Version July 2025
Because the use of 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 and reassess all patients regularly for the development of these behaviors and conditions.
Serious, life-threatening, or fatal respiratory depression may occur with use of remifentanil, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of remifentanil are essential.
Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of remifentanil and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
General anesthesia:
Induction: Continuous infusion: IV: 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: Continuous infusion: IV: 1 mcg/kg/minute.
Maintenance:
Intermittent: IV: 1 mcg/kg administered every 2 to 5 minutes.
Continuous infusion: IV: 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%): IV: 0.4 mcg/kg/minute (range: 0.1 to 2 mcg/kg/minute).
With isoflurane: IV: 0.25 mcg/kg/minute (range: 0.05 to 2 mcg/kg/minute).
With propofol: IV: 0.25 mcg/kg/minute (range: 0.05 to 2 mcg/kg/minute).
Coronary bypass surgery: Continuous infusion: IV: 1 mcg/kg/minute (range: 0.125 to 4 mcg/kg/minute); supplemental dose: 0.5 to 1 mcg/kg.
Postoperative recovery/Postanesthesia care unit (ie, immediate postoperative period):
Note: Bolus doses are not recommended.
Continuous infusion: IV: 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. Infusion rates >0.2 mcg/kg/minute are associated with respiratory depression.
Coronary bypass surgery, continuation as an analgesic into the ICU: Continuous infusion: IV: 1 mcg/kg/minute (range: 0.05 to 1 mcg/kg/minute).
Analgesia during monitored anesthesia care:
Note: Supplemental oxygen is recommended.
Single IV dose administered 90 seconds prior to local anesthetic:
Remifentanil alone: IV: 1 mcg/kg over 30 to 60 seconds.
With midazolam: IV: 0.5 mcg/kg over 30 to 60 seconds.
Continuous infusion beginning 5 minutes prior to local anesthetic:
Remifentanil alone: IV: 0.1 mcg/kg minute.
With midazolam: IV: 0.05 mcg/kg/minute.
Continuous infusion administered after local anesthetic:
Remifentanil alone: IV: 0.05 mcg/kg/minute (range: 0.025 to 0.2 mcg/kg/minute).
With midazolam: IV: 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.
Mechanically ventilated patients in the ICU, pain and sedation (off-label use):
Loading dose: IV: 1.5 mcg/kg once.
Maintenance dose: Continuous infusion: IV: 0.008 to 0.25 mcg/kg/minute (or 0.5 to 15 mcg/kg/hour) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, remifentanil pharmacokinetics are unchanged in patients with end stage renal disease.
There are no dosage adjustments provided in the manufacturer's labeling; however, remifentanil pharmacokinetics are unchanged in patients with severe hepatic impairment.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):
Use adjusted body weight for initial weight-based dose calculations (based on indication), then titrate to clinical effect (Ref). Clinicians should not change dosing weight from one weight metric to another during therapy (ie, adjusted body weight to/from actual body weight) (Ref). Refer to "Dosing: Adult" for indication-specific doses.
Rationale for recommendations:
Studies evaluating other opioids in patients with obesity have shown large variations in opioid requirements with no relationship to actual body weight (Ref). Pharmacokinetic studies evaluating remifentanil, a highly lipophilic compound, have shown pharmacokinetic parameters are more closely related to lean body weight (LBW) or fat-free mass than to actual body weight. These studies suggest dosing based on ideal body weight or corrected LBW for target-controlled infusion systems (Ref).
Guidelines have suggested using LBW for initial weight-based dosing of opioids, titrated to effect (Ref); however, there are concerns with calculation errors when using the complex LBW formula, especially in critical situations (Ref). There are also concerns with underdosing in clinical situations where rapid sedation is needed (eg, induction of anesthesia, ICU sedation) (Ref). Use of an alternative size descriptor (ie, adjusted body weight) is recommended for dosing in patients with class 1, 2, or 3 obesity (BMI ≥30 kg/m2) (Ref).
