Desflurane
Liquid · Respiratory (inhalation)
Uses
Desflurane, USP, Liquid for Inhalation, a general anesthetic, is an inhalation agent indicated: for induction and/or maintenance of anesthesia in adults ( 1.1 ) for maintenance of anesthesia in pediatric patients following induction with agents other than Desflurane, USP, Liquid for Inhalation and intubation. 1.1 Induction of Anesthesia Desflurane, USP, Liquid for Inhalation is indicated as an inhalation agent for induction of anesthesia for inpatient and outpatient surgery in adults. Desflurane, USP, Liquid for Inhalation is contraindicated as an inhalation agent for the induction of anesthesia in pediatric patients because of a high incidence of moderate to severe upper airway adverse events. 1.2 Maintenance of Anesthesia Desflurane, USP, Liquid for Inhalation is indicated as an inhalation agent for maintenance of anesthesia for inpatient and outpatient surgery in adults and in pediatric patients. After induction of anesthesia with agents other than Desflurane, USP, Liquid for Inhalation, and tracheal intubation, Desflurane, USP, Liquid for Inhalation is indicated for maintenance of anesthesia in infants and children. Desflurane, USP, Liquid for Inhalation is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm, and secretions [See Warnings and Precautions (5.3) and Clinical Studies (14.5) ] .
Dosage and administration
Only persons trained in the administration of general anesthesia should administer Desflurane, USP, Liquid for Inhalation. Only a vaporizer specifically designed and designated for use with desflurane should be utilized for its administration. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, and circulatory resuscitation must be immediately available. Desflurane, USP, Liquid for Inhalation is administered by inhalation. The administration of general anesthesia must be individualized based on the patient’s response. Hypotension and respiratory depression increase as anesthesia with Desflurane, USP, Liquid for Inhalation is deepened. The minimum alveolar concentration (MAC) of Desflurane, USP, Liquid for Inhalation decreases with increasing patient age. The MAC for Desflurane, USP, Liquid for Inhalation is also reduced by concomitant N 2 O administration (See Table 1 ) . The dose should be adjusted accordingly. The following table provides mean relative potency based upon age and effect of N 2 O in predominately ASA physical status I or II patients. Benzodiazepines and opioids decrease the MAC of Desflurane, USP, Liquid for Inhalation [See Drug Interactions (7.1, Table 3) ] . Desflurane, USP, Liquid for Inhalation also decreases the doses of neuromuscular blocking agents required [See Drug Interactions (7.2, Table 4) ] . The dose should be adjusted accordingly. Table 1 Effect of Age on Minimum Alveolar Concentration of Desflurane Mean ± SD (percent atmospheres) Age N O 2 100% N N 2 O 60%/40% O 2 2 weeks 6 9.2 ± 0 - - 10 weeks 5 9.4 ± 0.4 - - 9 months 4 10 ± 0.7 5 7.5 ± 0.8 2 years 3 9.1 ± 0.6 - - 3 years - - 5 6.4 ± 0.4 4 years 4 8.6 ± 0.6 - - 7 years 5 8.1 ± 0.6 - - 25 years 4 7.3 ± 0 4 4 ± 0.3 45 years 4 6 ± 0.3 6 2.8 ± 0.6 70 years 6 5.2 ± 0.6 6 1.7 ± 0.4 N = number of crossover pairs (using up-and-down method of quantal response) Desflurane, USP, Liquid for Inhalation should be administered only by persons trained in the administration of general anesthesia. It should only be administered using a vaporizer specifically designed and designated for use with desflurane. ( 2 ) The administration of general anesthesia must be individualized based on the patient’s response, including cardiovascular and pulmonary changes. ( 2 ) Desflurane, USP, Liquid for Inhalation should not be used as the sole agent for anesthetic induction in patients with coronary artery disease or where increases in heart rate or blood pressure are undesirable. ( 2.6 ) For dosing considerations in patients with intracranial space occupying lesions, see Full Prescribing Information. ( 2.7 ) 2.1 Preanesthetic Medication Issues such as whether or not to premedicate and the choice of premedication(s) must be individualized. In clinical studies, patients scheduled to be anesthetized with Desflurane, USP, Liquid for Inhalation frequently received IV preanesthetic medication, such as opioid and/or benzodiazepine. 