संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

alembic pharmaceuticals limited - oseltamivir phosphate (unii: 4a3o49ngez) (oseltamivir acid - unii:k6106lv5q8) - oseltamivir phosphate capsules are indicated for the treatment of acute, uncomplicated illness due to influenza a and b infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. oseltamivir phosphate capsules are indicated for the prophylaxis of influenza a and b in patients 1 year and older. - oseltamivir phosphate capsules are not a substitute for early influenza vaccination on an annual basis as recommended by the centers for disease control and prevention advisory committee on immunization practices. - influenza viruses change over time. emergence of resistance substitutions could decrease drug effectiveness. other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate capsules[see microbiology (12.4)] . - oseltamivir phosphate capsules are not recomm

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

trupharma, llc - oxazepam (unii: 6gow6dwn2a) (oxazepam - unii:6gow6dwn2a) -       oxazepam is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. anxiety associated with depression is also responsive to oxazepam therapy. this product has been found particularly useful in the management of anxiety, tension, agitation, and irritability in older patients. alcoholics with acute tremulousness, inebriation, or with anxiety, associated with alcohol withdrawal are responsive to therapy. the effectiveness of oxazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. the physician should periodically reassess the usefulness of the drug for the individual patient. history of previous hypersensitivity reaction to oxazepam. oxazepam is not indicated in psychoses. an increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide,

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

trupharma llc - clomipramine hydrochloride (unii: 2lxw0l6gwj) (clomipramine - unii:nuv44l116d) - clomipramine hydrochloride capsules usp are indicated for the treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (ocd). the obsessions or compulsions must cause marked distress, be time-consuming, or significantly interfere with social or occupational functioning, in order to meet the dsm-iii-r (circa 1989) diagnosis of ocd. obsessions are recurrent, persistent ideas, thoughts, images, or impulses that are ego-dystonic. compulsions are repetitive, purposeful, and intentional behaviors performed in response to an obsession or in a stereotyped fashion, and are recognized by the person as excessive or unreasonable. the effectiveness of clomipramine hydrochloride capsules for the treatment of ocd was demonstrated in multicenter, placebo-controlled, parallel-group studies, including two 10-week studies in adults and one 8-week study in children and adolescents 10 to 17 years of age. patients in all studies had moderate-to-severe ocd (dsm-iii), with mean baseline ratings on the y

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

mylan institutional llc - eptifibatide (unii: na8320j834) (eptifibatide - unii:na8320j834) - eptifibatide injection is indicated to decrease the rate of a combined endpoint of death or new myocardial infarction (mi) in patients with acs (unstable angina [ua]/non-st- elevation myocardial infarction [nstemi]), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (pci). eptifibatide injection is indicated to decrease the rate of a combined endpoint of death, new mi, or need for urgent intervention in patients undergoing pci, including those undergoing intracoronary stenting [see clinical studies (14.1, 14.2)] . treatment with eptifibatide is contraindicated in patients with: risk summary available data on eptifibatide use in pregnant women from published literature and the pharmacovigilance database are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. untreated myocardial infarction can be fatal to the pregnant woman and fetus (see clinical considerations) . in animal reproduc