Decrease initial dose by 50% and cautiously titrate to effect. Refer to adult dosing.
(For additional information see "Remifentanil: Pediatric drug information")
Note: For use of continuous IV infusion in obese patients, dose should be based on ideal body weight (IBW) in obese patients (>30% over IBW).
Analgesia, postoperative; mechanically ventilated patient: Limited data available: Children and Adolescents 3-16 years: Continuous IV infusion: 0.1 mcg/kg/minute with or without adjunctive medication, titrate to effect; dosing based on a randomized, double-blind comparative trial of remifentanil versus fentanyl in 22 postoperative orthopedic spinal surgery patients requiring mechanical ventilation (remifentanil group, n=11; age: Mean:13 years, range: 3-16 years); similar efficacy and adverse effect profile were reported with both treatment groups (Ref).
Analgesia/Sedation in mechanically ventilated patients: Limited data available: Infants ≤2 months: Continuous IV infusion: Initial: 0.15 mcg/kg/minute, titrate to effect; dosing based on a randomized, double-blind, comparative study of neonates and young infants (n=23; GA: ≥36 weeks; PNA: <60 days) requiring mechanical ventilation who were given a combination of either midazolam/remifentanil (n=11) or midazolam/fentanyl (n=12); mean remifentanil effective dose: 0.23 mcg/kg/minute; maximum reported dose: 0.5 mcg/kg/minute; efficacy data and adverse effect profile were similar to fentanyl(Ref).
Anesthesia, maintenance of anesthesia: Continuous IV infusion:
Infants 1-2 months: Maintenance of anesthesia with nitrous oxide (70%): 0.4 mcg/kg/minute (range: 0.4-1 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
Infants ≥3 months, Children, and Adolescents: Limited data available: Maintenance of anesthesia with halothane, sevoflurane, or isoflurane: 0.25 mcg/kg/minute (range: 0.05-1.3 mcg/kg/minute); supplemental bolus dose of 1 mcg/kg may be administered every 2-5 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%. May titrate every 2-5 minutes.
Anesthesia, total intravenous (TIVA); with or without propofol induction: Limited data available: Infants, Children, and Adolescents: IV: Loading dose (may omit if propofol induction used): 0.5 mcg/kg/minute for 3 minutes (total dose: 1.5 mcg/kg) or 1 mcg/kg over 1 minute; followed by an initial maintenance dose: 0.05-0.1 mcg/kg/minute; titrate in 0.05 mcg/kg/minute increments every 3 minutes to effect; usual effective range: 0.2-0.5 mcg/kg/minute; has been used in combination with propofol (bolus and/or infusion) (Ref).
Endotracheal intubation for elective procedures: Limited data available:
IV: Infants, Children, and Adolescents: Usual range: 1-3 mcg/kg/dose, doses as high as 4 mcg/kg have been used. Dosing based on multiple trials in patients undergoing elective procedures requiring intubation who were not receiving neuromuscular blockers and remifentanil administered in combination with other induction agents such as propofol, ketamine, or sevoflurane (Ref).
Intranasal (using parenteral 100 mcg/mL formulation): Children ≤7 years: 4 mcg/kg/dose; administer half of the total dose in each nostril; wait 2-3 minutes before attempting intubation. Dosing based on a double-blind, randomized, controlled trial (n=188), remifentanil was administered after sevoflurane induction and overall, was found more effective than saline placebo at both endpoints of 2 minutes and 3 minutes postdose. Results also showed that within the remifentanil treatment groups, good or excellent intubation conditions were reported more often at 3 minutes postdose than at 2 minutes (91.7% vs 68.2%) (Ref).