2.2 Induction In adults, some premedicated with opioid, a frequent starting concentration was 3% Desflurane, USP, Liquid for Inhalation, increased in 0.5% to 1% increments every 2 to 3 breaths. End-tidal concentrations of 4% to 11%, Desflurane, USP, Liquid for Inhalation with and without N 2 O, produced anesthesia within 2 minutes to 4 minutes. When Desflurane, USP, Liquid for Inhalation was tested as the primary anesthetic induction agent, the incidence of upper airway irritation (apnea, breathholding, laryngospasm, coughing and secretions) was high. During induction in adults, the overall incidence of oxyhemoglobin desaturation (SpO 2 < 90%) was 6% [ See Adverse Reactions (6.1) ]. After induction in adults with an intravenous drug such as thiopental or propofol, Desflurane, USP, Liquid for Inhalation can be started at approximately 0.5 to 1 MAC, whether the carrier gas is O 2 or N 2 O/O 2 . Inspired concentrations of Desflurane, USP, Liquid for Inhalation greater than 12% have been safely administered to patients, particularly during induction of anesthesia. Such concentrations will proportionately dilute the concentration of oxygen; therefore, maintenance of an adequate concentration of oxygen may require a reduction of nitrous oxide or air if these gases are used concurrently. 2.3 Maintenance Surgical levels of anesthesia in adults may be maintained with concentrations of 2.5% to 8.5% Desflurane, USP, Liquid for Inhalation with or without the concomitant use of nitrous oxide. In children, surgical levels of anesthesia may be maintained with concentrations of 5.2% to 10% Desflurane, USP, Liquid for Inhalation with or without the concomitant use of nitrous oxide. During the maintenance of anesthesia with inflow rates of 2 L/min or more, the alveolar concentration of Desflurane, USP, Liquid for Inhalation will usually be within 10% of the inspired concentration [F A /F I , see Figure 2 in Clinical Pharmacology (12.3) ] . During the maintenance of anesthesia, increasing concentrations of Desflurane, USP, Liquid for Inhalation produce dose-dependent decreases in blood pressure. Excessive decreases in blood pressure may be due to depth of anesthesia and in such instances may be corrected by decreasing the inspired concentration of Desflurane, USP, Liquid for Inhalation. Concentrations of Desflurane, USP, Liquid for Inhalation exceeding 1 MAC may increase heart rate. Thus with this drug, an increased heart rate may not serve reliably as a sign of inadequate anesthesia. 2.4 Maintenance of Anesthesia in Intubated Pediatric Patients Desflurane, USP, Liquid for Inhalation is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other thanDesflurane, USP, Liquid for Inhalation, and tracheal intubation. Desflurane, USP, Liquid for Inhalation, with or without N 2 O, and halothane, with or without N 2 O were studied in three clinical trials of pediatric patients aged 2 weeks to 12 years (median 2 years) and ASA physical status I or II.
Dosage forms and strengths
Desflurane, USP, Liquid for Inhalation is a colorless, non-flammable, volatile liquid (below 22.8°C) for inhalation, 100% desflurane. Liquid (volatile): 100% ( 3 )
Contraindications
The use of Desflurane, USP, Liquid for Inhalation is contraindicated in the following conditions: Known or suspected genetic susceptibility to malignant hyperthermia [See Warnings and Precautions (5.1), Clinical Pharmacology (12.5)] . Patients in whom general anesthesia is contraindicated. Induction of anesthesia in pediatric patients. Patients with known sensitivity to Desflurane, USP, Liquid for Inhalation or to other halogenated agents [See Warnings and Precautions (5.6) ] . Patients with a history of moderate to severe hepatic dysfunction following anesthesia with Desflurane, USP, Liquid for Inhalation or other halogenated agents and not otherwise explained [See Warnings and Precautions (5.6) ] . Patients with known or suspected genetic susceptibility to malignant hyperthermia ( 4 ) Patients in whom general anesthesia is contraindicated ( 4 ) Induction of anesthesia in pediatric patients ( 4 ) Patients with known sensitivity to halogenated agents ( 4 ) Patients with a history of moderate to severe hepatic dysfunction following anesthesia with halogenated agents and not otherwise explained. ( 4 )
Warnings and precautions
