These Highlights Do Not Include All The Information Needed To Use Escitalopram Tablets Safely And Effectively. See Full Prescribing Information For Escitalopram Tablets.

Escitalopram 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.

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that information.

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

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

The following have been reported with escitalopram tablets 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 an escitalopram tablets overdose.

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

Risk Summary

Data from the published literature report the presence of escitalopram and desmethylescitalopram in human milk (see Data). There are reports of excessive sedation, restlessness, agitation, poor feeding and poor weight gain in infants exposed to escitalopram, through breast milk (see Clinical Considerations). There are no data on the effects of escitalopram or its metabolites on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for escitalopram and any potential adverse effects on the breastfed child from Escitalopram or from the underlying maternal condition.

Clinical Considerations

Infants exposed to escitalopram should be monitored for excess sedation, restlessness, agitation, poor feeding and poor weight gain.

Data

A study of 8 nursing mothers on escitalopram with daily doses of 10-20 mg/day showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram.

Escitalopram tablets contains 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(dimethylamino) propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrile oxalate with the following structural formula:

The molecular formula is C ₂₀H ₂₁FN _2O• C ₂H ₂O ₄ and the molecular weight is 414.40. 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, for oral use, are film-coated, round tablets containing 6.38 mg, 12.75 mg, 25.5 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: colloidal silicon dioxide, corn starch, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, talc, and a film coating agent. The film coating agent, Opadry II White Y-22-7719, contains the following ingredients: hypromellose; polydextrose; polyethylene glycol; triacetin; and titanium dioxide.

Meets USP Dissolution Test 2.

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.

Dispense with Medication Guide.

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Medication Guide

Escitalopram Tablets, USP

(ES-sye-TAL-oh-pram)

What is the most important information I should know about Escitalopram tablets?

Escitalopram tablets may cause serious side effects, including:

• Increased risk of suicidal thoughts or actions. Escitalopram tablets and other antidepressant medicines increase the risk of suicidal thoughts and actions in people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed.
• Depression or other mental illnesses are the most important causes of suicidal thoughts or actions.

How can I watch for and try to prevent suicidal thoughts and actions?

• Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts, or feelings, or if you or your child develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the dose is changed.
• Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings or if you or your child develop suicidal thoughts or actions.
• Keep all follow-up visits with your healthcare provider as scheduled and call your healthcare provider between visits if you are worried about symptoms.

Call your healthcare provider or get emergency medical help right away if you or your child have any of the following symptoms, especially if they are new, worse, or worry you:

• attempts to commit suicide or acting on dangerous impulses
• acting aggressive, being angry or violent or thoughts about suicide or dying
• new or worse depression or new or worsening anxiety
• panic attacks or feeling very agitated or restless
• new or worse irritability or trouble sleeping
• an extreme increase in activity or talking (mania) or other unusual changes in behavior or mood

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 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 patients 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 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 and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that information.

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 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.

Escitalopram tablets are contraindicated in patients:

• taking MAOIs with escitalopram tablets or within 14 days of stopping treatment with escitalopram tablets because of an increased risk of serotonin syndrome. The use of escitalopram tablets 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 tablets 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 tablets.

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)]

Table 6 presents clinically important drug interactions with escitalopram.

Pharmacokinetics of escitalopram in patients with a creatinine clearance less than 20 mL/minute has not been evaluated. No dosage adjustment is necessary for patients with mild or moderate renal impairment [see Dosage and Administration (2.5) , Clinical Pharmacology (12.3) ].

In vitro and in vivo studies in animals suggest that escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate. Tolerance to a model of antidepressant effect in rats was not induced by long-term (up to 5 weeks) treatment with escitalopram. Escitalopram has no or very low affinity for serotonergic (5-HT _1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D _1-5), histamine (H _1-3), muscarinic (M _1-5), and benzodiazepine receptors. Escitalopram also does not bind to, or has low affinity for, various ion channels including Na ⁺, K ⁺, Cl ^-, and Ca ⁺⁺ channels. Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular side effects of other psychotropic drugs.

The single- and multiple-dose pharmacokinetics of escitalopram are linear and dose-proportional in a dose range of 10 to 30 mg/day.

