(+)-Citalopram

414.43

324.39

812-870-6

4O4S742ANY

DTXSID8048440

C61754

N06AB10|N - Nervous system

2932999099

36.3

3.5

Solid

1.18±0.1 g/cm3(Predicted)

147-152C

428.3±45.0 °C(Predicted)

212.8±28.7 °C

1.591

Sparingly soluble

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature 2-8 °C. Store with desiccant. /Escitalopram oxalate/|Store at 25 °C (77 °F); excursions permitted to 15 - 30 °C (59-86 °F).

1.13X10-7 mm Hg at 25 °C (est)

D +12.33° (c = 1 in methanol)

9.5None

Henry's Law constant = 2.69X10-11 atm-cu m/mol at 25 °C (est)

9.5|pKa = 9.80 (amine moiety) /Trimethylamine/ (conjugate acid)

Fine white to slightly yellow powder. Crystals from acetone. MP: 147-148 °C. Specific optical rotation: +12.31 deg at 25 °C/D (c = 1 in methanol). Freely soluble in methanol, DMSO; soluble in isotonic saline; sparingly soluble in water, ethanol. slightly soluble in ethyl acetate; insoluble in heptane /Escitalopram oxalate/|Hydroxyl radical reaction rate constant = 9.21X10-11 cu cm/molec-sec at 25 °C (est)

Stable under recommended storage conditions. /Escitalopram oxalate/

P261, P264, P270, P272, P280, P301+P312, P302+P352, P321, P330, P333+P313, P363, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product. /Escitalopram oxalate/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including escitalopram oxalate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Escitalopram oxalate/

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P280, P301+P312, P302+P352, P321, P330, P333+P313, P363, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Escitalopram oxalate/|Skin protection: Handle with gloves. /Escitalopram oxalate/|Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. /Escitalopram oxalate/|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Escitalopram oxalate/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Escitalopram oxalate/|Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /Escitalopram oxalate/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. /Escitalopram oxalate/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. /Escitalopram oxalate/|Precautions for safe handling: Avoid contact with skin and eyes. Provide appropriate exhaust ventilation at places where dust is formed. /Escitalopram oxalate/|Appropriate engineering controls: General industrial hygiene practice. /Escitalopram oxalate/|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Escitalopram oxalate/|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Symptoms of overdose may include CNS effects (dizziness, convulsions, coma, somnolence), gastrointestinal distress (nausea, vomiting), and/or cardiac abnormalities (hypotension, tachycardia, ECG changes). There is no specific antidote for escitalopram overdose. Management of overdose should focus on monitoring for cardiac abnormalities and changes to vital signs as well as treatment with supportive measures as indicated. As escitalopram is highly distributed into tissue following oral administration, forced diuresis, dialysis, and other methods of extracting drug from plasma are unlikely to be beneficial.|IDENTIFICATION AND USE: Escitalopram is a second-generation antidepressive agent. It is used for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age. HUMAN STUDIES: Antidepressant discontinuation syndrome (ADS) frequently occurs in patients who undergo an abrupt discontinuation of their antidepressant medication. For escitalopram ADS was observed in 14 of 25 patients. Frequent symptoms were dizziness (44%), muscle tension (44%), chills (44%), confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). Major manifestations of escitalopram overdose were serotonin toxicity, QT prolongation, and bradycardia. Other symptoms accompanying escitalopram overdose, alone or in combination with other drugs and/or alcohol, included convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, and somnolence. Acute renal failure has been very rarely reported accompanying overdose. Escitalopram does not appear to be associated with an increased risk for major malformations but appears to increase the risk for low birth weight. In addition, the higher rates of spontaneous abortions have been observed. A case of serotonin toxicity due to in utero exposure to escitalopram was described. In human peripheral lymphocytes sister chromatid exchange increase caused by 5 and 10 ug/mL of escitalopram was found, while no increase was observed in DNA damage and micronucleus (MN) formation. Racemic form of the drug was not clastogenic in the in vitro chromosomal aberration assay in human lymphocytes. ANIMAL STUDIES: In a one-year toxicology study, 5 of 10 beagle dogs receiving oral racemic drug doses of 8 mg/kg/day died suddenly between weeks 17 and 31 following initiation of treatment. Sudden deaths were not observed in rats at doses of racemic drug up to 120 mg/kg/day. A subsequent intravenous dosing study demonstrated that in beagle dogs, racemic metabolites caused QT prolongation. Pathologic changes (degeneration/atrophy) were observed in the retinas of albino rats in the 2-year carcinogenicity study with racemic drug. There was an increase in both incidence and severity of retinal pathology in both male and female rats receiving 80 mg/kg/day. Similar findings were not present in rats receiving 24 mg/kg/day of racemic drug for two years, in mice receiving up to 240 mg/kg/day of racemic drug for 18 months, or in dogs receiving up to 20 mg/kg/day of racemic drug for one year. In two rat embryo/fetal development studies, oral administration of racemic drug (32, 56, or 112 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose. This dose was also associated with maternal toxicity in rats. In a rabbit study, no adverse effects on embryo/fetal development were observed at doses of racemic citalopram of up to 16 mg/kg/day. Racemic drug was mutagenic in the in vitro bacterial reverse mutation assay (Ames test) in 2 of 5 bacterial strains (Salmonella TA98 and TA1537) in the absence of metabolic activation. It was clastogenic in the in vitro Chinese hamster lung cell assay for chromosomal aberrations in the presence and absence of metabolic activation. Racemic drug was not mutagenic in the in vitro mammalian forward gene mutation assay (HPRT) in mouse lymphoma cells or in a coupled in vitro/in vivo unscheduled DNA synthesis (UDS) assay in rat liver. ECOTOXICITY STUDIES: There were noticeable gender differences in the behavior responses to escitalopram in zebrafish. At the end of exposures, both length and weight of the females exposed to 1.50 ug/L escitalopram were significantly less than the group of control fish. In addition, males exposed to 1.50 ug/L escitalopram were significantly shorter than control fish.