Malignant Hyperthermia: Malignant hyperthermia may occur, especially in individuals with known or suspected susceptibility based on genetic factors or family history. Discontinue triggering agents, administer intravenous dantrolene sodium, and apply supportive therapies. ( 5.1 ) Perioperative Hyperkalemia: Perioperative hyperkalemia may occur. Patients with latent or overt neuromuscular disease, particularly with Duchenne muscular dystrophy, appear to be most vulnerable. Early, aggressive intervention is recommended. ( 5.2 ) Respiratory Adverse Reactions in Pediatric Patients: - Not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions. Monitor and treat accordingly. ( 5.3 ) - May cause airway narrowing and increased airway resistance in children with asthma or a history of recent upper airway infection. Monitor and treat accordingly.( 5.3 ) QTc Prolongation: Carefully monitor cardiac rhythm when administering desflurane to susceptible patients. ( 5.4 ) Interactions with Desiccated Carbon Dioxide (CO 2 ) Absorbents: May react with desiccated CO 2 absorbents to produce carbon monoxide. Replace desiccated CO 2 absorbent before administration of desflurane. ( 5.5 ) Hepatobiliary Disorders: May cause sensitivity hepatitis in patients sensitized by previous exposure to halogenated anesthetics. Approach repeated anesthesia with caution ( 5.6 ) Pediatric Neurotoxicity: In developing animals, exposures greater than 3 hours cause neurotoxicity. Weigh benefits against potential risks when considering elective procedures in children under 3 years old. ( 5.7 ) Postoperative Agitation in Children: May cause postoperative agitation during emergence from anesthesia in children. ( 5.9 ) 5.1 Malignant Hyperthermia In susceptible individuals, volatile anesthetic agents, including desflurane, may trigger malignant hyperthermia, a skeletal muscle hypermetabolic state leading to high oxygen demand. Fatal outcomes of malignant hyperthermia have been reported. The risk of developing malignant hyperthermia increases with the concomitant administration of succinylcholine and volatile anesthetic agents. Desflurane can induce malignant hyperthermia in patients with known or suspected susceptibility based on genetic factors or family history, including those with certain inherited ryanodine receptor ( RYR1 ) or dihydropyridine receptor ( CACNA1S ) variants [See Contraindications (4), Clinical Pharmacology (12.5)] . Signs consistent with malignant hyperthermia may include hyperthermia, hypoxia, hypercapnia, muscle rigidity (e.g., jaw muscle spasm), tachycardia (e.g., particularly that unresponsive to deepening anesthesia or analgesic medication administration), tachypnea, cyanosis, arrhythmias, hypovolemia, and hemodynamic instability. Skin mottling, coagulopathies, and renal failure may occur later in the course of the hypermetabolic process. Successful treatment of malignant hyperthermia depends on early recognition of the clinical signs. If malignant hyperthermia is suspected, discontinue all triggering agents (i.e., volatile anesthetic agents and succinylcholine), administer intravenous dantrolene sodium, and initiate supportive therapies. Consult prescribing information for intravenous dantrolene sodium for additional information on patient management. Supportive therapies include administration of supplemental oxygen and respiratory support based on clinical need, maintenance of hemodynamic stability and adequate urinary output, management of fluid and electrolyte balance, correction of acid base derangements, and institution of measures to control rising temperature. 5.2 Perioperative Hyperkalemia Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease. 5.3 Respiratory Adverse Reactions in Pediatric Patients Desflurane is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm and secretions [See Clinical Studies (14.5) ] . Children, particularly if 6 years old or younger, who are under an anesthetic maintenance of desflurane delivered via laryngeal mask airway (LMA™ mask) are at increased risk for adverse respiratory reactions, e.g., coughing and laryngospasm, especially with removal of the laryngeal mask airway under deep anesthesia [See Clinical Studies (14.5) ] . Therefore, closely monitor these patients for signs and symptoms associated with laryngospasm and treat accordingly. When desflurane is used for maintenance of anesthesia in children with asthma or a history of recent upper airway infection, there is an increased risk for airway narrowing and increases in airway resistance. Therefore, closely monitor these patients for signs and symptoms associated with airway narrowing and treat accordingly . 5.4 QTc Prolongation QTc prolongation, associated with torsade de pointes, has been reported [See Adverse Reactions ( 6.2 )].
