escitalopram oxalate 10 MG Oral Tablet

Generic Name: ESCITALOPRAM OXALATE
Brand Name: escitalopram oxalate
  • Substance Name(s):
  • ESCITALOPRAM OXALATE

DRUG INTERACTIONS

7 • Concomitant use with SSRIs, SNRIs or Tryptophan is not recommended ( 7 ) • Use caution when concomitant use with drugs that affect Hemostasis (NSAIDs, Aspirin, Warfarin) ( 7 ) Table 6 presents clinically important drug interactions with escitalopram.

TABLE 6 Clinically Important Drug Interactions with Escitalopram Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: Concomitant use of SSRIs, including Escitalopram, and MAOIs increases the risk of serotonin syndrome.

Intervention: Escitalopram is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2.7 ), Contraindications ( 4 ), and Warnings and Precautions ( 5.2 )] .

Pimozide Clinical Impact: Concomitant use of racemic citalopram with pimozide increases plasma concentrations of pimozide, a drug with a narrow therapeutic index, and may increase the risk of QT prolongation and/or ventricular arrhythmias compared to use of racemic citalopram alone [see Clinical Pharmacology ( 12.3 )] .

Intervention: Escitalopram is contraindicated in patients taking pimozide [see Contraindications ( 4 )] .

Other Serotonergic Drugs Clinical Impact: Concomitant use of escitalopram and other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St.

John’s Wort) increases the risk of serotonin syndrome.

Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during Escitalopram initiation and dosage increases.

If serotonin syndrome occurs, consider discontinuation of Escitalopram and/or concomitant serotonergic drugs [see Warning and Precautions ( 5.2 )] .

Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Clinical Impact: Concomitant use of Escitalopram and an antiplatelet or anticoagulant may potentiate the risk of bleeding.

Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of Escitalopram and antiplatelet agents and anticoagulants.

For patients taking warfarin, carefully monitor the international normalized ratio [see Warning and Precautions ( 5.7 )] .

Sumatriptan Clinical Impact: There have been postmarketing reports describing patients with weakness, hyperreflexia, and incoordination following the use of an SSRI and sumatriptan.

Intervention: If concomitant treatment with sumatriptan and an SSRI is clinically warranted, appropriate observation of the patient is advised [see Warning and Precautions ( 5.2 )] .

Carbamazepine Clinical Impact: 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.

Intervention: 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.

Drugs Metabolized by CYP2D6 Clinical Impact: 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 Cmax and a 100% increase in AUC of desipramine.

Intervention: The clinical significance of this finding is unknown.

Exercise caution during coadministration of escitalopram and drugs metabolized by CYP2D6.

OVERDOSAGE

10 The following have been reported with escitalopram tablet overdosage: Seizures, which may be delayed, and altered mental status including coma.

Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, and torsade de pointes.

Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol.

Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk).

Prolonged cardiac monitoring is recommended in escitalopram tablets overdosage ingestions due to the arrhythmia risk.

Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a escitalopram overdose.

Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

DESCRIPTION

11 Escitalopram tablets contain escitalopram a selective serotonin reuptake inhibitor (SSRI), present as escitalopram oxalate salt.

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 20 H 21 FN 2 O • C 2 H 2 O 4 and the molecular weight is 414.40.

Escitalopram oxalate, USP occurs as a fine, white to slightly-yellow powder and is freely soluble in methanol and dimethyl sulfoxide (DMSO), soluble in isotonic saline solution, sparingly soluble in water and ethanol, slightly soluble in ethyl acetate, and insoluble in heptane.

Escitalopram tablets, USP are white to off-white, round, biconvex, film-coated tablets containing 6.38 mg, 12.75 mg and 25.55 mg escitalopram oxalate in strengths equivalent to 5 mg, 10 mg, and 20 mg, respectively, of escitalopram base.

The 10 and 20 mg tablets are scored.

The tablets also contain the following inactive ingredients: cellulose microcrystalline, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, povidone and talc.

