NDC 70518-1857 Escitalopram

Escitalopram Oxalate

NDC Product Code 70518-1857

NDC Code: 70518-1857

Proprietary Name: Escitalopram What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Escitalopram Oxalate What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
WHITE (C48325 - WHITE)
Shape: OVAL (C48345)
Size(s):
8 MM
Imprint(s):
B;3;C
Score: 2

NDC Code Structure

  • 70518 - Remedyrepack Inc.
    • 70518-1857 - Escitalopram

NDC 70518-1857-0

Package Description: 30 TABLET, FILM COATED in 1 BLISTER PACK

NDC Product Information

Escitalopram with NDC 70518-1857 is a a human prescription drug product labeled by Remedyrepack Inc.. The generic name of Escitalopram is escitalopram oxalate. The product's dosage form is tablet, film coated and is administered via oral form.

Labeler Name: Remedyrepack Inc.

Dosage Form: Tablet, Film Coated - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a thin layer of a water-insoluble or water-soluble polymer.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Escitalopram Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • ESCITALOPRAM OXALATE 10 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • TALC (UNII: 7SEV7J4R1U)
  • CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)
  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • HYPROMELLOSES (UNII: 3NXW29V3WO)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Serotonin Reuptake Inhibitor - [EPC] (Established Pharmacologic Class)
  • Serotonin Uptake Inhibitors - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Remedyrepack Inc.
Labeler Code: 70518
FDA Application Number: ANDA202280 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 02-07-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Escitalopram Product Label Images

Escitalopram Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Warnings: Suicidality And Antidepressant Drugs

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 escitalopram 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. Escitalopram is not approved for use in pediatric patients less than 12 years of age.


[See Warnings and Precautions: Clinical Worsening and Suicide Risk (


5.1), Patient Counseling Information: Information for Patients (


17.1), and Use in Specific Populations: Pediatric Use (


8.4)].

1.1 Major Depressive Disorder

Escitalopram tablets are indicated for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age [


see Clinical Studies (


14.1)


].


 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.

1.2 Generalized Anxiety Disorder

Escitalopram tablets are indicated for the acute treatment of Generalized Anxiety Disorder (GAD) in adults [


see Clinical Studies (


14.2)


]. 


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.

2 Dosage And Administration

Escitalopram  tablets should be administered once daily, in the morning or evening, with or without food.

Initial Treatment

AdolescentsThe recommended dose of escitalopram tablets is 10 mg once daily. A flexible-dose trial of escitalopram tablets (10 to 20 mg/day) demonstrated the effectiveness of escitalopram tablets [


see


Clinical Studies (14.1)]


. If the dose is increased to 20 mg, this should occur after a minimum of three weeks.


Adults


The recommended dose of escitalopram tablets is 10 mg once daily. A fixed-dose trial of escitalopram tablets demonstrated the effectiveness of both 10 mg and 20 mg of escitalopram tablets but failed to demonstrate a greater benefit of 20 mg over 10 mg [


see


Clinical Studies (14.1)]


. If the dose is increased to 20 mg, this should occur after a minimum of one week.


Maintenance Treatment


It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of continuing escitalopram tablets 10 or 20 mg/day in adults patients with major depressive disorder who responded while taking escitalopram tablets during an 8-week, acute-treatment phase demonstrated a benefit of such maintenance treatment [


see


Clinical Studies (14.1)]. Nevertheless, the physician who elects to use escitalopram tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.  Patients should be periodically reassessed to determine the need for maintenance treatment.

2.2 Generalized Anxiety Disorder

Initial Treatment


Adults


The recommended starting dose of escitalopram tablets is 10 mg once daily. If the dose is increased to 20 mg, this should occur after a minimum of one week.


Maintenance Treatment


Generalized anxiety disorder is recognized as a chronic condition. The efficacy of escitalopram tablets in the treatment of GAD beyond 8 weeks has not been systematically studied. The physician who elects to use escitalopram tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

2.3 Special Populations

10 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment.


No dosage adjustment is necessary for patients with mild or moderate renal impairment. Escitalopram tablets should be used with caution in patients with severe renal impairment.

2.4 Discontinuation Of Treatment With Escitalopram Tablets

Symptoms associated with discontinuation of escitalopram tablets and other SSRIs and SNRIs have been reported [


see


Warnings and Precautions (


5.3)


]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

2.5 Switching A Patient To Or From A Monoamine Oxidase Inhibitor (Maoi) Intended To Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with escitalopram tablets. Conversely, at least 14 days should be allowed after stopping escitalopram tablets before starting an MAOI intended to treat psychiatric disorders [


see Contraindications (


4.1)


]


.

2.6 Use Of Escitalopram Tablets With Other Maois Such As Linezolid Or Methylene Blue

Do not start escitalopram tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered


[see Contraindications (


4.1)].


In some cases, a patient already receiving escitalopram tablets therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, escitalopram tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with escitalopram tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue


[see Warnings and Precautions (


5.2)].


The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with escitalopram tablets is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use


[see Warnings and Precautions (


5.2)].

3.1 Tablets

  • Escitalopram  tablets, USP 5 mg are white, round, biconvex, film-coated tablets, debossed with ‘B2’ on one side and ‘C’ on the other side.
  • Escitalopram  tablets, USP 10 mg are white, oval shaped, biconvex, film-coated tablets, with scoreline on one side, debossed with ‘B’ on left side of scoreline and ‘3’ on right side of scoreline and with ‘C’ on the other side.
  • Escitalopram  tablets, USP 20 mg are white, oval shaped, biconvex, film-coated tablets, with scoreline on one side, debossed with ‘B4’on left side of scoreline and ‘C’ on right side of scoreline and plain on the other side.