Side effects
Most common adverse reactions (incidence>10%) are coughing, breath holding, apnea, nausea, vomiting. (6) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse event information is derived from controlled clinical trials, the majority of which were conducted in the United States. The studies were conducted using a variety of premedications, other anesthetics, and surgical procedures of varying length. Most adverse events reported were mild and transient, and may reflect the surgical procedures, patient characteristics (including disease) and/or medications administered. Of the 2,143 patients exposed to desflurane in clinical trials, 370 adults and 152 children were induced with desflurane alone and 987 patients were maintained principally with desflurane. The frequencies given reflect the percent of patients with the event. Each patient was counted once for each type of adverse event. They are presented in alphabetical order according to body system. Table 2 Frequency of Events Occurring in Greater Than 1% of Clinical Trial Patients (in Reports Deemed “Probably Causally Related”) Induction (use as a mask inhalation agent) Adult Patients (N=370): Coughing 34%, breathholding 30%, apnea 15%, increased secretions Incidence of events 3% to 10% , laryngospasm , oxyhemoglobin desaturation (SpO 2 < 90%) , pharyngitis . Maintenance or Recovery Adult and Intubated Pediatric Patients (N=687): Body as a Whole Headache Cardiovascular Bradycardia, hypertension, nodal arrhythmia, tachycardia Digestive Nausea 27%, vomiting 16% Nervous system Increased salivation Respiratory Apnea , breathholding, cough increased , laryngospasm , pharyngitis Special Senses Conjunctivitis (conjunctival hyperemia) Frequency of Events Occurring in Less Than 1% of Patients (in Reports Deemed “Probably Causally Related”) Reported in 3 or more patients, regardless of severity Adverse reactions reported only from postmarketing experience or in the literature, not seen in clinical trials, are considered rare and are italicized. Cardiovascular Arrhythmia, bigeminy, abnormal electrocardiogram, myocardial ischemia, vasodilation Digestive Hepatitis Nervous System Agitation, dizziness Respiratory Asthma, dyspnea, hypoxia Frequency of Events Occurring in Less Than 1% of Clinical Trial Patients (in Reports Deemed “Causal Relationship Unknown”) Reported in 3 or more patients, regardless of severity Body as a Whole Fever Cardiovascular Hemorrhage, myocardial infarction Metabolic and Nutrition Increased creatinine phosphokinase Musculoskeletal System Myalgia Skin and Appendages Pruritus 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of desflurane. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders : Coagulopathy Metabolism and Nutrition Disorders : Hyperkalemia, Hypokalemia, metabolic acidosis Nervous System Disorders : Convulsion, Post-operative agitation in children Eye Disorders: Ocular icterus Cardiac Disorders: Cardiac arrest, QTc prolongation, torsade de pointes, ventricular failure, ventricular hypokinesia, atrial fibrillation Vascular Disorders: Malignant hypertension, hemorrhage, hypotension, shock Respiratory, Thoracic and Mediastinal Disorders: Respiratory arrest, respiratory failure, respiratory distress, bronchospasm, hemoptysis Gastrointestinal Disorders : Pancreatitis acute, abdominal pain Hepatobiliary Disorders: Hepatic failure, hepatic necrosis, hepatitis, cytolytic hepatitis, cholestasis, jaundice, hepatic function abnormal, liver disorder Skin and Subcutaneous Tissue Disorder : Urticaria, erythema Musculoskeletal, Connective Tissue and Bone Disorders: Rhabdomyolysis General Disorders and Administration Site Conditions: Hyperthermia malignant, asthenia, malaise Investigations: Electrocardiogram ST-T change, electrocardiogram T-wave inversion, tranaminases increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, coagulation test abnormal, ammonia increased Injury, Poisoning, and Procedural Complications*: Tachyarrhythmia, palpitations, eye burns, blindness transient, encephalopathy, ulcerative keratitis, ocular hyperemia, visual acuity reduced, eye irritation, eye pain, dizziness, migraine, fatigue, accidental exposure, skin burning sensation, drug administration error *Reactions categorized within this System Organ Class (SOC) were accidental exposures to non-patients.
Drug interactions
