Isoflurane
Generic: ISOFLURANE
Basic Information
Manufacturer
Shandong New Time Pharmaceutical Co., Ltd.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
RESPIRATORY (INHALATION)
FDA Set ID
662ceaf6-650b-4dea-bbee-652f46426024
Indications & Usage
1 INDICATIONS AND USAGE Isoflurane, USP liquid for inhalation may be used for induction and maintenance of general anesthesia.
Adequate data have not been developed to establish its application in obstetrical anesthesia.
Isoflurane, USP liquid for inhalation, a general anesthetic, is an inhalation agent indicated for induction and maintenance of general anesthesia.
(1)
Adequate data have not been developed to establish its application in obstetrical anesthesia.
Isoflurane, USP liquid for inhalation, a general anesthetic, is an inhalation agent indicated for induction and maintenance of general anesthesia.
(1)
Adverse Reactions
6.
ADVERSE REACTIONS Most common adverse reactions (incidence ≥ 5%) are agitation, cough, breath holding, nausea, chills/shivering, vomiting, laryngospasm, delirium.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Emprise Pharma LLC.
at (610) 933-1969 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience The following adverse reactions were identified from controlled clinical trials of adult and pediatric subjects exposed to isoflurane, USP liquid for inhalation.
The trials were conducted using a variety of pre-medications, other anesthetics, and surgical procedures of varying lengths.
The most serious reported adverse reactions in alphabetical order are agitation, arrhythmia, breath holding, elevated liver enzyme, hypotension and laryngospasm.
The most frequent adverse reactions (incidence ≥ 5%) described in Table 1 are agitation, breath holding, chills/shivering, cough, delirium, laryngospasm, nausea, and vomiting.
Adverse reactions with an incidence between 1% and 5% are provided in Table 2.
Adverse reactions with an incidence less than 1% are provided in Table 3.
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.
Table 2: Adverse Reactions ≥ 5% System Organ Class (SOC) Adverse Reaction Frequency PSYCHIATRIC DISORDERS Delirium 6.2% (N=2830) NERVOUS SYSTEM DISORDERS Agitation (Excitement) Induction 51.8% (N=515) 1 RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS Breath holding Induction 23.9% (N=515) 1 Cough Induction 28.2% (N=515) 1 Laryngospasm Induction 8.0% (N=515) 1 GASTROINTESTINAL DISORDERS Nausea Recovery 15.4 % (N=2830) Vomiting Recovery 9.5% (N=2830) GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS Chills/shivering 14.0% (N=1691) 2 1 Represents patients not receiving intravenous agents or neuromuscular blocking agents for intubation (i.e., patients receiving inhalation induction).
2 Reflects the number of patients with recorded body temperature measurements.
Table 3: Adverse Reactions between 1% and 5% System Organ Class (SOC) Adverse Reaction Frequency NERVOUS SYSTEM DISORDERS Movement Maintenance 1.8% (N=2830) CARDIAC DISORDERS Ventricular arrhythmia (Intraoperative) Induction 2.1% (N=2161) Maintenance 2.7% (N=2253) Nodal arrhythmia (Intraoperative) Induction 4.0% (N=2161) Maintenance 1.7% (N=2253) Atrial arrhythmia (Intraoperative) Induction 1.6% (N=2161) Maintenance 2.2% (N=2253) Arrhythmia (Postoperative) 1.1% (N=2830) RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS Breath holding Maintenance 1.1% (N=359) 1 Cough Maintenance 4.2 % (N=359) 1 1 Represents patients not receiving intravenous agents or neuromuscular blocking agents for intubation (i.e., patients receiving inhalation induction).
