FDA

Escitalopram Oxalate

Approved 2 Apr 2012OralSolution

The FDA lists this product in 60 strengths and forms.

Indications

Escitalopram oral solution is 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 and pediatric patients 7 years of age and older. Escitalopram oral solution 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 and pediatric patients 7 years and older ( 1 )

Contraindications

Escitalopram oral solution is contraindicated in patients: taking MAOIs with escitalopram oral solution or within 14 days of stopping treatment with escitalopram oral solution because of an increased risk of serotonin syndrome. The use of escitalopram oral solution within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.7) and Warnings and Precautions (5.2) ] .

Starting escitalopram oral solution 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) ]. taking pimozide [see Drug Interactions (7) ] . with a hypersensitivity to escitalopram or citalopram or any of the inactive ingredients in escitalopram oral solution.

Do not use MAOIs intended to treat psychiatric disorders with escitalopram oral solution or within 14 days of stopping treatment with escitalopram oral solution. Do not use escitalopram oral solution within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start escitalopram oral solution in a patient who is being treated with linezolid or intravenous methylene blue ( 4 ) Concomitant use of pimozide ( 4 ) Known hypersensitivity to escitalopram or citalopram or any of the inactive ingredients ( 4 )

Warnings and precautions

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents but also when taken alone. If it occurs, discontinue escitalopram oral solution and serotonergic agents and initiate supportive treatment ( 4 , 5.2 ) Discontinuation syndrome: When discontinuing escitalopram oral solution, 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 oral solution may cause symptoms of sexual dysfunction ( 5.11 )

At a glance

Brand name: Escitalopram Oxalate
Route: Oral
Dosage form: Solution
Applicant: Aurobindo Pharma LTD
Status: Prescription
FDA approval: 2 Apr 2012
Application: ANDA079062-001

Indications

Contraindications

Warnings and precautions

Interactions

Table 6 presents clinically important drug interactions with escitalopram oral solution. TABLE 6 Clinically Important Drug Interactions with Escitalopram Oral Solution Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: Concomitant use of SSRIs, including escitalopram oral solution, and MAOIs increases the risk of serotonin syndrome. Intervention: Escitalopram oral solution 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 oral solution is contraindicated in patients taking pimozide [see Contraindications (4) ].

Other Serotonergic Drugs Clinical Impact: Concomitant use of escitalopram oral solution 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 oral solution initiation and dosage increases.

If serotonin syndrome occurs, consider discontinuation of escitalopram oral solution 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 oral solution 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 oral solution 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 C max 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.

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 )

Pregnancy and breastfeeding

8.1Pregnancy 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 advise patients to register by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/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 oral solution, 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 oral solution 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 oral solution, 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 1000 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.

Adverse reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling: Suicidal thoughts and behaviors in adolescents and young adults [see Warnings and Precautions (5.1) ] Serotonin syndrome [see Warnings and Precautions (5.2) ] Discontinuation syndrome [see Warnings and Precautions (5.3) ] Seizures [ see Warnings and Precautions (5.4) ] Activation of mania or hypomania [see Warnings and Precautions (5.5) ] Hyponatremia [see Warnings and Precautions (5.6) ] Increased Risk of Bleeding [see Warnings and Precautions (5.7) ] Interference with Cognitive and Motor Performance [see Warnings and Precautions (5.8) ] Angle-closure glaucoma [see Warnings and Precautions (5.9) ] Use in Patients with Concomitant Illness [see Warnings and Precautions (5.10) ] Sexual Dysfunction [see Warnings and Precautions (5.11) ] Most commonly observed adverse reactions (incidence ≥ 5% and at least twice the incidence of placebo patients) are: insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased, fatigue and somnolence, decreased libido, and anorgasmia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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 Adults Adverse reactions information for escitalopram oral solution 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 reaction information for escitalopram oral solution 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 reactions 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 reactions without first grouping similar types of reactions 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 reactions. 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. Pediatric Patients Adverse reaction information for pediatric patients was collected in double-blind placebo-controlled studies in 576 pediatric patients 6 to 17 years of age, (286 escitalopram oral solution, 290 placebo) with major depressive disorder and in 273 pediatric patients 7 to 17 years of age (137 escitalopram oral solution, 136 placebo) with generalized anxiety disorder.

The safety and effectiveness of escitalopram oral solution have not been established in pediatric patients less than 12 years of age with MDD or less than 7 years of age with GAD. Adverse Reactions Associated with Discontinuation of Treatment Major Depressive Disorder Adults Among the 715 depressed patients who received escitalopram oral solution 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 reactions in patients receiving 10 mg/day escitalopram oral solution was not significantly different from the rate of discontinuation for adverse reactions in patients receiving placebo. The rate of discontinuation for adverse reactions in patients assigned to a fixed dose of 20 mg/day escitalopram oral solution was 10%, which was significantly different from the rate of discontinuation for adverse reactions in patients receiving 10 mg/day escitalopram oral solution (4%) and placebo (3%).

Adverse reactions that were associated with the discontinuation of at least 1% of patients treated with escitalopram oral solution, and for which the rate was at least twice that of placebo, were nausea (2%) and ejaculation disorder (2% of male patients). Pediatric Patients Adverse reactions in pediatric patients 6 to 17 years of age were associated with discontinuation of 3.5% of 286 patients receiving escitalopram oral solution and 1% of 290 patients receiving placebo.

The most common adverse reaction (incidence at least 1% for escitalopram oral solution and greater than placebo) associated with discontinuation was insomnia (1% escitalopram oral solution, 0% placebo). The safety and effectiveness of escitalopram oral solution have not been established in pediatric patients less than 12 years of age with MDD. Generalized Anxiety Disorder Adults Among the 429 GAD patients who received escitalopram oral solution 10 to 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 reactions that were associated with the discontinuation of at least 1% of patients treated with escitalopram oral solution, and for which the rate was at least twice the placebo rate, were nausea (2%), insomnia (1%), and fatigue (1%). Pediatric Patients Adverse reactions in pediatric patients 7 to 17 years were associated with discontinuation of 2.9% of 137 patients receiving escitalopram oral solution and 1.5% of 136 patients receiving placebo.

The most common adverse reaction (incidence at least 1% for escitalopram oral solution and greater than placebo) associated with discontinuation was activation syndrome (1% escitalopram oral solution, 0% placebo), intentional self injury (1% escitalopram oral solution, 0% placebo), epistaxis (1% escitalopram oral solution, 0% placebo), and nausea (1% escitalopram oral solution, 0% placebo). Incidence of Adverse Reactions in Placebo-Controlled Clinical Trials Major Depressive Disorder Adults The most commonly observed adverse reactions in escitalopram oral solution 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 adverse reactions that occurred among 715 depressed patients who received escitalopram oral solution at doses ranging from 10 to 20 mg/day in placebo-controlled trials. Reactions included are those occurring in 2% or more of patients treated with escitalopram oral solution and for which the incidence in patients treated with escitalopram oral solution was greater than the incidence in placebo-treated patients.

TABLE 2 Adverse Reactions observed with a frequency of ≥ 2% and greater than placebo for Major Depressive Disorder (Adults) Adverse Reaction Escitalopram oral solution Placebo (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 Disorde

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Escitalopram Oxalate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Escitalopram Oxalate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Suicidal Thoughts and Behaviors in Adolescents and Young Adults

5.2Serotonin Syndrome

5.3Discontinuation Syndrome

5.4Seizures

5.5Activation of Mania or Hypomania

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information