4.1 Monoamine Oxidase Inhibitors (Maois)

The use of MAOIs intended to treat psychiatric disorders with escitalopram or within 14 days of stopping treatment with escitalopram is contraindicated because of an increased risk of serotonin syndrome. The use of escitalopram  within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [


see Dosage and Administration (


2.5), and Warnings and Precautions (


5.2)


]


.Starting escitalopram 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 [


see Dosage and Administration (


2.6), and Warnings and Precautions (


5.2)


].

4.2 Pimozide

Concomitant use in patients taking pimozide is contraindicated [


see Drug Interactions (


7.10)


].

4.3 Hypersensitivity To Escitalopram Or Citalopram

Escitalopram is contraindicated in patients with a hypersensitivity to escitalopram or citalopram or any of the inactive ingredients in escitalopram tablets.

5.1 Clinical Worsening And Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. 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 with antidepressants compared to placebo in adults aged 65 and older.The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in


Table 1.


TABLE 1Age RangeDrug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients TreatedIncreases Compared to Placebo<1814 additional cases18-245 additional casesDecreases Compared to Placebo25-641 fewer case≥656 fewer casesNo suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms [


see Dosage and Administration (


2.4)


].


Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers [


see also Patient Counseling Information (


17.1)


]. Prescriptions for escitalopram should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

5.2 Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including escitalopram, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination) seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination) seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome. The concomitant use of escitalopram with MAOIs intended to treat psychiatric disorders is contraindicated. Escitalopram should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking escitalopram. Escitalopram should be discontinued before initiating treatment with the MAOI [
].
The concomitant use of escitalopram with MAOIs intended to treat psychiatric disorders is contraindicated. Escitalopram should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking escitalopram. Escitalopram should be discontinued before initiating treatment with the MAOI [


see Contraindications (


4.1) and Dosage and Administration (


2.5 and


2.6)


].


If concomitant use of escitalopram 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. Treatment with escitalopram and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated. Treatment with escitalopram and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

5.3 Discontinuation Of Treatment With Escitalopram

During marketing of escitalopram and other SSRIs and SNRIs (serotonin and norepinephrine reuptake inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.


Patients should be monitored for these symptoms when discontinuing treatment with escitalopram. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate [


see Dosage and Administration (


2.4)


].

5.4 Seizures

Although anticonvulsant effects of racemic citalopram have been observed in animal studies, escitalopram  has not been systematically evaluated in patients with a seizure disorder. These patients were excluded from clinical studies during the product's premarketing testing. In clinical trials of escitalopram, cases of convulsion have been reported in association with escitalopram treatment. Like other drugs effective in the treatment of major depressive disorder, escitalopram should be introduced with care in patients with a history of seizure disorder.

5.5 Activation Of Mania/Hypomania

In placebo-controlled trials of escitalopram in major depressive disorder, activation of mania/hypomania was reported in one (0.1%) of 715 patients treated with escitalopram and in none of the 592 patients treated with placebo. One additional case of hypomania has been reported in association with escitalopram   treatment. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorders treated with racemic citalopram and other marketed drugs effective in the treatment of major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, escitalopram should be used cautiously in patients with a history of mania.

5.6 Hyponatremia

Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including escitalopram. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was reversible when escitalopram was discontinued. Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk [


see Geriatric Use


(8.5)]


. Discontinuation of escitalopram should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.


Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death.

5.7 Abnormal Bleeding

SSRIs and SNRIs, including escitalopram, may increase the risk of bleeding events.  Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to the risk.  Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.


Patients should be cautioned about the risk of bleeding associated with the concomitant use of escitalopram  and NSAIDs, aspirin, or other drugs that affect coagulation.

5.8 Interference With Cognitive  And Motor Performance

In a study in normal volunteers, escitalopram 10 mg/day did not produce impairment of intellectual function or psychomotor performance. Because any psychoactive drug may impair judgment, thinking, or motor skills, however, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that escitalopram therapy does not affect their ability to engage in such activities.

5.9 Angle Closure Glaucoma

Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs including escitalopram may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

5.10 Use In Patients With Concomitant Illness

Clinical experience with escitalopram in patients with certain concomitant systemic illnesses is limited. Caution is advisable in using escitalopram in patients with diseases or conditions that produce altered metabolism or hemodynamic responses. Escitalopram has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were generally excluded from clinical studies during the product's premarketing testing.In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma concentrations were increased. The recommended dose of escitalopram in hepatically impaired patients is 10 mg/day [


see Dosage and Administration


(2.3)


]


.Because escitalopram is extensively metabolized, excretion of unchanged drug in urine is a minor route of elimination. Until adequate numbers of patients with severe renal impairment have been evaluated during chronic treatment with escitalopram, however, it should be used with caution in such patients [


see Dosage and Administration


(2.3)].