Procedural sedation: Limited data available, dosage not established: Infants, Children, and Adolescents: IV: 0.5 mcg/kg with propofol has been used to induce analgesia and adjunct sedation prior to esophagogastroduodenoscopy (n=22; age range: 2-12 years) and short hemato-oncologic invasive procedures (n=30, age range: 2-18 years) (Ref). A higher dose of 3 mcg/kg was used in already sedated (sevoflurane) infants and young children who required apnea for CT or MRI imaging (n=12, age range: 6-16 months) (Ref). In a dose-finding trial, continuous IV infusion of remifentanil at 0.2 mcg/kg/minute has been shown more effective than a lower 0.1 mcg/kg/minute in 60 children 2-12 years undergoing diagnostic cardiac catheterization; pretreatment with oral midazolam and local groin anesthetic also utilized (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Removed by hemodialysis (30%). There are no dosage adjustments provided in the manufacturer's labeling; however, remifentanil pharmacokinetics are unchanged in patients with end stage renal disease.
There are no dosage adjustments provided in the manufacturer's labeling; however, remifentanil pharmacokinetics are unchanged in patients with severe hepatic impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise indicated.
>10%:
Cardiovascular: Hypotension (4% to 29%)
Dermatologic: Pruritus (≤18%)
Gastrointestinal: Nausea (neonates, infants, and children: 8%; adults: ≤44%), vomiting (neonates, infants, and children: 12%; adults: ≤22%)
Nervous system: Headache (≤18%)
Neuromuscular & skeletal: Muscle rigidity (1% to 17%; chest wall rigidity: 5%)
1% to 10%:
Cardiovascular: Bradycardia (1% to 7%), flushing (1%), hypertension (1% to 2%)
Dermatologic: Diaphoresis (6%)
Local: Localized warm feeling (1%), pain at injection site (1%)
Nervous system: Agitation (≤1%), chills (1%), dizziness (≤5%), shivering (neonates, infants, children, and adults: ≤5%)
Respiratory: Apnea (3%), cough (neonates, infants, children, and adults: ≤1%), respiratory depression (≤7%), rhonchi (neonates, infants, children, and adults: ≤3%), stridor (neonates, infants, children, and adults: ≤1%)
<1%:
Cardiovascular: Cardiac arrhythmia, heart block, increased serum creatine kinase, ischemic heart disease, syncope, tachycardia
Dermatologic: Skin rash, urticaria
Endocrine & metabolic: Electrolyte disorder, hyperglycemia
Gastrointestinal: Abdominal distress, constipation, diarrhea, dysphagia, gastroesophageal reflux disease, hiccups, intestinal obstruction, xerostomia
Genitourinary: Dysuria, oliguria, urinary incontinence, urinary retention
Hematologic: Anemia, leukocytosis, lymphocytopenia, thrombocytopenia
Hepatic: Abnormal liver function
Hypersensitivity: Anaphylaxis
Local: Infusion-site reaction (including erythema at injection site, injection-site pruritus, rash at injection site)
Nervous system: Amnesia, anxiety, awareness under anesthesia without pain, confusion, decreased body temperature, delayed recovery from neuromuscular block, disorientation, dysphoria, hallucination, involuntary body movements, nightmares, paresthesia, prolonged emergence from anesthesia, rapid awakening from anesthesia, seizure, tremor, twitching
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen, laryngospasm, musculoskeletal chest pain
Ophthalmic: Nystagmus disorder
Respiratory: Bronchitis, bronchospasm, dyspnea, hypoxia, nasal congestion, pharyngitis, pleural effusion, pulmonary edema, rales, rhinorrhea
Miscellaneous: Fever
Frequency not defined: Nervous system: Drug abuse, opioid dependence
Postmarketing:
Cardiovascular: Asystole
Nervous system: Allodynia (opioid-induced hyperalgesia) (FDA Safety Communication 2023)
Hypersensitivity (eg, anaphylaxis) to remifentanil or any component of the formulation; intrathecal or epidural administration.