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

mckesson corporation dba sky packaging - gabapentin (unii: 6cw7f3g59x) (gabapentin - unii:6cw7f3g59x) - gabapentin is indicated for: • management of postherpetic neuralgia in adults • adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), such as gabapentin, during pregnancy. encourage women who are taking gabapentin during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling the toll free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary there are no adequate data on the developmental risks associated with the use of gabapentin in pregnant women. in nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered to pregnant animals at doses similar to or lower than those used clinically [see data]. 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. the background risk of major birth defects and miscarriage for the indicated population is unknown. data animal data   when pregnant mice received oral doses of gabapentin (500, 1000, or 3000 mg/kg/day) during the period of organogenesis, embryofetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses. the no-effect dose for embryofetal developmental toxicity in mice (500 mg/kg/day) is less than the maximum recommended human dose (mrhd) of 3600 mg on a body surface area (mg/m2 ) basis. in studies in which rats received oral doses of gabapentin (500 to 2000 mg/kg/day) during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses. the lowest dose tested is similar to the mrhd on a mg/m2 basis. when pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryofetal mortality was observed at all doses tested (60, 300, or 1500 mg/kg). the lowest dose tested is less than the mrhd on a mg/m2 basis. in a published study, gabapentin (400 mg/kg/day) was administered by intraperitoneal injection to neonatal mice during the first postnatal week, a period of synaptogenesis in rodents (corresponding to the last trimester of pregnancy in humans). gabapentin caused a marked decrease in neuronal synapse formation in brains of intact mice and abnormal neuronal synapse formation in a mouse model of synaptic repair. gabapentin has been shown in vitro to interfere with activity of the α2δ subunit of voltage-activated calcium channels, a receptor involved in neuronal synaptogenesis. the clinical significance of these findings is unknown. risk summary gabapentin is secreted in human milk following oral administration. the effects on the breastfed infant and on milk production are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for gabapentin and any potential adverse effects on the breastfed infant from gabapentin or from the underlying maternal condition. safety and effectiveness of gabapentin in the management of postherpetic neuralgia in pediatric patients have not been established. safety and effectiveness as adjunctive therapy in the treatment of partial seizures in pediatric patients below the age of 3 years has not been established [see clinical studies (14.2)]. the total number of patients treated with gabapentin in controlled clinical trials in patients with postherpetic neuralgia was 336, of which 102 (30%) were 65 to 74 years of age, and 168 (50%) were 75 years of age and older. there was a larger treatment effect in patients 75 years of age and older compared to younger patients who received the same dosage.   since gabapentin is almost exclusively eliminated by renal excretion, the larger treatment effect observed in patients ≥ 75 years may be a consequence of increased gabapentin exposure for a given dose that results from an age-related decrease in renal function. however, other factors cannot be excluded. the types and incidence of adverse reactions were similar across age groups except for peripheral edema and ataxia, which tended to increase in incidence with age. clinical studies of gabapentin in epilepsy did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients [see dosage and administration (2.4), adverse reactions (6), and clinical pharmacology (12.3)] . dosage adjustment in adult patients with compromised renal function is necessary [see dosage and administration (2.3) and clinical pharmacology (12.3)] . pediatric patients with renal insufficiency have not been studied. dosage adjustment in patients undergoing hemodialysis is necessary [see dosage and administration (2.3) and clinical pharmacology (12.3)] . gabapentin is not a scheduled drug. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. gabapentin does not exhibit affinity for benzodiazepine, opioid (mu, delta or kappa), or cannabinoid 1 receptor sites. gabapentin misuse and abuse have been reported in the postmarketing setting and published literature. most of the individuals described in these reports had a history of polysubstance abuse. some of these individuals were taking higher than recommended doses of gabapentin for unapproved uses. when prescribing gabapentin, carefully evaluate patients for a history of drug abuse and observe them for signs and symptoms of gabapentin misuse or abuse (e.g., self-dose escalation and drug-seeking behavior). the abuse potential of gabapentin has not been evaluated in human studies. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. there are rare postmarketing reports of individuals experiencing withdrawal symptoms shortly after discontinuing higher than recommended doses of gabapentin used to treat illnesses for which the drug is not approved. such symptoms included agitation, disorientation and confusion after suddenly discontinuing gabapentin that resolved after restarting gabapentin. the dependence potential of gabapentin has not been evaluated in human studies.

