Remifentanil Hydrochloride 1 mg/mL Injection, Powder, Lyophilized, For Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Opioid Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Remifentanil is a specialized opioid used only in surgery and closely monitored settings. It works within seconds and wears off within minutes, which gives your anesthesia team pre...
- Why am I getting remifentanil instead of a regular pain medicine?
- Remifentanil controls pain but cannot put you to sleep on its own, so it is always used together with other anesthetics that do cause unconsciousness. Your team combines it with me...
- Will I be awake or remember anything during surgery if I'm given this?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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15 mg / 1 mL
UNII TE7660XO1C
Glycine is an amino acid used in medicines as a buffer to help stabilize pH and improve taste. It may also serve as a filler or binder to give the product proper form and consistency.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
2 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Remifentanil Hydrochloride 1 mg/mL 00143-9391-10 | Hikma | 10 vials | — | AP | FDA listed | — |
| Remifentanil Hydrochloride 1 mg/mLthis 63323-0723-06 | Fresenius | 10 vials | — | AP | FDA listed | — |
| Ultiva 1 mg/mL 67457-0912-01 | Mylan | 10 vials | — | AP | FDA listed | — |
| Ultiva 1 mg/mL 72078-0034-01 | Mylan | 10 vials | — | AP | FDA listed | — |
| Remifentanil Hydrochloride 1 mg/mL 63323-0725-10 | Fresenius | 10 vials | — | AP | FDA listed | — |
| Ultiva 1 mg/mL 67457-0913-02 | Mylan | 10 vials | — | AP | FDA listed | — |
| Remifentanil Hydrochloride 1 mg/mL 63323-0724-05 | Fresenius | 10 vials | — | AP | FDA listed | — |
| Ultiva 1 mg/mL 67457-0914-05 | Mylan | 10 vials | — | AP | FDA listed | — |
| Ultiva 1 mg/mL 72078-0035-02 | Mylan | 10 vials | — | AP | FDA listed | — |
| Ultiva 1 mg/mL 72078-0036-05 | Mylan | 10 vials | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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💊 Medicaid utilization by pack size
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 63323-0723-03 | 10 VIAL, SINGLE-DOSE in 1 CARTON (63323-723-03) / 3 mL in 1 VIAL, SINGLE-DOSE (63323-723-01) | 2018-01-19 | Active |
| 63323-0723-06 You're viewing this | 10 VIAL, SINGLE-DOSE in 1 CARTON (63323-723-06) / 3 mL in 1 VIAL, SINGLE-DOSE (63323-723-04) | 2018-01-19 | Active |
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: ADDICTION, ABUSE, AND MISUSE Addiction, Abuse, and Misuse Remifentanil hydrochloride for injection 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 Remifentanil hydrochloride for injection [see Warnings and Precautions ( 5.1 )] . WARNING: ADDICTION, ABUSE, AND MISUSE See full prescribing information for complete boxed warning .
Remifentanil hydrochloride for injection exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. ( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Remifentanil hydrochloride (HCl) for injection is indicated for intravenous (IV) administration: • As an analgesic agent for use during the induction and maintenance of general anesthesia for inpatient and outpatient procedures. • For continuation as an analgesic into the immediate postoperative period in adult patients under the direct supervision of an anesthesia practitioner in a postoperative anesthesia care unit or intensive care setting. • As an analgesic component of monitored anesthesia care in adult patients.
Remifentanil hydrochloride for injection is an opioid agonist indicated for intravenous administration: • As an analgesic agent for use during the induction and maintenance of general anesthesia for inpatient and outpatient procedures. ( 1 ) • For continuation as an analgesic into the immediate postoperative period in adult patients under the direct supervision of an anesthesia practitioner in a postoperative anesthesia care unit or intensive care setting. ( 1 ) • As an analgesic component of monitored anesthesia care in adult patients.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Monitor patients closely for respiratory depression when initiating therapy and following dosage increases and adjust the dosage accordingly. ( 2.1 ) • Initial Dosage in Adults : See full prescribing information for recommended doses in adult patients. ( 2.2 , 2.3 ) • Initial Dosage in Pediatric Patients : See full prescribing information for recommended doses in pediatric patients.