Canadian labeling: Additional contraindications (not in US labeling): Known or suspected mechanical GI obstruction (eg, bowel obstruction or strictures) or any diseases/conditions that affect bowel transit (eg, ileus of any type); suspected surgical abdomen (eg, acute appendicitis or pancreatitis); mild pain that can be managed with other pain medications; acute or severe bronchial asthma, chronic obstructive airway, status asthmaticus; acute respiratory depression; hypercapnia; cor pulmonale; acute alcoholism, delirium tremens, and convulsive disorders; severe CNS depression, increased cerebrospinal or intracranial pressure and head injury; concurrent use or use within 14 days of an MAO inhibitor
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Hyperalgesia: Opioid-induced hyperalgesia (OIH) has occurred with short-term and prolonged use of opioid analgesics. Symptoms may include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily nonpainful stimuli; symptoms may be suggestive of OIH if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Consider decreasing the current opioid dose or opioid rotation in patients who experience OIH.
• 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: Fatal respiratory depression may occur. 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.
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.
• Older adult: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Other warnings/precautions:
• Abuse/misuse/diversion: Use with caution in patients with a history of substance use disorder; potential for drug dependency exists. Other factors associated with increased risk for misuse include concomitant depression or other mental health conditions, higher opioid dosages, or taking other CNS depressants.
• 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Ultiva: 1 mg (1 ea)
Generic: 2 mg (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Ultiva: 1 mg (1 ea); 2 mg (1 ea); 5 mg (1 ea)
Generic: 1 mg (1 ea); 2 mg (1 ea); 5 mg (1 ea)
Yes
Solution (reconstituted) (Remifentanil HCl Intravenous)
1 mg (per each): $50.40 - $87.97
2 mg (per each): $147.00 - $154.34
5 mg (per each): $312.00 - $407.95
Solution (reconstituted) (Ultiva Intravenous)
1 mg (per each): $80.83
2 mg (per each): $161.66
5 mg (per each): $343.96
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Generic: 1 mg (1 ea); 2 mg (1 ea)
C-II
IV: 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.
IV: An infusion pump should be used to administer continuous infusions. During the maintenance of general anesthesia, IV boluses ≤1 mcg/kg may be administered over 30 to 60 seconds; for doses >1 mcg/kg, administer over >60 seconds (to reduce the potential to develop skeletal muscle and chest wall rigidity). 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.
General anesthesia: Analgesic for use during the induction and maintenance of general anesthesia; continued analgesia into the immediate postoperative period in adults under the direct supervision of an anesthesia practitioner in a postoperative anesthesia care unit or intensive care setting; analgesic component of monitored anesthesia in adults.
Mechanically ventilated patients in the ICU, pain and sedation
Remifentanil may be confused with ALfentanil
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (opioids, all formulations and routes of administration) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Clinically Relevant Anticholinergic Effects: May increase adverse/toxic effects of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alvimopan: Opioid Agonists may increase adverse/toxic effects 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. Risk D: Consider Therapy Modification
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Amphetamines: May increase analgesic effects of Opioid Agonists. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
Buprenorphine: May decrease therapeutic effects of Opioid Agonists. Management: Seek alternatives to buprenorphine in patients receiving pure opioid agonists. If combined in certain pain management situations (eg, surgery), monitor for symptoms of therapeutic failure/high dose requirements or opioid withdrawal symptoms. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider Therapy Modification
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists 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. Risk D: Consider Therapy Modification
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Desmopressin: Opioid Agonists may increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Diuretics: Opioid Agonists may increase adverse/toxic effects of Diuretics. Opioid Agonists may decrease therapeutic effects of Diuretics. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Eluxadoline: Opioid Agonists may increase constipating effects of Eluxadoline. Risk X: Avoid
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid
Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider Therapy Modification
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Gastrointestinal Agents (Prokinetic): Opioid Agonists may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): May decrease therapeutic effects of Opioid Agonists. Opioid Agonists may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Monoamine Oxidase Inhibitors: Remifentanil may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Management: The use of remifentanil is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and titrate small doses of remifentanil frequently. Risk D: Consider Therapy Modification
