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

Initial Treatment

Storage and Handling

Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature]

Although escitalopram oral solution 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 oral solution is not recommended.

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.

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 oral solution and lithium are coadministered.

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

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

There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of escitalopram oral solution 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) ].

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.

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

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/

Escitalopram oxalate is an orally administered selective serotonin reuptake inhibitor (SSRI). Escitalopram is the pure S-enantiomer (single isomer) of the racemic bicyclic phthalane derivative citalopram. Escitalopram oxalate is designated S-(+)-1-[3-(dimethyl-amino)propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrile oxalate with the following structural formula:

The molecular formula is C ₂₀H ₂₁FN ₂O ∙ C ₂H ₂O ₄and the molecular weight is 414.40.

Escitalopram oxalate 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 oxalate is available as an oral solution.

Escitalopram oral solution USP contains escitalopram oxalate equivalent to 1 mg/mL escitalopram base. It also contains the following inactive ingredients: citric acid, glycerin, malic acid, methylparaben, natural peppermint flavor, propylene glycol, propylparaben, purified water, sodium citrate, and sorbitol.

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.

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.

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 _maxof 43% and 39%, respectively. The clinical significance of these findings is unknown.

Administration of 20 mg/day escitalopram oral solution for 21 days in healthy volunteers resulted in a 50% increase in C _maxand 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 oral solution and metoprolol had no clinically significant effects on blood pressure or heart rate.

Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including escitalopram oral solution. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was reversible when escitalopram oral solution 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 oral solution 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.

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.

Read the Medication Guide that comes with escitalopram oral solution 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 oral solution?

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

1. Suicidal thoughts or actions:

• Escitalopram oral solution and other antidepressant medicines may increase suicidal thoughts or actionsin 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 oral solution 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 oral solution 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 oral solution 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 anti-inflammatory 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.

10. Sexual problems (dysfunction).Taking selective serotonin reuptake inhibitors (SSRIs), including escitalopram oral solution, may cause sexual problems.

Symptoms in males may include:

• Delayed ejaculation or inability to have an ejaculation
• Decreased sex drive
• Problems getting or keeping an erection

Symptoms in females may include:

• Decreased sex drive
• Delayed orgasm or inability to have an orgasm

Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with escitalopram oral solution. There may be treatments your healthcare provider can suggest.

Do not stop escitalopram oral solution without first talking to your healthcare provider.Stopping escitalopram oral solution 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 is escitalopram oral solution?

Escitalopram oral solution 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 oral solution is 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 oral solution treatment.

Who should not take escitalopram oral solution?

Do not take escitalopram oral solution if you:

• are allergic to escitalopram or citalopram or any of the ingredients in escitalopram oral solution. See the end of this Medication Guide for a complete list of ingredients in escitalopram oral solution.
• 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 oral solution unless directed to do so by your physician.
• Do not start escitalopram oral solution if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.
  
  People who take escitalopram oral solution 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 oral solution with Orap ^®(pimozide) because taking these two drugs together can cause serious heart problems.

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

Before starting escitalopram oral solution, 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. Taking escitalopram oral solution late in pregnancy may lead to an increased risk of certain problems in your newborn. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy.
  • If you become pregnant while taking escitalopram oral solution, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1-844-405-6185 or go to https://womensmentalhealth.org/clinical-andresearchprograms/pregnancyregistry/antidepressants/.

• are breast-feeding or plan to breast-feed. Escitalopram oral solution may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if taking escitalopram oral solution.

Tell your healthcare provider about all the medicines that you take,including prescription and non-prescription medicines, vitamins, and herbal supplements. Escitalopram oral solution 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 oral solution with your other medicines. Do not start or stop any medicine while taking escitalopram oral solution without talking to your healthcare provider first.

How should I take escitalopram oral solution?

