Remifentanil
Looking up MedlinePlus…
From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF ULTIVA Addiction, Abuse, and Misuse Because the use of ULTIVA exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1) ] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of ULTIVA, especially during initiation or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of ULTIVA are essential [see Warnings and Precautions (5.2) ] . Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of ULTIVA and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3) , Drug Interactions (7) ] .
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF ULTIVA See full prescribing information for complete boxed warning. • ULTIVA exposes users to the risks of addiction, abuse, and misuse. Assess patient’s risk before prescribing and reassess regularly for the development of these behaviors and conditions. ( 5.1 ) • Serious, life-threatening, or fatal respiratory depression may occur with use of ULTIVA, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of ULTIVA are essential.
( 5.2 ) • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate. ( 5.3 , 7 )
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
Prepare this dose
Your numbers for remifentanil. Take vial strength, diluent, and limits from the label below.
Enter a dose to see draw volume, final concentration, and rates.
Important Dosage and Administration Information
Monitor patients closely for respiratory depression when initiating therapy and following dosage increases with ULTIVA and adjust the dosage accordingly [see Warnings and Precautions ].
ULTIVA is for IV use only.
ULTIVA should not be administered without dilution.
Continuous infusions of ULTIVA should be administered only by an infusion device. IV bolus administration of ULTIVA should be used only during the maintenance of general anesthesia. In nonintubated patients, single doses of ULTIVA should be administered over 30 to 60 seconds.
Interruption of an infusion of ULTIVA will result in rapid offset of effect. Rapid clearance and lack of drug accumulation result in rapid dissipation of respiratory depressant and analgesic effects upon discontinuation of ULTIVA at recommended doses. Discontinuation of an infusion of ULTIVA should be preceded by the establishment of adequate postoperative analgesia.
Injections of ULTIVA should be made into IV tubing at or close to the venous cannula. Upon discontinuation of ULTIVA, the IV tubing should be cleared to prevent the inadvertent administration of ULTIVA at a later point in time. Failure to adequately clear the IV tubing to remove residual ULTIVA has been associated with the appearance of respiratory depression, apnea, and muscle rigidity upon the administration of additional fluids or medications through the same IV tubing.
Consider an alternative to ULTIVA for patients taking mixed agonist/antagonist and partial agonist opioid analgesics due to reduced analgesic effect or potential withdrawal symptoms. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue ULTIVA if patient is not responding appropriately to treatment.
Discard unused portion.
Preparation for Administration To reconstitute solution, add 1 mL of diluent per mg of remifentanil. Shake well to dissolve. When reconstituted as directed, the solution contains approximately 1 mg of remifentanil activity per 1 mL.
ULTIVA should be diluted to a recommended final concentration of 20, 25, 50, or 250 mcg/mL prior to administration (see Table 5). ULTIVA should not be administered without dilution. [See table below.] 2 mg 40 mL 5 mg 100 mL 250 mcg/mL 5 mg 20 mL Continuous IV infusions of ULTIVA should be administered only by an infusion device.
Infusion rates of ULTIVA can be individualized for each patient using Table 6: [See table below.] 0.24 0.048 0.25 0.75 0.6 0.3 0.06 0.5 1.5 1.2 0.6 0.12 0.75 2.25 1.8 0.9 0.18 1.0 3.0 2.4 1.2 0.24 1.25 3.75 3.0 1.5 0.3 1.5 4.5 3.6 1.8 0.36 1.75 5.25 4.2 2.1 0.42 2.0 6.0 4.8 2.4
Compatibility and Stability Reconstitution and Dilution Prior to Administration ULTIVA is stable for 24 hours at room temperature after reconstitution and further dilution to concentrations of 20 to 250 mcg/mL with the IV fluids listed below. Sterile Water for Injection, USP 5% Dextrose Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP 0.9% Sodium Chloride Injection, USP 0.45% Sodium Chloride Injection, USP Lactated Ringer’s and 5% Dextrose Injection, USP ULTIVA is stable for 4 hours at room temperature after reconstitution and further dilution to concentrations of 20 to 250 mcg/mL with Lactated Ringer’s Injection, USP.
ULTIVA has been shown to be compatible with these IV fluids when coadministered into a running IV administration set. Compatibility with Other Therapeutic Agents ULTIVA has been shown to be compatible with Diprivan ® (propofol) Injection when coadministered into a running IV administration set. The compatibility of ULTIVA with other therapeutic agents has not been evaluated.
Incompatibilities Nonspecific esterases in blood products may lead to the hydrolysis of remifentanil to its carboxylic acid metabolite. Therefore, administration of ULTIVA into the same IV tubing with blood is not recommended. Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Product should be a clear, colorless liquid after reconstitution and free of visible particulate matter. ULTIVA does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions.
