1.1 Major Depressive Disorder

Escitalopram tablet, is indicated for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age [ see Clinical Studies ( 14.1) ].

A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation.

1.2 Generalized Anxiety Disorder

Escitalopram tablet, is indicated for the acute treatment of Generalized Anxiety Disorder (GAD) in adults [ see Clinical Studies ( 14.2) ].

Generalized Anxiety Disorder (DSM-IV) is characterized by excessive anxiety and worry (apprehensive expectation) that is persistent for at least 6 months and which the person finds difficult to control. It must be associated with at least 3 of the following symptoms: restlessness or feeling keyed up or on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, and sleep disturbance.

2.1 Major Depressive Disorder

2.2 Generalized Anxiety Disorder

2.3 Special Populations

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

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

2.4 Discontinuation of Treatment with Escitalopram Tablets

Symptoms associated with discontinuation of escitalopram tablets and other SSRIs and SNRIs have been reported [ see Warnings and Precautions ( 5.3) ]. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

2.5 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with escitalopram tablets. Conversely, at least 14 days should be allowed after stopping escitalopram tablets before starting an MAOI intended to treat psychiatric disorders [ see Contraindications ( 4.1) ].

2.6 Use of Escitalopram Tablets with Other MAOIs such as Linezolid or Methylene Blue

Do not start escitalopram tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [ see Contraindications ( 4.1) ].

In some cases, a patient already receiving escitalopram tablets therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, escitalopram tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with escitalopram tablets may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [ see Warnings and Precautions ( 5.2) ].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with escitalopram tablet is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [ see Warnings and Precautions ( 5.2) ].

3.1 Tablets

Escitalopram tablets, USP are film-coated, round tablets containing escitalopram oxalate in strengths equivalent to 5 mg, 10 mg and 20 mg escitalopram base. The 10 and 20 mg tablets are scored. Debossed with either "5", “10”, or “20” on the one side according to their respective strengths and plain on other side.

4.1 Monoamine Oxidase Inhibitors (MAOIs)

The use of MAOIs intended to treat psychiatric disorders with escitalopram tablets or within 14 days of stopping treatment with escitalopram tablet is contraindicated 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 ( 2.5), 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) ].

4.2 Pimozide

Concomitant use in patients taking pimozide is contraindicated [ see Drug Interactions ( 7.10) ].

4.3 Hypersensitivity to escitalopram or citalopram

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

5.1 Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms [ see Dosage and Administration ( 2.4) ].

Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers [ see also Patient Counseling Information ( 17.1) ]. Prescriptions for escitalopram oxalate should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

5.2 Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including escitalopram oxalate, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination) seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.

The concomitant use of escitalopram oxalate with MAOIs intended to treat psychiatric disorders is contraindicated. Escitalopram oxalate should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking escitalopram oxalate. Escitalopram oxalate should be discontinued before initiating treatment with the MAOI [ see Contraindications ( 4.1) and Dosage and Administration ( 2.5 and 2.6) ].

If concomitant use of escitalopram oxalate with other serotonergic drugs including, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, amphetamine, and St. John’s Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

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

5.3 Discontinuation of Treatment with Escitalopram Oxalate

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

Patients should be monitored for these symptoms when discontinuing treatment with escitalopram oxalate. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate [ see Dosage and Administration ( 2.4) ].

5.4 Seizures

Although anticonvulsant effects of racemic citalopram have been observed in animal studies, escitalopram oxalate 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 oxalate, cases of convulsion have been reported in association with escitalopram oxalate treatment. Like other drugs effective in the treatment of major depressive disorder, escitalopram oxalate should be introduced with care in patients with a history of seizure disorder.

5.5 Activation of Mania/Hypomania

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

5.6 Hyponatremia

Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including escitalopram oxalate. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was reversible when escitalopram oxalate was discontinued. Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk [ see Geriatric Use ( 8.5)]. Discontinuation of escitalopram oxalate should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.

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

5.7 Abnormal Bleeding

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

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

5.8 Interference with Cognitive and Motor Performance

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

5.9 Angle Closure Glaucoma

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

5.10 Use in Patients with Concomitant Illness

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

Escitalopram oxalate 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 oxalate in hepatically impaired patients is 10 mg/day [ see Dosage and Administration ( 2.3) ].

Because escitalopram is extensively metabolized, excretion of unchanged drug in urine is a minor route of elimination. Until adequate numbers of patients with severe renal impairment have been evaluated during chronic treatment with escitalopram oxalate, however, it should be used with caution in such patients [ see Dosage and Administration ( 2.3) ].