• Take escitalopram oral solution exactly as prescribed. Your healthcare provider may need to change the dose of escitalopram oral solution until it is the right dose for you.
• Escitalopram oral solution may be taken with or without food.
• If you miss a dose of escitalopram oral solution, 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 oral solution at the same time.
• If you take too much escitalopram oral solution, call your healthcare provider or poison control center right away, or get emergency treatment.

What should I avoid while taking escitalopram oral solution?

Escitalopram oral solution 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 oral solution affects you. Do not drink alcohol while using escitalopram oral solution.

What are the possible side effects of escitalopram oral solution?

Escitalopram oral solution may cause serious side effects, including allof those described in the section entitled "What is the most important information I should know about escitalopram oral solution?"

Common possible side effects in people who take escitalopram oral solution 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 oral solution.

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 oral solution. 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 oral solution?

• Store escitalopram oral solution at 68° to 77°F (20° to 25°C) [see USP Controlled Room Temperature].
• Keep escitalopram oral solution bottle closed tightly.

Keep escitalopram oral solution and all medicines out of the reach of children.

General information about escitalopram oral solution

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

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

For more information about escitalopram oral solution call 1-866-923-4914or go to www.taro.com.

What are the ingredients in escitalopram oral solution?

Active ingredient: escitalopram oxalate

Inactive ingredients: citric acid, glycerin, malic acid, methylparaben, natural peppermint flavor, propylene glycol, propylparaben, purified water, sodium citrate, and sorbitol

Mfd. by: Taro Pharmaceuticals Inc.

Brampton, Ontario, Canada L6T 1C1

Dist. by: Taro Pharmaceuticals U.S.A., Inc.

Hawthorne, NY 10532

*The brands listed are registered trademarks of their respective owners and are not trademarks of Taro Pharmaceuticals U.S.A., Inc. or its affiliates.

Revised: July 2021

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

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.

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

The safety and effectiveness of escitalopram oral solution 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 oral solution 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 oral solution.

Safety and effectiveness of escitalopram oral solution 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 oral solution.

Approximately 6% of the 1144 patients receiving escitalopram in controlled trials of escitalopram oral solution in major depressive disorder and GAD were 60 years of age or older; elderly patients in these trials received daily doses of escitalopram oral solution between 10 mg 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 oral solution cannot be ruled out.

SSRIs and SNRIs, including escitalopram oral solution, 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 _maxwas 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.

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.

• Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with escitalopram oral solution or within 14 days of stopping treatment with escitalopram oral solution. Do not use escitalopram oral solution within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start escitalopram oral solution in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1).
• Pimozide: Do not use concomitantly ( 4.2).
• Known hypersensitivity to escitalopram or citalopram or any of the inactive ingredients ( 4.3).

Most commonly observed adverse reactions (incidence ≥ 5% and at least twice the incidence of placebo patients) are: insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased, fatigue and somnolence, decreased libido, and anorgasmia ( 6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Concomitant use with SSRIs, SNRIs or Tryptophan is not recommended ( 7.2).

Use caution when concomitant use with drugs that affect Hemostasis (NSAIDs, Aspirin, Warfarin) ( 7.6).

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 oral solution 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.

In vitroand in vivostudies 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 mg/day 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.

SSRIs and SNRIs, including escitalopram oral solution, 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 oral solution and NSAIDs, aspirin, or other drugs that affect coagulation.

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including escitalopram oral solution, 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 oral solution with MAOIs intended to treat psychiatric disorders is contraindicated. Escitalopram oral solution 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 oral solution. Escitalopram oral solution should be discontinued before initiating treatment with the MAOI [ see Contraindications (4.1)and Dosage and Administration (2.5and 2.6) ].

If concomitant use of escitalopram oral solution 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 oral solution and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

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

Escitalopram oral solution is a selective serotonin reuptake inhibitor (SSRI) indicated for:

• Acute and Maintenance Treatment of Major Depressive Disorder (MDD) in adults and adolescents aged 12 to 17 years ( 1.1)
• Acute Treatment of Generalized Anxiety Disorder (GAD) in adults ( 1.2)

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 oral solution should be used with caution in patients with severe renal impairment.