Table 4: Adverse Reactions less than 1% System Organ Class (SOC) Adverse Reaction Frequency PSYCHIATRIC DISORDERS Mood changes 0.3% (N=2830) Nightmare 0.4% (N=2175) 1 NERVOUS SYSTEM DISORDERS Convulsive pattern on electroencephalogram 0.5% (N=200) 2 Seizure 0.04% (N=2830) VASCULAR DISORDERS Hypotension Postoperative 0.3% (N=2830) Hypertension Postoperative 0.1% (N=2830) RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS Laryngospasm Maintenance 0.8% (N=359) 3 Secretions Induction 0.2% (N=515) 3 Maintenance 0.0% (N=359) 3 GASTROINTESTINAL DISORDERS Vomiting Induction 0.8% (N=515) 3 Retching Induction 1.0% (N=515) 3 Maintenance 0.8% (N=359) 3 SKIN AND SUBCUTANEOUS TISSUE DISORDERS Diaphoresis Induction 0.2% (N=515) 3 Maintenance 0.0% (N=359) 3 1 Reflects the number of patients interviewed by a physician in the recovery period.
2 Reflects the number of recorded electroencephalograms.
3 Represents patients not receiving intravenous agents or neuromuscular blocking agents for intubation (i.e., patients receiving inhalation induction).
The following adverse reactions (see Table 5) were observed, but due to limited data, frequency could not be determined.
Table 5: Adverse Reactions with Unknown Frequency Blood and Lymphatic System Disorders: White blood cell count increased Metabolism and Nutrition Disorders: Blood glucose increased Psychiatric Disorders: Confused state, Nervousness Nervous System Disorders: Ataxia; Dizziness; Drowsiness; Intellectual function decrease Vascular Disorders: Hypotension (Intraoperative); Hypertension (Intraoperative) Hepatobiliary Disorders: Blood bilirubin increased; Bromsulphthalein clearance decreased; Alanine aminotransferase increased; Aspartate aminotransferase increased; Blood alkaline phosphatase increased; Blood lactate dehydrogenase increased.
Musculoskeletal, Connective Tissue and Bone Disorders: Myalgia General Disorders and Administrative Site Conditions: Asthenia; Fatigue 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of isoflurane, USP liquid for inhalation.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Post-marketing adverse reactions are listed by MedDRA System Organ Class (SOC), then by preferred term in order of decreasing severity.
BLOOD AND LYMPHATIC SYSTEM DISORDERS: Carboxyhemoglobin increased IMMUNE SYSTEM DISORDERS: Anaphylactic reaction METABOLISM AND NUTRITION DISORDERS : Hyperkalemia in patients with underlying myopathies PSYCHIATRIC DISORDERS: Withdrawal syndrome (following multi-day exposure; symptoms include seizure, hallucination, ataxia, agitation, confusion ) NERVOUS SYSTEM DISORDERS: Brain edema, Intracranial pressure increased, Migraine, Myoclonus, Nystagmus, Pupils unequal, Headache CARDIAC DISORDERS: Cardiac arrest, Ventricular fibrillation, Torsade de pointes, Myocardial infarction, Myocardial ischemia, Atrioventricular block complete, Atrioventricular block second degree, Atrial fibrillation, Electrocardiogram QT prolonged, Atrioventricular block first degree, Ventricular tachycardia, Ventricular extrasystoles, Tachycardia, Bradycardia, Cardiac output decreased VASCULAR DISORDERS: Flushing RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS: Apnea, Hypoxia, Bronchospasm, Airway obstruction, Respiratory depression, Hypercapnia, Stridor, Hiccough GASTROINTESTINAL DISORDERS: Pancreatitis HEPATOBILIARY DISORDERS: Hepatic necrosis, Hepatic failure, Hepatitis fulminant, Cholestatic hepatitis, Hepatitis, Hepatic steatosis, Jaundice, Gamma-glutamyltransferase increased SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Rash MUSCULOSKELETAL, CONNECTIVE TISSUE AND BONE DISORDERS: Rhabdomyolysis RENAL AND URINARY DISORDERS: Acute renal failure**, Oliguria** GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Malignant hyperthermia, hypothermia INJURY, POISONING, AND PROCEDURAL COMPLICATIONS*: Unwanted awareness during anesthesia; Dyspnea, Bronchospasm, Stridor, Cough, Dizziness, Paresthesia, Hepatic reactions, Flushing, Rash, Contact dermatitis, Erythema, Periorbital edema, Eye irritation, Conjunctival hyperemia, Headache *All reactions categorized within this SOC, with the exception of, Unwanted awareness during anesthesia, were from occupational exposure in non-patients.