No clinically significant adverse interactions with commonly used preanesthetic drugs, or drugs used during anesthesia (muscle relaxants, intravenous agents, and local anesthetic agents) were reported in clinical trials. The effect of desflurane on the disposition of other drugs has not been determined. Similar to isoflurane, desflurane does not predispose to premature ventricular arrhythmias in the presence of exogenously infused epinephrine in swine. Concomitant use of N 2 O, benzodiazepines and/or opioids reduces the MAC of desflurane. Adjust dose accordingly. ( 7.1 , 7.3 ) Desflurane decreases the doses of neuromuscular blocking agents required. Adjust dose accordingly. ( 7.2 ) 7.1 Benzodiazepines and Opioids (MAC Reduction) Benzodiazepines and opioids decrease the amount of desflurane (MAC) needed to produce anesthesia. This effect is shown in Table 3 for intravenous midazolam (25 mcg/kg to 50 mcg/kg) and intravenous fentanyl (3 mcg/kg to 6 mcg/kg) in patients of two different age groups. Table 3 Desflurane MAC with Fentanyl or Midazolam Mean ± SD (percent reduction) Dose 18 to 30 years 31 to 65 years No fentanyl 6.4 ± 0 6.3 ± 0.4 3 mcg/kg fentanyl 3.5 ± 1.9 (46%) 3.1 ± 0.6 (51%) 6 mcg/kg fentanyl 3 ± 1.2 (53%) 2.3 ± 1 (64%) No midazolam 6.9 ± 0.1 5.9 ± 0.6 25 mcg/kg midazolam - 4.9 ± 0.9 (16%) 50 mcg/kg midazolam - 4.9 ± 0.5 (17%) 7.2 Neuromuscular Blocking Agents Anesthetic concentrations of desflurane at equilibrium (administered for 15 or more minutes before testing) reduced the ED 95 of succinylcholine by approximately 30% and that of atracurium and pancuronium by approximately 50% compared to N 2 O/opioid anesthesia (See Table 4 ) . The effect of desflurane on duration of nondepolarizing neuromuscular blockade has not been studied. Table 4 Dosage of Muscle Relaxant Causing 95% Depression in Neuromuscular Blockade Desflurane Concentration Mean ED 95 (mcg/kg) Pancuronium Atracurium Succinylcholine Vecuronium 0.65 MAC 60% N 2 O/O 2 26 133 - - 1.25 MAC 60% N 2 O/O 2 18 119 - - 1.25 MAC O 2 22 120 360 19 Dosage reduction of neuromuscular blocking agents during induction of anesthesia may result in delayed onset of conditions suitable for endotracheal intubation or inadequate muscle relaxation, because potentiation of neuromuscular blocking agents requires equilibration of muscle with the delivered partial pressure of desflurane. Among nondepolarizing drugs, pancuronium, atracurium, and vecuronium interactions have been studied. In the absence of specific guidelines: For endotracheal intubation, do not reduce the dose of nondepolarizing muscle relaxants or succinylcholine. During maintenance of anesthesia, the dose of nondepolarizing muscle relaxants is likely to be reduced compared to that during N 2 O/opioid anesthesia. Administration of supplemental doses of muscle relaxants should be guided by the response to nerve stimulation. 7.3 Concomitant use with N 2 O Concomitant administration of N 2 O reduces the MAC of desflurane [See Dosage and Administration (2), Table 1 ] .
Use in specific populations
Geriatric Use: The minimum alveolar concentration (MAC) of desflurane decreases with increasing patient age. ( 8.5 ) 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, embryo-fetal toxicity (reduced viable fetuses and/or increased post-implantation loss) was noted in pregnant rats and rabbits administered 1 MAC desflurane for 4 hours a day (4 MAC-hours/day) during organogenesis. Published studies in pregnant primates demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of peak brain development increases neuronal apoptosis in the developing brain of the offspring when used for longer than 3 hours. There are no data on pregnancy exposures in primates corresponding to periods prior to the third trimester in humans [See Data] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Labor or Delivery The safety of desflurane during labor or delivery has not been demonstrated. Desflurane is a uterine-relaxant. Data Animal Data Pregnant rats were exposed to 8.2% desflurane (1 MAC; 60% oxygen) for 0.5, 1, or 4 hours (0.5, 1, or 4 MAC-hours) per day during organogenesis (Gestation Day 6 to 15). Embryo-fetal toxicity (increased post-implantation loss and reduced viable fetuses) was noted in the 4 hour treatment group in the presence of maternal toxicity (reduced body weight gain). There was no evidence of malformations in any group. Pregnant rabbits were exposed to 8.9% desflurane (1 MAC; 60% oxygen) for 0.5, 1, or 3 hours per day during organogenesis (Gestation Days 6 to 18). Fetal toxicity (reduced viable fetuses) was noted in the 3 hour treatment group in the presence of maternal toxicity (reduced body weight). There was no evidence of malformations in any group. Pregnant rats were exposed to 8.2% desflurane (1 MAC; 60% oxygen) for 0.5, 1, or 4 hours per day from late gestation and through lactation (Gestation Day 15 to Lactation Day 21). Pup body weights were reduced in the 4 hours per day group in the presence of maternal toxicity (increased mortality and reduced body weight gain). This study did not evaluate neurobehavioral function including learning and memory or reproductive behavior in the first generation (F1) pups. In a published study in primates, administration of an anesthetic dose of ketamine for 24 hours on Gestation Day 122 increased neuronal apoptosis in the developing brain of the fetus. In other published studies, administration of either isoflurane or propofol for 5 hours on Gestation Day 120 resulted in increased neuronal and oligodendrocyte apoptosis in the developing brain of the offspring. With respect to brain development, this time period corresponds to the third trimester of gestation in the human. The clinical significance of these findings is not clear; however, studies in juvenile animals suggest neuroapoptosis correlates with long-term cognitive deficits [See Warnings and Precautions (5.7) , Use in Specific Populations (8.4) , and Nonclinical Toxicology (13.2) ] . 