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Isoflurane: Drug information

Isoflurane: Drug information
(For additional information see "Isoflurane: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Forane;
  • Terrell
Pharmacologic Category
  • General Anesthetic, Inhalation
Dosing: Adult

Note: Coughing, breath-holding, bronchospasm, or laryngospasm may occur during induction; use of an ultra short-acting barbiturate may avoid these symptoms. MAC is increased in the young and decreased in the elderly. Premedication should be selected according to the need of the individual patient, taking into account that secretions are weakly stimulated by isoflurane, and the heart rate tends to be increased. Dosage must be individualized based on patient response.

Anesthesia

Anesthesia: Inhalation:

Induction: 1.5% to 3% isoflurane with oxygen or oxygen-nitrous oxide mixture.

Maintenance: With nitrous oxide: 1% to 2.5%; additional 0.5% to 1% with oxygen alone.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dosing: Older Adult

Refer to adult dosing. Minimum alveolar concentration is decreased in the elderly.

Dosing: Pediatric
Anesthesia

Anesthesia: Inhalation: Refer to adult dosing.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adult and pediatric patients.

>10%:

Gastrointestinal: Nausea (recovery: 15%)

Nervous system: Agitation (induction: 52%), chills (≤14%), shivering (≤14%)

Respiratory: Breath-holding (induction: 24%; maintenance: 1%), cough (induction: 28%; maintenance: 4%)

1% to 10%:

Cardiovascular: Atrial arrhythmia (intraoperative: 2%), atrioventricular nodal arrhythmia (intraoperative: 2% to 4%), cardiac arrhythmia (postoperative: 1%), ventricular arrhythmia (intraoperative: 2% to 3%)

Gastrointestinal: Retching (induction and maintenance: ≤1%), vomiting (recovery: 10%; induction: <1%)

Nervous system: Delirium (6%), involuntary muscle movements (maintenance: 2%)

Neuromuscular & skeletal: Laryngospasm (induction: 8%; maintenance: <1%)

<1%:

Cardiovascular: Hypertension (intraoperative and postoperative), hypotension (intraoperative and postoperative)

Dermatologic: Diaphoresis (induction)

Nervous system: Abnormal electroencephalogram (convulsive pattern), mood changes, nightmares, seizure

Respiratory: Change in bronchial secretions (induction and maintenance)

Frequency not defined:

Endocrine & metabolic: Decreased blood urea nitrogen, decreased serum cholesterol, increased lactate dehydrogenase, increased serum glucose

Gastrointestinal: Intestinal obstruction

Hematologic & oncologic: Leukocytosis

Hepatic: Abnormal hepatic function tests (bromsulphthalein clearance decreased), decreased serum alkaline phosphatase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin

Nervous system: Ataxia, cognitive dysfunction, confusion, dizziness, drowsiness, fatigue, nervousness

Neuromuscular & skeletal: Asthenia, myalgia

Renal: Increased serum creatinine

Postmarketing:

Cardiovascular: Acute myocardial infarction, atrial fibrillation, bradycardia, complete atrioventricular block, first degree atrioventricular block, flushing, ischemic heart disease, low cardiac output, prolonged QT interval on ECG, second degree atrioventricular block, tachycardia, torsades de pointes, ventricular fibrillation, ventricular premature contractions, ventricular tachycardia

Dermatologic: Skin rash

Endocrine & metabolic: Hyperkalemia (with underlying myopathies or perioperative), increased gamma-glutamyl transferase

Gastrointestinal: Hiccups, pancreatitis

Genitourinary: Oliguria

Hematologic & oncologic: Increased hemoglobin (carboxyhemoglobin)

Hepatic: Cholestatic hepatitis, fulminant hepatitis, hepatic failure, hepatic necrosis, hepatitis, hepatotoxicity (idiosyncratic; Chalasani 2014), jaundice, liver steatosis

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

Nervous system: Awareness under anesthesia without pain, brain edema, headache, hypothermia, increased intracranial pressure, malignant hyperthermia, migraine, myoclonus, withdrawal syndrome (following multi-day exposure)