The film coating contains hypromellose, polyethylene glycol 400 and titanium dioxide.

Meets USP Dissolution Test 2.

1

CLINICAL STUDIES

14 14.1 Major Depressive Disorder 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 daily escitalopram and 20 mg daily escitalopram to placebo and 40 mg daily citalopram.

The 10 mg daily and 20 mg daily 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 daily escitalopram and placebo, the 10 mg daily 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 mg and 20 mg daily, to placebo and citalopram, titrated between 20 mg and 40 mg daily, 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 mg or 20 mg daily, 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.

Pediatric Patients 12 years of age and older The efficacy of escitalopram as a treatment for major depressive disorder in pediatric patients 12 to 17 years was established in an 8-week, flexible-dose, placebo-controlled study that compared escitalopram tablets (10 mg to 20 mg daily) to placebo in outpatients 12 to 17 years of age inclusive who met DSM-IV criteria for major depressive disorder (MDD).

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 treatment of major depressive disorder in pediatric patients 12 to 17 years was established, in part, on the basis of extrapolation from the 8-week, flexible-dose, placebo-controlled study with racemic citalopram 20 mg to 40 mg daily.

In this outpatient study in pediatric patients 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 12 to 17 year subgroup.

Two additional flexible-dose, placebo-controlled MDD studies (one escitalopram study in patients ages 7 to 17 years and one citalopram study patients 13 to 18 years) did not demonstrate efficacy.

The safety and effectiveness of escitalopram have not been established in pediatric patients less than 12 years of age with MDD.

14.2 Generalized Anxiety Disorder Adults The efficacy of escitalopram in the treatment of generalized anxiety disorder (GAD) in adults was demonstrated in three, 8-week, multicenter, flexible-dose, placebo-controlled studies that compared escitalopram tablets (10 mg to 20 mg daily) to placebo in 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.

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets.

However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

HOW SUPPLIED

16 /STORAGE AND HANDLING How Supplied Escitalopram tablets, USP 5 mg are white to off-white, round, biconvex, film coated tablets debossed with ‘135’ on one side and ‘5’ on other side.

Bottles of 30 NDC 13668-135-30 Bottles of 100 NDC 13668-135-01 Bottles of 500 NDC 13668-135-05 Bottles of 1000 NDC 13668-135-10 Bottles of 4000 NDC 13668-135-40 Escitalopram tablets, USP 10 mg are white to off-white, round, biconvex, film coated tablets debossed with break line on one side, separating ’11’ and ’36’ on one side, and ’10’ on other side.

Bottles of 30 NDC 13668-136-30 Bottles of 100 NDC 13668-136-01 Bottles of 500 NDC 13668-136-05 Bottles of 1000 NDC 13668-136-10 Bottles of 3000 NDC 13668-136-43 Escitalopram tablets, USP 20 mg are white to off-white, round, biconvex, film coated tablets debossed with break line on one side, separating ’11’ and ’37’ on one side, and ’20’ on other side.

Bottles of 30 NDC 13668-137-30 Bottles of 100 NDC 13668-137-01 Bottles of 500 NDC 13668-137-05 Bottles of 1000 NDC 13668-137-10 Bottles of 2000 NDC 13668-137-20 Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

RECENT MAJOR CHANGES

Indications ( 1 ) 5/2023 Dosage and Administration ( 2.2 , 2.3 , 2.5 ) 5/2023 Dosage and Administration, Use of Escitalopram with Other MAOIs such as Linezolid or Methylene Blue ( 2.7 ) – Removed 5/2023 Warnings and Precautions ( 5.2 , 5.7 ) 8/2023

GERIATRIC USE

8.5 Geriatric Use Approximately 69 patients (6%) of the 1,144 patients receiving escitalopram in controlled trials of escitalopram in major depressive disorder and GAD were 60 years of age or older [see Clinical Studies ( 14.1 , 14.2 )] .

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.

In two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in subjects 65 years and older as compared to young subjects and C max was unchanged [see Clinical Pharmacology ( 12.3 )] .