8.2 Lactation It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when desflurane is administered to a nursing woman. 8.4 Pediatric Use Respiratory Adverse Reactions in Pediatric Patients Desflurane is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than desflurane, and tracheal intubation. Is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing (26%), laryngospasm (13%) and secretions (12%) [See Clinical Studies (14.5) ] . Children, particularly if 6 years old or younger, who are under an anesthetic maintenance of desflurane delivered via laryngeal mask airway (LMA™ mask) are at increased risk for adverse respiratory reactions, e.g., coughing and laryngospasm, especially with removal of the laryngeal mask airway under deep anesthesia [See Clinical Studies (14.5) ] . Therefore, closely monitor these patients for signs and symptoms associated with laryngospasm and treat accordingly. When desflurane is used for maintenance of anesthesia in children with asthma or a history of recent upper airway infection, there is an increased risk for airway narrowing and increases in airway resistance. Therefore, closely monitor these patients for signs and symptoms associated with airway narrowing and treat accordingly. Published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as desflurane, that either block NMDA receptors or potentiate the activity of GABA during the period of rapid brain growth or synaptogenesis, results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately 3 years of age in humans. In primates, exposure to 3 hours of ketamine that produced a light surgical plane of anesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer of isoflurane increased neuronal cell loss.
Pregnancy
8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, embryo-fetal toxicity (reduced viable fetuses and/or increased post-implantation loss) was noted in pregnant rats and rabbits administered 1 MAC desflurane for 4 hours a day (4 MAC-hours/day) during organogenesis. Published studies in pregnant primates demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of peak brain development increases neuronal apoptosis in the developing brain of the offspring when used for longer than 3 hours. There are no data on pregnancy exposures in primates corresponding to periods prior to the third trimester in humans [See Data] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Labor or Delivery The safety of desflurane during labor or delivery has not been demonstrated. Desflurane is a uterine-relaxant. Data Animal Data Pregnant rats were exposed to 8.2% desflurane (1 MAC; 60% oxygen) for 0.5, 1, or 4 hours (0.5, 1, or 4 MAC-hours) per day during organogenesis (Gestation Day 6 to 15). Embryo-fetal toxicity (increased post-implantation loss and reduced viable fetuses) was noted in the 4 hour treatment group in the presence of maternal toxicity (reduced body weight gain). There was no evidence of malformations in any group. Pregnant rabbits were exposed to 8.9% desflurane (1 MAC; 60% oxygen) for 0.5, 1, or 3 hours per day during organogenesis (Gestation Days 6 to 18). Fetal toxicity (reduced viable fetuses) was noted in the 3 hour treatment group in the presence of maternal toxicity (reduced body weight). There was no evidence of malformations in any group. Pregnant rats were exposed to 8.2% desflurane (1 MAC; 60% oxygen) for 0.5, 1, or 4 hours per day from late gestation and through lactation (Gestation Day 15 to Lactation Day 21). Pup body weights were reduced in the 4 hours per day group in the presence of maternal toxicity (increased mortality and reduced body weight gain). This study did not evaluate neurobehavioral function including learning and memory or reproductive behavior in the first generation (F1) pups. In a published study in primates, administration of an anesthetic dose of ketamine for 24 hours on Gestation Day 122 increased neuronal apoptosis in the developing brain of the fetus. In other published studies, administration of either isoflurane or propofol for 5 hours on Gestation Day 120 resulted in increased neuronal and oligodendrocyte apoptosis in the developing brain of the offspring. With respect to brain development, this time period corresponds to the third trimester of gestation in the human. The clinical significance of these findings is not clear; however, studies in juvenile animals suggest neuroapoptosis correlates with long-term cognitive deficits [See Warnings and Precautions (5.7) , Use in Specific Populations (8.4) , and Nonclinical Toxicology (13.2) ] .