**Cases of acute renal failure and oliguria have been reported after isoflurane anesthesia.
These events may be secondary to hypotension or other effects of isoflurane
ADVERSE REACTIONS Most common adverse reactions (incidence ≥ 5%) are agitation, cough, breath holding, nausea, chills/shivering, vomiting, laryngospasm, delirium.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Emprise Pharma LLC.
at (610) 933-1969 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience The following adverse reactions were identified from controlled clinical trials of adult and pediatric subjects exposed to isoflurane, USP liquid for inhalation.
The trials were conducted using a variety of pre-medications, other anesthetics, and surgical procedures of varying lengths.
The most serious reported adverse reactions in alphabetical order are agitation, arrhythmia, breath holding, elevated liver enzyme, hypotension and laryngospasm.
The most frequent adverse reactions (incidence ≥ 5%) described in Table 1 are agitation, breath holding, chills/shivering, cough, delirium, laryngospasm, nausea, and vomiting.
Adverse reactions with an incidence between 1% and 5% are provided in Table 2.
Adverse reactions with an incidence less than 1% are provided in Table 3.
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.
Table 2: Adverse Reactions ≥ 5% System Organ Class (SOC) Adverse Reaction Frequency PSYCHIATRIC DISORDERS Delirium 6.2% (N=2830) NERVOUS SYSTEM DISORDERS Agitation (Excitement) Induction 51.8% (N=515) 1 RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS Breath holding Induction 23.9% (N=515) 1 Cough Induction 28.2% (N=515) 1 Laryngospasm Induction 8.0% (N=515) 1 GASTROINTESTINAL DISORDERS Nausea Recovery 15.4 % (N=2830) Vomiting Recovery 9.5% (N=2830) GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS Chills/shivering 14.0% (N=1691) 2 1 Represents patients not receiving intravenous agents or neuromuscular blocking agents for intubation (i.e., patients receiving inhalation induction).
2 Reflects the number of patients with recorded body temperature measurements.
Table 3: Adverse Reactions between 1% and 5% System Organ Class (SOC) Adverse Reaction Frequency NERVOUS SYSTEM DISORDERS Movement Maintenance 1.8% (N=2830) CARDIAC DISORDERS Ventricular arrhythmia (Intraoperative) Induction 2.1% (N=2161) Maintenance 2.7% (N=2253) Nodal arrhythmia (Intraoperative) Induction 4.0% (N=2161) Maintenance 1.7% (N=2253) Atrial arrhythmia (Intraoperative) Induction 1.6% (N=2161) Maintenance 2.2% (N=2253) Arrhythmia (Postoperative) 1.1% (N=2830) RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS Breath holding Maintenance 1.1% (N=359) 1 Cough Maintenance 4.2 % (N=359) 1 1 Represents patients not receiving intravenous agents or neuromuscular blocking agents for intubation (i.e., patients receiving inhalation induction).
Table 4: Adverse Reactions less than 1% System Organ Class (SOC) Adverse Reaction Frequency PSYCHIATRIC DISORDERS Mood changes 0.3% (N=2830) Nightmare 0.4% (N=2175) 1 NERVOUS SYSTEM DISORDERS Convulsive pattern on electroencephalogram 0.5% (N=200) 2 Seizure 0.04% (N=2830) VASCULAR DISORDERS Hypotension Postoperative 0.3% (N=2830) Hypertension Postoperative 0.1% (N=2830) RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS Laryngospasm Maintenance 0.8% (N=359) 3 Secretions Induction 0.2% (N=515) 3 Maintenance 0.0% (N=359) 3 GASTROINTESTINAL DISORDERS Vomiting Induction 0.8% (N=515) 3 Retching Induction 1.0% (N=515) 3 Maintenance 0.8% (N=359) 3 SKIN AND SUBCUTANEOUS TISSUE DISORDERS Diaphoresis Induction 0.2% (N=515) 3 Maintenance 0.0% (N=359) 3 1 Reflects the number of patients interviewed by a physician in the recovery period.