6.1 Clinical Trials Experience

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

6.2 Post-Marketing Experience

7.1 Monoamine Oxidase Inhibitors (MAOIs)

[ see Dosage and Administration ( 2.5 and 2.6), Contraindications ( 4.1) and Warnings and Precautions ( 5.2) ].

7.2 Serotonergic Drugs

[ see Dosage and Administration ( 2.5 and 2.6), Contraindications ( 4.1) and Warnings and Precautions ( 5.2) ].

7.3 Triptans

There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of escitalopram oxalate with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [ see Warnings and Precautions ( 5.2) ].

7.4 CNS Drugs

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

7.5 Alcohol

Although escitalopram oxalate 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 oxalate is not recommended.

7.6 Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.)

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

7.7 Cimetidine

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

7.8 Digoxin

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

7.9 Lithium

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

7.10 Pimozide and Celexa

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

7.11 Sumatriptan

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

7.12 Theophylline

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

7.13 Warfarin

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

7.14 Carbamazepine

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

7.15 Triazolam

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

7.16 Ketoconazole

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

7.17 Ritonavir

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

7.18 CYP3A4 and -2C19 Inhibitors

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

7.19 Drugs Metabolized by Cytochrome P4502D6

In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism. However, there are limited in vivo data suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in C max and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless, caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.

7.20 Metoprolol

Administration of 20 mg/day escitalopram oxalate 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 oxalate and metoprolol had no clinically significant effects on blood pressure or heart rate.

7.21 Electroconvulsive Therapy (ECT)

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

8.1 Pregnancy

8.2 Labor and Delivery

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

8.3 Nursing Mothers

Escitalopram is excreted in human breast milk. Limited data from women taking 10 to 20 mg escitalopram showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram. There were two reports of infants experiencing excessive somnolence, decreased feeding, and weight loss in association with breastfeeding from a racemic citalopram-treated mother; in one case, the infant was reported to recover completely upon discontinuation of racemic citalopram by its mother and, in the second case, no follow-up information was available. Caution should be exercised and breastfeeding infants should be observed for adverse reactions when escitalopram oxalate is administered to a nursing woman.

8.4 Pediatric Use

The safety and effectiveness of escitalopram oxalate have been established in adolescents (12 to 17 years of age) for the treatment of major depressive disorder [see Clinical Studies ( 14.1)]. Although maintenance efficacy in adolescent patients with major depressive disorder has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.

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

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

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

8.5 Geriatric Use

Approximately 6% of the 1144 patients receiving escitalopram in controlled trials of escitalopram oxalate in major depressive disorder and GAD were 60 years of age or older; elderly patients in these trials received daily doses of escitalopram oxalate between 10 and 20 mg. The number of elderly patients in these trials was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. Nevertheless, greater sensitivity of some elderly individuals to effects of escitalopram oxalate cannot be ruled out.

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

In two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in elderly subjects as compared to young subjects and C max was unchanged [ see Clinical Pharmacology ( 12.3) ]. 10 mg/day is the recommended dose for elderly patients [ see Dosage and Administration ( 2.3) ].

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

9.2 Abuse and Dependence

10.1 Human Experience

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

Symptoms most often accompanying escitalopram overdose, alone or in combination with other drugs and/or alcohol, included convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation and very rare cases of torsade de pointes). Acute renal failure has been very rarely reported accompanying overdose.

10.2 Management of Overdose

Establish and maintain an airway to ensure adequate ventilation and oxygenation. Gastric evacuation by lavage and use of activated charcoal should be considered. Careful observation and cardiac and vital sign monitoring are recommended, along with general symptomatic and supportive care. Due to the large volume of distribution of escitalopram, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. There are no specific antidotes for escitalopram oxalate.

In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose.

12.1 Mechanism of Action

The mechanism of antidepressant action of escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).

12.2 Pharmacodynamics

In vitro and in vivo studies in animals suggest that escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate. Tolerance to a model of antidepressant effect in rats was not induced by long-term (up to 5 weeks) treatment with escitalopram. Escitalopram has no or very low affinity for serotonergic (5-HT 1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D 1-5), histamine (H 1-3), muscarinic (M 1-5), and benzodiazepine receptors. Escitalopram also does not bind to, or has low affinity for, various ion channels including Na +, K +, Cl -, and Ca ++ channels. Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular side effects of other psychotropic drugs.

12.3 Pharmacokinetics

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

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14.1 Major Depressive Disorder

14.2 Generalized Anxiety Disorder

The efficacy of escitalopram oxalate in the acute treatment of Generalized Anxiety Disorder (GAD) was demonstrated in three, 8-week, multicenter, flexible-dose, placebo-controlled studies that compared escitalopram oxalate 10 to 20 mg/day to placebo in adult outpatients between 18 and 80 years of age who met DSM-IV criteria for GAD. In all three studies, escitalopram oxalate 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 oxalate has differential effects in these groups. There was no difference in response to escitalopram oxalate between men and women.