Use of SSRIs, including escitalopram oral solution, 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 oral solution 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).

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 _maxof pimozide. The mechanism of this pharmacodynamic interaction is not known.

• Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including escitalopram oral solution, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort). If such symptoms occur, discontinue escitalopram oral solution and initiate supportive treatment. If concomitant use of escitalopram oral solution with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases ( 4, 5.2).
• Discontinuation of Treatment with Escitalopram Oral Solution: A gradual reduction in dose rather than abrupt cessation is recommended whenever possible ( 5.3).
• Seizures: Prescribe with care 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 SIADH ( 5.6).
• Abnormal Bleeding: Use caution in concomitant use with NSAIDs, aspirin, warfarin or other drugs that affect coagulation ( 5.7).
• Interference with Cognitive and Motor Performance: Use caution when operating machinery ( 5.8).
• Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants ( 5.9).
• Use in Patients with Concomitant Illness: Use caution in patients with diseases or conditions that produce altered metabolism or hemodynamic responses ( 5.10).
• Sexual Dysfunction: Escitalopram oral solution may cause symptoms of sexual dysfunction. ( 5.11)

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

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 oral solution.

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.

Escitalopram oral solution should be administered once daily, in the morning or evening, with or without food.

• Oral solution: 1 mg per mL

Escitalopram oral solution 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.

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).

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.

Escitalopram oral solution 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.

In vitrostudies 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.

The efficacy of escitalopram oral solution in the acute treatment of Generalized Anxiety Disorder (GAD) was demonstrated in three, 8-week, multicenter, flexible-dose, placebo-controlled studies that compared escitalopram oral solution 10 mg/day 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 oral solution 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 oral solution has differential effects in these groups. There was no difference in response to escitalopram oral solution between men and women.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Escitalopram Oral Solution USP, 5 mg/5 mLis available in a peppermint flavor, sizes of:

4 fl oz (120 mL) - NDC 51672-1348-8

8 fl oz (240 mL) - NDC 51672-1348-1

16 fl oz (480 mL) - NDC 51672-1348-9

In patients with bipolar disorder, treating a depressive episode with escitalopram oral solution or another antidepressant may precipitate a mixed/manic episode. In placebo-controlled trials of escitalopram oral solution in major depressive disorder, activation of mania/hypomania was reported in one (0.1%) of 715 patients treated with escitalopram oral solution and in none of the 592 patients treated with placebo. One additional case of hypomania has been reported in association with escitalopram oral solution 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 oral solution, screen patients for any personal or family history of bipolar disorder, mania, or hypomania [ see Dosage and Administration (2.3) ].

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

The use of MAOIs intended to treat psychiatric disorders with escitalopram oral solution or within 14 days of stopping treatment with escitalopram oral solution is contraindicated because of an increased risk of serotonin syndrome. The use of escitalopram oral solution within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [ see Dosage and Administration (2.5), and Warnings and Precautions (5.2) ].

Starting escitalopram oral solution in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [ see Dosage and Administration (2.6), and Warnings and Precautions (5.2) ].

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

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 oral solution is not approved for use in pediatric patients less than 12 years of age [ see Use in Specific Populations (8.4) ].

In vitrostudies 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 vivodata 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 _maxand 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.

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

Escitalopram oral solution 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 oral solution 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 oral solution, however, it should be used with caution in such patients [ see Dosage and Administration (2.3) ].

NDC 51672-1348-1

8 fl oz

(240 mL)

Dispense the accompanying

Medication Guide to each patient.

Escitalopram

Oral Solution, USP

5 mg*/5 mL

Rx only

TARO

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

During marketing of escitalopram 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 oral solution. 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) ].

In a study in normal volunteers, escitalopram oral solution 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 oral solution therapy does not affect their ability to engage in such activities.