Pediatric use
8.4 Pediatric Use Respiratory Adverse Reactions in Pediatric Patients Desflurane is indicated for maintenance of anesthesia in infants and children after induction of anesthesia with agents other than desflurane, and tracheal intubation. Is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing (26%), laryngospasm (13%) and secretions (12%) [See Clinical Studies (14.5) ] . Children, particularly if 6 years old or younger, who are under an anesthetic maintenance of desflurane delivered via laryngeal mask airway (LMA™ mask) are at increased risk for adverse respiratory reactions, e.g., coughing and laryngospasm, especially with removal of the laryngeal mask airway under deep anesthesia [See Clinical Studies (14.5) ] . Therefore, closely monitor these patients for signs and symptoms associated with laryngospasm and treat accordingly. When desflurane is used for maintenance of anesthesia in children with asthma or a history of recent upper airway infection, there is an increased risk for airway narrowing and increases in airway resistance. Therefore, closely monitor these patients for signs and symptoms associated with airway narrowing and treat accordingly. Published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as desflurane, that either block NMDA receptors or potentiate the activity of GABA during the period of rapid brain growth or synaptogenesis, results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately 3 years of age in humans. In primates, exposure to 3 hours of ketamine that produced a light surgical plane of anesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer of isoflurane increased neuronal cell loss. Data from isoflurane-treated rodents and ketamine-treated primates suggest that the neuronal and oligodendrocyte cell losses are associated with prolonged cognitive deficits in learning and memory. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in pregnant women, neonates, and young children who require procedures with the potential risks suggested by the nonclinical data [See Warnings and Precautions (5.7) , Use in Specific Populations (8.1) , and Nonclinical Toxicology (13.2) ] .
Geriatric use
8.5 Geriatric Use The minimum alveolar concentration (MAC) of desflurane decreases with increasing patient age. The dose should be adjusted accordingly. The average MAC for desflurane in a 70 year old patient is two-thirds the MAC for a 20 year old patient [See Dosage and Administration (2) Table 1 and Clinical Studies (14.3) ] .
Overdosage
The symptoms of overdosage of desflurane can present as a deepening of anesthesia, cardiac and/or respiratory depression in spontaneously breathing patients, and cardiac depression in ventilated patients in whom hypercapnia and hypoxia may occur only at a late stage. In the event of overdosage, or suspected overdosage, take the following actions: discontinue administration of desflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.
Description
Desflurane, USP, Liquid for Inhalation, a nonflammable liquid administered via vaporizer, is a general inhalation anesthetic. It is (±)1,2,2,2-tetrafluoroethyl difluoromethyl ether: Some physical constants are: Molecular weight 168.04 Specific gravity (at 20°C/4°C) 1.465 Vapor pressure in mmHg 669 mmHg @ 20°C 731 mmHg @ 22°C 757 mmHg @ 22.8°C (boiling point;1atm) 764 mmHg @ 23°C 798 mmHg @ 24°C 869 mmHg @ 26°C Partition coefficients at 37°C: Blood/Gas 0.424 Olive Oil/Gas 18.7 Brain/Gas 0.54 Mean Component/Gas Partition Coefficients: Polypropylene (Y piece) 6.7 Polyethylene (circuit tube) 16.2 Latex rubber (bag) 19.3 Latex rubber (bellows) 10.4 Polyvinylchloride (endotracheal tube) 34.7 Desflurane, USP is nonflammable as defined by the requirements of International Electrotechnical Commission 601-2-13. Desflurane, USP is a colorless, volatile liquid below 22.8°C. Data indicate that desflurane, USP is stable when stored under normal room lighting conditions according to instructions. Desflurane, USP is chemically stable. The only known degradation reaction is through prolonged direct contact with soda lime producing low levels of fluoroform (CHF 3 ). The amount of CHF 3 obtained is similar to that produced with MAC-equivalent doses of isoflurane. No discernible degradation occurs in the presence of strong acids. Desflurane, USP does not corrode stainless steel, brass, aluminum, anodized aluminum, nickel plated brass, copper, or beryllium. Structure
How supplied
Desflurane, USP, Liquid for Inhalation, NDC 0781-6172-22, is available in amber-colored glass bottle containing 240 mL desflurane, USP. Each individual bottle is supplied in a carton of 6, NDC 0781-6172-86. 16.1 Safety and Handling Occupational Caution There is no specific work exposure limit established for Desflurane, USP, Liquid for Inhalation. However, the National Institute for Occupational Safety and Health Administration (NIOSH) recommends that no worker should be exposed at ceiling concentrations greater than 2 ppm of any halogenated anesthetic agent over a sampling period not to exceed one hour. Principle routes of exposure include: Skin contact – May cause skin irritation. In case of contact, immediately flush skin with plenty of water. Remove contaminated clothing and shoes. Seek medical attention if irritation develops. Eye contact – May cause eye irritation. In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Seek medical attention if irritation develops. Ingestion – No specific hazards other than therapeutic effects. Do NOT induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. If large quantities of