Neuromuscular & skeletal: Rhabdomyolysis

Ophthalmic: Anisocoria, nystagmus disorder

Renal: Acute kidney injury

Respiratory: Airway obstruction, apnea, bronchospasm, hypercapnia, hypoxia, respiratory depression, stridor

Contraindications

Known sensitivity to isoflurane, other halogenated agents, or any component of the formulation; patients in whom general anesthesia is contraindicated; known or suspected genetic susceptibility to malignant hyperthermia; history of hepatitis due to a halogenated inhalational anesthetic or a history of unexplained moderate to severe liver dysfunction (eg, jaundice associated with fever and/or eosinophilia) after anesthesia with isoflurane or other halogenated inhalational anesthetics.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: Decrease in BP is dose dependent due to peripheral vasodilation; cardiac output is maintained. Use caution in patients who are hypovolemic, hypotensive, or hemodynamically compromised; use caution in patients with coronary artery disease to avoid risk of myocardial ischemia. May prolong the QT interval and rarely torsades de pointes; use caution in patients at risk of QT prolongation. May produce cardiac steal (due to coronary vasodilation) and reflex tachycardia, but does not depress cardiac conduction nor does it sensitize the myocardium to catecholamine-induced arrhythmias like halothane (not available in the United States) (Golembiewski 2004).

• CNS depression: Advise patients to wait at least 24 hours after administration before engaging in activities which require mental alertness (operating machinery or driving).

• Decreased blood flow: May cause decrease in hepatic, renal, and splenic blood flow (Gelman 1984).

• Hepatic effects: Postoperative mild to severe hepatic dysfunction (including fatal hepatic necrosis and hepatic failure) and hepatitis with or without jaundice have been reported; may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics. Risk may be increased with repeated isoflurane exposure in a short time.

• Hyperkalemia: Use of inhaled anesthetics has been associated with rare cases of perioperative hyperkalemia that have resulted in cardiac arrhythmias (including fatalities) in pediatric patients; concomitant use of succinylcholine was associated with many of the reported cases, but not all. Risk of hyperkalemia is increased in pediatric patients with underlying neuromuscular disease (eg, Duchenne muscular dystrophy). Other abnormalities may include elevation in creatinine kinase (CK) and myoglobinuria. Monitor closely for hyperkalemic-associated arrhythmias; aggressively identify and treat.

• Hypersensitivity: Hypersensitivity reactions (eg, anaphylaxis, cardiovascular collapse, difficulty breathing, hypotension, rash) have been reported.

• Increased intracranial pressure: Dilates the cerebral vasculature and may, in certain conditions, increase intracranial pressure.

• Malignant hyperthermia: May trigger malignant hyperthermia; some reported cases have been fatal. Risk may be increased with concomitant administration of succinylcholine and volatile anesthetic agents and patients with genetic factors or family history of malignant hyperthermia, including ryanodine receptor or dihydropyridine receptor inherited variants. Signs of malignant hyperthermia may include arrhythmias, cyanosis, hemodynamic instability, hypercapnia, hyperthermia, hypovolemia, hypoxia, muscle rigidity, tachycardia, and tachypnea; coagulopathies, renal failure, and skin mottling may also occur. If malignant hyperthermia is suspected, discontinue triggering agents and institute appropriate therapy (eg, dantrolene) and other supportive measures.

• Obstetrical anesthesia: Increased blood loss comparable with that seen with halothane has been reported during abortions.

• Respiratory depression: Causes dose-dependent respiratory depression and blunted ventilatory response to hypoxia and hypercapnia (Golembiewski 2004).

Disease-related concerns:

• Heart failure: In a scientific statement from the American Heart Association, isoflurane has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Hepatic impairment: Use with caution in patients with history of hepatic impairment or taking medications known to cause hepatic impairment; evaluate need for repeated exposure in a short time as clinically indicated.

Special populations:

• Pediatric neurotoxicity: In pediatric and neonatal patients <3 years and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on child or fetal brain development and may contribute to various cognitive and behavioral problems. Epidemiological studies in humans have reported various cognitive and behavioral problems including neurodevelopmental delay (and related diagnoses), learning disabilities, and ADHD. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk vs benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed.