Liver test abnormalities have been reported to occur in less than 1% of patients on citalopram, and elevations are usually modest and rarely require dose modification or discontinuation. Rare instances of acute, clinically apparent episodes of liver injury with marked liver enzyme elevations with or without jaundice have been reported in patients on citalopram and escitalopram. The typical presentation is with fatigue, nausea and abdominal pain 2 to 10 weeks after starting the medication, followed by dark urine and mild jaundice. Both cholestatic and hepatocellular patterns of serum enzyme elevations have been described. Autoimmune (autoantibodies) and immunoallergic features (rash, fever, eosinophilia) are uncommon. Recovery is usually rapid once the agent is stopped.

Although the antidepressant and anxiolytic effects of selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors are well-documented, less is known about their cognitive effects. Escitalopram, a selective serotonin reuptake inhibitor, and atomoxetine, a selective noradrenaline reuptake inhibitor, were used to evaluate the interaction between noradrenergic and serotonergic neurotransmission in the modulation of contextual fear conditioning in rats. Contextual fear-conditioning test was used to investigate the acute effects of escitalopram, alone or in combination with atomoxetine, in different stages of learning and memory in rats. Furthermore, microdialysis in freely moving animals was used to investigate the effect of escitalopram on serotonin, dopamine, and noradrenaline levels in the rat hippocampus. Escitalopram significantly increased conditioned responses when applied before the acquisition, but decreased responses, when applied before the recall test. When administered during memory consolidation, escitalopram dose-dependently enhanced conditioned responding. These effects were blocked by atomoxetine. Escitalopram (at a dose that affects memory consolidation) increased hippocampal serotonin levels fourfold without changing dopamine or noradrenaline. Atomoxetine, at dose levels that blocked the effects of escitalopram on contextual fear conditioning, increased the extracellular levels of noradrenaline eightfold but did not change dopamine or serotonin. A combined treatment of escitalopram and atomoxetine caused a significant attenuation of escitalopram-induced increase in serotonin levels, while noradrenaline levels were not affected. These findings indicate that escitalopram affects fear memory in rats, likely modulated by increases in serotonin levels in the brain. This effect is impaired by atomoxetine, probably due to a noradrenaline-mediated decrease in serotonin levels. Further studies are warranted to study the effects of potential differences among antidepressant therapies on long-term cognitive outcomes.|A 63-year-old woman with a history of long-standing depression, maintained on escitalopram, presented with altered mental status. Patient had recently been prescribed dextromethorphan-promethazine cough syrup 2?weeks prior for an upper respiratory tract infection. On admission, she was lethargic and obtunded and found to have inducible myoclonus on examination. The rest of her physical exam was unremarkable. Pertinent lab and imaging findings showed QTc prolongation on ECG, negative electroencephalogram and CT head findings, essentially normal blood tests and a negative toxicology screen. The patient was admitted to the step down unit for close observation; both escitalopram and the cough syrup were suspended and was supportively managed. Overnight the patient's mental status improved and the serial EcGs showed resolution of the prolonged QTc. Patient was discharged home without further complication.