Data from FDA (Food and Drug Administration, USA) - Curated by Marshall Pearce - Last updated 10 October 2017

Indication(s)

INDICATIONS AND USAGE Isoflurane may be used for induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia.

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Advisory information

contraindications
CONTRAINDICATIONS Known sensitivity to isoflurane, or to other halogenated agents. Known or suspected genetic susceptibility to malignant hyperthermia.
Special warnings and precautions
PRECAUTIONS General As with any potent general anesthetic isoflurane should only be administered in an adequately equipped anesthetizing environment by those who are familiar with the pharmacology of the drug and qualified by training and experience to manage the anesthetized patient. Regardless of the anesthetics employed, maintenance of normal hemodynamics is important to the avoidance of myocardial ischemia in patients with coronary artery disease 4,5,6,7. Isoflurane, like some other inhalational anesthetics, can react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide which may result in elevated levels of carboxyhemoglobin in some patients. Case reports suggest that barium hydroxide lime and soda lime become desiccated when fresh gases are passed through the CO2 absorber canister at high flow rates over many hours or days. When a clinician suspects that CO2 absorbent may be desiccated, it should be replaced before the administration of isoflurane. As with other halogenated anesthetic agents, isoflurane may cause sensitivity hepatitis in patients who have been sensitized by previous exposure to halogenated anesthetics. Information to Patients Isoflurane, as well as other general anesthetics, may cause a slight decrease in intellectual function for 2 or 3 days following anesthesia. As with other anesthetics, small changes in moods and symptoms may persist for up to 6 days after administration. 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. Because some animal data suggest that the window of vulnerability includes the 3rd trimester of pregnancy, discuss with pregnant women the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs. (See Warnings! Pediatric Neurotoxicity) Laboratory Tests Transient increases in BSP retention, blood glucose and serum creatinine with decrease in BUN, serum cholesterol and alkaline phosphatase have been observed. Drug Interactions Isoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably nondepolarizing muscle relaxants, and MAC (minimum alveolar concentration) is reduced by concomitant administration of N2O. See CLINICAL PHARMACOLOGY. Carcinogenesis Swiss ICR mice were given isoflurane to determine whether such exposure might induce neoplasia. Isoflurane was given at 1/2, 1/8 and 1/32 MAC for four in-utero exposures and for 24 exposures to the pups during the first nine weeks of life. The mice were killed at 15 months of age. The incidence of tumors in these mice was the same as in untreated control mice which were given the same background gases, but not the anesthetic. Pregnancy Pregnancy Category C Isoflurance has been shown to have a possible anesthetic - related fetotoxic effect in mice when given doses 6 times the human does. There are no adequate and well-controlled studies in pregnant women. Isoflurane should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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. In a published study, 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/ Pediatric Neurotoxicity, Precautions/ Pediatric Use, and Animal Pharmacology and/or Toxicology). Nursing Mothers 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 isoflurane is administered to a nursing woman. Pediatric Use Published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as Halothane, 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/ Pediatric Neurotoxicity, Precautions/ Pregnancy, and Animal Pharmacology and/or Toxicology).
Adverse reactions
ADVERSE REACTIONS Adverse reactions encountered in the administration of isoflurane are in general dose dependent extensions of pharmacophysiologic effects and include respiratory depression, hypotension and arrhythmias. Shivering, nausea, vomiting and ileus have been observed in the postoperative period. As with all other general anesthetics, transient elevations in white blood count have been observed even in the absence of surgical stress. See WARNINGS for information regarding malignant hyperthermia and elevated carboxyhemoglobin levels. During marketing, there have been rare reports of mild, moderate and severe (some fatal) post-operative hepatic dysfunction and hepatitis. Post-Marketing Events The following adverse events have been identified during post-approval use of isoflurane, USP. Due to the spontaneous nature of these reports, the actual incidence and relationship of isoflurane, USP to these events cannot be established with certainty. Cardiac Disorders: Cardiac arrest Hepatobiliary Disorders: Hepatic necrosis, Hepatic failure.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION Premedication 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. The use of anticholinergic drugs is a matter of choice. Inspired Concentration The concentration of isoflurane being delivered from a vaporizer during anesthesia should be known. This may be accomplished by using: a)vaporizers calibrated specifically for isoflurane; b)vaporizers from which delivered flows can be calculated, such as vaporizers delivering a saturated vapor which is then diluted. The delivered concentration from such a vaporizer may be calculated using the formula: % isoflurane = 100 PvFv ––––––––– FT (PA-PV) where: PA = Pressure of atmosphere PV = Vapor pressure of isoflurane FV = Flow of gas through vaporizer (mL/min) FT = Total gas flow (mL/min) Isoflurane contains no stabilizer. Nothing in the agent alters calibration or operation of these vaporizers. Induction Induction with isoflurane in oxygen or in combination with oxygen-nitrous oxide mixtures may produce coughing, breath holding, or laryngospasm. These difficulties may be avoided by the use of a hypnotic dose of an ultra-short-acting barbiturate. Inspired concentrations of 1.5 to 3.0% isoflurane usually produce surgical anesthesia in 7 to 10 minutes. Maintenance Surgical levels of anesthesia may be sustained with a 1.0 to 2.5% concentration when nitrous oxide is used concomitantly. An additional 0.5 to 1.0% may be required when isoflurane is given using oxygen alone. If added relaxation is required, supplemental doses of muscle relaxants may be used. The level of blood pressure during maintenance is an inverse function of isoflurane concentration in the absence of other complicating problems. Excessive decreases may be due to depth of anesthesia and in such instance may be corrected by lightening anesthesia.
Pregnancy and lactation
Nursing Mothers 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 isoflurane is administered to a nursing woman.

Interactions

Drug Interactions Isoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably nondepolarizing muscle relaxants, and MAC (minimum alveolar concentration) is reduced by concomitant administration of N2O. See CLINICAL PHARMACOLOGY.

More information

Category Value
Authorisation number ANDA075225
Agency product number CYS9AKD70P
Orphan designation No
Product NDC 12164-012
Date Last Revised 28-08-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 542347
Storage and handling Storage Store at controlled room temperature 15° - 30°C (59° - 86°F) (see USP). Isoflurane contains no additives and has been demonstrated to be stable at room temperature for a period om excess of five years.
Marketing authorisation holder Halocarbon Products Corp.