6.1 Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Clinical Trial Data Sources

Pediatrics (6 - 17 years) Adverse events were collected in 576 pediatric patients (286 escitalopram, 290 placebo) with major depressive disorder in double-blind placebo-controlled studies. Safety and effectiveness of escitalopram in pediatric patients less than 12 years of age has not been established. Adults Adverse events information for escitalopram was collected from 715 patients with major depressive disorder who were exposed to escitalopram and from 592 patients who were exposed to placebo in double-blind, placebo-controlled trials. An additional 284 patients with major depressive disorder were newly exposed to escitalopram in open-label trials. The adverse event information for escitalopram in patients with GAD was collected from 429 patients exposed to escitalopram and from 427 patients exposed to placebo in double-blind, placebo-controlled trials. Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify reported adverse events. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Adverse Events Associated with Discontinuation of TreatmentMajor Depressive Disorder  Pediatrics (6 - 17 years)


Adverse events were associated with discontinuation of 3.5% of 286 patients receiving escitalopram   and 1% of 290 patients receiving placebo.  The most common adverse event (incidence at least 1% for escitalopram and greater than placebo) associated with discontinuation was insomnia (1% escitalopram, 0% placebo).  


Adults


Among the 715 depressed patients who received escitalopram in placebo-controlled trials, 6% discontinued treatment due to an adverse event, as compared to 2% of 592 patients receiving placebo. In two fixed-dose studies, the rate of discontinuation for adverse events in patients receiving 10 mg/day escitalopram was not significantly different from the rate of discontinuation for adverse events in patients receiving placebo. The rate of discontinuation for adverse events in patients assigned to a fixed dose of 20 mg/day escitalopram was 10%, which was significantly different from the rate of discontinuation for adverse events in patients receiving 10 mg/day escitalopram (4%) and placebo (3%). Adverse events that were associated with the discontinuation of at least 1% of patients treated with escitalopram, and for which the rate was at least twice that of placebo, were nausea (2%) and ejaculation disorder (2% of male patients).

Generalized Anxiety Disorder

Adults Among the 429 GAD patients who received escitalopram 10-20 mg/day in placebo-controlled trials, 8% discontinued treatment due to an adverse event, as compared to 4% of 427 patients receiving placebo. Adverse events that were associated with the discontinuation of at least 1% of patients treated with escitalopram, and for which the rate was at least twice the placebo rate, were nausea (2%), insomnia (1%), and fatigue (1%).Incidence of Adverse Reactions in Placebo-Controlled Clinical Trials Major Depressive Disorder Pediatrics (6 -17 years) The overall profile of adverse reactions in pediatric patients was generally similar to that seen in adult studies, as shown in


Table 2. However, the following adverse reactions (excluding those which appear in


Table 2 and those for which the coded terms were uninformative or misleading) were reported at an incidence of at least 2% for escitalopram and greater than placebo: back pain, urinary tract infection, vomiting, and nasal congestion.


Adults The most commonly observed adverse reactions in escitalopram patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased, fatigue, and somnolence.


Table 2 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 715 depressed patients who received escitalopram at doses ranging from 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with escitalopram and for which the incidence in patients treated with escitalopram was greater than the incidence in placebo-treated patients.


TABLE 2Treatment-Emergent Adverse Reactions observed with a frequency of ≥2% and greater than placebo for Major Depressive DisorderAdverse ReactionEscitalopramPlacebo(N=715)


%(N=592)


%Autonomic Nervous System Disorders Dry Mouth 6% 5% Sweating Increased 5% 2%Central & Peripheral Nervous System Disorders Dizziness 5% 3%Gastrointestinal Disorders Nausea 15% 7% Diarrhea 8% 5% Constipation 3% 1% Indigestion 3% 1% Abdominal Pain 2% 1%General Influenza-like Symptoms 5% 4% Fatigue 5% 2%Psychiatric Disorders Insomnia 9% 4% Somnolence 6% 2% Appetite Decreased 3% 1% Libido Decreased 3% 1%Respiratory System Disorders Rhinitis 5% 4% Sinusitis 3% 2%Urogenital Ejaculation Disorder


1,2 9% <1% Impotence


2 3% <1% Anorgasmia


3 2% <1%1Primarily ejaculatory delay.


2Denominator used was for males only (N=225 Escitalopram; N=188 placebo).


3Denominator used was for females only (N=490 Escitalopram; N=404 placebo).


Generalized Anxiety DisorderAdults The most commonly observed adverse reactions in escitalopram  patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were nausea, ejaculation disorder (primarily ejaculatory delay), insomnia, fatigue, decreased libido, and anorgasmia. Table 3 enumerates the incidence, rounded to the nearest percent of treatment-emergent adverse events that occurred among 429 GAD patients who received escitalopram 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with escitalopram and for which the incidence in patients treated with escitalopram was greater than the incidence in placebo-treated patients.


TABLE 3Treatment-Emergent Adverse Reactions observed with a frequency of ≥ 2% and greater than placebo for Generalized Anxiety DisorderAdverse ReactionsEscitalopramPlacebo(N=429)


%(N=427)


%Autonomic Nervous System Disorders Dry Mouth 9% 5% Sweating Increased 4% 1%Central & Peripheral Nervous System Disorders Headache 24% 17% Paresthesia 2% 1%Gastrointestinal Disorders Nausea 18% 8% Diarrhea 8% 6% Constipation 5% 4% Indigestion 3% 2% Vomiting 3% 1% Abdominal Pain 2% 1% Flatulence 2% 1% Toothache 2% 0%General Fatigue 8% 2% Influenza-like Symptoms 5% 4%Musculoskeletal System Disorder Neck/Shoulder Pain 3% 1%Psychiatric Disorders Somnolence 13% 7% Insomnia 12% 6% Libido Decreased 7% 2% Dreaming Abnormal 3% 2% Appetite Decreased 3% 1% Lethargy 3% 1%Respiratory System Disorders Yawning 2% 1%Urogenital Ejaculation Disorder


1,2 14% 2% Anorgasmia


3 6% <1% Menstrual Disorder 2% 1%1Primarily ejaculatory delay.


