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Remifentanil

Pronunciation

(rem i FEN ta nil)

Index Terms

  • GI87084B

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Ultiva: 1 mg (1 ea); 2 mg (1 ea); 5 mg (1 ea)

Brand Names: U.S.

  • Ultiva

Pharmacologic Category

  • Analgesic, Opioid
  • Anilidopiperidine Opioid

Pharmacology

Binds with stereospecific mu-opioid receptors at many sites within the CNS, increases pain threshold, alters pain reception, inhibits ascending pain pathways

Distribution

Pediatric patients (Ross 2001): Vdss:

Neonates ≤2 months: 453 ± 145 mL/kg

Infants and Children >2 months to <2 years: 308 ± 89 mL/kg

Children 2 to 6 years: 240 mL/kg ± 131 mL/kg

Children 7 to 12 years: 249 mL/kg ± 91 mL/kg

Adolescents 13 to <16 years: 223 ± 31 mL/kg

Adolescents 16 to 18 years: 243 ± 109 mL/kg

Adults: Vd: Initial: 100 mL/kg; Vdss: 350 mL/kg

Metabolism

Rapid via blood and tissue esterases; not metabolized by plasma cholinesterase (pseudocholinesterase) and is not appreciably metabolized by the liver

Excretion

Urine

Clearance:

Pediatric patients (Ross 2001):

Neonates ≤2 months of age: 90.5 ± 36.8 mL/minute/kg

Infants and Children >2 months to <2 years: 92.1 ± 25.8 mL/minute/kg

Children 2 to 6 years: 76.0 ± 22.4 mL/minute/kg

Children 7 to 12 years: 59.7 ± 22.5 mL/minute/kg

Adolescents 13 to <16 years: 57.2 ± 21.2 mL/minute/kg

Adolescents 16 to 18 years: 46.5 ± 2.1 mL/minute/kg

Adults: ~40 mL/minute/kg

Onset of Action

IV: 1 to 3 minutes; Peak effect: 3 to 5 minutes

Time to Peak

Intranasal: Children ≤7 years: ~3.5 minutes (Verghese 2008)

Duration of Action

3 to 10 minutes (Scott 2005)

Half-Life Elimination

Dose dependent:

Pediatric patients (Ross 2001): Effective:

Neonates ≤2 months: 5.4 minutes (range: 3 to 8 minutes)

Infants and Children >2 months to <2 years: 3.4 minutes (range: 2 to 6 minutes)

Children 2 to 6 years: 3.6 minutes (range: 1 to 6 minutes)

Children 7 to 12 years: 5.3 minutes (range: 3 to 7 minutes)

Adolescents: 13 to <16 years: 3.7 minutes (range: 2 to 5 minutes)

Adolescents 16 to 18 years: 5.7 minutes (range: 5 to 6 minutes)

Adults: Terminal: 10 to 20 minutes; Effective: 3 to 10 minutes

Protein Binding

~70% (primarily alpha1 acid glycoprotein)

Special Populations: Elderly

Clearance is reduced ~25%.

Use: Labeled Indications

Anesthesia: Analgesic for use during the induction and maintenance of general anesthesia; continued analgesia into the immediate postoperative period in adults; analgesic component of monitored anesthesia in adults

Off Label Uses

Pain in mechanically-ventilated patients (management)

Based on the American College of Critical Care Medicine (ACCM) Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit, remifentanil is an effective and recommended agent for management of pain in critically ill patients.

Contraindications

Hypersensitivity (eg, anaphylaxis) to remifentanil or any component of the formulation; intrathecal or epidural administration.

Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Anesthesia: IV continuous infusion:

Induction of anesthesia: 0.5 to 1 mcg/kg/minute; if endotracheal intubation is to occur in <8 minutes, an initial dose of 1 mcg/kg may be administered over 30 to 60 seconds

Coronary bypass surgery: 1 mcg/kg/minute

Maintenance of anesthesia: Supplemental bolus dose of 1 mcg/kg may be administered every 2 to 5 minutes. Consider increasing concomitant anesthetics with infusion rate >1 mcg/kg/minute. Infusion rate can be titrated upward in increments of 25% to 100% or downward in decrements of 25% to 50% every 2 to 5 minutes.

With nitrous oxide (66%): 0.4 mcg/kg/minute (range: 0.1 to 2 mcg/kg/minute)

With isoflurane: 0.25 mcg/kg/minute (range: 0.05 to 2 mcg/kg/minute)

With propofol: 0.25 mcg/kg/minute (range: 0.05 to 2 mcg/kg/minute)

Coronary bypass surgery: 1 mcg/kg/minute (range: 0.125 to 4 mcg/kg/minute); supplemental dose: 0.5 to 1 mcg/kg

Continuation as an analgesic in immediate postoperative period: 0.1 mcg/kg/minute (range: 0.025 to 0.2 mcg/kg/minute). Infusion rate may be adjusted every 5 minutes in increments of 0.025 mcg/kg/minute. Bolus doses are not recommended. Infusion rates >0.2 mcg/kg/minute are associated with respiratory depression.