The recommended dosage of escitalopram tablets for elderly patients is 10 mg daily [see Dosage and Administration ( 2.5 )] .

SSRIs, including escitalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions ( 5.6 )] .

Of 4,422 patients in clinical studies of racemic citalopram, 1,357 were 60 and over, 1,034 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 geriatric and younger patients, but again, greater sensitivity of some elderly individuals cannot be ruled out.

DOSAGE FORMS AND STRENGTHS

3 Tablets: 5 mg, 10 mg (scored), and 20 mg (scored) Escitalopram tablets, USP are film-coated, round tablets containing escitalopram oxalate in strengths equivalent to 5 mg, 10 mg and 20 mg escitalopram base.

The 10 and 20 mg tablets are scored.

5 mg tablets are debossed with ‘135’ on one side and ‘5’ on other side.

10 mg tablets are debossed with break line on one side, separating ’11’ and ’36’ on one side, and ’10’ on other side.

20 mg tablets are debossed with break line on one side, separating ’11’ and ’37’ on one side, and ’20’ on other side.

MECHANISM OF ACTION

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).

INDICATIONS AND USAGE

1 Escitalopram is a selective serotonin reuptake inhibitor (SSRI) indicated for the: • treatment of major depressive disorder (MDD) in adults and pediatric patients 12 years of age and older ( 1 ) • treatment of generalized anxiety disorder (GAD) in adults ( 1 ) Escitalopram tablets are indicated for the treatment of: • major depressive disorder (MDD) in adults and pediatric patients 12 years of age and older.

• generalized anxiety disorder (GAD) in adults Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets.

However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

PEDIATRIC USE

8.4 Pediatric Use Major Depressive Disorder The safety and effectiveness of escitalopram for the treatment of major depressive disorder have been established in pediatric patients 12 years of age and older.

Use of escitalopram for this indication is supported by evidence from adequate and well-controlled studies in adults with additional evidence from an 8-week, flexible-dose, placebo-controlled study that compared escitalopram tablets 10 mg to 20 mg once daily to placebo in pediatric patients 12 to 17 years of age with major depressive disorder [see Clinical Studies ( 14.1 )] .

The safety of escitalopram was similar to adult patients with MDD [see Adverse Reactions ( 6.1 )] .

The safety and effectiveness of escitalopram for the treatment of major depressive disorder have not been established in pediatric patients younger than 12 years of age.

In a 24-week, open-label safety study in 118 pediatric patient (aged 7 to 11 years) who had major depressive disorder, the safety findings were consistent with the known safety and tolerability profile for escitalopram.

Generalized Anxiety Disorder The safety and effectiveness of escitalopram for the treatment of generalized anxiety disorder have not been established in pediatric patients younger than 7 years of age.

Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Warnings and Precautions ( 5.1 )] .

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.

Juvenile Animal Toxicity Data In a juvenile animal study, male and female rats were administered escitalopram at 5, 40, or 80 mg/kg/day by oral gavage from postnatal day (PND) 21 to PND 69.

A delay in sexual maturation was observed in both males and females at ≥ 40 mg/kg/day with a No Observed Adverse Effect Level (NOAEL) of 5 mg/kg/day.

This NOAEL was associated with plasma AUC levels less than those measured at the maximum recommended dose (MRHD) in pediatrics (20 mg).

However, there was no effect on reproductive function.

Increased motor activity (both ambulatory and fine movements) was observed in females prior to daily dosing at ≥ 40 mg/kg/day (3.5 times the MRHD based on AUC levels).

A reversible disruption of learning and memory function was observed in males at 80 mg/kg/day with a NOAEL of 40 mg/kg/day, which was associated with an AUC level 3.5 times those measured at the MRHD in pediatrics.

There was no effect on learning and memory function in treated female rats.

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets.

However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

PREGNANCY

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy.

Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.

Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions ( 5.7 ) and Clinical Considerations] .

Available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage.