With once-daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of escitalopram in plasma in young healthy subjects was 2.2-2.5 times the plasma concentrations observed after a single dose.

Absorption

The absolute bioavailability of citalopram is about 80% relative to an intravenous dose. The tablet and the oral solution dosage forms of escitalopram oxalate are bioequivalent. Following a single oral dose (20 mg tablet or solution) of escitalopram, peak blood levels occur at about 5 hours. Absorption of escitalopram is not affected by food.

Distribution

The binding of escitalopram to human plasma proteins is approximately 56%. The volume of distribution of citalopram is about 12 L/kg. Data specific on escitalopram are unavailable.

Elimination

Biotransformation of escitalopram is mainly hepatic, with a mean terminal half-life of about 27-32 hours. The oral clearance of escitalopram is 600 mL/min, with approximately 7% of that due to renal clearance.

Metabolism

Escitalopram is metabolized to S-DCT and S-didemethylcitalopram (S-DDCT). In humans, unchanged escitalopram is the predominant compound in plasma. At steady state, the concentration of the escitalopram metabolite S-DCT in plasma is approximately one-third that of escitalopram. The level of S-DDCT was not detectable in most subjects. In vitro studies show that escitalopram is at least 7 and 27 times more potent than S-DCT and S-DDCT, respectively, in the inhibition of serotonin reuptake, suggesting that the metabolites of escitalopram do not contribute significantly to the antidepressant actions of escitalopram. S-DCT and S-DDCT also have no or very low affinity for serotonergic (5-HT _1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D _1-5), histamine (H _1-3), muscarinic (M _1-5), and benzodiazepine receptors. S-DCT and S-DDCT also do not bind to various ion channels including Na ⁺, K ⁺, Cl ^-, and Ca ⁺⁺ channels. In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram.

Excretion

Following oral administrations of escitalopram, the fraction of drug recovered in the urine as escitalopram and S-demethylcitalopram (S-DCT) is about 8% and 10%, respectively.

Specific Populations

Pediatric Patients

Pediatric patients 12 to 17 years of age: In a single dose study of 10 mg escitalopram, AUC of escitalopram decreased by 19%, and C _max increased by 26% in healthy pediatric subjects 12 to 17 years of age compared to adults. Following multiple dosing of 40 mg/day citalopram, escitalopram elimination half-life, steady-state C _max and AUC were similar in pediatric patients 12 to 17 years of age with MDD compared to adults [see Use in Specific Populations(8.4) ].

Geriatric Patients

Escitalopram pharmacokinetics in subjects ≥ 65 years of age were compared to adults in a single dose and a multiple-dose study. Escitalopram AUC and half-life were increased by approximately 50% in elderly subjects, and C _max was unchanged [see Dosage and Administration (2.5) , Use in Specific Populations (8.5) ].

Male and Female Patients

Based on data from single- and multiple-dose studies measuring escitalopram in elderly, young adults, and adolescents, no dosage adjustment on the basis of gender is needed.

Patients with Hepatic Impairment

Citalopram oral clearance was reduced by 37% and half-life was doubled in patients with reduced hepatic function compared to normal subjects [see Dosage and Administration (2.5) , Use in Specific Populations (8.6) ].

Patients with Renal Impairment

In patients with mild to moderate renal function impairment, oral clearance of citalopram was reduced by 17% compared to normal subjects. No information is available about the pharmacokinetics of escitalopram in patients with severely reduced renal function (creatinine clearance < 20 mL/min) [see Use in Specific Populations (8.7) ].

Drug Interaction Studies

In vitro enzyme inhibition data did not reveal an inhibitory effect of escitalopram on CYP3A4, -1A2, -2C9, -2C19, and -2E1. Based on in vitro data, escitalopram would be expected to have little inhibitory effect on in vivo metabolism mediated by these cytochromes. While in vivo data to address this question are limited, results from drug interaction studies suggest that escitalopram, at a dose of 20 mg, has no 3A4 inhibitory effect and a modest 2D6 inhibitory effect [see Drug Interactions (7) ].