|Linezolid, an anti-infective agent that is also a reversible monoamine oxidase (MAO) inhibitor, has been associated with drug interactions resulting in serotonin syndrome, including some associated with serotonin-reuptake inhibitors (SSRIs). Because of this potential risk, linezolid generally should not be used in patients receiving escitalopram. However, the FDA states that certain life-threatening or urgent situations may necessitate immediate linezolid treatment in a patient receiving a serotonergic drug. In such emergency situations, the availability of alternative anti-infectives should be considered and the benefits of linezolid should be weighed against the risk of serotonin syndrome. If linezolid is indicated in such emergency situations, escitalopram must be immediately discontinued and the patient monitored for symptoms of CNS toxicity for 2 weeks or until 24 hours after the last linezolid dose, whichever comes first. Treatment with escitalopram may be resumed 24 hours after the last linezolid dose. If nonemergency use of linezolid is being planned for a patient receiving escitalopram, escitalopram should be withheld for at least 2 weeks prior to initiating linezolid. Treatment with escitalopram should not be initiated in a patient receiving linezolid; when necessary, escitalopram may be started 24 hours after the last linezolid dose.|Potential pharmacologic interaction (potentially serious serotonin syndrome) when isoniazid, an antituberculosis agent that appears to have some monoamine oxidase (MAO)-inhibiting activity, is used concomitantly with escitalopram.|For more Interactions (Complete) data for Escitalopram (18 total), please visit the HSDB record page.

/AQUATIC SPECIES/ Selective serotonin re-uptake inhibitors are pharmaceuticals used to treat a range of psychological disorders. They are frequently found in surface waters in populated areas. In recent years, they have been shown to affect the behavior of various aquatic organisms in a way that can have ecological effects. In this study, ...zebrafish of both sexes /were exposed/ to nominally 0.00, 0.15 and 1.50 ug/L Escitalopram in flow-through tanks for three weeks. Subsequently, ten swimming behavior parameters were quantified using high-resolution video tracking. There were noticeable gender differences in the behavior responses to Escitalopram. Female fish exposed to 1.50 ug/L Escitalopram had a lower maximum swimming velocity, stopped less often and exhibited increased boldness (reduced thigmotaxis) compared to controls. Male fish exposed to 1.50 ug/L had a lower maximum swimming velocity compared to control fish. At the end of exposures, both length and weight of the females exposed to 1.50 ug/L Escitalopram were significantly less than the group of control fish. In addition, males exposed to 1.50 ug/L Escitalopram were significantly shorter than control fish. The behavior, weight and body length of the fish exposed to nominally 0.15 ug/L was not significantly different from control fish in either sex. The results of this study demonstrate that Escitalopram can affect subtle but ecologically important aspects of fish behavior and lends further credibility to the assumption that Escitalopram is an environmentally active pharmaceutical.

Although anticonvulsant effects of racemic citalopram have been observed in animal studies, escitalopram has not been systematically evaluated in patients with seizure disorders. Seizures have been reported in patients receiving escitalopram in clinical trials; therefore, as with other antidepressants, escitalopram therapy should be initiated with caution in patients with a history of seizure disorder.|In clinical studies, clearance of racemic citalopram was decreased by 37% and elimination half-life was doubled relative to that in patients with normal hepatic function. Dosage reduction is recommended for patients with hepatic impairment.|Activation of mania and hypomania has occurred in patients receiving escitalopram or citalopram. Escitalopram should be used with caution in patients with a history of mania.