2 Reflects the number of recorded electroencephalograms.
3 Represents patients not receiving intravenous agents or neuromuscular blocking agents for intubation (i.e., patients receiving inhalation induction).
The following adverse reactions (see Table 5) were observed, but due to limited data, frequency could not be determined.
Table 5: Adverse Reactions with Unknown Frequency Blood and Lymphatic System Disorders: White blood cell count increased Metabolism and Nutrition Disorders: Blood glucose increased Psychiatric Disorders: Confused state, Nervousness Nervous System Disorders: Ataxia; Dizziness; Drowsiness; Intellectual function decrease Vascular Disorders: Hypotension (Intraoperative); Hypertension (Intraoperative) Hepatobiliary Disorders: Blood bilirubin increased; Bromsulphthalein clearance decreased; Alanine aminotransferase increased; Aspartate aminotransferase increased; Blood alkaline phosphatase increased; Blood lactate dehydrogenase increased.
Musculoskeletal, Connective Tissue and Bone Disorders: Myalgia General Disorders and Administrative Site Conditions: Asthenia; Fatigue 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of isoflurane, USP liquid for inhalation.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Post-marketing adverse reactions are listed by MedDRA System Organ Class (SOC), then by preferred term in order of decreasing severity.
BLOOD AND LYMPHATIC SYSTEM DISORDERS: Carboxyhemoglobin increased IMMUNE SYSTEM DISORDERS: Anaphylactic reaction METABOLISM AND NUTRITION DISORDERS : Hyperkalemia in patients with underlying myopathies PSYCHIATRIC DISORDERS: Withdrawal syndrome (following multi-day exposure; symptoms include seizure, hallucination, ataxia, agitation, confusion ) NERVOUS SYSTEM DISORDERS: Brain edema, Intracranial pressure increased, Migraine, Myoclonus, Nystagmus, Pupils unequal, Headache CARDIAC DISORDERS: Cardiac arrest, Ventricular fibrillation, Torsade de pointes, Myocardial infarction, Myocardial ischemia, Atrioventricular block complete, Atrioventricular block second degree, Atrial fibrillation, Electrocardiogram QT prolonged, Atrioventricular block first degree, Ventricular tachycardia, Ventricular extrasystoles, Tachycardia, Bradycardia, Cardiac output decreased VASCULAR DISORDERS: Flushing RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS: Apnea, Hypoxia, Bronchospasm, Airway obstruction, Respiratory depression, Hypercapnia, Stridor, Hiccough GASTROINTESTINAL DISORDERS: Pancreatitis HEPATOBILIARY DISORDERS: Hepatic necrosis, Hepatic failure, Hepatitis fulminant, Cholestatic hepatitis, Hepatitis, Hepatic steatosis, Jaundice, Gamma-glutamyltransferase increased SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Rash MUSCULOSKELETAL, CONNECTIVE TISSUE AND BONE DISORDERS: Rhabdomyolysis RENAL AND URINARY DISORDERS: Acute renal failure**, Oliguria** GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Malignant hyperthermia, hypothermia INJURY, POISONING, AND PROCEDURAL COMPLICATIONS*: Unwanted awareness during anesthesia; Dyspnea, Bronchospasm, Stridor, Cough, Dizziness, Paresthesia, Hepatic reactions, Flushing, Rash, Contact dermatitis, Erythema, Periorbital edema, Eye irritation, Conjunctival hyperemia, Headache *All reactions categorized within this SOC, with the exception of, Unwanted awareness during anesthesia, were from occupational exposure in non-patients.
**Cases of acute renal failure and oliguria have been reported after isoflurane anesthesia.
These events may be secondary to hypotension or other effects of isoflurane