CYP3A4 and CYP2C19 Inhibitors

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

Cimetidine

In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of 400 mg twice a day cimetidine for 8 days resulted in an increase in citalopram AUC and C _max of 43% and 39%, respectively. The clinical significance of these findings is unknown.

Digoxin

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

Lithium

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

Theophylline

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

Ketoconazole

Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the C _max and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.

Ritonavir

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

Triazolam

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

Metoprolol

Administration of 20 mg/day escitalopram for 21 days in healthy volunteers resulted in a 50% increase in C _max and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100 mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of escitalopram and metoprolol had no clinically significant effects on blood pressure or heart rate.

Alcohol

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

Warfarin

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

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that information.

SSRIs, including escitalopram, 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 for the emergence of serotonin syndrome. Discontinue treatment with escitalopram 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.

Increased citalopram exposure occurs in patients with hepatic impairment [see Clinical Pharmacology (12.3) ]. The recommended dosage of escitalopram in patients with hepatic impairment is 10 mg daily [see Dosage and Administration (2.5) ].

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)

Use of SSRIs, including escitalopram tablets, 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 tablets 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.

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).

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

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

• 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)

5 mg: Round, white to off-white, biconvex, film coated tablets, debossed with “P 5” on one side and plain on the other side.

10 mg: Round, white to off-white, biconvex, scored film coated tablets, debossed with “P 10” on the scored side and plain on the other side.

20 mg: Round, white to off-white, biconvex, scored film coated tablets, debossed with “P 20” on the scored side and plain on the other side.

During marketing of escitalopram 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) ].

Pregnancy: SSRI use, particularly later in pregnancy, may increase the risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulties, hypotonia, tremor, irritability) in the neonate ( 8.1)

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that information.

Administer escitalopram tablets orally once daily, in the morning or evening, with or without food

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 Population (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) ].

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.

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 (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 and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that 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 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 and to discuss any tapering regimen with their healthcare provider. Inform patients that adverse reactions can occur when escitalopram is 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 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 tablets 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 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. 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) ].

Dispense with Medication Guide.

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PACKAGING INFORMATION

American Health Packaging unit dose blisters (see How Supplied section) containdrug product from BluePoint Laboratories as follows:

5 mg / 100 UD) NDC 60687-865-01 packaged from NDC 68001-591

Distributed by:

American Health Packaging

Columbus, OH 43217

8486501/0924

How Supplied

Escitalopram Tablets, USP, 5 mg are round, white to off-white, biconvex, film coated tablets, debossed with “P 5” on one side and plain on the other side. They are supplied in:

Unit dose packages of 100 (10 x 10) NDC 60687-865-01

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

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) ].

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

Clinical experience with escitalopram in patients with certain concomitant systemic illnesses is limited. Caution is advisable in using escitalopram in patients with diseases or conditions that produce altered metabolism or hemodynamic responses.

Escitalopram has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were generally excluded from clinical studies during the product’s premarketing testing.

In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma concentrations were increased. The recommended dose of escitalopram in hepatically impaired patients is 10 mg 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, however, it should be used with caution in such patients [see Dosage and Administration (2.5) and Use in Specific Populations (8.7)].

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)].

NDC 60687- 865-01

Escitalopram

Tablets USP

5 mg

100 Tablets (10 × 10)               Rx Only

PHARMACIST: Dispense with Medication Guide to each patient.

Each Tablet Contains:

Escitalopram oxalate, USP equivalent to 5 mg Escitalopram.

Usual Dosage: See full prescribing information.

Store at 20º to 25ºC (68º to 77ºF); excursions permitted between

15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature].

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

The drug product contained in this package is from

NDC # 68001-591, BluePoint Laboratories

Distributed by: American Health Packaging, Columbus, Ohio 43217

786501

0486501/0924

Escitalopram Tablet, USP

5 mg

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 therapy does not affect their ability to engage in such activities.

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.

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.

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 tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

Prior to initiating treatment with escitalopram or another antidepressant, screen patients for a personal family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.5) ]

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) ].

Escitalopram 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.

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that information.

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

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

The following have been reported with escitalopram tablets 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 an escitalopram tablets overdose.