Escitalopram exhibits relatively low protein binding at approximately 55-56%.

Escitalopram's production and administration as a medication(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 5500(SRC), determined from a structure estimation method(2), indicates that escitalopram is expected to be immobile in soil(SRC). A pKa of 9.8 for the amine moiety of escitalopram (based upon trimethylamine)(3) indicates that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an cation and cations do not volatilize. Escitalopram is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2018).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 5500(SRC), determined from a structure estimation method(2), indicates that escitalopram is expected to adsorb to suspended solids and sediment(SRC). A pKa of 9.8 for the amine moiety of escitalopram (based upon trimethylamine)(3) indicates escitalopram will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 140(SRC), from an estimated log Kow of 3.74(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Biodegradation data in water were not available(SRC, 2018).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), escitalopram, which has an estimated vapor pressure of 1.1X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase escitalopram is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 4 hrs(SRC), calculated from its rate constant of 9.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase escitalopram may be removed from the air by wet and dry deposition(SRC). Escitalopram does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of escitalopram with photochemically-produced hydroxyl radicals has been estimated as 9.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Escitalopram is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Escitalopram does not contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 140 was calculated in fish for escitalopram(SRC), using an estimated log Kow of 3.74(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of escitalopram can be estimated to be 5500(SRC). According to a classification scheme(2), this estimated Koc value suggests that escitalopram is expected to be immobile soil. The pKa of the amine moiety of escitalopram (based upon trimethylamine) is 9.8(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

A pKa of 9.8 for the amine moiety of escitalopram (based upon trimethylamine)(1) indicates trimethylamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces is not expected to be an important fate process(SRC). Escitalopram is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-7 mm Hg(SRC), determined from a fragment constant method(2)

While data specific to escitalopram were not located(SRC, 2018), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are, therefore, discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Occupational exposure to escitalopram may occur through inhalation and dermal contact with this compound at workplaces where escitalopram is produced or used. The general public is not likely to be exposed to escitalopram unless by direct medical treatment. (SRC)

Escitalopram is indicated for both acute and maintenance treatment of major depressive disorder (MDD) and for the acute treatment of generalized anxiety disorder (GAD). It is additionally indicated for symptomatic relief of obsessive-compulsive disorder (OCD) in Canada.

Citalopram and escitalopram are selective serotonin reuptake inhibitors (SSRIs) and widely used antidepressants. Citalopram is a racemic mixture, whereas escitalopram is its S-enantiomer. Both agents have similar profiles of clinical efficacy and side effects. Both have been associated with rare instances of clinically apparent acute liver injury.

Antidepressant Agents

Serotonin Uptake Inhibitors; Antidepressive Agents, Second-Generation|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Escitalopram is included in the database.|Lexapro (escitalopram) is indicated for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age. A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. /Included in US product label/|Lexapro is indicated for the acute treatment of Generalized Anxiety Disorder (GAD) in adult. Generalized Anxiety Disorder (DSM-IV) is characterized by excessive anxiety and worry (apprehensive expectation) that is persistent for at least 6 months and which the person finds difficult to control. It must be associated with at least 3 of the following symptoms: restlessness or feeling keyed up or on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, and sleep disturbance. /Included in US product label/|For more Therapeutic Uses (Complete) data for Escitalopram (9 total), please visit the HSDB record page.

/BOXED WARNING/ WARNING: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Lexapro or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Lexapro is not approved for use in pediatric patients less than 12 years of age.|Potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with selective serotonin-reuptake inhibitors (SSRIs), including escitalopram, and selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs) alone, but particularly with concurrent use of other serotonergic drugs (including serotonin (5-hydroxytryptamine; 5-HT) type 1 receptor agonists ("triptans")), drugs that impair the metabolism of serotonin (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists. Manifestations of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea). In its most severe form, serotonin syndrome may resemble NMS, which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation in vital signs, and mental status changes. Patients receiving escitalopram should be monitored for the development of serotonin syndrome or NMS-like signs and symptoms.|The use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders with Lexapro or within 14 days of stopping treatment with Lexapro is contraindicated because of an increased risk of serotonin syndrome. The use of Lexapro within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. Starting Lexapro in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome.|If concomitant use of Lexapro with other serotonergic drugs including, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, amphetamine and St. John's Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.|For more Drug Warnings (Complete) data for Escitalopram (20 total), please visit the HSDB record page.