Special handling:

• Occupational caution: There is no specific work exposure limit established for isoflurane. However, the National Institute for Occupational Safety and Health (NIOSH) recommends no worker be exposed to >2 ppm (ceiling concentrations) over a period of 1 hour. Precautions (eg, adequate ventilation, scavenging-systems, minimizing leaks/spills) can help to lessen any potential risk.

Other warnings/precautions:

• Desiccated absorbents: Reaction of isoflurane with desiccated CO2 absorbents produce carbon monoxide, which may result in elevated carboxyhemoglobin levels in some patients.

Dosage Forms: US

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

Solution, Inhalation:

Forane: USP: >= 99.9 mL/100 mL (100 mL, 250 mL)

Terrell: USP: >= 99.9 mL/100 mL (100 mL, 250 mL)

Generic: USP: >= 99.9 mL/100 mL (100 mL, 250 mL)

Generic Equivalent Available: US

Yes

Administration: Adult

Via isoflurane-specific calibrated vaporizer or vaporizer with calculated flow required

Administration: Pediatric

Inhalation: Administer via isoflurane-specific calibrated vaporizer or vaporizer with calculated flow required

Use: Labeled Indications

Anesthesia: For induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia.

Medication Safety Issues
Sound-alike/look-alike issues:

Isoflurane may be confused with enflurane

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP2E1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

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

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect 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 enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Bambuterol: May enhance the arrhythmogenic effect of Inhalational Anesthetics. Management: Some labels recommend specifically avoiding halothane; others recommend separating administration by at least 6 hours; other bambuterol labels do not mention this possible interaction. Monitor for increased sensitivity to arrhythmias if coadministered. Risk D: Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect 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 enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

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

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

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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

Calcium Channel Blockers: Inhalational Anesthetics may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: 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. Risk D: Consider therapy modification

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

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dabrafenib: QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect 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

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect 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

Dexmethylphenidate-Methylphenidate: May enhance the hypertensive effect of Inhalational Anesthetics. Risk X: Avoid combination

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

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

DOPamine: Inhalational Anesthetics may enhance the arrhythmogenic effect of DOPamine. Risk C: Monitor therapy

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect 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

DroPERidol: May enhance the CNS depressant effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). DroPERidol may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Consider dose reductions and monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

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

Ephedra: May enhance the arrhythmogenic effect of Inhalational Anesthetics. Risk X: Avoid combination

EPHEDrine (Nasal): May enhance the arrhythmogenic effect of Inhalational Anesthetics. Risk X: Avoid combination

EPHEDrine (Systemic): May enhance the arrhythmogenic effect of Inhalational Anesthetics. Risk X: Avoid combination

EPINEPHrine (Nasal): Inhalational Anesthetics may enhance the arrhythmogenic effect of EPINEPHrine (Nasal). Risk C: Monitor therapy

EPINEPHrine (Oral Inhalation): Inhalational Anesthetics may enhance the arrhythmogenic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

EPINEPHrine (Systemic): Inhalational Anesthetics may enhance the arrhythmogenic effect of EPINEPHrine (Systemic). Management: Administer epinephrine with added caution in patients receiving, or who have recently received, inhalational anesthetics. Use lower than normal doses of epinephrine and monitor for the development of cardiac arrhythmias. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Fenoterol: Inhalational Anesthetics may enhance the arrhythmogenic effect of Fenoterol. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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

Fluorouracil Products: QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Haloperidol: May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect 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 enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Isoproterenol: Inhalational Anesthetics may enhance the arrhythmogenic effect of Isoproterenol. Risk X: Avoid combination

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect 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

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Metaraminol: Inhalational Anesthetics may enhance the arrhythmogenic effect of Metaraminol. Risk X: Avoid combination

Methadone: QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the CNS depressant effect of Methadone. Methadone may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation, ventricular arrhythmias, sedation, and respiratory depression. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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

Neuromuscular-Blocking Agents: Isoflurane may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Inhalational Anesthetics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Management: When initiating a non-depolarizing neuromuscular blocking agent (NMBA) in a patient receiving an inhalational anesthetic, initial NMBA doses should be reduced 15% to 25% and doses of continuous infusions should be reduced 30% to 60%. Risk D: Consider therapy modification