( 2.2 ) • Geriatric Patients : The starting doses should be decreased by 50% in elderly patients (> 65 years). ( 2.6 )
2.1Important Dosage and Administration Instructions Monitor patients closely for respiratory depression when initiating therapy and following dosage increases with remifentanil HCl and adjust the dosage accordingly [see Warnings and Precautions ( 5.2 )]. Remifentanil HCl is for intravenous use only. Continuous infusions of remifentanil HCl should be administered only by an infusion device.
The injection site should be close to the venous cannula and all IV tubing should be cleared at the time of discontinuation of infusion. Remifentanil HCl should not be administered without dilution. Consider an alternative to remifentanil HCl 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 remifentanil HCl if patient is not responding appropriately to treatment. Discard unused portion.
2.2General Anesthesia Remifentanil HCl is not recommended as the sole agent in general anesthesia because loss of consciousness cannot be assured and because of a high incidence of apnea, muscle rigidity, and tachycardia. Remifentanil HCl is synergistic with other anesthetics; therefore, clinicians may need to reduce doses of thiopental, propofol, isoflurane, and midazolam by up to 75% with the coadministration of remifentanil HCl. The administration of remifentanil HCl must be individualized based on the patient's response.
Induction of Anesthesia Remifentanil HCl should be administered at an infusion rate of 0.5 to 1 mcg/kg/min with a hypnotic or volatile agent for the induction of anesthesia. If endotracheal intubation is to occur less than 8 minutes after the start of the infusion of remifentanil HCl, then an initial dose of 1 mcg/kg may be administered over 30 to 60 seconds. Remifentanil HCl should not be used as a sole agent for induction of anesthesia because loss of consciousness cannot be assured and because of a high incidence of apnea, muscle rigidity, and tachycardia.
Maintenance of Anesthesia After endotracheal intubation, the infusion rate of remifentanil HCl should be decreased in accordance with the dosing guidelines in Tables 1 (adults, predominately ASA physical status I, II, or III) and 2 (pediatric patients). • Due to the fast onset and short duration of action of remifentanil HCl, the rate of administration during anesthesia can be titrated upward in 25% to 100% increments in adult patients or up to 50% increments in pediatric patients, or downward in 25% to 50% decrements every 2 to 5 minutes to attain the desired level of μ-opioid effect. • In response to light anesthesia or transient episodes of intense surgical stress, supplemental bolus doses of 1 mcg/kg may be administered every 2 to 5 minutes. • At infusion rates > 1 mcg/kg/min, increases in the concomitant anesthetic agents should be considered to increase the depth of anesthesia. [See Clinical Pharmacology: Specific Populations: Pediatric Population ( 12.3 ) and Dosage and Administration, Table 2 ( 2.2 ).] Table 1: Dosing Guidelines in Adults – General Anesthesia and Continuing as an Analgesic into the Postoperative Care Unit or Intensive Care Setting a Phase Continuous IV Infusion of Remifentanil HCl (mcg/kg/min) Range of Infusion Dose Remifentanil HCl (mcg/kg/min) Supplemental IV Bolus Dose of Remifentanil HCl (mcg/kg…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS For injection: 1 mg, 2 mg, and 5 mg: 3 mL Vial 1 mg lyophilized powder 5 mL Vial 2 mg lyophilized powder 10 mL Vial 5 mg lyophilized powder For injection: 1 mg, 2 mg, and 5 mg for intravenous administration after reconstitution and dilution. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Remifentanil HCl 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 )] . Remifentanil hydrochloride for injection 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 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Respiratory Depression in Spontaneously Breathing Patients : Monitor closely, particularly during initiation and titration. ( 5.2 ) • Risks from Use as Postoperative Analgesia with Concomitant Benzodiazepines or other CNS Depressants : Hypotension, profound sedation, respiratory depression, coma, and death may result from the concomitant use of Remifentanil hydrochloride for injection with benzodiazepines or other CNS depressants. ( 5.3 ) • Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration.
