piramal critical care, inc. - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - isoflurane 1 ml in 1 ml - isoflurane usp 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 is contraindicated in patients: • in whom general anesthesia is contraindicated. • with known sensitivity to isoflurane usp or to other halogenated agents [see warnings and precautions ( 5.3)]. • with known or suspected genetic susceptibility to malignant hyperthermia [see warnings and precautions ( 5.1), clinical pharmacology ( 12.5)]. • with a history of confirmed hepatitis due to a halogenated inhalational anesthetic or a history of unexplained moderate to severe hepatic dysfunction (e.g., jaundice associated with fever and/or eosinophilia) after anesthesia with isoflurane or other halogenated inhalational anesthetics. in the event of overdosage, or what may appear to be overdosage, the following action should be taken, as appropriate: stop drug administration, establish a clear airway, and initiate assisted or controlled ventilation with pure oxygen. monitor cardiovascular function and manage signs of poor end-organ perfusion as clinically indicated. risk summary there are no adequate and well-controlled studies in pregnant women. in animal reproduction studies, embryofetal toxicity was noted in pregnant mice exposed to 0.075% (increased post implantation losses) and 0.3% isoflurane (increased post implantation losses and decreased livebirth index) 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 2-4% and 15- 20%, respectively. data animal data pregnant rats were exposed to isoflurane at concentrations of 0%, 0.1%, or 0.4% for two hours per day during organogenesis (gestational days 6-15). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant mice exposed to isoflurane at concentrations of 0%, 0.075%, or 0.30% for 2 hours per day during organogenesis (gestational days 6-15). isoflurane increased fetal toxicity (higher post implantation losses at 0.075 and 0.3% groups and significantly lower live-birth index in the 0.3% isoflurane treatment group). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant rats were exposed to concentrations of isoflurane at 0%, 0.1%, or 0.4% for 2 hours per day during late gestation (gd 15-20). animals appeared slightly sedated during exposure. no adverse effects on the offspring or evidence of maternal toxicity were reported. this study did not evaluate neurobehavioral function including learning and memory in the first generation (f1) of 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 (5.8), nonclinical toxicology (13.2) ]. due to insufficient information regarding the excretion of isoflurane in human milk, the potential risks and benefits for each specific patient should be carefully considered before isoflurane is administered to nursing women. during the induction of anesthesia, saliva flow and tracheobronchial secretion can increase and can be the cause of larynogospasm, particularly in children. published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as isoflurane usp, 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 (5.8), nonclinical toxicology (13.2)]. the minimum alveolar concentration (mac) of isoflurane decreases with increasing patient age. the dose should be adjusted accordingly [see dosage and administration (2.4)].

akorn - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - isoflurane 1 ml in 1 ml - isoflurane, usp is used for induction and maintenance of general anesthesia in horses and dogs. isoflurane, usp is contraindicated in horses and dogs with known sensitivity to isoflurane or to other halogenated agents.

piramal critical care inc - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - isoflurane 1 ml in 1 ml - isoflurane, usp is used for induction and maintenance of general anesthesia in horses and dogs. isoflurane, usp is contraindicated in horses and dogs with known sensitivity to isoflurane or to other halogenated agents.

patterson veterinary - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - isoflurane 1 ml in 1 ml - isoflurane, usp is used for induction and maintenance of general anesthesia in horses and dogs. isoflurane, usp is contraindicated in horses and dogs with known sensitivity to isoflurane or to other halogenated agents.

clipper distributing company llc - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - isoflurane 1 ml in 1 ml - isoflurane, usp is used for induction and maintenance of general anesthesia in horses and dogs. isoflurane, usp is contraindicated in horses and dogs with known sensitivity to isoflurane or to other halogenated agents.

clipper distributing co. - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - isoflurane 1 ml in 1 ml - isoflurane, usp is used for induction and maintenance of general anesthesia in horses and dogs. isoflurane, usp is contraindicated in horses and dogs with known sensitivity to isoflurane or to other halogenated agents.

halocarbon life sciences, llc - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - isoflurane 1 ml in 1 ml - isoflurane may be used for induction and maintenance of general anesthesia. adequate data have not been developed to establish its application in obstetrical anesthesia. known sensitivity to isoflurane, or to other halogenated agents. known or suspected genetic susceptibility to malignant hyperthermia.

shandong new time pharmaceutical co., ltd. - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - 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 is contraindicated in patients: - in whom general anesthesia is contraindicated. - with known sensitivity to isoflurane, usp liquid for inhalation or to other halogenated agents [see warnings and precautions (5.3)] . - with known or suspected genetic susceptibility to malignant hyperthermia [see warnings and precautions (5.1), clinical pharmacology (12.5)]. - with a history of confirmed hepatitis due to a halogenated inhalational anesthetic or a history of unexplained moderate to severe hepatic dysfunction (e.g., jaundice associated with fever and/or eosinophilia) after anesthesia with isoflurane or other halogenated inhalational anesthetics. risk summary there are no adequate and well-controlled studies in pregnant women. in animal reproduction studies, embryofetal toxicity was noted in pregnant mice exposed to 0.075% (increased post implantation losses) and 0.3% isoflurane (increased post implantation losses and decreased livebirth index) 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 2-4% and 15-20%, respectively. data animal data pregnant rats were exposed to isoflurane at concentrations of 0%, 0.1%, or 0.4% for two hours per day during organogenesis (gestational days 6-15). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant mice exposed to isoflurane at concentrations of 0%, 0.075%, or 0.30% for 2 hours per day during organogenesis (gestational days 6-15). isoflurane increased fetal toxicity (higher post implantation losses at 0.075 and 0.3% groups and significantly lower live-birth index in the 0.3% isoflurane treatment group). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant rats were exposed to concentrations of isoflurane at 0%, 0.1%, or 0.4% for 2 hours per day during late gestation (gd 15-20). animals appeared slightly sedated during exposure. no adverse effects on the offspring or evidence of maternal toxicity were reported. this study did not evaluate neurobehavioral function including learning and memory in the first generation (f1) of 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 (5.8), nonclinical toxicology (13.2)]. due to insufficient information regarding the excretion of isoflurane in human milk, the potential risks and benefits for each specific patient should be carefully considered before isoflurane is administered to nursing women. during the induction of anesthesia, saliva flow and tracheobronchial secretion can increase and can be the cause of larynogospasm, particularly in children. published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as isoflurane, usp liquid for inhalation, 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 (5.8), nonclinical toxicology (13.2)] . the minimum alveolar concentration (mac) of isoflurane decreases with increasing patient age. the dose should be adjusted accordingly [see dosage and administration (2.4)] .

