escitalopram

1 INDICATIONS AND USAGE Escitalopram Capsules are indicated for the treatment of: Major depressive disorder (MDD) in adults younger than 65 years of age [see Dosage and Administration ( 2.1 )] and pediatric patients 12 years of age and older. Generalized anxiety disorder (GAD) in adults younger than 65 years of age [see Dosage and Administration (2.1)] . Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets and LEXAPRO (escitalopram) oral solution. However, due to AbbVie Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. Escitalopram Capsules are a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of: ( 1 ) Major depressive disorder in adults younger than 65 years of age and pediatric patients 12 years of age and older Generalized anxiety disorder in adults younger than 65 years of age

2 DOSAGE AND ADMINISTRATION Escitalopram Capsules are only available in a 15 mg strength ( 2.1 ) Use another escitalopram product for dosage initiation, titration, dosages other than 15 mg once daily, and for discontinuation ( 2.1 ) Escitalopram Capsules are not indicated in geriatric patients and not recommended in patients with hepatic impairment ( 2.1 ) Recommended starting dosage is 10 mg orally once daily of another escitalopram product. Based on response and tolerability, may increase to the maximum recommended dosage of 20 mg once daily of another escitalopram product ( 2.2 , 2.3 ) Escitalopram Capsules 15 mg orally once daily may be initiated in patients experiencing unfavorable tolerability to a 20 mg escitalopram dosage ( 2.2 , 2.3 ) Administer orally once daily with or without food. Swallow capsules whole ( 2.4 ) When discontinuing, reduce dosage gradually using another escitalopram product ( 2.7 , 5.3 ) 2.1 Important Dosage Information Escitalopram Capsules are only available in a 15 mg strength. Use another escitalopram product for initial dosage, dosage titration, administration of dosages other than 15 mg once daily, and to taper during discontinuation [see Dosage and Administration ( 2.2 , 2.3 , 2.7 )] . Refer to the Prescribing Information of other escitalopram products for the recommended dosage for those products. Escitalopram Capsules may be initiated in patients experiencing unfavorable tolerability to a 20 mg escitalopram dosage [see Dosage and Administration ( 2.2 , 2.3 )] . Escitalopram Capsules are not indicated in geriatric patients. Avoid use of Escitalopram Capsules in geriatric patients because the recommended dosage in these patients cannot be achieved with the Escitalopram Capsules 15 mg strength [see Use in Specific Populations ( 8.5 )] . Escitalopram Capsules are not recommended in patients with hepatic impairment because the recommended dosage in such patients cannot be achieved with the Escitalopram Capsules 15 mg strength [see Use in Specific Populations ( 8.6 )] . 2.2 Recommended Dosage for Major Depressive Disorder The recommended starting dosage of escitalopram for MDD in adults younger than 65 years of age and pediatric patients 12 years of age and older is 10 mg orally once daily. Use another escitalopram product for dosage initiation. Based on clinical response and tolerability, the dosage may be increased to the maximum recommended dosage of 20 mg once daily of another escitalopram product after at least 1 week in adults younger than 65 years of age and after 3 weeks in pediatric patients 12 years of age and older. Escitalopram Capsules 15 mg orally once daily may be initiated in patients experiencing unfavorable tolerability to a 20 mg escitalopram dosage. 2.3 Recommended Dosage for Generalized Anxiety Disorder The recommended starting dosage of escitalopram for GAD in adults younger than 65 years of age is 10 mg orally once daily. Use another escitalopram product for dosage initiation. Based on clinical response and tolerability, the dosage may be increased to the maximum recommended dosage of 20 mg once daily of another escitalopram product after at least 1 week in adults younger than 65 years of age. Escitalopram Capsules 15 mg orally once daily may be initiated in patients experiencing unfavorable tolerability to a 20 mg escitalopram dosage. Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets and LEXAPRO (escitalopram) oral solution. However, due to AbbVie Inc. ’s marketing exclusivity rights, this drug product is not labeled with that information. 2.4 Administration Information Administer Escitalopram Capsules orally once daily, in the morning or evening, with or without food [see Clinical Pharmacology ( 12.3 )] . Swallow capsules whole; do not open, crush, or chew. 2.5 Screen for Bipolar Disorder Prior to Starting Escitalopram Capsules Prior to initiating treatment with Escitalopram Capsules or another antidepressant, screen patient…

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 Capsules and serotonergic agents and initiate supportive treatment ( 4 , 5.2 , 7) Discontinuation Syndrome: When discontinuing reduce dosage gradually whenever possible, and monitor for discontinuation symptoms ( 2.7 , 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 anticoagulants may increase risk ( 5.7 , 7) Interference with Cognitive and Motor Performance: Use caution when operating machinery ( 5.8 ) Angle Closure Glaucoma: Avoid use of antidepressants, including Escitalopram Capsules, in patients with untreated anatomically narrow angles ( 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 Capsules 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 1000 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 1000 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 Capsules, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome SSRIs, including Escitalopram Capsules, 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, t…