Symptoms associated with discontinuation of escitalopram oral solution 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 oral solution, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

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 oral solution is initiated or discontinued.

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

Do not start escitalopram oral solution 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 oral solution 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 oral solution 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 oral solution 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 oral solution 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) ].

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

Initial Treatment

Storage and Handling

Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature]

Although escitalopram oral solution 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 oral solution is not recommended.

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.

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 oral solution and lithium are coadministered.

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

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

There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of escitalopram oral solution 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) ].

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.

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

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/

Escitalopram oxalate is an orally administered selective serotonin reuptake inhibitor (SSRI). Escitalopram is the pure S-enantiomer (single isomer) of the racemic bicyclic phthalane derivative citalopram. Escitalopram oxalate is designated S-(+)-1-[3-(dimethyl-amino)propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrile oxalate with the following structural formula:

The molecular formula is C ₂₀H ₂₁FN ₂O ∙ C ₂H ₂O ₄and the molecular weight is 414.40.

Escitalopram oxalate 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 oxalate is available as an oral solution.

Escitalopram oral solution USP contains escitalopram oxalate equivalent to 1 mg/mL escitalopram base. It also contains the following inactive ingredients: citric acid, glycerin, malic acid, methylparaben, natural peppermint flavor, propylene glycol, propylparaben, purified water, sodium citrate, and sorbitol.

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.

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.

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 _maxof 43% and 39%, respectively. The clinical significance of these findings is unknown.

Administration of 20 mg/day escitalopram oral solution for 21 days in healthy volunteers resulted in a 50% increase in C _maxand 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 oral solution and metoprolol had no clinically significant effects on blood pressure or heart rate.

Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including escitalopram oral solution. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was reversible when escitalopram oral solution 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 oral solution 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.

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.

Read the Medication Guide that comes with escitalopram oral solution 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 oral solution?

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

1. Suicidal thoughts or actions:

• Escitalopram oral solution and other antidepressant medicines may increase suicidal thoughts or actionsin 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 oral solution 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 oral solution 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 oral solution 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 anti-inflammatory 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.

10. Sexual problems (dysfunction).Taking selective serotonin reuptake inhibitors (SSRIs), including escitalopram oral solution, may cause sexual problems.

Symptoms in males may include:

• Delayed ejaculation or inability to have an ejaculation
• Decreased sex drive
• Problems getting or keeping an erection

Symptoms in females may include:

• Decreased sex drive
• Delayed orgasm or inability to have an orgasm

Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with escitalopram oral solution. There may be treatments your healthcare provider can suggest.

Do not stop escitalopram oral solution without first talking to your healthcare provider.Stopping escitalopram oral solution 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 is escitalopram oral solution?

Escitalopram oral solution 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 oral solution is 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 oral solution treatment.

Who should not take escitalopram oral solution?

Do not take escitalopram oral solution if you:

• are allergic to escitalopram or citalopram or any of the ingredients in escitalopram oral solution. See the end of this Medication Guide for a complete list of ingredients in escitalopram oral solution.
• 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 oral solution unless directed to do so by your physician.
• Do not start escitalopram oral solution if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.
  
  People who take escitalopram oral solution 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 oral solution with Orap ^®(pimozide) because taking these two drugs together can cause serious heart problems.

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

Before starting escitalopram oral solution, 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. Taking escitalopram oral solution late in pregnancy may lead to an increased risk of certain problems in your newborn. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy.
  • If you become pregnant while taking escitalopram oral solution, talk to your healthcare provider about registering with the National Pregnancy Registry for Antidepressants. You can register by calling 1-844-405-6185 or go to https://womensmentalhealth.org/clinical-andresearchprograms/pregnancyregistry/antidepressants/.

• are breast-feeding or plan to breast-feed. Escitalopram oral solution may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if taking escitalopram oral solution.