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nalfurafine: Opioid Agonists may increase adverse/toxic effects of Nalfurafine. Opioid Agonists may decrease therapeutic effects of Nalfurafine. Risk C: Monitor
Nalmefene: May decrease therapeutic effects of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider Therapy Modification
Naltrexone: May decrease therapeutic effects of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Obinutuzumab: May increase hypotensive effects 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. Risk D: Consider Therapy Modification
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists 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. Risk D: Consider Therapy Modification
Opioids (Mixed Agonist / Antagonist): May decrease analgesic effects of Opioid Agonists. 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. Risk X: Avoid
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Pegvisomant: Opioid Agonists may decrease therapeutic effects of Pegvisomant. Risk C: Monitor
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider Therapy Modification
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Ramosetron: Opioid Agonists may increase constipating effects of Ramosetron. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Samidorphan: May decrease therapeutic effects of Opioid Agonists. Risk X: Avoid
Serotonergic Agents (High Risk): Opioid Agonists may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification
Siponimod: Bradycardia-Causing Agents may increase bradycardic effects of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider Therapy Modification
Somatostatin Analogs: Opioid Agonists may decrease analgesic effects of Somatostatin Analogs. Opioid Agonists may increase analgesic effects of Somatostatin Analogs. Risk C: Monitor
Succinylcholine: May increase bradycardic effects of Opioid Agonists. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Tilidine: May increase therapeutic effects of Opioid Agonists. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Remifentanil crosses the placenta; fetal and maternal concentrations may be similar.
Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. Opioids used as part of obstetric analgesia/anesthesia during labor and delivery may temporarily affect the fetal heart rate (ACOG 209 2019). Opioids may cause respiratory depression and psychophysiologic effects in the neonate; newborns of mothers receiving remifentanil during labor should be closely monitored (Devroe 2015; Noskova 2015).
Pharmacokinetic properties of remifentanil are not significantly altered by pregnancy; dosing adjustment is not required for maternal indications (Smith 2017). Remifentanil is used to treat maternal pain during labor and immediately postpartum (ACOG 209 2019; Devroe 2015; Weibel 2017).
The ACOG recommends that pregnant women should not be denied medically necessary surgery, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 775 2019).
It is not known if remifentanil is present in breast milk.
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother; monitor infants for excess sedation and respiratory depression. Remifentanil has a limited duration of action; use may be appropriate for breastfeeding women undergoing short procedures (ABM [Reece-Stremtan 2017]).
The Academy of Breast Feeding Medicine recommends postponing elective surgery until milk supply and breastfeeding are established. Milk should be expressed ahead of surgery when possible. In general, when the child is healthy and full term, breastfeeding may resume, or milk may be expressed once the mother is awake and in recovery. For children who are at risk for apnea, hypotension, or hypotonia, milk may be saved for later use when the child is at lower risk (ABM [Reece-Stremtan 2017]).
Respiratory and cardiovascular status, blood pressure, heart rate
Critically ill: The Numeric Rating Scale should be used in patients who are able to self-report pain. In patients who are unable to self-report pain, the Behavioral Pain Scale and the Critical-Care Pain Observational Tool can be used in intubated or nonintubated patients (SCCM [Devlin 2018]).
Binds with stereospecific mu-opioid receptors at many sites within the CNS, increases pain threshold, alters pain reception, inhibits ascending pain pathways
Note: In pediatric patients (neonates through adolescents), pharmacokinetic data showed variable age-related changes with distribution (ie, highest Vd associated with lowest age) and clearance (ie, fastest clearance in the youngest patients); however, no age-related changes with half-life (Ross 2001).
Onset of action: IV: 1 to 3 minutes; Peak effect: 3 to 5 minutes
Duration: 3 to 10 minutes (Scott 2005)
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
Protein binding: ~70% (primarily alpha-1 acid glycoprotein)
Metabolism: Rapid via blood and tissue esterases; not metabolized by plasma cholinesterase (pseudocholinesterase) and is not appreciably metabolized by the liver
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
Time to peak, serum: Intranasal: Children ≤7 years: ~3.5 minutes (Verghese 2008)
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
Older adult: Clearance is reduced ~25%.