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

Risk Summary

Data from the published literature report the presence of escitalopram and desmethylescitalopram in human milk (see Data). There are reports of excessive sedation, restlessness, agitation, poor feeding and poor weight gain in infants exposed to escitalopram, through breast milk (see Clinical Considerations). There are no data on the effects of escitalopram or its metabolites on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for escitalopram and any potential adverse effects on the breastfed child from Escitalopram or from the underlying maternal condition.

Clinical Considerations

Infants exposed to escitalopram should be monitored for excess sedation, restlessness, agitation, poor feeding and poor weight gain.

Data

A study of 8 nursing mothers on escitalopram with daily doses of 10-20 mg/day showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram.

Escitalopram tablets contains 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(dimethylamino) propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrile oxalate with the following structural formula:

The molecular formula is C ₂₀H ₂₁FN _2O• C ₂H ₂O ₄ and the molecular weight is 414.40. 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, for oral use, are film-coated, round tablets containing 6.38 mg, 12.75 mg, 25.5 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: colloidal silicon dioxide, corn starch, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, talc, and a film coating agent. The film coating agent, Opadry II White Y-22-7719, contains the following ingredients: hypromellose; polydextrose; polyethylene glycol; triacetin; and titanium dioxide.

Meets USP Dissolution Test 2.

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.

Dispense with Medication Guide.

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8486501/0924

Medication Guide

Escitalopram Tablets, USP

(ES-sye-TAL-oh-pram)

What is the most important information I should know about Escitalopram tablets?

Escitalopram tablets may cause serious side effects, including:

• Increased risk of suicidal thoughts or actions. Escitalopram tablets and other antidepressant medicines increase the risk of suicidal thoughts and actions in people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed.
• Depression or other mental illnesses are the most important causes of suicidal thoughts or actions.

How can I watch for and try to prevent suicidal thoughts and actions?

• Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts, or feelings, or if you or your child develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the dose is changed.
• Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings or if you or your child develop suicidal thoughts or actions.
• Keep all follow-up visits with your healthcare provider as scheduled and call your healthcare provider between visits if you are worried about symptoms.

Call your healthcare provider or get emergency medical help right away if you or your child have any of the following symptoms, especially if they are new, worse, or worry you:

• attempts to commit suicide or acting on dangerous impulses
• acting aggressive, being angry or violent or thoughts about suicide or dying
• new or worse depression or new or worsening anxiety
• panic attacks or feeling very agitated or restless
• new or worse irritability or trouble sleeping
• an extreme increase in activity or talking (mania) or other unusual changes in behavior or mood

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 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 patients 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 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 and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that information.

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 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.

Escitalopram tablets are contraindicated in patients:

• taking MAOIs with escitalopram tablets or within 14 days of stopping treatment with escitalopram tablets because of an increased risk of serotonin syndrome. The use of escitalopram tablets 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 tablets 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 tablets.

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)]

Table 6 presents clinically important drug interactions with escitalopram.

Pharmacokinetics of escitalopram in patients with a creatinine clearance less than 20 mL/minute has not been evaluated. No dosage adjustment is necessary for patients with mild or moderate renal impairment [see Dosage and Administration (2.5) , Clinical Pharmacology (12.3) ].

In vitro and in vivo studies in animals suggest that escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate. Tolerance to a model of antidepressant effect in rats was not induced by long-term (up to 5 weeks) treatment with escitalopram. Escitalopram has no or very low affinity for serotonergic (5-HT _1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D _1-5), histamine (H _1-3), muscarinic (M _1-5), and benzodiazepine receptors. Escitalopram also does not bind to, or has low affinity for, various ion channels including Na ⁺, K ⁺, Cl ^-, and Ca ⁺⁺ channels. Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular side effects of other psychotropic drugs.

The single- and multiple-dose pharmacokinetics of escitalopram are linear and dose-proportional in a dose range of 10 to 30 mg/day.

With once-daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of escitalopram in plasma in young healthy subjects was 2.2-2.5 times the plasma concentrations observed after a single dose.