5 mg Tablets:

Bottle of 30                    NDC 16729-168-10

Bottle of 100                  NDC 16729-168-01

Bottle of 500                  NDC 16729-168-16

Bottle of 1,000               NDC 16729-168-17

10 x 10 Unit Dose          NDC 16729-168-43

White to off-white, round, biconvex, film coated tablets, debossed with “5” on one side and plain on other side.

10 mg Tablets:

Bottle of 30                    NDC 16729-169-10

Bottle of 100                  NDC 16729-169-01

Bottle of 500                  NDC 16729-169-16

Bottle of 1,000      �        NDC 16729-169-17

10 x 10 Unit Dose          NDC 16729-169-43

White to off-white, round, biconvex, film -coated tablets, debossed with "10” on one side and break line on other side.

20 mg Tablets:

Bottle of 30                    NDC 16729-170-10

Bottle of 100                  NDC 16729-170-01

Bottle of 500                  NDC 16729-170-16

Bottle of 1,000               NDC 16729-170-17

10 x 10 Unit Dose          NDC 16729-170-43

White to off-white, round, biconvex, film coated tablets, debossed with “20” on one side and break line on other side.

Storage and Handling

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

17.1 Information for Patients

Physicians are advised to discuss the following issues with patients for whom they prescribe escitalopram oxalate.

17.2 FDA-Approved Medication Guide

                                                                                                  Medication Guide

                                                                                           Escitalopram Tablets

                                                                                              (ES-sye-TAL-oh-pram)

Read the Medication Guide that comes with escitalopram tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about.

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

Escitalopram tablets and other antidepressant medicines may cause serious side effects, including:

1. Suicidal thoughts or actions:
   • Escitalopram tablets and other antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers or young adults within the first few months of treatment or when the dose is changed.
   • Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions.
   • Watch for these changes and call your healthcare provider right away if you notice:
     • New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe.
     • Pay particular attention to such changes when escitalopram tablet is started or when the dose is changed.

       Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms.

   Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you:

   • attempts to commit suicide
   • acting on dangerous impulses
   • acting aggressive or violent
   • thoughts about suicide or dying
   • new or worse depression
   • new or worse anxiety or panic attacks
   • feeling agitated, restless, angry or irritable
   • trouble sleeping
   • an increase in activity or talking more than what is normal for you
   • other unusual changes in behavior or mood

   Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Escitalopram tablets may be associated with these serious side effects:

2. Serotonin Syndrome. This condition can be life-threatening and may include:
   • agitation, hallucinations, coma or other changes in mental status
   • coordination problems or muscle twitching (overactive reflexes)
   • racing heartbeat, high or low blood pressure
   • sweating or fever
   • nausea, vomiting, or diarrhea
   • muscle rigidity
3. Severe allergic reactions:
   • trouble breathing
   • swelling of the face, tongue, eyes or mouth
   • rash, itchy welts (hives) or blisters, alone or with fever or joint pain
4. Abnormal bleeding: Escitalopram tablets and other antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin ®, Jantoven ®), a non-steroidal antiinflammatory drug (NSAIDs, like ibuprofen or naproxen), or aspirin.
5. Seizures or convulsions
6. Manic episodes:
   • greatly increased energy
   • severe trouble sleeping
   • racing thoughts
   • reckless behavior
   • unusually grand ideas
   • excessive happiness or irritability
   • talking more or faster than usual
7. Changes in appetite or weight. Children and adolescents should have height and weight monitored during treatment.
8. Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include:
   • headache
   • weakness or feeling unsteady
   • confusion, problems concentrating or thinking or memory problems
9. Visual problems.
   • eye pain
   • changes in vision
   • swelling or redness in or around the eye

Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.

Do not stop escitalopram tablets without first talking to your healthcare provider. Stopping escitalopram tablets too quickly may cause serious symptoms including:

• anxiety, irritability, high or low mood, feeling restless or changes in sleep habits
• headache, sweating, nausea, dizziness
• electric shock-like sensations, shaking, confusion

What are escitalopram tablets?

Escitalopram tablet is a prescription medicine used to treat depression. It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider.

Escitalopram tablets are also used to treat:

• Major Depressive Disorder (MDD)
• Generalized Anxiety Disorder (GAD)

Talk to your healthcare provider if you do not think that your condition is getting better with escitalopram tablets treatment.

Who should not take escitalopram tablets?