2Denominator used was for males only (N=182 Escitalopram; N=195 placebo).


3Denominator used was for females only (N=247 Escitalopram; N=232 placebo).


Dose Dependency of Adverse Reactions The potential dose dependency of common adverse reactions (defined as an incidence rate of ≥5% in either the 10 mg or 20 mg escitalopram groups) was examined on the basis of the combined incidence of adverse reactions in two fixed-dose trials. The overall incidence rates of adverse events in 10 mg escitalopram-treated patients (66%) was similar to that of the placebo-treated patients (61%), while the incidence rate in 20 mg/day escitalopram-treated patients was greater (86%).


Table 4 shows common adverse reactions that occurred in the 20 mg/day escitalopram group with an incidence that was approximately twice that of the 10 mg/day escitalopram group and approximately twice that of the placebo group.


TABLE 4Incidence of Common Adverse Reactions  in Patients with Major Depressive DisorderAdverse ReactionPlacebo10 mg/day20 mg/day(N=311)Escitalopram  Escitalopram  (N=310)(N=125)Insomnia 4% 7% 14%Diarrhea 5% 6% 14%Dry Mouth 3% 4% 9%Somnolence 1% 4% 9%Dizziness 2% 4% 7%Sweating Increased <1% 3% 8%Constipation 1% 3% 6%Fatigue 2% 2% 6%Indigestion 1% 2% 6%Male and Female Sexual Dysfunction with SSRIsAlthough changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences.Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling are likely to underestimate their actual incidence.TABLE 5 Incidence of Sexual Side Effects in Placebo-Controlled Clinical TrialsAdverse EventEscitalopram PlaceboIn Males Only(N=407)(N=383)Ejaculation Disorder


(primarily ejaculatory delay)


12%


1%


Libido Decreased6%2%Impotence2%<1%In Females Only(N=737)(N=636)Libido Decreased3%1%Anorgasmia3%<1%There are no adequately designed studies examining sexual dysfunction with escitalopram treatment.Priapism has been reported with all SSRIs.While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.

7.1 Monoamine Oxidase Inhibitors (Maois)

[See Dosage and Administration (


2.5 and


2.6), Contraindications


(4.1) and Warnings and Precautions


(5.2)].

7.2 Serotonergic Drugs

[See Dosage and Administration (


2.5 and


2.6), Contraindications (


4.1) and Warnings and Precautions (


5.2)].

7.3 Triptans

There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of escitalopram  with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [


see Warnings and Precautions (


5.2)


]


.

7.4 Cns Drugs

Given the primary CNS effects of escitalopram, caution should be used when it is taken in combination with other centrally acting drugs.

7.5 Alcohol

Although escitalopram did not potentiate the cognitive and motor effects of alcohol in a clinical trial, as with other psychotropic medications, the use of alcohol by patients taking escitalopram is not recommended.

7.6 Drugs That Interfere With Hemostasis (Nsaids, Aspirin, Warfarin, Etc.)

Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate the risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are coadministered with warfarin.  Patients receiving warfarin therapy should be carefully monitored when escitalopram  is initiated or discontinued.

7.7 Cimetidine

In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of 400 mg twice a day cimetidine for 8 days resulted in an increase in citalopram AUC and C


max of 43% and 39%, respectively. The clinical significance of these findings is unknown.

7.8 Digoxin

In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin.

7.9 Lithium

Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when escitalopram and lithium are coadministered.

7.10 Pimozide And Celexa

In a controlled study, a single dose of pimozide 2 mg co-administered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or C


max of pimozide. The mechanism of this pharmacodynamic interaction is not known.

7.11 Sumatriptan

There have been rare postmarketing reports describing patients with weakness, hyperreflexia, and incoordination following the use of an SSRI and sumatriptan. If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) is clinically warranted, appropriate observation of the patient is advised.

7.12 Theophylline

Combined administration of racemic citalopram (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated.

7.13 Warfarin

Administration of 40 mg/day racemic citalopram for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown.

7.14 Carbamazepine

Combined administration of racemic citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two drugs are coadministered.

7.15 Triazolam

Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.

7.16 Ketoconazole

Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the C


max and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.

7.17 Ritonavir

Combined administration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of either ritonavir or escitalopram.

7.18 Cyp3a4 And -2C19 Inhibitors

In vitro studies indicated that CYP3A4 and -2C19 are the primary enzymes involved in the metabolism of escitalopram. However, coadministration of escitalopram (20 mg) and ritonavir (600 mg), a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escitalopram is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram clearance.

7.19 Drugs Metabolized By Cytochrome P4502d6

In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism. However, there are limited


in vivo data suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in C


max and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless, caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.

7.20 Metoprolol

Administration of 20 mg/day escitalopram for 21 days in healthy volunteers resulted in a 50% increase in C


max and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100 mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of escitalopram and metoprolol had no clinically significant effects on blood pressure or heart rate.

7.21 Electroconvulsive Therapy (Ect)

There are no clinical studies of the combined use of ECT and escitalopram.

Pregnancy Category C

In a rat embryo/fetal development study, oral administration of escitalopram (56, 112, or 150 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased fetal body weight and associated delays in ossification at the two higher doses (approximately ≥ 56 times the maximum recommended human dose [MRHD] of 20 mg/day on a body surface area [mg/m


2] basis). Maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild at 56 mg/kg/day, was present at all dose levels. The developmental no-effect dose of 56 mg/kg/day is approximately 28 times the MRHD on a mg/m


2 basis. No teratogenicity was observed at any of the doses tested (as high as 75 times the MRHD on a mg/m


2 basis).