Absorption

The absolute bioavailability of citalopram is about 80% relative to an intravenous dose. The tablet and the oral solution dosage forms of escitalopram oxalate are bioequivalent. Following a single oral dose (20 mg tablet or solution) of escitalopram, peak blood levels occur at about 5 hours. Absorption of escitalopram is not affected by food.

Distribution

The binding of escitalopram to human plasma proteins is approximately 56%. The volume of distribution of citalopram is about 12 L/kg. Data specific on escitalopram are unavailable.

Elimination

Biotransformation of escitalopram is mainly hepatic, with a mean terminal half-life of about 27-32 hours. The oral clearance of escitalopram is 600 mL/min, with approximately 7% of that due to renal clearance.

Metabolism

Escitalopram is metabolized to S-DCT and S-didemethylcitalopram (S-DDCT). In humans, unchanged escitalopram is the predominant compound in plasma. At steady state, the concentration of the escitalopram metabolite S-DCT in plasma is approximately one-third that of escitalopram. The level of S-DDCT was not detectable in most subjects. In vitro studies show that escitalopram is at least 7 and 27 times more potent than S-DCT and S-DDCT, respectively, in the inhibition of serotonin reuptake, suggesting that the metabolites of escitalopram do not contribute significantly to the antidepressant actions of escitalopram. S-DCT and S-DDCT also have no or very low affinity for serotonergic (5-HT _1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D _1-5), histamine (H _1-3), muscarinic (M _1-5), and benzodiazepine receptors. S-DCT and S-DDCT also do not bind to various ion channels including Na ⁺, K ⁺, Cl ^-, and Ca ⁺⁺ channels. In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram.

Excretion

Following oral administrations of escitalopram, the fraction of drug recovered in the urine as escitalopram and S-demethylcitalopram (S-DCT) is about 8% and 10%, respectively.

Specific Populations

Pediatric Patients

Pediatric patients 12 to 17 years of age: In a single dose study of 10 mg escitalopram, AUC of escitalopram decreased by 19%, and C _max increased by 26% in healthy pediatric subjects 12 to 17 years of age compared to adults. Following multiple dosing of 40 mg/day citalopram, escitalopram elimination half-life, steady-state C _max and AUC were similar in pediatric patients 12 to 17 years of age with MDD compared to adults [see Use in Specific Populations(8.4) ].

Geriatric Patients

Escitalopram pharmacokinetics in subjects ≥ 65 years of age were compared to adults in a single dose and a multiple-dose study. Escitalopram AUC and half-life were increased by approximately 50% in elderly subjects, and C _max was unchanged [see Dosage and Administration (2.5) , Use in Specific Populations (8.5) ].

Male and Female Patients

Based on data from single- and multiple-dose studies measuring escitalopram in elderly, young adults, and adolescents, no dosage adjustment on the basis of gender is needed.

Patients with Hepatic Impairment

Citalopram oral clearance was reduced by 37% and half-life was doubled in patients with reduced hepatic function compared to normal subjects [see Dosage and Administration (2.5) , Use in Specific Populations (8.6) ].

Patients with Renal Impairment

In patients with mild to moderate renal function impairment, oral clearance of citalopram was reduced by 17% compared to normal subjects. No information is available about the pharmacokinetics of escitalopram in patients with severely reduced renal function (creatinine clearance < 20 mL/min) [see Use in Specific Populations (8.7) ].

Drug Interaction Studies

In vitro enzyme inhibition data did not reveal an inhibitory effect of escitalopram on CYP3A4, -1A2, -2C9, -2C19, and -2E1. Based on in vitro data, escitalopram would be expected to have little inhibitory effect on in vivo metabolism mediated by these cytochromes. While in vivo data to address this question are limited, results from drug interaction studies suggest that escitalopram, at a dose of 20 mg, has no 3A4 inhibitory effect and a modest 2D6 inhibitory effect [see Drug Interactions (7) ].

CYP3A4 and CYP2C19 Inhibitors

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

Cimetidine

In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of 400 mg twice a day cimetidine for 8 days resulted in an increase in citalopram AUC and C _max of 43% and 39%, respectively. The clinical significance of these findings is unknown.

Digoxin

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

Lithium

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

Theophylline

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

Ketoconazole

Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the C _max and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.