Coronary bypass surgery, continuation as an analgesic into the ICU: 1 mcg/kg/minute (range: 0.05 to 1 mcg/kg/minute)

Analgesic component of monitored anesthesia care:

Note: Supplemental oxygen is recommended:

Single IV dose administered 90 seconds prior to local anesthetic:

Remifentanil alone: 1 mcg/kg over 30 to 60 seconds

With midazolam: 0.5 mcg/kg over 30 to 60 seconds

Continuous infusion beginning 5 minutes prior to local anesthetic:

Remifentanil alone: 0.1 mcg/kg minute

With midazolam: 0.05 mcg/kg/minute

Continuous infusion administered after local anesthetic:

Remifentanil alone: 0.05 mcg/kg/minute (range: 0.025 to 0.2 mcg/kg/minute)

With midazolam: 0.025 mcg/kg/minute (range: 0.025 to 0.2 mcg/kg/minute)

Note: Following local or anesthetic block, infusion rate should be decreased to 0.05 mcg/kg/minute; rate adjustments of 0.025 mcg/kg/minute may be done at 5-minute intervals. Infusion rates >0.2 mcg/kg/minute are associated with respiratory depression.

Critically-ill patients (off-label dose): Loading dose: 1.5 mcg/kg; followed by 0.008 to 0.25 mcg/kg/minute (or 0.5 to 15 mcg/kg/hour) (SCCM [Barr 2013])

Dosing: Geriatric

Decrease initial dose by 50% and cautiously titrate to effect. Refer to adult dosing.

Dosing: Pediatric

Maintenance of anesthesia: Continuous IV infusion:

Neonates and Infants to 2 months: Maintenance of anesthesia with nitrous oxide (70%): 0.4 mcg/kg/minute (range: 0.4 to 1 mcg/kg/minute); supplemental bolus dose of 1 mcg/kg may be administered; smaller bolus dose may be required with potent inhalation agents, potent neuraxial anesthesia, significant comorbidities, significant fluid shifts, or without atropine pretreatment. Clearance in neonates is highly variable; dose should be carefully titrated.

Infants ≥3 months (off-label) and Children ≤12 years: Maintenance of anesthesia with halothane, sevoflurane, or isoflurane: 0.25 mcg/kg/minute (range: 0.05 to 1.3 mcg/kg/minute); supplemental bolus dose of 1 mcg/kg may be administered every 2 to 5 minutes. Consider increasing concomitant anesthetics with infusion rate >1 mcg/kg/minute. Infusion rate can be titrated upward in increments up to 50% or titrated downward in decrements of 25% to 50% every 2 to 5 minutes.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling; however, remifentanil pharmacokinetics are unchanged in patients with end stage renal disease.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling; however, remifentanil pharmacokinetics are unchanged in patients with severe hepatic impairment.

Dosing: Obesity

Initial dose should be based on ideal body weight (IBW) in obese patients (>30% over IBW).

Reconstitution

Add 1 mL of D5LR, D5NS, D5W, 1/2NS, NS, or SWFI per 1 mg of remifentanil (resulting solution: 1 mg/mL). Shake well. Further dilute to a final concentration of 20, 25, 50, or 250 mcg/mL.

Administration

For IV use only. An infusion device should be used to administer continuous infusions. During the maintenance of general anesthesia, IV boluses may be administered over 30 to 60 seconds. Injections should be given into IV tubing close to the venous cannula; tubing should be cleared after treatment to prevent residual effects when other fluids are administered through the same IV line.

Storage

Store intact vials at 2°C to 25°C (36°F to 77°F). Stable for 24 hours at room temperature after reconstitution and further dilution in SWFI, D5LR, D5NS, D5W, 1/2NS, or NS to concentrations of 20 to 250 mcg/mL (4 hours if diluted with LR).

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Anticholinergic Agents: May enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Beta-Blockers: Anilidopiperidine Opioids may enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): Anilidopiperidine Opioids may enhance the bradycardic effect of Calcium Channel Blockers (Nondihydropyridine). Anilidopiperidine Opioids may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Diuretics: Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Gastrointestinal Agents (Prokinetic): Analgesics (Opioid) may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Avoid combination

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nalmefene: May diminish the therapeutic effect of Analgesics (Opioid). Management: Avoid the concomitant use of nalmefene and opioid analgesics. Discontinue nalmefene 1 week prior to any anticipated use of opioid analgesics. If combined, larger doses of opioid analgesics will likely be required. Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Ramosetron: Analgesics (Opioid) may enhance the constipating effect of Ramosetron. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

Frequency of adverse events may vary based on surgical procedures and rate of infusion.