Discontinue Remifentanil hydrochloride for injection if serotonin syndrome is suspected. ( 5.4 ) • Administration : Continuous infusions of Remifentanil hydrochloride for injection should be administered only by an infusion device. ( 5.5 ) • Skeletal Muscle Rigidity : is related to the dose and speed of administration.
Muscle rigidity induced by Remifentanil hydrochloride for injection should be managed in the context of the patient's clinical condition. ( 5.6 ) • Potential Inactivation by Nonspecific Esterases in Blood Products : Remifentanil hydrochloride for injection should not be administered into the same IV tubing with blood due to potential inactivation by nonspecific esterases in blood products. ( 5.7 ) • Bradycardia : Monitor heart rate during dosage initiation and titration.
It is responsive to ephedrine or anticholinergic drugs. ( 5.8 ) • Hypotension : Monitor blood pressure during dosage initiation and titration. It is responsive to decreases in the administration of Remifentanil hydrochloride for injection or to IV fluids or catecholamine administration.
( 5.9 ) • Intraoperative Awareness : Inoperative awareness has been reported in patients under 55 years of age when Remifentanil hydrochloride for injection has been administered with propofol infusion rates of ≤ 75 mcg/kg/min. ( 5.10 ) • Risks of Use in Spontaneously Breathing Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Monitor for sedation and respiratory depression. ( 5.11 ) • Risks of Use in Patients with Biliary Tract Disease : Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
( 5.12 ) • Increased Risk of Seizures in Patients with Seizure Disorders : Monitor patients with a history of seizure disorders for worsened seizure control during Remifentanil hydrochloride for injection therapy. ( 5.13 ) • Rapid Offset of Action : Standard monitoring should be maintained in the postoperative period to ensure adequate recovery without stimulation. ( 5.14 )
5.1Addiction, Abuse, and Misuse Remifentanil HCl contains remifentanil, a Schedule II controlled substance. As an opioid, remifentanil HCl exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence ( 9 )]. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Consider these risks when handling remifentanil HCl. Strategies to reduce these risks include proper product storage and control practices for a C-II drug. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
5.2Respiratory Depression in Spontaneously Breathing Patients Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Remifentanil HCl should be administered only by persons specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, including respiration and cardiac resuscitation of patients in the age group being treated.
Such training must include the establishment and maintenance of a patent airway and assisted ventilat…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] • Respiratory Depression in Spontaneously Breathing Patients [see Warnings and Precautions ( 5.2 )] • Interactions with Benzodiazepines or other CNS Depressants [see Warnings and Precautions ( 5.3 )] • Serotonin Syndrome [see Warnings and Precautions ( 5.4 )] • Skeletal Muscle Rigidity [see Warnings and Precautions ( 5.6 )] • Bradycardia [see Warnings and Precautions ( 5.8 )] • Hypotension [see Warnings and Precautions ( 5.9 )] • Biliary Tract Disease [see Warnings and Precautions ( 5.12 )] • Seizures [see Warnings and Precautions ( 5.13 )] Most common adverse reactions (incidence ≥ 1%) were respiratory depression, bradycardia, hypotension, and skeletal muscle rigidity.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse event information is derived from controlled clinical studies that were conducted in a variety of surgical procedures of varying duration, using a variety of premedications and other anesthetics, and in patient populations with diverse characteristics including underlying disease.
Adults Approximately 2,770 adult patients were exposed to remifentanil HCl in controlled clinical studies. The frequencies of adverse events during general anesthesia with the recommended doses of remifentanil HCl are given in Table 11. Each patient was counted once for each type of adverse event.