Ritonavir

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

Triazolam

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

Metoprolol

Administration of 20 mg/day escitalopram for 21 days in healthy volunteers resulted in a 50% increase in C _max and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100 mg). Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of escitalopram and metoprolol had no clinically significant effects on blood pressure or heart rate.

Alcohol

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

Warfarin

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

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that information.

SSRIs, including escitalopram, 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 for the emergence of serotonin syndrome. Discontinue treatment with escitalopram 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.

Increased citalopram exposure occurs in patients with hepatic impairment [see Clinical Pharmacology (12.3) ]. The recommended dosage of escitalopram in patients with hepatic impairment is 10 mg daily [see Dosage and Administration (2.5) ].

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)

Use of SSRIs, including escitalopram tablets, 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 tablets 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.

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).

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

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

• 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)

5 mg: Round, white to off-white, biconvex, film coated tablets, debossed with “P 5” on one side and plain on the other side.

10 mg: Round, white to off-white, biconvex, scored film coated tablets, debossed with “P 10” on the scored side and plain on the other side.

20 mg: Round, white to off-white, biconvex, scored film coated tablets, debossed with “P 20” on the scored side and plain on the other side.

During marketing of escitalopram 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) ].

Pregnancy: SSRI use, particularly later in pregnancy, may increase the risk for persistent pulmonary hypertension and symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulties, hypotonia, tremor, irritability) in the neonate ( 8.1)

Additional pediatric use information is approved for AbbVie Inc.’s LEXAPRO (escitalopram) tablets and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that information.

Administer escitalopram tablets orally once daily, in the morning or evening, with or without food

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 Population (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) ].

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.

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 (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 and LEXAPRO (escitalopram) oral solutions. However, due to AbbVie Inc’s marketing exclusivity rights, this drug product is not labeled with that 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 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 and to discuss any tapering regimen with their healthcare provider. Inform patients that adverse reactions can occur when escitalopram is 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 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 tablets 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 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. 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) ].

Dispense with Medication Guide.

To order more Medication Guides call American Health Packaging at 1‐800‐707‐4621.

PACKAGING INFORMATION

American Health Packaging unit dose blisters (see How Supplied section) containdrug product from BluePoint Laboratories as follows:

5 mg / 100 UD) NDC 60687-865-01 packaged from NDC 68001-591

Distributed by:

American Health Packaging

Columbus, OH 43217

8486501/0924

How Supplied

Escitalopram Tablets, USP, 5 mg are round, white to off-white, biconvex, film coated tablets, debossed with “P 5” on one side and plain on the other side. They are supplied in:

Unit dose packages of 100 (10 x 10) NDC 60687-865-01

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

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) ].

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

Clinical experience with escitalopram in patients with certain concomitant systemic illnesses is limited. Caution is advisable in using escitalopram in patients with diseases or conditions that produce altered metabolism or hemodynamic responses.

Escitalopram has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were generally excluded from clinical studies during the product’s premarketing testing.

In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma concentrations were increased. The recommended dose of escitalopram in hepatically impaired patients is 10 mg 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, however, it should be used with caution in such patients [see Dosage and Administration (2.5) and Use in Specific Populations (8.7)].

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)].

NDC 60687- 865-01

Escitalopram

Tablets USP

5 mg

100 Tablets (10 × 10)               Rx Only

PHARMACIST: Dispense with Medication Guide to each patient.

Each Tablet Contains:

Escitalopram oxalate, USP equivalent to 5 mg Escitalopram.

Usual Dosage: See full prescribing information.

Store at 20º to 25ºC (68º to 77ºF); excursions permitted between

15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature].

FOR YOUR PROTECTION: Do not use if blister is torn or broken.

The drug product contained in this package is from

NDC # 68001-591, BluePoint Laboratories

Distributed by: American Health Packaging, Columbus, Ohio 43217

786501

0486501/0924

Escitalopram Tablet, USP

5 mg

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 therapy does not affect their ability to engage in such activities.

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.

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.

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 tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

Prior to initiating treatment with escitalopram or another antidepressant, screen patients for a personal family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.5) ]

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) ].