When female rats were treated with escitalopram  (6, 12, 24, or 48 mg/kg/day) during pregnancy and through weaning, slightly increased offspring mortality and growth retardation were noted at 48 mg/kg/day which is approximately 24 times the MRHD on a mg/m


2 basis. Slight maternal toxicity (clinical signs and decreased body weight gain and food consumption) was seen at this dose. Slightly increased offspring mortality was also seen at 24 mg/kg/day. The no-effect dose was 12 mg/kg/day which is approximately 6 times the MRHD on a mg/m


2 basis.


In animal reproduction studies, racemic citalopram has been shown to have adverse effects on embryo/fetal and postnatal development, including teratogenic effects, when administered at doses greater than human therapeutic doses.


In two rat embryo/fetal development studies, oral administration of racemic citalopram (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 (clinical signs, decreased body weight gain). The developmental no-effect dose was 56 mg/kg/day. 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. Thus, teratogenic effects of racemic citalopram were observed at a maternally toxic dose in the rat and were not observed in the rabbit.


When female rats were treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first 4 days after birth and persistent offspring growth retardation were observed at the highest dose. The no-effect dose was 12.8 mg/kg/day. Similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day. A no-effect dose was not determined in that study.


There are no adequate and well-controlled studies in pregnant women; therefore, escitalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


Pregnancy-Nonteratogenic EffectsNeonates exposed to escitalopram and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [


see Warnings and Precautions (


5.2)


].  


Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 - 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Several recent epidemiologic studies suggest a positive statistical association between SSRI use (including escitalopram) in pregnancy and PPHN. Other studies do not show a significant statistical association.Physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression, who were either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period, and were in remission. Women who discontinued antidepressant medication during pregnancy showed a significant increase in relapse of their major depression compared to those women who remained on antidepressant medication throughout pregnancy. When treating a pregnant woman with escitalopram, the physician should carefully consider both the potential risks of taking an SSRl, along with the established benefits of treating depression with an antidepressant. This decision can only be made on a case by case basis [see


Dosage and Administration (2.1)].

8.2 Labor And Delivery

The effect of escitalopram on labor and delivery in humans is unknown.

8.3 Nursing Mothers

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. There were two reports of infants experiencing excessive somnolence, decreased feeding, and weight loss in association with  breastfeeding from a racemic citalopram-treated mother; in one case, the infant was reported to recover completely upon discontinuation of racemic citalopram by its mother and, in the second case, no follow-up information was available. Caution should be exercised and breastfeeding infants should be observed for adverse reactions when escitalopram  is administered to a nursing woman.

8.4 Pediatric Use

The safety and effectiveness of escitalopram have been established in adolescents (12 to 17 years of age) for the treatment of major depressive disorder [


see Clinical Studies (


14.1)


]. Although maintenance efficacy in adolescent patients with major depressive disorder has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.


The safety and effectiveness of escitalopram have not been established in pediatric (younger than 12 years of age) patients with major depressive disorder. In a 24-week, open-label safety study in 118 children (aged 7 to 11 years) who had major depressive disorder, the safety findings were consistent with the known safety and tolerability profile for escitalopram.


Safety and effectiveness of escitalopram  has not been established in pediatric patients less than 18 years of age with Generalized Anxiety Disorder.


Decreased appetite and weight loss have been observed in association with the use of SSRIs. Consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an SSRI such as escitalopram.

8.5 Geriatric Use

Approximately 6% of the 1144 patients receiving escitalopram in controlled trials of escitalopram  in major depressive disorder and GAD were 60 years of age or older; elderly patients in these trials received daily doses of escitalopram between 10 and 20 mg. The number of elderly patients in these trials was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. Nevertheless, greater sensitivity of some elderly individuals to effects of escitalopram cannot be ruled out. SSRIs and SNRIs, including escitalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [


seeHyponatremia (


5.6)


].


In two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in elderly subjects as compared to young subjects and C


max was unchanged [


see Clinical Pharmacology (


12.3)


]. 10 mg/day is the recommended dose for elderly patients [


see Dosage and Administration (


2.3)


].


Of 4422 patients in clinical studies of racemic citalopram, 1357 were 60 and over, 1034 were 65 and over, and 457 were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but again, greater sensitivity of some elderly individuals cannot be ruled out.

10.1 Human Experience

In clinical trials of escitalopram, there were reports of escitalopram overdose, including overdoses of up to 600 mg, with no associated fatalities. During the postmarketing evaluation of escitalopram, escitalopram  overdoses involving overdoses of over 1000 mg have been reported.  As with other SSRIs, a fatal outcome in a patient who has taken an overdose of escitalopram has been rarely reported. 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.

10.2 Management Of Overdose

Establish and maintain an airway to ensure adequate ventilation and oxygenation. Gastric evacuation by lavage and use of activated charcoal should be considered. Careful observation and cardiac and vital sign monitoring are recommended, along with general symptomatic and supportive care. Due to the large volume of distribution of escitalopram, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. There are no specific antidotes for escitalopram.In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose.