Escitalopram belongs to a class of medications called selective serotonin re-uptake inhibitors (SSRIs). These agents cause an increase in serotonin levels in neuronal synapses by preventing the re-uptake of serotonin (5-HT) into the presynaptic terminals of serotonergic neurons. As compared to other SSRIs, it appears to have a relatively quick onset of effect due to its potency. SSRIs as a class have been associated with abnormal bleeding, particularly in patients receiving concomitant therapy with other medications affecting hemostasis, and with the development of serotonin syndrome. Use escitalopram with caution in patients with a higher-than-baseline risk of bleeding and in patients receiving concomitant therapy with other serotonergic drugs. Escitalopram may also cause a discontinuation syndrome with abrupt removal of the drug, and should be slowly tapered if discontinuation of therapy is warranted.

A structurally and mechanistically diverse group of drugs that are not tricyclics or monoamine oxidase inhibitors. The most clinically important appear to act selectively on serotonergic systems, especially by inhibiting serotonin reuptake. (See all compounds classified as Antidepressive Agents, Second-Generation.)|Compounds that specifically inhibit the reuptake of serotonin in the brain. (See all compounds classified as Serotonin Uptake Inhibitors.)

Absorption of escitalopram following oral administration is expected to be almost complete, with an estimated absolute bioavailability of approximately 80%. T_max occurs after about 4-5 hours. C_max and AUC appear to follow dose proportionality - at steady state, patients receiving 10mg of escitalopram daily had a C_max of 21 ng/mL and a 24h AUC of approximately 360 ng*h/mL, while patients receiving 30mg daily had a roughly 3-fold increase in both C_max and 24h AUC, comparatively.|After oral administration of escitalopram, approximately 8% of the total dose is eliminated in the urine as unchanged escitalopram and 10% is eliminated in the urine as S-desmethylcitalopram. The apparent hepatic clearance of escitalopram amounts to approximately 90% of the total dose.|Escitalopram appears to distribute extensively into tissues, with an apparent volume of distribution of approximately 12-26 L/kg.|The oral plasma clearance of escitalopram is 600 mL/min, of which approximately 7% is due to renal clearance.|/MILK/ Escitalopram is excreted in human breast milk. Limited data from women taking 10-20 mg escitalopram showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram.|The absolute bioavailability of citalopram is about 80% relative to an intravenous dose, and the volume of distribution of citalopram is about 12 L/kg. Data specific on escitalopram are unavailable. The binding of escitalopram to human plasma proteins is approximately 56%.|Following a single oral dose (20 mg tablet or solution) of escitalopram, peak blood levels occur at about 5 hours. Absorption of escitalopram is not affected by food.