Do not take escitalopram tablets if you:

• are allergic to escitalopram or citalopram or any of the ingredients in escitalopram tablets. See the end of this Medication Guide for a complete list of ingredients in escitalopram tablets.
• Take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or a pharmacist if you are not sure if you take an MAOI, including linezolid.
• Do not take an MAOI within 2 weeks of stopping escitalopram tablets unless directed to do so by your physician.
• Do not start escitalopram tablets if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.

People who take escitalopram tablets close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms:

• high fever
• uncontrolled muscle spasms
• stiff muscles
• rapid changes in heart rate or blood pressure
• confusion
• loss of consciousness (pass out)
• Do not take escitalopram tablets with Orap ® (pimozide) because taking these two drugs together can cause serious heart problems.

What should I tell my healthcare provider before taking escitalopram tablets? Ask if you are not sure.

Before starting escitalopram tablets, tell your healthcare provider if you:

• Are taking certain drugs such as:
  • Triptans used to treat migraine headache
  • Medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium, SSRIs, SNRIs, amphetamines, or antipsychotics
  • Tramadol
  • Over-the-counter supplements such as tryptophan or St. John’s Wort
• have liver problems
• have kidney problems
• have heart problems
• have or had seizures or convulsions
• have bipolar disorder or mania
• have low sodium levels in your blood
• have a history of a stroke
• have high blood pressure
• have or had bleeding problems
• are pregnant or plan to become pregnant. It is not known if escitalopram tablets will harm your unborn baby. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy
• are breast-feeding or plan to breast-feed. Some escitalopram may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking escitalopram tablets.

Tell your healthcare provider about all the medicines that you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Escitalopram tablets and some medicines may interact with each other, may not work as well, or may cause serious side effects.

Your healthcare provider or pharmacist can tell you if it is safe to take escitalopram tablets with your other medicines. Do not start or stop any medicine while taking escitalopram tablets without talking to your healthcare provider first.

How should I take escitalopram tablets?

• Take escitalopram tablets exactly as prescribed. Your healthcare provider may need to change the dose of escitalopram tablets until it is the right dose for you.
• Escitalopram tablets may be taken with or without food.
• If you miss a dose of escitalopram tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of escitalopram tablets at the same time.
• If you take too much escitalopram tablets, call your healthcare provider or poison control center right away, or get emergency treatment.

What should I avoid while taking escitalopram tablets?

Escitalopram tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how escitalopram tablets affects you. Do not drink alcohol while using escitalopram tablets.

What are the possible side effects of escitalopram tablets?

Escitalopram tablets may cause serious side effects, including all of those described in the section entitled “What is the most important information I should know about escitalopram tablets?”

Common possible side effects in people who take escitalopram tablets include:

• Nausea
• Sleepiness
• Weakness
• Dizziness
• Feeling anxious
• Trouble sleeping
• Sexual problems
• Sweating
• Shaking
• Not feeling hungry
• Dry mouth
• Constipation
• Infection
• Yawning

Other side effects in children and adolescents include:

• increased thirst
• abnormal increase in muscle movement or agitation
• nose bleed
• difficult urination
• heavy menstrual periods
• possible slowed growth rate and weight change.

Your child’s height and weight should be monitored during treatment with escitalopram tablets.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of escitalopram tablets. For more information, ask your healthcare provider or pharmacist.

CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088.

How should I store escitalopram tablets?

• Store escitalopram tablets at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C).[see USP Controlled Room Temperature].
• Keep escitalopram tablets bottle closed tightly.

Keep escitalopram tablets and all medicines out of the reach of children.

General information about escitalopram tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use escitalopram tablets for a condition for which it was not prescribed. Do not give escitalopram tablets to other people, even if they have the same condition. It may harm them.



This Medication Guide summarizes the most important information about escitalopram tablets. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about escitalopram tablets that is written for healthcare professionals.

For more information, go to www.accordhealthcare.us or call Accord Healthcare Inc. at 1-866-941-7875.

What are the ingredients in escitalopram tablets?



Active ingredient: escitalopram oxalate

Inactive ingredients:

• Tablets: croscarmellose sodium, microcrystalline cellulose, hypromellose, colloidal anhydrous silica, magnesium stearate and talc. The film coating contains hypromellose, titanium dioxide, and polyethylene glycol.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Coumadin ® is registered trademark of Bristol-Myers Squibb Company.

Jantoven ® is registered trademark of Upsher-Smith Laboratories, Inc.

Orap ® is registered trademark of Teva Pharmaceuticals USA

Medication guide available at www.accordhealthcare.us/medication-guides.

Manufactured For:

Accord Healthcare, Inc.,

1009 Slater Road,

Suite 210-B,

Durham, NC 27703,

USA.

Manufactured By:

Intas Pharmaceuticals Limited,

Ahmedabad -380054, India.



10 0653 3 697356



Issued May 2019