11 Description

Escitalopram oxalate, USP is an orally administered selective serotonin reuptake inhibitor (SSRI). Escitalopram is the pure S-enantiomer (single isomer) of the racemic bicyclic phthalane derivative citalopram. Escitalopram oxalate is designated S-(+)-1-[3-(dimethyl-amino)propyl]-1-(
p-fluorophenyl)-5-phthalancarbonitrile oxalate with the following structural formula:
The molecular formula is C
20H
21FN
2O • C
2H
2O
4 and the molecular weight is 414.43.
Escitalopram oxalate, USP occurs as white to almost white crystalline powder and is soluble in methanol.Escitalopram tablets, USP are film-coated, containing escitalopram oxalate, USP in strengths equivalent to 5 mg, 10 mg, and 20 mg escitalopram base. The 10 and 20 mg tablets are scored. The tablets also contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and talc. The film coating contains polyethylene glycol, hypromellose, and titanium dioxide.

12.1 Mechanism Of Action

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).

12.2 Pharmacodynamics

In vitro and


in vivo studies in animals suggest that escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate. Tolerance to a model of antidepressant effect in rats was not induced by long-term (up to 5 weeks) treatment with escitalopram. Escitalopram has no or very low affinity for serotonergic (5-HT


1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D


1-5), histamine (H


1-3), muscarinic (M


1-5), and benzodiazepine receptors. Escitalopram also does not bind to, or has low affinity for, various ion channels including Na


+, K


+, Cl


-, and Ca


++ channels. Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular side effects of other psychotropic drugs.

12.3 Pharmacokinetics

The single- and multiple-dose pharmacokinetics of escitalopram are linear and dose-proportional in a dose range of 10 to 30 mg/day. Biotransformation of escitalopram is mainly hepatic, with a mean terminal half-life of about 27-32 hours. With once-daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of escitalopram in plasma in young healthy subjects was 2.2-2.5 times the plasma concentrations observed after a single dose. The tablet and the oral solution dosage forms of escitalopram oxalate are bioequivalent.

14.1 Major Depressive Disorder

Adolescents


The efficacy of escitalopram  as an acute treatment for major depressive disorder in adolescent patients was established in an 8-week, flexible-dose, placebo-controlled study that compared escitalopram 10-20 mg/day to placebo in outpatients 12 to 17 years of age inclusive who met DSM-IV criteria for major depressive disorder. The primary outcome was change from baseline to endpoint in the Children’s Depression Rating Scale - Revised (CDRS-R). In this study, escitalopram  showed statistically significant greater mean improvement compared to placebo on the CDRS-R.


The efficacy of escitalopram  in the acute treatment of major depressive disorder in adolescents was established, in part, on the basis of extrapolation from the 8-week, flexible-dose, placebo-controlled study with racemic citalopram 20-40 mg/day. In this outpatient study in children and adolescents 7 to 17 years of age who met DSM-IV criteria for major depressive disorder, citalopram treatment showed statistically significant greater mean improvement from baseline, compared to placebo, on the CDRS-R; the positive results for this trial largely came from the adolescent subgroup.


Two additional flexible-dose, placebo-controlled MDD studies (one escitalopram study in patients ages 7 to 17 and one citalopram study in adolescents) did not demonstrate efficacy.


Although maintenance efficacy in adolescent patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.


Adults


The efficacy of escitalopram  as a treatment for major depressive disorder was established in three, 8-week, placebo-controlled studies conducted in outpatients between 18 and 65 years of age who met DSM-IV criteria for major depressive disorder. The primary outcome in all three studies was change from baseline to endpoint in the Montgomery Asberg Depression Rating Scale (MADRS). 


A fixed-dose study compared 10 mg/day escitalopram and 20 mg/day escitalopram  to placebo and 40 mg/day citalopram. The 10 mg/day and 20 mg/day escitalopram  treatment groups showed statistically significant greater mean improvement compared to placebo on the MADRS. The 10 mg and 20 mg escitalopram groups were similar on this outcome measure. 


In a second fixed-dose study of 10 mg/day escitalopram and placebo, the 10 mg/day escitalopram  treatment group showed statistically significant greater mean improvement compared to placebo on the MADRS. 


In a flexible-dose study, comparing escitalopram, titrated between 10 and 20 mg/day, to placebo and citalopram, titrated between 20 and 40 mg/day, the escitalopram treatment group showed statistically significant greater mean improvement compared to placebo on the MADRS. 


Analyses of the relationship between treatment outcome and age, gender, and race did not suggest any differential responsiveness on the basis of these patient characteristics. 


In a longer-term trial, 274 patients meeting (DSM-IV) criteria for major depressive disorder, who had responded during an initial 8-week, open-label treatment phase with escitalopram  10 or 20 mg/day, were randomized to continuation of escitalopram at their same dose, or to placebo, for up to 36 weeks of observation for relapse. Response during the open-label phase was defined by having a decrease of the MADRS total score to ≤ 12. Relapse during the double-blind phase was defined as an increase of the MADRS total score to ≥  22, or discontinuation due to insufficient clinical response. Patients receiving continued escitalopram  experienced a statistically significant longer time to relapse compared to those receiving placebo.

14.2 Generalized Anxiety Disorder

The efficacy of escitalopram  in the acute treatment of Generalized Anxiety Disorder (GAD) was demonstrated in three, 8-week, multicenter, flexible-dose, placebo-controlled studies that compared escitalopram 10-20 mg/day to placebo in adult outpatients between 18 and 80 years of age who met DSM-IV criteria for GAD. In all three studies, escitalopram  showed statistically significant greater mean improvement compared to placebo on the Hamilton Anxiety Scale (HAM-A). 


There were too few patients in differing ethnic and age groups to adequately assess whether or not escitalopram  has differential effects in these groups. There was no difference in response to escitalopram  between men and women.

16.1 Tablets

Escitalopram  tablets, USP 5 mg are white, round, biconvex, film-coated tablets, debossed with ‘B2’ on one side and ‘C’ on the other side.