4 CONTRAINDICATIONS Escitalopram Capsules are contraindicated in patients: Taking, or within 14 days of stopping, MAOIs, including linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see Dosage and Administration ( 2.6 ), Warnings and Precautions ( 5.2 ), Drug Interactions ( 7 )] . Taking pimozide because of the risk of QT prolongation [see Drug Interactions ( 7 )] . With known hypersensitivity to escitalopram or citalopram or any of the inactive ingredients in Escitalopram Capsules. Concomitant use of monoamine oxidase inhibitor (MAOI) or within 14 days of stopping an MAOI ( 4 , 5.2 , 7) Concomitant use of pimozide ( 4 , 7) Known hypersensitivity to escitalopram or citalopram or any inactive ingredient in Escitalopram Capsules ( 4 )

7 DRUG INTERACTIONS Table 6 presents clinically important drug interactions with Escitalopram Capsules. Table 6: Clinically Important Drug Interactions with Escitalopram Capsules Monoamine Oxidase Inhibitors (MAOIs) Prevention or Management Escitalopram Capsules are contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2.6 ), Contraindications ( 4 ), Warnings and Precautions ( 5.2 )] . Mechanism and Clinical Effect(s) Concomitant use of SSRIs, including Escitalopram Capsules, and MAOIs increases the risk of serotonin syndrome. Pimozide Prevention or Management Escitalopram Capsules are contraindicated in patients taking pimozide [see Contraindications ( 4 )] . Mechanism and Clinical Effect(s) 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. The mechanism of this pharmacodynamic interaction is not known [see Clinical Pharmacology ( 12.3 )] . Other Serotonergic Drugs Prevention or Management Monitor patients for signs and symptoms of serotonin syndrome, particularly during escitalopram initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of Escitalopram Capsules and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )] . Mechanism and Clinical Effect(s) Concomitant use of Escitalopram Capsules 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. Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.) Prevention or Management Inform patients of the increased risk of bleeding associated with the concomitant use of Escitalopram Capsules and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions ( 5.7 )] . Mechanism and Clinical Effect(s) Concomitant use of Escitalopram Capsules and an antiplatelet or anticoagulant may potentiate the risk of bleeding. Sumatriptan Prevention or Management If concomitant use of Escitalopram Capsules and sumatriptan is clinically warranted, appropriate observation of the patient is advised [see Warnings and Precautions ( 5.2 )] . Mechanism and Clinical Effect(s) There have been postmarketing reports of weakness, hyperreflexia, and incoordination following the concomitant use of an SSRI and sumatriptan. Lithium Prevention or Management Monitor plasma lithium levels with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Mechanism and Clinical Effect(s) Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when Escitalopram Capsules is used concomitantly with lithium. Alcohol Prevention or Management Concomitant use of Escitalopram Capsules and alcohol is not recommended. Mechanism and Clinical Effect(s) Alcohol may potentiate the psychotropic effects of escitalopram. Drugs Metabolized by CYP2D6 Prevention or Management The clinical significance of this finding is unknown. Exercise caution during coadministration of Escitalopram Capsules and drugs metabolized by CYP2D6. Mechanism and Clinical Effect(s) Coadministration of escitalopram with the tricyclic antidepressant desipramine, a substrate for CYP2D6, resulted in a 40% increase in Cmax and a 100% increase in AUC of desipramine. See full prescribing information for clinically significant drug interactions ( 7 )

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 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 ), 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 Capsules, 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 Capsules 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 Capsules, 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 1-2 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 (MR…

6 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 common adverse reactions (≥ 5% and at least twice the incidence of placebo) are: insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, increased sweating, fatigue and somnolence, decreased libido, and anorgasmia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Almatica Pharma LLC at 1-877-447-7979 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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. The safety of Escitalopram Capsules 15 mg once daily for the treatment of major depressive disorder (MDD) in adults younger than 65 years of age and pediatric patients 12 years of age and older and for the treatment of generalized anxiety disorder (GAD) in adults younger than 65 years of age is based upon adequate and well-controlled studies of another escitalopram product with dosing ranging from 10 to 20 mg once daily. The results of these adequate and well-controlled studies are presented below. Clinical Trial Data Sources Adults Adverse reaction data in adults with MDD were collected from 715 patients who were exposed to escitalopram and from 592 patients who were exposed to placebo in double-blind, placebo-controlled trials. An additional 284 adults with MDD were newly exposed to escitalopram in open-label trials. The adverse reaction data in adults with GAD were collected from 429 patients exposed to escitalopram and from 427 patients exposed to placebo in double-blind, placebo-controlled trials. Pediatric Patients Adverse reaction data for pediatric patients with MDD were collected in double-blind placebo-controlled studies in 576 pediatric patients 6 to 17 years of age, (286 escitalopram, 290 placebo). The safety and effectiveness of Escitalopram Capsules have not been established in pediatric patients less than 12 years of age with MDD. Adverse Reactions Associated with Discontinuation of Treatment Major Depressive Disorder in Adults Among the 715 adults with MDD who received escitalopram in placebo-controlled trials, 6% discontinued treatment due to an adverse reaction, as compared to 2% of 592 patients receiving placebo. The rate of discontinuation for adverse reactions 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 reactions in patients receiving 10 mg/day escitalopram (4%) and placebo (3%). Adverse reactions that were associated with discontinuation in at least 1% of escitalopram-treated patients, and at least twice that of placebo, were nausea (2%) and ejaculation disorder (2% of male patients). Major Depressive Disorder in Pediatric Patients In pediatric patients 6 to 17 years of age with MDD, adverse reactions were associated with discontinuation in 3.5% of 286 patients receiving escitalopram and 1% of 290 patients receiving placebo. The most common adverse reaction (incidence at least 1% for…