>10%:

Cardiovascular: Hypotension (2% to 19%)

Central nervous system: Headache (<2% to 18%)

Dermatologic: Pruritus (<2% to 18%)

Gastrointestinal: Nausea (<36% to 44%), vomiting (<16% to 22%)

Neuromuscular & skeletal: Muscle rigidity (≤11%; includes chest wall rigidity)

1% to 10%:

Cardiovascular: Bradycardia (1% to 7%; dose-dependent), shivering (<5%), hypertension (1% to 2%; dose-dependent), flushing (1%), flushing sensation (1%), tachycardia (≤1%; dose-dependent)

Central nervous system: Dizziness (<5%), chills (1%), agitation (≤1%)

Dermatologic: Diaphoresis (6%)

Local: Pain at injection site (1%)

Respiratory: Respiratory depression (<7%), apnea (<3%), hypoxia (≤1%)

Miscellaneous: Fever (<5%), postoperative pain (<2%)

Rare but important or life-threatening: Abdominal distress, amnesia, anaphylaxis, anxiety, awareness under anesthesia without pain, bronchitis, bronchospasm, cardiac arrhythmia, chest pain, confusion, constipation, cough, diarrhea, disorientation, disruption of body temperature regulation, dysphagia, dysphoria, dyspnea, dysuria, ECG changes, electrolyte disturbance, erythema, gastroesophageal reflux disease, hallucination, heart block, heartburn, hepatic insufficiency, hiccups, hyperglycemia, increased creatine phosphokinase, intestinal obstruction, involuntary body movements, laryngospasm, leukocytosis, lymphocytopenia, nasal congestion, nightmares, nystagmus, oliguria, paresthesia, pharyngitis, pleural effusion, prolonged emergence from anesthesia, pulmonary edema, rales, rapid awakening from anesthesia, rhinorrhea, rhonchi, seizure, skin rash, sleep disorder, stridor, syncope, thrombocytopenia, tremor, twitching, urinary incontinence, urinary retention, urticaria, xerostomia

ALERT: U.S. Boxed Warning

Addiction, abuse, and misuse:

Remifentanil 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.

Warnings/Precautions

Concerns related to adverse effects:

• Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration.

• Intraoperative awareness: Intraoperative awareness has been reported when used with propofol infusion rates of ≤75 mcg/kg/minute in patients <55 years.

• Respiratory depression: Serious, life-threatening, or fatal respiratory depression, even when used as recommended may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with concomitant use of remifentanil and serotonergic agents (eg, SSRIs, SNRIs, triptans, TCAs, 5-HT3 receptor antagonists, mirtazapine, trazodone, tramadol) and agents that impair metabolism of serotonin (eg, MAO inhibitors). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue remifentanil if serotonin syndrome is suspected.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

• Bradycardia: Use with caution when administering to patients with bradycardia.

• Delirium tremens: Use with caution in patients with delirium tremens.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Obesity: Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Psychosis: Use with caution in patients with toxic psychosis.

• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages.

• Seizures: Use with caution in patients with a history of seizure disorders; may increase risk or exacerbate preexisting seizure disorders.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Benzodiazepines or other CNS depressants: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in hypotension, profound sedation, respiratory depression, coma, and death. Alcohol should be avoided for 24 hours after surgery.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.

Other warnings/precautions:

• Abuse/misuse/diversion: [US Boxed Warning]: Remifentanil exposes 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.

• Appropriate use: Inadequate clearing of IV tubing following administration has been associated with muscle rigidity, respiratory depression, and apnea when another fluid is administered through the same line. Do not administer into the same IV tubing with blood due to potential inactivation by nonspecific esterases in blood products.

• Discontinuation of therapy: Interruption of an infusion will result in offset of effect within 5 to 10 minutes; the discontinuation of an infusion should be preceded by the establishment of adequate postoperative analgesia.

• General anesthesia use: Not recommended as the sole agent for induction of anesthesia, because the loss of consciousness cannot be assured.

• Rapid infusion: Rapid IV infusion (single dose >1 mcg/kg over 30 to 60 seconds and infusion rates >0.1 mcg/kg/minute) should only be used during maintenance of general anesthesia; rapid infusion may result in skeletal muscle and chest wall rigidity. Chest wall rigidity may resolve by decreasing the infusion rate, discontinuing the infusion, or by administering a neuromuscular blocking agent.

• Trained individuals: Remifentanil should only be administered by health care providers specifically trained in the use of anesthetic agents. Should not be used in diagnostic or therapeutic procedures outside the monitored anesthesia setting; resuscitative and intubation equipment should be readily available.

Monitoring Parameters

Respiratory and cardiovascular status, blood pressure, heart rate

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Remifentanil has been shown to cross the placenta; fetal and maternal concentrations may be similar. Use during labor and delivery is not recommended by the manufacturer.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience itching, nausea, vomiting, headache, or constipation. Have patient report immediately to prescriber signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), slow breathing, shallow breathing, difficulty breathing, severe headache, severe dizziness, passing out, bradycardia, or abnormal heartbeat (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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