Table 11: Adverse Events Reported in ≥ 1% of Adult Patients in General Anesthesia Studies a at the Recommended Doses b of Remifentanil HCl Adverse Event Induction/Maintenance Postoperative Analgesia After Discontinuation Remifentanil HCl (n = 921) Alfentanil/ Fentanyl (n = 466) Remifentanil HCl (n = 281) Morphine (n = 98) Remifentanil HCl (n = 929) Alfentanil/ Fentanyl (n = 466) Nausea 8 (< 1%) 0 61 (22%) 15 (15%) 339 (36%) 202 (43%) Hypotension 178 (19%) 30 (6%) 0 0 16 (2%) 9 (2%) Vomiting 4 (< 1%) 1 (< 1%) 22 (8%) 5 (5%) 150 (16%) 91 (20%) Muscle rigidity 98 (11%) c 37 (8%) 7 (2%) 0 2 (< 1%) 1 (< 1%) Bradycardia 62 (7%) 24 (5%) 3 (1%) 3 (3%) 11 (1%) 6 (1%) Shivering 3 (< 1%) 0 15 (5%) 9 (9%) 49 (5%) 10 (2%) Fever 1 (< 1%) 0 2 (< 1%) 0 44 (5%) 9 (2%) Dizziness 0 0 1 (< 1%) 0 27 (3%) 9 (2%) Visual disturbance 0 0 0 0 24 (3%) 14 (3%) Headache 0 0 1 (< 1%) 1 (1%) 21 (2%) 8 (2%) Respiratory depression 1 (< 1%) 0 19 (7%) 4 (4%) 17 (2%) 20 (4%) Apnea 0 1 (< 1%) 9 (3%) 2 (2%) 2 (< 1%) 1 (< 1%) Pruritus 2 (< 1%) 0 7 (2%) 1 (1%) 22 (2%) 7 (2%) Tachycardia 6 (< 1%) 7 (2%) 0 0 10 (1%) 8 (2%) Postoperative pain 0 0 7 (2%) 0 4 (< 1%) 5 (1%) Hypertension 10 (1%) 7 (2%) 5 (2%) 3 (3%) 12 (1%) 8 (2%) Agitation 2 (< 1%) 0 3 (1%) 1 (1%) 6 (< 1%) 1 (< 1%) Hypoxia 0 0 1 (< 1%) 0 10 (1%) 7 (2%) a Does not include adverse events from cardiac studies or the neonatal study.
See Tables 14, 15, and 16 for cardiac information. b See Table 1 for recommended doses. Not all doses of remifentanil HCl were equipotent to the comparator opioid. Administration of remifentanil HCl in excess of the recommended dose (i.e., doses > 1 and up to 20 mcg/kg) resulted in a higher incidence of some adverse events: muscle rigidity (37%), bradycardia (12%), hypertension (4%), and tachycardia (4%). c Included in the muscle rigidity incidence is chest wall rigidity (5%).
The overall muscle rigidity incidence is < 1% when remifentanil is administered concurrently or after a hypnotic induction agent. In the elderly population (> 65 years), the incidence of hypotension is higher, whereas the incidence of nausea…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 18 includes clinically significant drug interactions with remifentanil HCl. Table 18: Clinically Significant Drug Interactions with Remifentanil HCl 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. 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, 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 ( 5.4 )]. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue remifentanil HCl 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 ( 5.4 )] or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions ( 5.2 )].
If urgent use of remifentanil HCl 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 remifentanil HCl 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 remifentanil HCl and/or precipitate withdrawal symptoms.
Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Consider discontinuing remifentanil HCl 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 Remifentanil hydrochloride for injection and/or precipitate withdrawal symptoms.
If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. ( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy : May cause fetal harm. ( 8.1 ) • Labor or Delivery : Respiratory depression and other opioid effects may occur in newborns whose mothers are given Remifentanil hydrochloride for injection shortly before delivery. ( 8.1 ) • Lactation : Infants exposed to Remifentanil hydrochloride for injection through breast milk should be monitored for excess sedation and respiratory depression.
( 8.2 ) • Pediatric Use : Remifentanil hydrochloride for injection has not been studied in pediatric patients for use as a postoperative analgesic or as an analgesic component of monitored anesthesia care. ( 8.4 )
8.1Pregnancy Risk Summary Prolonged use of opioid analgesics 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 antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate.
Remifentanil HCl 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 HCl, 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 remifentanil doses of 0.5, 1.6, or 5 mg/kg/day (0.2, 0.7, or 2.2 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min based on body surface area for a surgical procedure lasting 3 hours based on body surface area, respectively). Reduced fetal weights were reported in the high dose group; however, no malformations were reported in surviving fetuses despite a non-dose dependent increase in maternal mortality.