Bottle of 30        NDC 59746-279-30


Bottle of 90        NDC 59746-279-90


Bottle of 100      NDC 59746-279-01


Bottle of 500      NDC 59746-279-05


Bottle of 1000    NDC 59746-279-10


Escitalopram  tablets, USP 10 mg  are white, oval shaped, biconvex, film-coated tablets, with scoreline on one side, debossed with ‘B’ on left side of scoreline and ‘3’ on right side of scoreline and with ‘C’ on the other side.


Bottle of 30        NDC 59746-280-30


Bottle of 90        NDC 59746-280-90


Bottle of 100      NDC 59746-280-01


Bottle of 500      NDC 59746-280-05


Bottle of 1000    NDC 59746-280-10


Escitalopram  tablets,  USP 20 mg  are white, oval shaped, biconvex, film-coated tablets, with scoreline on one side, debossed with ‘B4’ on left side of scoreline and ‘C’ on right side of the scoreline and plain on the other side.


Bottle of 30        NDC 59746-281-30


Bottle of 90        NDC 59746-281-90


Bottle of 100      NDC 59746-281-01


Bottle of 500      NDC 59746-281-05


Bottle of 1000    NDC 59746-281-10 


Storage and Handling


Store at 20˚C to 25˚C (68˚F to 77˚F); excursions permitted to 15˚C to 30˚C (59˚F to 86˚F) [See USP Controlled Room Temperature].


Dispense in a well-closed container as defined in the USP.

17  Patient Counseling Information

See FDA-approved Medication Guide

17.1 Information For Patients

  • Physicians are advised to discuss the following issues with patients for whom they prescribe escitalopram. General Information about Medication Guide
  • Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with escitalopram and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for escitalopram. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
  • Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking escitalopram.
  • Clinical Worsening and Suicide Risk
  • Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication [
  • See Warnings and Precautions
  • (5.1)]
  • . Serotonin Syndrome
  • Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of
  • Escitalopram with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines and St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid) [
  • See Warnings and Precautions
  • (5.2)]
  • .Abnormal Bleeding
  • Patients should be cautioned about the concomitant use of escitalopram and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding [
  • See Warnings and Precautions
  • (5.7)].
  • Angle Closure Glaucoma
  • Patients should be advised that taking escitalopram can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible
  • [see Warnings and Precautions
  • (5.9)].
  • Concomitant Medications
  • Since escitalopram is the active isomer of racemic citalopram (Celexa), the two agents should not be coadministered. Patients should be advised to inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, as there is a potential for interactions.
  • Continuing the Therapy Prescribed
  • While patients may notice improvement with escitalopram therapy in 1 to 4 weeks, they should be advised to continue therapy as directed.
  • Interference with Psychomotor Performance
  • Because psychoactive drugs may impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that escitalopram therapy does not affect their ability to engage in such activities.
  • Alcohol
  • Patients should be told that, although escitalopram has not been shown in experiments with normal subjects to increase the mental and motor skill impairments caused by alcohol, the concomitant use of escitalopram and alcohol in depressed patients is not advised.
  • Pregnancy and Breast Feeding
  • Patients should be advised to notify their physician if they
  • Become pregnant or intend to become pregnant during therapy. are breastfeeding an infant. Need for Comprehensive Treatment Program
  • Escitalopram is indicated as an integral part of a total treatment program for MDD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all adolescents with this syndrome.  Safety and effectiveness of escitalopram   in MDD has not been established in pediatric patients less than 12 years of age. Antidepressants are not intended for use in the adolescent who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe antidepressant medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms.
  • R
  • X Only
  • Manufactured by:
  • Jubilant Generics Limited
  • Roorkee - 247661, India
  • Marketed by:
  • Jubilant Cadista Pharmaceuticals Inc.
  • Salisbury, MD 21801, USA
  • Revised: 10/2017