this material are swallowed, seek medical attention immediately. Inhalation – If individuals smell vapors, or experience dizziness or headaches, they should be moved to an area with fresh air. Individuals could also experience the following: Cardiovascular effects: may include fluctuations in heart rate, changes in blood pressure, chest pain. Respiratory effects: may include shortness of breath, bronchospasms, laryngospasms, respiratory depression. Gastrointestinal effects: may include nausea, upset stomach, loss of appetite. Nervous System effects: may include ataxia, tremor, disturbance of speech, lethargy, headache, dizziness, blurred vision. The predicted effects of acute overexposure by inhalation of Desflurane, USP, Liquid for Inhalation include headache, dizziness or (in extreme cases) unconsciousness [See Overdosage (10) ] . There are no documented adverse effects of chronic exposure to halogenated anesthetic vapors ( W aste A nesthetic G ases or WAGs) in the workplace. Although results of some epidemiological studies suggest a link between exposure to halogenated anesthetics and increased health problems (particularly spontaneous abortion), the relationship is not conclusive. Since exposure to WAGs is one possible factor in the findings for these studies, operating room personnel, and pregnant women in particular, should minimize exposure. Precautions include adequate general ventilation in the operating room, the use of a well-designed and well-maintained scavenging system; work practices to minimize leaks and spills while the anesthetic agent is in use, and routine equipment maintenance to minimize leaks. Consistent with clinical data, concentrations would need to reach 2% to 3% in inspired air before individuals would likely experience dizziness or other physiologic effects. 16.2 Storage Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature] . Desflurane, USP, Liquid for Inhalation has been demonstrated to be stable for the period defined by the expiration dating on the label. Preserve in tight, light-resistant container. Replace the cap securely after each use.
Storage
16.2 Storage Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature] . Desflurane, USP, Liquid for Inhalation has been demonstrated to be stable for the period defined by the expiration dating on the label. Preserve in tight, light-resistant container. Replace the cap securely after each use.
Patient information
Anesthesia providers need to obtain the following information from patients prior to administration of anesthesia: Medications they are taking, including herbal supplements Drug allergies, including allergic reactions to anesthetic agents (including hepatic sensitivity) Any history of severe reactions to prior administration of anesthetic If the patient or a member of the patient’s family has a history of malignant hyperthermia or if the patient has a history of Duchenne muscular dystrophy or other latent neuromuscular disease Anesthesia providers should inform patients of the risks associated with desflurane, USP: Post-operative nausea and vomiting and respiratory adverse effects including coughing. There is no information of the effects of desflurane, USP following anesthesia on the ability to operate an automobile or other heavy machinery. However, patients should be advised that the ability to perform such tasks may be impaired after receiving anesthetic agents. Anesthesia providers should inform parents and caregivers of pediatric patients that emergence from anesthesia in children may evoke a brief state of agitation that may hinder cooperation. Effect of anesthetic and sedation drugs on early brain development Studies conducted in young animals and children suggest repeated or prolonged use of general anesthetic or sedation drugs in children younger than 3 years may have negative effects on their developing brains. Discuss with parents and caregivers the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs [See Warnings and Precautions (5.7) ] .
Label text from the FDA structured product label by Sandoz Inc. (revised Nov 8, 2022). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Desflurane in 2 products
Desflurane NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0781-6172 | Desflurane 240 mL/240mL Liquid | Sandoz Inc. | ANDA |
| 66794-021 | Desflurane 250 mL/250mL Liquid | Piramal Critical Care Inc | UNAPPROVED DRUG OTHER |
Desflurane recalls
- D-0042-2021 Oct 28, 2020 · Class III · Terminated
DEFECTIVE CONTAINER: Desflurane Liquid for Inhalation 240 mL may be leaking.
Frequently asked questions
What is Desflurane used for?
Desflurane, USP, Liquid for Inhalation, a general anesthetic, is an inhalation agent indicated: for induction and/or maintenance of anesthesia in adults ( 1.1 ) for maintenance of anesthesia in pediatric patients following induction with agents other than Desflurane, USP, Liquid for Inhalation and intubation. 1.1 Induction of Anesthesia Desflurane, USP, Liquid for Inhalation is indicated as an…
What are the side effects of Desflurane?
Most common adverse reactions (incidence>10%) are coughing, breath holding, apnea, nausea, vomiting. (6) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug… See the full label for the complete list.
Who makes Desflurane?
Desflurane is listed by 2 labelers in the FDA NDC directory, including Sandoz Inc., Piramal Critical Care Inc.
Has Desflurane been recalled?
The FDA enforcement database lists 1 recall for Desflurane, most recently D-0042-2021 (class iii): DEFECTIVE CONTAINER: Desflurane Liquid for Inhalation 240 mL may be leaking.