Pregnant rabbits were treated from Gestation Day 6 to 18 with intravenous remifentanil doses of 0.1, 0.5, or 0.8 mg/kg/day (0.09, 0.4, or 0.7 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min based on body surface area for a surgical procedure lasting 3 hours based on b…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Prolonged use of opioid analgesics 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 antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate.
Remifentanil HCl 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 HCl, 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 remifentanil doses of 0.5, 1.6, or 5 mg/kg/day (0.2, 0.7, or 2.2 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min based on body surface area for a surgical procedure lasting 3 hours based on body surface area, respectively). Reduced fetal weights were reported in the high dose group; however, no malformations were reported in surviving fetuses despite a non-dose dependent increase in maternal mortality.
Pregnant rabbits were treated from Gestation Day 6 to 18 with intravenous remifentanil doses of 0.1, 0.5, or 0.8 mg/kg/day (0.09, 0.4, or 0.7 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min based on body surface area for a surgical procedure lasting 3 hours based on body surface area, respectively). No malformations were reported in surviving fetuses despite clear maternal toxicity (decreased food consumption and body weights and increased mortality in all treatment groups).
Pregnant rats were treated from Gestation Day 6 to Lactation Day 21 with intravenous boluses of remifentanil 0.5, 1.6, or 5 mg/kg/day (0.2, 0.7, or 2.2 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min based on body surface area for a surgical procedure lasting 3 hours based on body surface area, respectively). Reduced birth weights were noted in the high-dose groups…
🧒 Pediatric Use ▾
8.4Pediatric Use The efficacy and safety of remifentanil HCl as an analgesic agent for use in the maintenance of general anesthesia in outpatient and inpatient pediatric surgery have been established in controlled clinical studies in pediatric patients from birth to 12 years [see Clinical Studies ( 14.4 )] . The initial maintenance infusion regimen of remifentanil HCl evaluated in pediatric patients from birth to 2 months of age was 0.4 mcg/kg/min, the approved adult regimen for use with N 2 O. The clearance rate observed in neonates was highly variable and on average was 2 times higher than in the young healthy adult population.
Therefore, while a starting infusion rate of 0.4 mcg/kg/min may be appropriate for some neonates, an increased infusion rate may be necessary to maintain adequate surgical anesthesia, and additional bolus doses may be required. The individual dose for each patient should be carefully titrated. [See Clinical Pharmacology: Specific Populations: Pediatric Population ( 12.3 ) and Dosage and Administration, Table 2 and Maintenance of Anesthesia ( 2.2 ).] Remifentanil HCl has not been studied in pediatric patients for use as a postoperative analgesic or as an analgesic component of monitored anesthesia care.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of subjects in clinical studies of remifentanil HCl, 486 were 65 and over (age range 66 to 90 years). While the effective biological half-life of remifentanil is unchanged, elderly patients have been shown to be twice as sensitive as the younger population to the pharmacodynamic effects of remifentanil. The recommended starting dose of remifentanil HCl should be decreased by 50% in patients over 65 years of age [see Clinical Pharmacology ( 12.3 ) and Dosage and Administration ( 2.2 )] .
Titrate the dosage of remifentanil HCl slowly in geriatric patients. [See Warnings and Precautions ( 5.4 ).] The clearance of remifentanil is reduced (approximately 25%) in the elderly (> 65 years of age) compared to young adults (average 25 years of age). However, remifentanil blood concentrations fall as rapidly after termination of administration in the elderly as in young adults.
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Presentation Acute overdose with remifentanil HCl can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 )] . Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed.
Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose.
For clinically significant respiratory or circulatory depression secondary to remifentanil overdose, stop the infusion or administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to remifentanil overdose. In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome.
The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Remifentanil HCl is a μ-opioid agonist with rapid onset and peak effect, and short duration of action. The μ-opioid activity of remifentanil HCl is antagonized by opioid antagonists such as naloxone. Unlike other opioids, remifentanil HCl is rapidly metabolized by hydrolysis of the propanoic acid-methyl ester linkage by nonspecific blood and tissue esterases.
Remifentanil HCl is not a substrate for plasma cholinesterase (pseudocholinesterase) and, therefore, patients with atypical cholinesterase are expected to have a normal duration of action.