The metabolism of escitalopram is mainly hepatic, mediated primarily by CYP2C19 and CYP3A4 and, to a lesser extent, CYP2D6. Oxidative N-demethylation by the CYP enzyme system results in S-desmethylcitalopram (S-DCT) and S-didesmethylcitalopram (S-DDCT) - these metabolites do not contribute to the pharmacologic activity of escitalopram, and exist in the plasma in small quantities relative to the parent compound (28-31% and <5%, respectively). There is also some evidence that escitalopram is metabolized to a propionic acid metabolite by monoamine oxidase A and B in the brain, and that these enzymes constitute the major route of escitalopram metabolism in the brain.|The antidepressant escitalopram is predominantly metabolized by the polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19 genotype on exposure and therapeutic failure of escitalopram in a large patient population. A total of 4,228 escitalopram serum concentration measurements from 2,087 CYP2C19-genotyped patients 10-30 hours after drug intake were collected retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo. The patients were divided into subgroups based on CYP2C19 genotype: those carrying inactive (CYP2C19Null) and gain-of-function (CYP2C19*17) variant alleles. The between-subgroup differences in escitalopram exposure (endpoint: dose-harmonized serum concentration) and therapeutic failure (endpoint: switching to another antidepressant within 1 year after the last escitalopram measurement) were evaluated by multivariate mixed model and chi-square analysis, respectively. Compared with the CYP2C19*1/*1 group, escitalopram serum concentrations were significantly increased 3.3-fold in the CYP2C19Null/Null group, 1.6-fold in the CYP2C19*Null/*1 group, and 1.4-fold in the CYP2C19Null/*17 group, whereas escitalopram serum concentrations were significantly decreased by 10% in the CYP2C19*1/*17 group and 20% in the CYP1C19*17/*17 group. In comparison to the CYP2C19*1/*1 group, switches from escitalopram to another antidepressant within 1 year were 3.3, 1.6, and 3.0 times more frequent among the CYP2C19Null/Null, CYP2C19*1/*17, and CYP1C19*17/*17 groups, respectively. The CYP2C19 genotype had a substantial impact on exposure and therapeutic failure of escitalopram, as measured by switching of antidepressant therapy. The results support the potential clinical utility of CYP2C19 genotyping for individualization of escitalopram therapy.|Escitalopram is metabolized to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT). In humans, unchanged escitalopram is the predominant compound in plasma. At steady state, the concentration of the escitalopram metabolite S-DCT in plasma is approximately one-third that of escitalopram. The level of S-DDCT was not detectable in most subjects. In vitro studies show that escitalopram is at least 7 and 27 times more potent than S-DCT and S-DDCT, respectively, in the inhibition of serotonin reuptake, suggesting that the metabolites of escitalopram do not contribute significantly to the antidepressant actions of escitalopram. S-DCT and S-DDCT also have no or very low affinity for serotonergic (5-HT1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5), and benzodiazepine receptors. S-DCT and S-DDCT also do not bind to various ion channels including Na+, K+, Cl-, and Ca++ channels. In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the Ndemethylation of escitalopram.

The elimination half-life of escitalopram is 27-32 hours, though this is increased by approximately 50% in the elderly and doubled in patients with reduced hepatic function. The elimination half-life of escitalopram's primary metabolite, S-desmethylcitalopram, is approximately 54 hours at steady state.|Biotransformation of escitalopram is mainly hepatic, with a mean terminal half-life of about 27-32 hours.