| Phase | Continuous IV Infusion ofULTIVA (mcg/kg/min) | Range of Infusion DoseULTIVA (mcg/kg/min) | Supplemental IV Bolus Dose of ULTIVA(mcg/kg) |
| Induction of Anesthesia (through intubation) | 0.5 – 1 | ||
| Maintenance of anesthesia with: | |||
| Nitrous oxide (66%) | 0.4 | 0.1 – 2 | 1 |
| Isoflurane (0.4 to 1.5 MAC) | 0.25 | 0.05 – 2 | 1 |
| Propofol (100 to 200 mcg/kg/min) | 0.25 | 0.05 – 2 | 1 |
| Continuation as an analgesic into the immediate postoperative period | 0.1 | 0.025 – 0.2 | not recommended |
| Phase | Continuous IV Infusion ofULTIVA (mcg/kg/min) | Range of Infusion Dose ULTIVA (mcg/kg/min) | Supplemental IV Bolus Dose of ULTIVA(mcg/kg) |
| Maintenance of anesthesia in patients aged 1 to 12 years old withAn initial dose of 1 mcg/kg may be administered over 30 to 60 seconds.: | |||
| Halothane (0.3 to 1.5 MAC) | 0.25 | 0.05 – 1.3 | 1 |
| Sevoflurane (0.3 to 1.5 MAC) | 0.25 | 0.05 – 1.3 | 1 |
| Isoflurane (0.4 to 1.5 MAC) | 0.25 | 0.05 – 1.3 | 1 |
| Maintenance of anesthesia for patients from birth to 2 months of age with: | |||
| Nitrous oxide (70%)The clearance rate in neonates is highly variable, on average two times higher than in the young healthy adult population. Therefore, an increased infusion rate may be necessary to maintain adequate surgical anesthesia, and additional bolus doses may be required. The use of atropine may blunt the potential for bradycardia that can occur upon administration of ULTIVA. [See Clinical Pharmacology: Specific Populations: Pediatric Population (12.3) and Clinical Studies (14.4).] | 0.4 | 0.4 – 1.0 | 1Boluses of 1 mcg/kg were studied in ASA 1 and 2, full-term patients weighing at least 2500 gm, undergoing pyloromyotomy who received pretreatment with atropine. Neonates receiving supplementation with potent inhalation agents or neuraxial anesthesia, those with significant co-morbidities or undergoing significant fluid shifts, or those who have not been pretreated with atropine, may require smaller bolus doses to avoid hypotension and/or bradycardia. |
| Method | Timing | ULTIVA Alone | ULTIVA + 2 mg Midazolam |
| Single IV Dose | Given 90 seconds before local anesthetic | 1 mcg/kg over 30 to 60 seconds | 0.5 mcg/kg over 30 to 60 seconds |
| Continuous IV Infusion | Beginning 5 minutes before local anesthetic | 0.1 mcg/kg/min | 0.05 mcg/kg/min |
| After local anesthetic | 0.05 mcg/kg/min (Range: 0.025 to 0.2 mcg/kg/min) | 0.025 mcg/kg/min (Range: 0.025 to 0.2 mcg/kg/min) |
Drug interactions
Check remifentanil against a medication listLabel text (6 paragraphs)
Table 18 includes clinically significant drug interactions with ULTIVA. Table 18: Clinically Significant Drug Interactions with ULTIVA Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, increases the risk of hypotension, respiratory depression, profound sedation, coma, and death [see Warnings and Precautions (5.3) ] . Intervention: Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation.
Patients should be advised to avoid alcohol for 24 hours after surgery [see Warnings and Precautions (5.3) ] . Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions (5.5) ] . Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
Discontinue ULTIVA if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome [see Warnings and Precautions (5.5) ] or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2) ]. If urgent use of ULTIVA is necessary, use test doses and frequent titration of small doses while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. Intervention: The use of ULTIVA is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of ULTIVA and/or precipitate withdrawal symptoms. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Consider discontinuing ULTIVA if patient is not responding appropriately to treatment and institute alternative analgesic treatment. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine • Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics : May reduce the analgesic effect of ULTIVA and/or precipitate withdrawal symptoms.
If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. ( 7 ) Drug Interactions In animals the duration of muscle paralysis from succinylcholine is not prolonged by remifentanil.
Contraindications
4 CONTRAINDICATIONS ULTIVA is contraindicated: • For epidural or intrathecal administration due to the presence of glycine in the formulation [see Nonclinical Toxicology (13) ] . • In patients with hypersensitivity to remifentanil (e.g., anaphylaxis) [see Adverse Reactions (6.2) ] . ULTIVA is contraindicated: • For epidural or intrathecal administration due to the presence of glycine in the formulation. ( 4 ) • In patients with hypersensitivity to remifentanil (e.g., anaphylaxis). ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for remifentanil. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with remifentanil hydrochloride in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, reduced fetal rat body weight and pup weights were reported at 2.2 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min 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 intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min for a surgical procedure lasting 3 hours [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate. ULTIVA is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate.
Opioid analgesics, including ULTIVA, 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. Data Human Data In a human clinical trial, the average maternal remifentanil concentrations were approximately twice those seen in the fetus. In some cases, however, fetal concentrations were similar to those in the mother.
The umbilical arteriovenous ratio of remifentanil concentrations was approximately 30% suggesting metabolism of remifentanil in the neonate. Animal Data Pregnant rats were treated from Gestation Day 6 to 15 with intravenous…
Breastfeeding (LactMed)
Because the half-life of remifentanil is extremely short, it is unlikely to cause any adverse effects in the breastfed newborn if it is given to the mother for labor analgesia or a surgical procedure. Maternal use of opioids during breastfeeding can cause infant drowsiness, which may progress to rare but severe central nervous system depression. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. If the mother of a newborn requires remifentanil, it is not a reason to discontinue breastfeeding; however, once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of remifentanil to a few days with close infant monitoring.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.