12.2Pharmacodynamics The analgesic effects of remifentanil HCl are rapid in onset and offset. Its effects and side effects are dose dependent and similar to other μ-opioids. Remifentanil HCl in humans has a rapid blood-brain equilibration half-time of 1 ± 1 minutes (mean ± SD) and a rapid onset of action.
The pharmacodynamic effects of remifentanil HCl closely follow the measured blood concentrations, allowing direct correlation between dose, blood levels, and response. Blood concentration decreases 50% in 3 to 6 minutes after a 1-minute infusion or after prolonged continuous infusion due to rapid distribution and elimination processes and is independent of duration of drug administration. Recovery from the effects of remifentanil HCl occurs rapidly (within 5 to 10 minutes).
New steady-state concentrations occur within 5 to 10 minutes after changes in infusion rate. When used as a component of an anesthetic technique, remifentanil HCl can be rapidly titrated to the desired depth of anesthesia/analgesia (e.g., as required by varying levels of intraoperative stress) by changing the continuous infusion rate or by administering an IV bolus injection. Effects on the Central Nervous System Remifentanil produces respiratory depression by direct action on brain stem respiratory centers.
The respiratory depression involves both a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation. Remifentanil causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings).
Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Effects on the Gastrointestinal Tract and Other Smooth Muscle Remifentanil causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased.
Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase. Effects on the Cardiovascular System Remifentanil produces peripheral vasodilation which may result in orthostatic hypotension or syncope.
Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes and sweating and/or orthostatic hypotension. Caution must be used in hypovolemic patients, such as those suffering acute myocardial infarction, because remifentanil may cause or further aggravate their hypotension. Caution must also be used in patients with cor pulmonale who have received therapeutic doses of opioids.
Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models.
The clinical significance of these findings is…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Remifentanil HCl is a μ-opioid agonist with rapid onset and peak effect, and short duration of action. The μ-opioid activity of remifentanil HCl is antagonized by opioid antagonists such as naloxone. Unlike other opioids, remifentanil HCl is rapidly metabolized by hydrolysis of the propanoic acid-methyl ester linkage by nonspecific blood and tissue esterases.
Remifentanil HCl is not a substrate for plasma cholinesterase (pseudocholinesterase) and, therefore, patients with atypical cholinesterase are expected to have a normal duration of action.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Remifentanil HCl for injection should be stored at 2° to 25°C (36° to 77°F). Remifentanil HCl for IV use is supplied as follows: Product Code Unit of Sale Strength Each 723103 NDC 63323-723-03 Unit of 10 1 mg per vial NDC 63323-723-01 3 mL Single Dose Vial 724105 NDC 63323-724-05 Unit of 10 2 mg per vial NDC 63323-724-01 5 mL Single Dose Vial 725110 NDC 63323-725-10 Unit of 10 5 mg per vial NDC 63323-725-01 10 mL Single Dose Vial Discard unused portion. The container closure is not made with natural rubber latex.
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📋 Description ▾
11 DESCRIPTION Remifentanil hydrochloride for injection is an opioid agonist. The chemical name is 3-[4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidine]propanoic acid methyl ester, hydrochloride salt. The molecular weight is 412.91.
Its molecular formula is C 20 H 28 N 2 O 5 •HCl, and it has the following chemical structure. Remifentanil hydrochloride for injection is a sterile, nonpyrogenic, preservative-free, white to off-white lyophilized powder for intravenous (IV) administration after reconstitution and dilution. Each vial contains 1 mg, 2 mg, or 5 mg of remifentanil base; 15 mg glycine; and hydrochloric acid to buffer the solutions to a nominal pH of 3 after reconstitution.
When reconstituted as directed, solutions of remifentanil HCl are clear and colorless and contain remifentanil hydrochloride (HCl) equivalent to 1 mg/mL of remifentanil base. The pH of reconstituted solutions of remifentanil HCl ranges from 2.5 to 3.5. Remifentanil HCl has a pKa of 7.07.
Remifentanil HCl has an n-octanol:water partition coefficient of 17.9 at pH 7.3. Chemical Structure