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

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

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

Nitrous Oxide: Isoflurane may enhance the CNS depressant effect of Nitrous Oxide. Nitrous Oxide may enhance the therapeutic effect of Isoflurane. Specifically, isoflurane MAC values may be decreased. Risk C: Monitor therapy

Norepinephrine: Inhalational Anesthetics may enhance the arrhythmogenic effect of Norepinephrine. Risk C: 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. Risk D: Consider therapy modification

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Ondansetron: May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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

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

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

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect 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 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. Risk D: Consider therapy modification

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

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

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

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Phenylephrine (Ophthalmic): May enhance the adverse/toxic effect of Inhalational Anesthetics. Specifically, the cardiovascular depressant effects of inhalational anesthetics may be increased. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

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

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

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

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

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

QT-prolonging Agents (Highest Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

QT-prolonging Antidepressants (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the hypotensive effect of other QT-Prolonging Inhalational Anesthetics (Moderate Risk). QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of other QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for hypotension and QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-Prolonging Inhalational Anesthetics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

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

Ritodrine: May enhance the adverse/toxic effect of Inhalational Anesthetics. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

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

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

Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: 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. Risk D: Consider therapy modification

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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect 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

Pregnancy Considerations

Isoflurane crosses the placenta (Dwyer 1995; Satoh 1995).

Based on animal data, repeated or prolonged use of general anesthetic and sedation medications that block N-methyl-D- aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity, may affect brain development. Evaluate benefits and potential risks of fetal exposure to isoflurane when duration of surgery is expected to be >3 hours (Olutoye 2018).

Use of isoflurane in obstetric anesthesia has been described (Abboud 1989; ACOG 209 2019; Devroe 2015; Ghaly 1988; Liu 2013). Maternal exposure should be minimized due to dose dependent uterine relaxation and fetal depression (ACOG 209 2019; Devroe 2015).

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).

Breastfeeding Considerations

It is not known if isoflurane is present in breast milk.

The manufacturer recommends that caution be exercised when administering isoflurane to breastfeeding women.

Based on pharmacokinetic properties, use of isoflurane in breastfeeding women may be considered acceptable (Lee 1993). 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]).

Monitoring Parameters

BP, electrocardiogram, serum potassium, oxygen saturation, respiration, end-tidal CO2 and isoflurane concentrations should be monitored prior to and throughout anesthesia; consider additional cardiac monitoring in patients with coronary artery disease; QT interval in patients at risk for QTc prolongation.

Mechanism of Action

Isoflurane is a general anesthetic agent capable of producing profound respiratory depression. Inhaled anesthetics alter activity of neuronal ion channels, particularly the fast synaptic neurotransmitter receptors (nicotinic acetylcholine, gamma-aminobutyric acid [GABA], and glutamate receptors). May depress myocardial contractility, decrease blood pressure through a decrease in systemic vascular resistance, and decrease sympathetic nervous activity (Stachnik 2006).

Pharmacokinetics (Adult Data Unless Noted)

Metabolism: Minimally hepatic (<0.2%), predominantly CYP2E1 (Golembiewski 2004)