Escitalopram, like other selective serotonin re-uptake inhibitors, enhances serotonergic activity by binding to the orthosteric (i.e. primary) binding site on the serotonin transporter (SERT), the same site to which endogenous 5-HT binds, and thus prevents the re-uptake of serotonin into the presynaptic neuron. Escitalopram, along with [paroxetine], is also considered an allosteric serotonin re-uptake inhibitor - it binds to a secondary allosteric site on the SERT molecule to more strongly inhibit 5-HT re-uptake. Its combination of orthosteric and allosteric activity on SERT allows for greater extracellular 5-HT levels, a faster onset of action, and greater efficacy as compared to other SSRIs. The sustained elevation of synaptic 5-HT eventually causes desensitization of 5-HT_1A auto-receptors, which normally shut down endogenous 5-HT release in the presence of excess 5-HT - this desensitization may be necessary for the full clinical effect of SSRIs and may be responsible for their typically prolonged onset of action. Escitalopram has shown little-to-no binding affinity at a number of other receptors, such as histamine and muscarinic receptors, and minor activity at these off-targets may explain some of its adverse effects.|The mechanism of antidepressant action of escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if needed. Administer supplemental oxygen. 2. Treat coma, hypotension, hypertension, and seizures if they occur. 3. For mild serotonin syndrome, benzodiazepines can be used for control of agitation and tremor. Severe serotonin syndrome with hyperthermia requires hospitalization and aggressive cooling measures, which often include neuromuscular paralysis and endotracheal intubation. ... /Antidepressants, general (noncyclic)/|For more Antidote and Emergency Treatment (Complete) data for Escitalopram (8 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ Citalopram, a selective serotonin reuptake inhibitor, is used as a neuroendocrine probe in human subjects to assess serotonin function as reflected in prolactin and plasma cortisol release. Citalopram is a racemic mixture of equal proportions of the S(+) and R(-) enantiomers. Inhibition of serotonin reuptake and, consequently, antidepressant activity is associated, almost exclusively, with the S(+) enantiomer ("escitalopram"). Studies in animal models indicate that the presence of the R(-) isomer may interfere with the serotonin reuptake activity of escitalopram. The current study compared the neuroendocrine effects of citalopram and escitalopram in healthy human volunteers. Plasma cortisol and prolactin levels following a single oral dose of citalopram (40 mg) or escitalopram (20 mg) were compared in samples taken every 15-30 min over a period of 240 min. Plasma citalopram concentration was determined at the same intervals. Escitalopram and citalopram caused equivalent increases in plasma cortisol and prolactin. The administration of dexamethasone prior to the escitalopram challenge blocked the evoked increase in cortisol. This is the first study to prove that a single dose of escitalopram acts centrally and not peripherally, providing further support of the use of oral escitalopram as a probe for brain serotonergic function.|/SIGNS AND SYMPTOMS/ Antidepressant discontinuation syndrome (ADS) frequently occurs in patients who undergo an abrupt discontinuation of their antidepressant medication. We evaluated 25 consecutive outpatients with depression who discontinued their use of escitalopram. The presence of ADS was evaluated according to the Antidepressants Discontinuation Syndrome checklist. Antidepressant discontinuation syndrome was observed in 14 of 25 patients. Frequent symptoms were dizziness (44%), muscle tension (44%), chills (44%), confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). The treatment doses and plasma concentrations of escitalopram were significantly higher in patients with ADS than in patients without ADS. No group differences were observed regarding age, sex, or duration of escitalopram treatment before the discontinuation. These findings suggest that a higher dose and lower clearance of escitalopram lead to a higher risk of ADS. Very slow tapering is recommended for all patients.|/SIGNS AND SYMPTOMS/ A review of escitalopram overdoses to a clinical toxicology unit was undertaken. Patient demographics, details of the ingestion, clinical effects, including evidence of serotonin toxicity, complications (arrhythmias and seizures), ICU admission, and length of stay were obtained. QT and QRS intervals were manually measured on ECGs by using a standardized approach. In a subgroup of 34 prospectively recruited patients, escitalopram was detected in blood from 33 patients. Medians and interquartile ranges (IQR) were reported, and QT versus pulse rate was plotted on a QT nomogram to investigate QT prolongation. Median ingested dose in the 79 presentations was 140 mg (IQR 75 to 260 mg; range 20 to 560 mg), and escitalopram was the only drug ingested or all coingested drugs were nontoxic in 46 cases. Median length of stay for patients receiving clinically important coingestants was 19 hours (IQR 9 to 33 hours) compared with that of patients receiving escitalopram alone (median 12 hours; IQR 7 to 19 hours). Serotonin toxicity occurred in 7 of the 46 escitalopram-alone ingestions (15%) but in only 1 of the 33 patients coingesting other medications. Common features were inducible clonus and hyperreflexia. Central nervous system depression and ICU admission were rare in escitalopram-alone overdoses compared with those in cases with sedative coingestants. Bradycardia (pulse rate <60 beats/min) occurred in 11 cases (14%) and an abnormal QT-HR pair in 11 (14%), which was associated with normal or slow pulse rates. There were no deaths, seizures, or arrhythmias. Major manifestations of escitalopram overdose were serotonin toxicity, QT prolongation, and bradycardia. The study suggests a potential for cardiac arrhythmias in escitalopram overdose.|/SIGNS AND SYMPTOMS/ Symptoms most often accompanying escitalopram overdose, alone or in combination with other drugs and/or alcohol, included convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation and very rare cases of torsade de pointes). Acute renal failure has been very rarely reported accompanying overdose.|For more Human Toxicity Excerpts (Complete) data for Escitalopram (23 total), please visit the HSDB record page.

Celexa

Table: Escitalopram Oxalate Preparations [Table#8468]

Escitalopram oxalate, a selective serotonin reuptake inhibitor, is the single-isomer version of the successful Celexa antidepressant. /Escitalopram oxalate/