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

eugia us llc - ketamine hydrochloride (unii: o18yuo0i83) (ketamine - unii:690g0d6v8h) - ketamine hydrochloride injection is indicated: - as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. - for the induction of anesthesia prior to the administration of other general anesthetic agents. - as a supplement to other anesthetic agents. - ketamine hydrochloride is contraindicated in patients for whom a significant elevation of blood pressure would constitute a serious hazard [see warnings and precautions (5.1)]. - ketamine hydrochloride is contraindicated in patients with known hypersensitivity to ketamine or to any excipient [see adverse reactions (6)]. risk summary there are no adequate and well-controlled studies of ketamine hydrochloride in pregnant women. in animal reproduction studies in rats developmental delays (hypoplasia of skeletal tissues) were noted at 0.3 times the human intramuscular dose of 10 mg/kg. in rabbits, developmental delays and increased fetal resorptions were noted at 0.6 times the human dose. 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. 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 ketamine hydrochloride use in pregnancy, including obstetrics (either vaginal or abdominal delivery), is not recommended because safe use has not been established [see warnings and precautions (5.5), use in specific populations (8.4) and nonclinical toxicology (13.2)] . data animal data pregnant rats were treated intramuscularly with 20 mg/kg ketamine (0.3 times the human dose of 10 mg/kg im based on body surface area) on either gestation days 6 to 10 or gestation days 11 to 15. ketamine treatment produced an increased incidence of hypoplastic skull, phalanges, and sternebrae in the pups. pregnant rabbits were treated intramuscularly with 20 mg/kg ketamine (0.6 times the human dose of 10 mg/kg im based on body surface area) on either gestation days 6 to 10 or gestation days 11 to 15. an increase in resorptions and skeletal hypoplasia of the fetuses were noted. additional pregnant rabbits were treated intramuscularly with a single dose 60 mg/kg (1.9 times the human dose of 10 mg/kg im based on body surface area) on gestation day 6 only. skeletal hypoplasia was reported in the fetuses. in a study where pregnant rats were treated intramuscularly with 20 mg/kg ketamine (0.3 times the human dose of 10 mg/kg im based on body surface area) from gestation day 18 to 21. there was a slight increase in incidence of delayed parturition by one day in treated dams of this group. no adverse effects on the litters or pups were noted; however, learning and memory assessments were not completed. three (3) pregnant beagle dogs were treated intramuscularly with 25 mg/kg ketamine (1.3 times the human dose of 10 mg/kg im based on body surface area) twice weekly for the three weeks of the first, second, and third trimesters of pregnancy, respectively, without the development of adverse effects in the 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 (5.5), use in specific populations (8.4), and nonclinical toxicology (13.2)] . safety and effectiveness in pediatric patients below the age of 16 have not been established. published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as ketamine hydrochloride, 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 neonates and young children who require procedures with the potential risks suggested by the nonclinical data [see warnings and precautions (5.5), use in specific populations (8.1), and nonclinical toxicology (13.2)] . clinical studies of ketamine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. ketamine hydrochloride contains ketamine, a schedule iii controlled substance under the controlled substance act. individuals with a history of drug abuse or dependence may be at greater risk for abuse and misuse of ketamine hydrochloride. abuse is the intentional, non-therapeutic use of a drug, even once, for its psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. in a context of drug abuse, ketamine hydrochloride may produce a variety of symptoms including anxiety, dysphoria, disorientation, insomnia, flashback, hallucinations, and feelings of floating, detachment and being "spaced out". recurrent high-dose ketamine misuse or abuse may be associated with memory and/or attention impairment. physical dependence has been reported with prolonged use of ketamine. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or significant dosage reduction of a drug. withdrawal symptoms have been reported after the discontinuation of frequently used (more than weekly), large doses of ketamine for long periods of time. reported symptoms of withdrawal associated with daily intake of large doses of ketamine include craving, fatigue, poor appetite, and anxiety. tolerance has been reported with prolonged use of ketamine. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

asclemed usa, inc. - oseltamivir phosphate (unii: 4a3o49ngez) (oseltamivir acid - unii:k6106lv5q8) - oseltamivir phosphate capsules are indicated for the treatment of acute, uncomplicated illness due to influenza a and b infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. oseltamivir phosphate capsules are indicated for the prophylaxis of influenza a and b in patients 1 year and older. • oseltamivir phosphate capsules are not a substitute for early influenza vaccination on an annual basis as recommended by the centers for disease control and prevention advisory committee on immunization practices. • influenza viruses change over time. emergence of resistance substitutions could decrease drug effectiveness. other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use oseltamivir phosphate capsules [ see microbiology ( 12.4)]. • oseltam

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

amring pharmaceuticals inc. - desmopressin acetate (unii: xb13hyu18u) (desmopressin - unii:enr1llb0fp) - desmopressin acetate 4 ug in 1 ml - desmopressin acetate injection is indicated as antidiuretic replacement therapy in the management of central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. limitations of use: desmopressin acetate is ineffective and not indicated for the treatment of nephrogenic diabetes insipidus. desmopressin acetate injection is indicated for patients with hemophilia a with factor viii coagulant activity levels greater than 5% without factor viii antibodies to: - maintain hemostasis during surgical procedures and postoperatively - reduce bleeding with episodes of spontaneous or traumatic injuries such as hemarthroses, intramuscular hematomas, or mucosal bleeding. desmopressin acetate injection is indicated for patients with mild to moderate von willebrand’s disease (type i) with factor viii levels greater than 5% to: - maintain hemostasis during surgical procedures and postoperatively - reduce bleeding with episodes of s