Excretion: Exhaled gases

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Aerrane | Forane;
  • (AR) Argentina: Forane | Isoflurano | Zuflax;
  • (AT) Austria: Forane | Isofluran | Isofluran Rhodia;
  • (AU) Australia: Aerrane | Forthane;
  • (BD) Bangladesh: Forane;
  • (BE) Belgium: Aerrane | Forene;
  • (BG) Bulgaria: Forane | Terrell;
  • (BR) Brazil: Isoflurano | Isoforine | Isoran | Isothane;
  • (CN) China: Aerrane | Forane | Ning fen | Terrell | Yi mei ning;
  • (CO) Colombia: Isoflurano | Isorane | Terrell;
  • (CZ) Czech Republic: Aerrane | Forane | Isofluran nicholas piramal;
  • (DE) Germany: Forane | Forene | Isofluran | Isofluran DeltaSelect;
  • (DO) Dominican Republic: Isoforine;
  • (EE) Estonia: Aerrane | Forane | Isofluran baxter | Isofluran piramal;
  • (EG) Egypt: Aerrane | Anahal | Forane | Isoflurane Sedico | Mira isoflurane;
  • (ES) Spain: Aerrane | Forane | Isoflurano inibsa;
  • (ET) Ethiopia: Forane;
  • (FI) Finland: Forene | Isofluran baxter | Isofluran Rhodia;
  • (FR) France: Aerrane | Cedaconda | Forane | Forene | Forene ecofil;
  • (GB) United Kingdom: Aerrane | Forane | Isoflurane abbott | Isoflurane bioglan;
  • (GR) Greece: Forenium;
  • (HK) Hong Kong: Aerrane | Forane;
  • (HU) Hungary: Aerrane | Forane;
  • (ID) Indonesia: Aerrane | Forane | Terrell;
  • (IE) Ireland: Forane;
  • (IN) India: Aerrane | Forane | Iflurane | Isifrane | Isorane | Isotroy;
  • (IT) Italy: Aerrane | Forane;
  • (JO) Jordan: Aerrane | Floran | Forane;
  • (JP) Japan: Escain | Forane | Isoflurane merck hoei;
  • (KE) Kenya: Forane | Isotroy;
  • (KR) Korea, Republic of: Aerane | Forane | I-Fran | Rhodiaisoflurane | Terrel;
  • (KW) Kuwait: Aerrane | Forane;
  • (LB) Lebanon: Forane;
  • (LT) Lithuania: Forane;
  • (LU) Luxembourg: Forene;
  • (LV) Latvia: Forane;
  • (MX) Mexico: Dorin | Fluduk | Forane | Isoflurano | Lisorane | Sofloran;
  • (MY) Malaysia: Aerrane | Forane | Isorane;
  • (NG) Nigeria: Forane | Isotroy;
  • (NL) Netherlands: Forene | Isofluraan | Sedaconda;
  • (NO) Norway: Aerrane | Forene | Isofluran | Sedaconda;
  • (NZ) New Zealand: Aerrane | Forane;
  • (PE) Peru: Isoflurano;
  • (PH) Philippines: Aerrane | Florane | Forane | Isorane | Pascual isoflurane;
  • (PK) Pakistan: Forane;
  • (PL) Poland: Aerrane | Forane;
  • (PR) Puerto Rico: Forane;
  • (PT) Portugal: Aerrane | Forene | Isoflurano;
  • (PY) Paraguay: Forane | Isoflurano interlabo | Isoflurano omicron | Isoflurano prosalud | Isoflurano quimfa | Isoflurano usp interlabo | Isoforine | Zuflax;
  • (QA) Qatar: Aerrane | Floran;
  • (RO) Romania: Aerrane | Anesteran | Forane;
  • (RU) Russian Federation: Aerrane | Forane;
  • (SA) Saudi Arabia: Aerrane | Floran | Forane;
  • (SE) Sweden: Aerrane | Forene | Isofluran baxter | Isofluran Rhodia | Isoflurane Medeva Europe | Sedaconda;
  • (SG) Singapore: Aerrane | Forane;
  • (SI) Slovenia: Forane | Isofluran;
  • (SK) Slovakia: Forane | Isofluran Rhodia;
  • (TH) Thailand: Aerrane | Forane | Isofluran Rhodia | Terrell;
  • (TN) Tunisia: Forene;
  • (TR) Turkey: Aerrane | Forane | Isoflurane usp;
  • (TW) Taiwan: Aerrane | Forane;
  • (UA) Ukraine: Forane;
  • (UG) Uganda: Forane | Isotroy;
  • (UY) Uruguay: Forane | Isoflurano Zeneca | Isoforine | Terrell;
  • (VE) Venezuela, Bolivarian Republic of: Forene | Isoflurano | Isoflurano usp;
  • (ZA) South Africa: Aerrane | Forane | Isofor;
  • (ZM) Zambia: Forane | Isotroy;
  • (ZW) Zimbabwe: Forane
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