Ultiva (remifentanil HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Remifentanil hydrochloride, a fentanyl analog, is a selective micro-receptor opiate agonist.
Remifentanil is a selective micro-receptor agonist with similar potency to fentanyl; the drug shares the actions of the opiate agonists. The drug's precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia. Remifentanil exhibits greater affinity for the micro-receptor than for the delta- or kappa-receptors; the drug does not substantially bind to other nonopiate receptors.
Agonist activity at the opiate micro-receptor can result in analgesia and respiratory depression. Respiratory depression may be mediated by micro-receptors, possibly micro2-receptors (which may be distinct from micro1-receptors involved in analgesia); kappa- and delta-receptors may also be involved in respiratory depression.
Opiate agonists alter perception of and emotional response to pain. Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus). Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.
Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.
Remifentanil does not substantially affect intracranial pressure, intraocular pressure, cerebral blood flow or cerebral capacity, or cerebrovascular reactivity to carbon dioxide. Remifentanil does not substantially affect cerebral cortical cells, thereby exerting minimal effect on cognitive function.
Remifentanil exhibits hypnotic-sparing effects similar to those of other opiates. The drug does not appear to cause histamine release and does not appear to alter intraocular pressure
Remifentanil has a rapid onset of action (within 1-1.5 minutes) and peak analgesic effect (within 1-3 minutes). Remifentanil exhibits a linear, dose-dependent pharmacokinetic profile. Plasma concentration of the drug directly correlates with patient response and decreases 50% in 3-6 minutes after a 1-minute infusion or after prolonged continuous infusion (due to rapid distribution and elimination) and is independent of duration of drug administration.
New steady-state concentrations are evident within 5-10 minutes after a change in the infusion rate. Increasing or decreasing the infusion rate by 0.1 mcg/kg per minute generally produces a 2- to 2.5-ng/mL change in plasma remifentanil concentrations within 5-10 minutes. A new, higher steady-state concentration may be achieved more rapidly (within 3-5 minutes) in intubated patients if 1 mcg/kg of remifentanil is given by rapid IV (bolus) injection in conjunction with an infusion rate increase.
Remifentanil is rapidly distributed throughout blood and highly perfused tissues; the drug is subsequently distributed into peripheral tissues. Remifentanil rapidly equilibrates across the blood-brain barrier. Unlike other opiate agonists, remifentanil does not accumulate at high doses or with prolonged administration.
Plasma protein binding of remifentanil is 70-92% (primarily to alpha1-acid glycoprotein).
Remifentanil is rapidly and extensively (exceeding 95%) hydrolyzed at the propanoic acid-methyl ester linkage by nonspecific esterases in blood and tissues, resulting in formation of an inactive carboxylic acid metabolite; the drug undergoes N-dealkylation to a lesser extent. Remifentanil is not metabolized by plasma cholinesterase and is not appreciably metabolized in the liver or lungs. Remifentanil is rapidly eliminated; at least 88% of a dose is eliminated in urine as the carboxylic acid metabolite.
Terminal elimination half-life of remifentanil is 8-40 minutes; effective biologic half-life is 3-10 minutes. The half-life of the carboxylic acid metabolite is 90-120 minutes.
Generic name: remifentanil HCl
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Ultiva
Indications
The following indications are listed for Ultiva:
- General Anesthesia Adjunct
- Local Anesthesia Adjunct
- Postoperative Acute Pain
Also known as: Adjunct General Anesthesia, Adjunct Local Anesthesia, Post-Op Acute Pain.
Dosing
Dosage of remifentanil hydrochloride is expressed in terms of remifentanil.
Because of synergistic activity with other anesthetics, dosage adjustment of concomitantly administered anesthetic(s) may be needed.
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Contains glycine; contraindicated for epidural or intrathecal administration.
*Known hypersensitivity to fentanyl analogs (e.g., remifentanil).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse reactions (>=1%) with remifentanil include respiratory depression, bradycardia, hypotension, and skeletal muscle rigidity.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of remifentanil for use in the maintenance phase of general anesthesia in outpatient and inpatient surgery have been established in pediatric patients from birth to 12 years of age.
Safety and efficacy of remifentanil as an analgesic in the immediate postoperative period or as an analgesic component of monitored anesthesia care have not been established in pediatric patients.
In pediatric patients 2-12 years of age receiving maintenance anesthesia with remifentanil (0.2-1.95 mcg/kg per minute) in conjunction with nitrous oxide or with nitrous oxide and either halothane or sevoflurane, times to spontaneous purposeful movement and extubation were 1-24 minutes. In pediatric patients 1-12 years of age receiving maintenance anesthesia with remifentanil (up to 0.75 mcg/kg per minute) in conjunction with nitrous oxide and isoflurane, median times to spontaneous purposeful movement and extubation were 15 (range: 2-75) and 13 (range: 4-31) minutes, respectively. In full-term neonates and infants younger than 8 weeks of age receiving maintenance anesthesia with remifentanil (0.4-1 mcg/kg per minute) and nitrous oxide, median times to spontaneous purposeful movement and extubation were 6.5 (range: 1-13) and 8.5 (range: 1-14) minutes, respectively.
Distribution volume of remifentanil is increased in younger pediatric patients and declines to young healthy adult values by 17 years of age. In pediatric patients, remifentanil clearance generally is higher in younger children and declines to young healthy adult values by 17 years of age. Neonatal clearance of the drug is variable and may average twice that observed in young adults.
Available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage with remifentanil.
In animal reproduction studies, reduced fetal rat body weight and pup weights were reported at a dose 2.2 times based on a comparable human IV infusion (induction and maintenance) dose for a surgical procedure lasting 3 hours. There were no malformations noted when remifentanil was administered via bolus injection to pregnant rats or rabbits during organogenesis at doses approximately 5 times and approximately equal, respectively, to a human IV infusion of an induction and maintenance dose for a surgical procedure lasting 3 hours.
Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Remifentanil is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate.
Opioid analgesics, including remifentanil, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.
Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome. Observe newborns for signs of this condition and manage accordingly.
Remifentanil crosses the placenta; average maternal remifentanil concentrations are about twice those observed in the fetus.
It is not known whether remifentanil is distributed into human milk. However, other fentanyl analogs distribute into human milk. Caution is advised if used in nursing women.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for remifentanil and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.
Infants exposed to remifentanil through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped.
Decrease initial and, possibly, subsequent doses of remifentanil by 50% in patients older than 65 years of age; titrate cautiously.
Consider extending anticipated time to clinical effect by 50-100% in geriatric patients.
Patients 65 years of age and older may have increased sensitivity to remifentanil. Respiratory depression is the primary risk for geriatric patients treated with opioids and has occurred after large initial doses were administered to patients who were not opioid tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of remifentanil slowly in these patients and frequently reevaluate the patient for signs of CNS and respiratory depression.
Geriatric patients may exhibit reduced clearance of remifentanil; however, half-life is unchanged, and plasma concentrations decline as rapidly after drug discontinuance as in young adults. Remifentanil is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Onset of action of remifentanil may be delayed in geriatric patients compared with younger individuals. Faster recovery times have been reported for patients younger than 60 years of age compared with those 60 years of age or older receiving remifentanil in conjunction with propofol; mean time to spontaneous respiration was 0.8 versus 3.2 minutes, respectively, and mean time to extubation was 5 versus 9 minutes, respectively.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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