There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and poor neonatal adaptation (see Clinical Considerations), with exposure to selective serotonin reuptake inhibitors (SSRIs), including escitalopram, during pregnancy.

There are risks associated with untreated depression in pregnancy (see Clinical Considerations).

In animal reproduction studies, both escitalopram and racemic citalopram have been shown to have adverse effects on embryo/fetal and postnatal development, including fetal structural abnormalities, when administered at doses greater than human therapeutic doses (see Data ).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S.

general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations Disease-associated maternal risk and/or embryo/fetal risk Women who discontinue antidepressants are more likely to experience a relapse of major depression than women who continue antidepressants.

This finding is from a prospective longitudinal study of 201 pregnant women with a history of major depression, who were euthymic and taking antidepressants at the beginning of pregnancy.

Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.

Maternal Adverse Reactions Use of escitalopram tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions ( 5.7 )].

Fetal/Neonatal adverse reactions Neonates exposed to SSRIs or SNRIs, including escitalopram, late in 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 )] .

Data Human Data Exposure to SSRIs, particularly later in pregnancy, may increase the risk for PPHN.

PPHN occurs in 1 to 2 per 1,000 live births in the general populations and is associated with substantial neonatal morbidity and mortality.

Animal Data 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 ≥ 55 times the maximum recommended human dose (MRHD) of 20 mg/day on a 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 27 times the MRHD of 20 mg on a mg/m 2 basis.

No malformations were observed at any of the doses tested (as high as 73 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 23 times the MRHD of 20 mg 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 of 20 mg on a mg/m 2 basis.

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, which is approximately 18 times the MRHD of 60 mg/day on a mg/m 2 basis.

This dose was also associated with maternal toxicity (clinical signs, decreased body weight gain).

The developmental no-effect dose was 56 mg/kg/day is approximately 9 times the MRHD on a mg/m 2 basis.

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, or approximately 5 times the MRHD on a mg/m 2 basis.

Thus, developmental 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, which is approximately 5 times the MRHD of 60 mg on a mg/m 2 basis.

The no-effect dose was 12.8 mg/kg/day is approximately 2 times the MRHD on a mg/m 2 basis.

Similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, approximately 4 times the MRHD on a mg/m 2 basis.

A no-effect dose was not determined in that study.

BOXED WARNING

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning .

Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants.

Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors ( 5.1 ).

Escitalopram tablets are not approved for use in pediatric patients less than 7 years of age ( 8.4 ).

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies.

Closely monitor all antidepressant -treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions ( 5.1 )].

Escitalopram tablets is not approved for use in pediatric patients less than 7 years of age [see Use in Specific Populations ( 8.4) ].

WARNING AND CAUTIONS

5 WARNINGS AND PRECAUTIONS • Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents but also when taken alone.

If it occurs, discontinue Escitalopram and serotonergic agents and initiate supportive treatment ( 4 , 5.2 ) • Discontinuation syndrome: When discontinuing Escitalopram, reduce dosage gradually whenever possible, and monitor for discontinuation symptoms ( 5.3 ) • Seizures: Use with caution in patients with a history of seizure ( 5.4 ) • Activation of Mania/Hypomania: Screen patients for bipolar disorder.

( 5.5 ) • Hyponatremia: Can occur in association with syndrome of inappropriate antidiuretic hormone secretion ( 5.6 ) • Increased Risk of Bleeding: Concomitant use of nonsteroidal anti-inflammatory drugs, aspirin, other antiplatelet drugs, warfarin and other drugs that affect coagulation may increase risk ( 5.7 ) • Interference with Cognitive and Motor Performance: Use caution when operating machinery ( 5.8 ) • Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants ( 5.9 ) • Use in Patients with Concomitant Illness: Use caution in patients with diseases or conditions that produce altered metabolism or hemodynamic responses ( 5.10 ) • Sexual Dysfunction: Escitalopram may cause symptoms of sexual dysfunction ( 5.11 ) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in the antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients.

There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied.

There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD.

The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1.

Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts and Behaviors per 1,000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18 to 24 years old 5 additional patients Decreases Compared to Placebo 25 to 64 years old 1 fewer patient ≥65 years old 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months.

However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.

Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes.

Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider.

Consider changing the therapeutic regimen, including possibly discontinuing escitalopram, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

5.2 Serotonin Syndrome SSRIs, including escitalopram tablets, can precipitate serotonin syndrome, a potentially life-threatening condition.

The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, meperidine, methadone, lithium, tramadol, tryptophan, buspirone, amphetamines, and St.

John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications ( 4 ) and Drug Interactions ( 7 )] .

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).

The concomitant use of escitalopram with MAOIs is contraindicated.

In addition, do not initiate Escitalopram in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue.

No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection).

If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Escitalopram, discontinue Escitalopram before initiating treatment with the MAOI [see Contraindications (4) and Dosage and Administration ( 2.7 )] .

Monitor all patients taking escitalopram tablets for the emergence of serotonin syndrome.

Discontinue treatment with escitalopram tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment.

If concomitant use of escitalopram with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

5.3 Discontinuation Syndrome During marketing of escitalopram tablets and other SSRIs, there have been spontaneous reports of adverse reactions 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.

Monitor 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 ( 2.6 )] .

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 tablets should be introduced with care in patients with a history of seizure disorder.

5.5 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with escitalopram or another antidepressant may precipitate a mixed/manic episode.

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.

Prior to initiating treatment with escitalopram, screen patients for any personal or family history of bipolar disorder, mania, or hypomania [see Dosage and Administration ( 2.4 )] .

5.6 Hyponatremia Hyponatremia may occur as a result of treatment with SSRIs , 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 Use in Specific Populations ( 8.5 )] .

Consider discontinuation of escitalopram 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 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including escitalopram, increase the risk of bleeding events.

Concomitant use of aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), other antiplatelet 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.

Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations ( 8.1 )].

Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.

Inform patients about the increased risk of bleeding associated with the concomitant use of escitalopram and antiplatelet agents or anticoagulants.

For patients taking warfarin, carefully monitor the international normalized ratio [see Drug Interactions ( 7 )] .

5.8 Interference with Cognitive and Motor Performance In a study in normal volunteers, escitalopram 10 mg daily 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 tablets therapy does not affect their ability to engage in such activities.

5.9 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 tablets 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 tablets in hepatically impaired patients is 10 mg daily [see Dosage and Administration ( 2.5 ) and Use in Specific Populations (8.6)] .

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 tablets, however, it should be used with caution in such patients [see Dosage and Administration ( 2.5 ) and Use in Specific Populations (8.7)] .

5.11 Sexual Dysfunction Use of SSRIs, including escitalopram, may cause symptoms of sexual dysfunction [see Adverse Reactions ( 6.1 )] .

In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction.

In female patients, SSRI use may result in decreased libido and delayed or absent orgasm.

It is important for prescribers to inquire about sexual function prior to initiation of escitalopram and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported.

When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder.

Discuss potential management strategies to support patients in making informed decisions about treatment.

INFORMATION FOR PATIENTS

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts and Behaviors Advise patients, their families and caregivers to look for the emergence of suicidal ideation and behavior, especially during treatment and when the dose is adjusted up or down, and instruct them to report such symptoms to their healthcare provider [see Boxed Warning and Warnings and Precautions ( 5.1 )].

Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the with the concomitant use of escitalopram with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, 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).

Instruct patients to contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7 )].

Discontinuation Syndrome Advise patients not to abruptly discontinue escitalopram tablets and to discuss any tapering regimen with their healthcare provider.

Inform patients that adverse reactions can occur when escitalopram tablets are discontinued [see Warnings and Precautions ( 5.3 )] .

Activation of Mania or Hypomania Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions ( 5.5 )].

Increased Risk of Bleeding Inform patients about the concomitant use of escitalopram with NSAIDs, aspirin, warfarin, other antiplatelet drugs, or other anticoagulants because the combined use has been associated with an increased risk of bleeding.