Tell your healthcare provider about all the medicines that you take,including prescription and non-prescription medicines, vitamins, and herbal supplements. Escitalopram oral solution 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 oral solution with your other medicines. Do not start or stop any medicine while taking escitalopram oral solution without talking to your healthcare provider first.

How should I take escitalopram oral solution?

• Take escitalopram oral solution exactly as prescribed. Your healthcare provider may need to change the dose of escitalopram oral solution until it is the right dose for you.
• Escitalopram oral solution may be taken with or without food.
• If you miss a dose of escitalopram oral solution, 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 oral solution at the same time.
• If you take too much escitalopram oral solution, call your healthcare provider or poison control center right away, or get emergency treatment.

What should I avoid while taking escitalopram oral solution?

Escitalopram oral solution 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 oral solution affects you. Do not drink alcohol while using escitalopram oral solution.

What are the possible side effects of escitalopram oral solution?

Escitalopram oral solution may cause serious side effects, including allof those described in the section entitled "What is the most important information I should know about escitalopram oral solution?"

Common possible side effects in people who take escitalopram oral solution 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 oral solution.

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 oral solution. 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 oral solution?

• Store escitalopram oral solution at 68° to 77°F (20° to 25°C) [see USP Controlled Room Temperature].
• Keep escitalopram oral solution bottle closed tightly.

Keep escitalopram oral solution and all medicines out of the reach of children.

General information about escitalopram oral solution

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

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

For more information about escitalopram oral solution call 1-866-923-4914or go to www.taro.com.

What are the ingredients in escitalopram oral solution?

Active ingredient: escitalopram oxalate

Inactive ingredients: citric acid, glycerin, malic acid, methylparaben, natural peppermint flavor, propylene glycol, propylparaben, purified water, sodium citrate, and sorbitol

Mfd. by: Taro Pharmaceuticals Inc.

Brampton, Ontario, Canada L6T 1C1

Dist. by: Taro Pharmaceuticals U.S.A., Inc.

Hawthorne, NY 10532

*The brands listed are registered trademarks of their respective owners and are not trademarks of Taro Pharmaceuticals U.S.A., Inc. or its affiliates.

Revised: July 2021

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

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.

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

The safety and effectiveness of escitalopram oral solution 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 oral solution 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 oral solution.

Safety and effectiveness of escitalopram oral solution 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 oral solution.

Approximately 6% of the 1144 patients receiving escitalopram in controlled trials of escitalopram oral solution in major depressive disorder and GAD were 60 years of age or older; elderly patients in these trials received daily doses of escitalopram oral solution between 10 mg 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 oral solution cannot be ruled out.

SSRIs and SNRIs, including escitalopram oral solution, 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 _maxwas 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.

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.

• Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with escitalopram oral solution or within 14 days of stopping treatment with escitalopram oral solution. Do not use escitalopram oral solution within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start escitalopram oral solution in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1).
• Pimozide: Do not use concomitantly ( 4.2).
• Known hypersensitivity to escitalopram or citalopram or any of the inactive ingredients ( 4.3).

Most commonly observed adverse reactions (incidence ≥ 5% and at least twice the incidence of placebo patients) are: insomnia, ejaculation disorder (primarily ejaculatory delay), nausea, sweating increased, fatigue and somnolence, decreased libido, and anorgasmia ( 6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Concomitant use with SSRIs, SNRIs or Tryptophan is not recommended ( 7.2).

Use caution when concomitant use with drugs that affect Hemostasis (NSAIDs, Aspirin, Warfarin) ( 7.6).

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 oral solution 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.

In vitroand in vivostudies 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 mg/day 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.

SSRIs and SNRIs, including escitalopram oral solution, 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 oral solution and NSAIDs, aspirin, or other drugs that affect coagulation.

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including escitalopram oral solution, 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 oral solution with MAOIs intended to treat psychiatric disorders is contraindicated. Escitalopram oral solution 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 oral solution. Escitalopram oral solution should be discontinued before initiating treatment with the MAOI [ see Contraindications (4.1)and Dosage and Administration (2.5and 2.6) ].