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

amneal pharmaceuticals of new york llc - dextroamphetamine sulfate (unii: jj768o327n) (dextroamphetamine - unii:tz47u051fi) - dextroamphetamine sulfate 5 mg - dextroamphetamine sulfate is indicated in: as an integral part of a total treatment program that typically includes other measures (psychological, educational, social) for patients (ages 6 years to 16 years) with this syndrome. a diagnosis of attention deficit hyperactivity disorder (adhd; dsm-iv) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. the symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in 2 or more settings, e.g., school (or work) and at home. the symptoms must not be better accounted for

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

par pharmaceutical, inc. - ketamine hydrochloride (unii: o18yuo0i83) (ketamine - unii:690g0d6v8h) - ketamine 10 mg in 1 ml -  ketalar (ketamine hydrochloride) injection is indicated: - as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. - for the induction of anesthesia prior to the administration of other general anesthetic agents. - as a supplement to other anesthetic agents. - ketalar is contraindicated in patients for whom a significant elevation of blood pressure would constitute a serious hazard [see warnings and precautions(5.1)] . - ketalar is contraindicated in patients with known hypersensitivity to ketamine or to any excipient [see adverse reactions (6)] . there are no adequate and well-controlled studies of ketalar in pregnant women. in animal reproduction studies in rats developmental delays (hypoplasia of skeletal tissues) were noted at 0.3 times the human intramuscular dose of 10 mg/kg. in rabbits, developmental delays and increased fetal resorptions were noted at 0.6 times the human dose. 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. 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. ketalar use in pregnancy, including obstetrics (either vaginal or abdominal delivery), is not recommended because safe use has not been established [see warnings and precautions (5.5), use in specific populations (8.4) and nonclinical toxicology (13.2)] . animal data pregnant rats were treated intramuscularly with 20 mg/kg ketamine (0.3 times the human dose of 10 mg/kg im based on body surface area) on either gestation days 6 to 10 or gestation days 11 to 15. ketamine treatment produced an increased incidence of hypoplastic skull, phalanges, and sternebrae in the pups. pregnant rabbits were treated intramuscularly with 20 mg/kg ketamine (0.6 times the human dose of 10 mg/kg im based on body surface area) on either gestation days 6 to 10 or gestation days 11 to 15. an increase in resorptions and skeletal hypoplasia of the fetuses were noted. additional pregnant rabbits were treated intramuscularly with a single dose 60 mg/kg (1.9 times the human dose of 10 mg/kg im based on body surface area) on gestation day 6 only. skeletal hypoplasia was reported in the fetuses. in a study where pregnant rats were treated intramuscularly with 20 mg/kg ketamine (0.3 times the human dose of 10 mg/kg im based on body surface area) from gestation day 18 to 21. there was a slight increase in incidence of delayed parturition by one day in treated dams of this group. no adverse effects on the litters or pups were noted; however, learning and memory assessments were not completed. three pregnant beagle dogs were treated intramuscularly with 25 mg/kg ketamine (1.3 times the human dose of 10 mg/kg im based on body surface area) twice weekly for the three weeks of the first, second, and third trimesters of pregnancy, respectively, without the development of adverse effects in the 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 (5.5), use in specific populations (8.4), and nonclinical toxicology (13.2)] . safety and effectiveness in pediatric patients below the age of 16 have not been established. published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as ketalar, 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 neonates and young children who require procedures with the potential risks suggested by the nonclinical data [see warnings and precautions (5.5), use in specific populations (8.1), and nonclinical toxicology (13.2)] . clinical studies of ketamine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. ketalar contains ketamine, a schedule iii controlled substance under the controlled substance act. individuals with a history of drug abuse or dependence may be at greater risk for abuse and misuse of ketalar. abuse is the intentional, non-therapeutic use of a drug, even once, for its psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. in a context of drug abuse, ketalar may produce a variety of symptoms including anxiety, dysphoria, disorientation, insomnia, flashback, hallucinations, and feelings of floating, detachment and being “spaced out”. recurrent high-dose ketamine misuse or abuse may be associated with memory and/or attention impairment. physical dependence has been reported with prolonged use of ketamine. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or significant dosage reduction of a drug. withdrawal symptoms have been reported after the discontinuation of frequently used (more than weekly), large doses of ketamine for long periods of time. reported symptoms of withdrawal associated with daily intake of large doses of ketamine include craving, fatigue, poor appetite, and anxiety. tolerance has been reported with prolonged use of ketamine. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).