Advise patients to inform their healthcare providers if they are taking or planning to take any prescription or over-the-counter medications that increase the risk of bleeding [see Warnings and Precautions ( 5.7 )] .

Angle Closure Glaucoma Advise patients that taking escitalopram tablets 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 )] .

Sexual Dysfunction Advise patients that use of escitalopram may cause symptoms of sexual dysfunction in both male and female patients.

Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions ( 5.11 )] .

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.

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 tablets 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 Advise pregnant women to notify their healthcare providers if they become pregnant or intend to become pregnant during treatment with escitalopram tablets.

Advise patients that escitalopram use later in pregnancy may lead to increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension (PPHN) of the newborn [see Use in Specific Populations ( 8.1 )].

Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to escitalopram during pregnancy [see Use in Specific Populations ( 8.1 )].

Lactation Advise breastfeeding women using escitalopram to monitor infants for excess sedation, restlessness, agitation, poor feeding and poor weight gain and to seek medical care if they notice these signs [see Use in Specific Populations ( 8.2 )].

Manufactured by: TORRENT PHARMACEUTICALS LTD., INDIA.

8094551 Revised: October 2023 Or VKT Pharma Private Limited, Srikakulam-532409, India.

8094553 Revised: October 2023 800204 Manufactured for: TORRENT PHARMA INC., Basking Ridge, NJ 07920.

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DOSAGE AND ADMINISTRATION

2 Indication and Population Recommended Dosage MDD in Adults ( 2.1 ) Initial: 10 mg once daily Recommended: 10 mg once daily Maximum: 20 mg once daily MDD in Pediatric Patients 12 years and older ( 2.1 ) Initial: 10 mg once daily Recommended: 10 mg once daily Maximum: 20 mg once daily GAD in Adults ( 2.2 ) Initial: 10 mg once daily Recommended: 10 mg once daily Maximum: 20 mg once daily • No additional benefits were seen at 20 mg once daily ( 2.1 ) • Administer once daily, morning or evening, with or without food ( 2.3 ) • Elderly patients: recommended dosage is 10 mg once daily ( 2.4 ) • Hepatic impairment: recommended dosage is 10 mg once daily ( 2.4 , 8.6 ) • When discontinuing Escitalopram tablets, reduce dose gradually whenever possible ( 2.5 ) 2.1 Major Depressive Disorder Adults The recommended dosage of escitalopram tablets in adults 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)].

Depending on clinical response and tolerability, dosage may be increased to the maximum recommended dosage of 20 mg once daily at an interval of no less than 1 week.

Pediatric Patients 12 years of age and older The recommended dosage of escitalopram tablets in pediatric patients 12 years of age and older is 10 mg once daily.

Depending on clinical response and tolerability, dosage may be increased to the maximum recommended dosage of 20 mg once daily at an interval of no less than 3 weeks.

2.2 Generalized Anxiety Disorder Adults The recommended starting dosage of escitalopram tablets in adults is 10 mg once daily.

Depending on clinical response and tolerability, dosage may be increased to the maximum recommended dosage of 20 mg once daily at an interval of no less than 1 week.

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets.

However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

2.3 Administration Information Administer escitalopram tablets orally once daily, in the morning or evening, with or without food.

2.4 Screen for Bipolar Disorder Prior to Starting Escitalopram Tablets Prior to initiating treatment with escitalopram tablets or another antidepressant, screen patients for a personal family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions ( 5.5 )] .

2.5 Recommended Dosage for Specific Populations The recommended dosage for most elderly patients and patients with hepatic impairment is 10 mg once daily [see Use in Specific Populations ( 8.5 , 8.6 )] .

The recommended dosage for escitalopram tablets in adults with a creatinine clearance less than 20 mL/minute has not been determined.

No dosage adjustment is necessary for patients with mild or moderate renal impairment [see Use in Specific Populations ( 8.7 )] .

2.6 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.

2.7 Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant 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 )] .