks gestational age): IV bolus 0.5-1 mcg/kg, then continuous infusion 0.4-0.6 mcg/kg/min. For infants 1-2 months: IV bolus 0.5-1 mcg/kg, then continuous infusion 0.5-1 mcg/kg/min. For children 2-12 years: IV bolus 1 mcg/kg, then continuous infusion 0.5-1 mcg/kg/min. For adolescents 12-16 years: IV bolus 0.5-1 mcg/kg, then continuous infusion 0.25-0.5 mcg/kg/min. |
| Geriatric use | Reduce initial bolus dose by 50% (0.5 mcg/kg) and continuous infusion rate by 50% (e.g., starting at 0.125 mcg/kg/min) due to increased sensitivity and decreased clearance. Titrate to effect and monitor for hypotension and bradycardia. |
| 1st trimester | Remifentanil crosses the placenta. Limited human data; animal studies show no teratogenic effects at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | Similar to first trimester; avoid prolonged use or high doses due to risk of fetal respiratory depression and withdrawal. |
| 3rd trimester | May cause neonatal respiratory depression and withdrawal if used near term. Use only if benefits outweigh risks; monitor neonate. |
Clinical note
Comprehensive clinical and safety monograph for ULTIVA (ULTIVA).
| Placental transfer | Rapidly crosses the placenta; fetal-maternal ratio approximately 0.88. |
| Breastfeeding | Remifentanil is excreted into breast milk in low concentrations, but due to its rapid metabolism, exposure to the infant is likely minimal. Caution is advised; monitor infant for sedation and respiratory depression. |
■ FDA Black Box Warning
Risk of respiratory depression, particularly in elderly, debilitated, or patients with respiratory disorders; must be administered only by trained personnel with resuscitation equipment available. Concomitant use with CNS depressants increases risk of respiratory depression. Avoid use in opioid non-tolerant patients for ambulatory surgery as continuous infusions require careful monitoring.
| Serious Effects |
Hypersensitivity to remifentanil or any component of the formulationUse as a sole agent for induction of anesthesia (loss of consciousness may not occur at low doses)Use in epidural or intrathecal administration (contains glycine, which is neurotoxic)
| Precautions | Respiratory depression: risk increased with higher doses, elderly, and concurrent CNS depressants, Muscle rigidity: may occur, especially after rapid bolus administration; treat with muscle relaxants or dose reduction, Bradycardia and hypotension: more common with concurrent volatile anesthetics, Serotonin syndrome risk: when used with serotonergic drugs (e.g., MAOIs, SSRIs), Seizures: rare but reported in patients with myoclonus, Abrupt discontinuation may lead to withdrawal symptoms in opioid-tolerant patients |
| Food/Dietary |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | ULTIVA (remifentanil) is classified as FDA Pregnancy Category C. Animal studies have shown increased fetal resorptions and delayed ossification at doses 2-4 times the human dose. No adequate human studies exist. First trimester: use only if clearly needed; potential for teratogenicity unknown. Second and third trimesters: chronic use may lead to neonatal opioid withdrawal syndrome; use during labor may cause neonatal respiratory depression. |
| Fetal Monitoring | Monitor maternal vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation) and level of consciousness. Continuous fetal heart rate monitoring during labor is recommended. Monitor for signs of neonatal respiratory depression and opioid withdrawal post-delivery. Assess for maternal chest wall rigidity or respiratory depression. |
| Fertility Effects | No specific human studies on fertility. Animal studies did not demonstrate impaired fertility at clinically relevant doses. However, opioids may cause hormonal alterations (e.g., decreased libido, amenorrhea) with chronic use. Effects are reversible upon discontinuation. |
| No specific food interactions are documented for ULTIVA (remifentanil). However, because it is used in a controlled clinical setting, patients are typically NPO (nothing by mouth) before and during anesthesia. Grapefruit juice is not expected to interact due to rapid esterase metabolism. |
| Clinical Pearls | ULTIVA (remifentanil) is an ultra-short-acting mu-opioid agonist with a rapid onset (1 minute) and offset (5-10 minutes) due to ester hydrolysis by non-specific blood and tissue esterases. It is used for continuous IV infusion or bolus administration during general anesthesia or monitored anesthesia care. Key pearls: (1) Must be administered via a dedicated IV line due to risk of inadvertent bolus if line is flushed. (2) Rapid elimination independent of renal or hepatic function makes it ideal for patients with organ dysfunction. (3) Postoperative pain management requires transition to longer-acting opioids because of its rapid offset. (4) Common side effects include bradycardia, hypotension, respiratory depression, and muscle rigidity. (5) Contraindicated in patients with hypersensitivity to opioids or fentanyl analogs, and for epidural or intrathecal administration due to glycine content. |
| Patient Advice | ULTIVA is a strong opioid used only during surgery or procedures to control pain and is given by a healthcare professional. · You may experience nausea, vomiting, dizziness, or slow breathing during or after receiving ULTIVA. · Tell your doctor if you have any allergies, especially to opioids or fentanyl-like drugs. · After the procedure, you will be given other pain medications as ULTIVA wears off quickly. · Do not drive or operate machinery for at least 24 hours after receiving ULTIVA, as it can cause drowsiness and impair coordination. · If you are pregnant or breastfeeding, inform your doctor before treatment. |