Medication Guide

  • Medication GuideEscitalopram Tablets(es'' sye tal' oh pram)
  • Read the Medication Guide that comes with escitalopram before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about.
  • What is the most important information I should know about escitalopram?
  • Escitalopram and other antidepressant medicines may cause serious side effects, including:
  • 1. Suicidal thoughts or actions:
  • Escitalopram and other antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults within the
  • First few months of treatment or when the dose is changed. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Watch for these changes and call your healthcare provider right away if you notice:
  • New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe.         Pay particular attention to such changes when escitalopram is started or when the dose is changed. Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms.
  • Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you: attempts to commit suicide acting on dangerous impulses acting aggressive or violentthoughts about suicide or dying new or worse depression new or worse anxiety or panic attacks feeling agitated, restless, angry or irritable trouble sleeping an increase in activity or talking more than what is normal for you  other unusual changes in behavior or mood Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Escitalopram may be associated with these serious side effects:
  • 2. Serotonin Syndrome. This condition can be life-threatening and may include:
  • Agitation, hallucinations, coma or other changes in mental statuscoordination problems or muscle twitching (overactive reflexes) racing heartbeat, high or low blood pressuresweating or fever nausea, vomiting, or diarrheamuscle rigidity  3. Severe allergic reactions:   trouble breathing swelling of the face, tongue, eyes or mouth rash, itchy welts (hives) or blisters, alone or with fever or joint pain 4.  Abnormal bleeding: Escitalopram and other antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin
  • ®, Jantoven
  • ®), a non-steroidal anti-inflammatory drug (NSAIDs, like ibuprofen or naproxen), or aspirin.
  • 5. Seizures or convulsions
  • 6. Manic episodes
  • Greatly increased energy severe trouble sleeping  racing thoughts reckless behavior unusually grand ideasexcessive happiness or irritabilitytalking more or faster than usual 7. Changes in appetite or weight. Children and adolescents should have height and weight monitored during treatment.
  • 8. Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include:
  • Headacheweakness or feeling unsteadyconfusion, problems concentrating or thinking or memory problems 9. Visual problems eye painchanges in vision swelling or redness in or around the eye Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.
  • Do not stop escitalopram without first talking to your healthcare provider
  • . Stopping escitalopram too quickly may cause serious symptoms including:
  • Anxiety, irritability, high or low mood, feeling restless or changes in sleep habits headache, sweating, nausea, dizziness electric shock-like sensations, shaking, confusion What is escitalopram?
  • Escitalopram is a prescription medicine used to treat depression. It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider. Escitalopram is also used to treat:
  • Major Depressive Disorder (MDD)  Generalized Anxiety Disorder (GAD)Talk to your healthcare provider if you do not think that your condition is getting better with escitalopram treatment.
  • Who should not take escitalopram?
  • Do not take escitalopram if you:
  • Are allergic to escitalopram oxalate or citalopram hydrobromide or any of the ingredients in escitalopram tablets. See the end of this Medication Guide for a complete list of ingredients in escitalopram tablets.take a monoamine oxidase inhibitor (MAOI).  Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 2 weeks of stopping escitalopram unless directed to do so by your physician.Do not start escitalopram if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.  People who take escitalopram close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms: high fever  uncontrolled muscle spasms  stiff muscles  rapid changes in heart rate or blood pressure confusion loss of consciousness (pass out)  take the antipsychotic medicine pimozide (Orap
  • ®) because taking  this drug with escitalopram can cause serious heart problems
  • .
  • What should I tell my healthcare provider before taking escitalopram? Ask if you are not sure.
  • Before starting escitalopram, tell your healthcare provider if you:
  • Are taking certain drugs such as:
  • Triptans used to treat migraine headache Medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium, SSRIs, SNRIs, amphetamines, or antipsychoticsTramadolOver-the-counter supplements such as tryptophan or St. John’s Wort  have liver problemshave kidney problems have heart problemshave or had seizures or convulsions have bipolar disorder or mania have low sodium levels in your blood have a history of a stroke have high blood pressure have or had bleeding problemsare pregnant or plan to become pregnant.  It is not known if escitalopram will harm your unborn baby. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy are breast-feeding or plan to breast-feed. Some escitalopram may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking escitalopram.Tell your healthcare provider about all the medicines
  • That you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Escitalopram and some medicines may interact with each other, may not work as well, or may cause serious side effects.
  • Your healthcare provider or pharmacist can tell you if it is safe to take escitalopram with your other medicines. Do not start or stop any medicine while taking escitalopram without talking to your healthcare provider first.
  • If you take escitalopram, you should not take any other medicines that contain escitalopram oxalate or citalopram hydrobromide including: Celexa.
  • How should I take escitalopram? Take escitalopram exactly as prescribed. Your healthcare provider may need to change the dose of escitalopram until it is the right dose for you. Escitalopram may be taken with or without food.If you miss a dose of escitalopram, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of escitalopram at the same time.If you take too much escitalopram, call your healthcare provider or poison control center right away, or get emergency treatment. What should I avoid while taking escitalopram?
  • Escitalopram can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how escitalopram affects you. Do not drink alcohol while using escitalopram.
  • What are the possible side effects of escitalopram?
  • Escitalopram may cause serious side effects, including all
  • Of those described in the section entitled “What is the most important information I should know about escitalopram?”
  • Common possible side effects in people who take escitalopram include:
  • Nausea  Sleepiness  Weakness Dizziness  Feeling anxious  Trouble sleeping Sexual problems  Sweating Shaking Not feeling hungry Dry mouth ConstipationInfection Yawning Other side effects in children and adolescents include: increased thirst abnormal increase in muscle movement or agitation  nose bleed  difficult urination heavy menstrual periods possible slowed growth rate and weight change. Your child’s height and weight should be monitored during treatment with escitalopram.Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of escitalopram. For more information, ask your healthcare provider or pharmacist.
  • CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088.
  • How should I store escitalopram tablets?
  • Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [See USP Controlled Room Temperature].Keep escitalopram tablets bottle closed tightly.  Keep escitalopram and all medicines out of the reach of children.
  • General information about escitalopram
  • Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use escitalopram for a condition for which it was not prescribed. Do not give escitalopram to other people, even if they have the same condition. It may harm them.
  • This Medication Guide summarizes the most important information about escitalopram. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about escitalopram that is written for healthcare professionals.
  • For more information, call toll-free 1-800-313-4623.
  • What are the ingredients in escitalopram tablets?
  • Active ingredient: escitalopram oxalate, USP
  • Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and talc. The film coating contains polyethylene glycol, hypromellose, and titanium dioxide.
  • The following are registered trademarks of their respective manufacturers and are not trademarks of Jubilant Generics Limited:
  • Celexa
  • ®, Coumadin
  • ®, Jantoven
  • ® and Orap
  • ®.
  • R
  • X Only
  • Manufactured by:
  • Jubilant Generics Limited
  • Roorkee - 247661, India
  • Marketed by:
  • Jubilant Cadista Pharmaceuticals Inc.
  • Salisbury, MD 21801, USA
  • Revised: 10/2017
  • This Medication Guide has been approved by the U.S. Food and Drug Administration.

* Please review the disclaimer below.

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