mullan pharmaceutical inc. - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - 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 is contraindicated in patients: - in whom general anesthesia is contraindicated. - with known sensitivity to isoflurane, usp liquid for inhalation or to other halogenated agents [see warnings and precautions (5.3)] . - with known or suspected genetic susceptibility to malignant hyperthermia [see warnings and precautions (5.1), clinical pharmacology (12.5)]. - with a history of confirmed hepatitis due to a halogenated inhalational anesthetic or a history of unexplained moderate to severe hepatic dysfunction (e.g., jaundice associated with fever and/or eosinophilia) after anesthesia with isoflurane or other halogenated inhalational anesthetics. risk summary there are no adequate and well-controlled studies in pregnant women. in animal reproduction studies, embryofetal toxicity was noted in pregnant mice exposed to 0.075% (increased post implantation losses) and 0.3% isoflurane (increased post implantation losses and decreased livebirth index) 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 2-4% and 15-20%, respectively. data animal data pregnant rats were exposed to isoflurane at concentrations of 0%, 0.1%, or 0.4% for two hours per day during organogenesis (gestational days 6-15). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant mice exposed to isoflurane at concentrations of 0%, 0.075%, or 0.30% for 2 hours per day during organogenesis (gestational days 6-15). isoflurane increased fetal toxicity (higher post implantation losses at 0.075 and 0.3% groups and significantly lower live-birth index in the 0.3% isoflurane treatment group). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant rats were exposed to concentrations of isoflurane at 0%, 0.1%, or 0.4% for 2 hours per day during late gestation (gd 15-20). animals appeared slightly sedated during exposure. no adverse effects on the offspring or evidence of maternal toxicity were reported. this study did not evaluate neurobehavioral function including learning and memory in the first generation (f1) of 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 (5.8), nonclinical toxicology (13.2)]. due to insufficient information regarding the excretion of isoflurane in human milk, the potential risks and benefits for each specific patient should be carefully considered before isoflurane is administered to nursing women. during the induction of anesthesia, saliva flow and tracheobronchial secretion can increase and can be the cause of larynogospasm, particularly in children. published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as isoflurane, usp liquid for inhalation, 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 (5.8), nonclinical toxicology (13.2)] . the minimum alveolar concentration (mac) of isoflurane decreases with increasing patient age. the dose should be adjusted accordingly [see dosage and administration (2.4)] .

piramal critical care, inc. - isoflurane (unii: cys9akd70p) (isoflurane - unii:cys9akd70p) - isoflurane usp 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 is contraindicated in patients: • in whom general anesthesia is contraindicated. • with known sensitivity to isoflurane usp or to other halogenated agents [see warnings and precautions ( 5.3 )]. • with known or suspected genetic susceptibility to malignant hyperthermia [see warnings and precautions ( 5.1 ), clinical pharmacology ( 12.5 )]. • with a history of confirmed hepatitis due to a halogenated inhalational anesthetic or a history of unexplained moderate to severe hepatic dysfunction (e.g., jaundice associated with fever and/or eosinophilia) after anesthesia with isoflurane or other halogenated inhalational anesthetics. . risk summary there are no adequate and well-controlled studies in pregnant women. in animal reproduction studies, embryofetal toxicity was noted in pregnant mice exposed to 0.075% (increased post implantation losses) and 0.3% isoflurane (increased post implantation losses and decreased livebirth index) 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 2-4% and 15- 20%, respectively. data animal data pregnant rats were exposed to isoflurane at concentrations of 0%, 0.1%, or 0.4% for two hours per day during organogenesis (gestational days 6-15). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant mice exposed to isoflurane at concentrations of 0%, 0.075%, or 0.30% for 2 hours per day during organogenesis (gestational days 6-15). isoflurane increased fetal toxicity (higher post implantation losses at 0.075 and 0.3% groups and significantly lower live-birth index in the 0.3% isoflurane treatment group). isoflurane did not cause malformations or clear maternal toxicity under these conditions. pregnant rats were exposed to concentrations of isoflurane at 0%, 0.1%, or 0.4% for 2 hours per day during late gestation (gd 15-20). animals appeared slightly sedated during exposure. no adverse effects on the offspring or evidence of maternal toxicity were reported. this study did not evaluate neurobehavioral function including learning and memory in the first generation (f1) of 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 (5.8), nonclinical toxicology (13.2) ]. due to insufficient information regarding the excretion of isoflurane in human milk, the potential risks and benefits for each specific patient should be carefully considered before isoflurane is administered to nursing women. during the induction of anesthesia, saliva flow and tracheobronchial secretion can increase and can be the cause of larynogospasm, particularly in children. published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as isoflurane usp, 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 (5.8), nonclinical toxicology (13.2)]. the minimum alveolar concentration (mac) of isoflurane decreases with increasing patient age. the dose should be adjusted accordingly [see dosage and administration (2.4)].