If concomitant use of escitalopram oral solution 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 oral solution and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

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

Escitalopram oral solution is a selective serotonin reuptake inhibitor (SSRI) indicated for:

• Acute and Maintenance Treatment of Major Depressive Disorder (MDD) in adults and adolescents aged 12 to 17 years ( 1.1)
• Acute Treatment of Generalized Anxiety Disorder (GAD) in adults ( 1.2)

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 oral solution should be used with caution in patients with severe renal impairment.

Use of SSRIs, including escitalopram oral solution, 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 oral solution 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).

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 _maxof pimozide. The mechanism of this pharmacodynamic interaction is not known.

• Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including escitalopram oral solution, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort). If such symptoms occur, discontinue escitalopram oral solution and initiate supportive treatment. If concomitant use of escitalopram oral solution with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases ( 4, 5.2).
• Discontinuation of Treatment with Escitalopram Oral Solution: A gradual reduction in dose rather than abrupt cessation is recommended whenever possible ( 5.3).
• Seizures: Prescribe with care 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 SIADH ( 5.6).
• Abnormal Bleeding: Use caution in concomitant use with NSAIDs, aspirin, warfarin or other drugs that affect coagulation ( 5.7).
• Interference with Cognitive and Motor Performance: Use caution when operating machinery ( 5.8).
• Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants ( 5.9).
• Use in Patients with Concomitant Illness: Use caution in patients with diseases or conditions that produce altered metabolism or hemodynamic responses ( 5.10).
• Sexual Dysfunction: Escitalopram oral solution may cause symptoms of sexual dysfunction. ( 5.11)

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

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 oral solution.

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.

Escitalopram oral solution should be administered once daily, in the morning or evening, with or without food.

• Oral solution: 1 mg per mL

Escitalopram oral solution 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.

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).

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.

Escitalopram oral solution 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.

In vitrostudies 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.

The efficacy of escitalopram oral solution in the acute treatment of Generalized Anxiety Disorder (GAD) was demonstrated in three, 8-week, multicenter, flexible-dose, placebo-controlled studies that compared escitalopram oral solution 10 mg/day 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 oral solution 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 oral solution has differential effects in these groups. There was no difference in response to escitalopram oral solution between men and women.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Escitalopram Oral Solution USP, 5 mg/5 mLis available in a peppermint flavor, sizes of:

4 fl oz (120 mL) - NDC 51672-1348-8

8 fl oz (240 mL) - NDC 51672-1348-1

16 fl oz (480 mL) - NDC 51672-1348-9

In patients with bipolar disorder, treating a depressive episode with escitalopram oral solution or another antidepressant may precipitate a mixed/manic episode. In placebo-controlled trials of escitalopram oral solution in major depressive disorder, activation of mania/hypomania was reported in one (0.1%) of 715 patients treated with escitalopram oral solution and in none of the 592 patients treated with placebo. One additional case of hypomania has been reported in association with escitalopram oral solution 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 oral solution, screen patients for any personal or family history of bipolar disorder, mania, or hypomania [ see Dosage and Administration (2.3) ].

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

The use of MAOIs intended to treat psychiatric disorders with escitalopram oral solution or within 14 days of stopping treatment with escitalopram oral solution is contraindicated because of an increased risk of serotonin syndrome. The use of escitalopram oral solution within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [ see Dosage and Administration (2.5), and Warnings and Precautions (5.2) ].

Starting escitalopram oral solution in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [ see Dosage and Administration (2.6), and Warnings and Precautions (5.2) ].

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

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 oral solution is not approved for use in pediatric patients less than 12 years of age [ see Use in Specific Populations (8.4) ].

In vitrostudies 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 vivodata 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 _maxand 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.

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

Escitalopram oral solution 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 oral solution 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 oral solution, however, it should be used with caution in such patients [ see Dosage and Administration (2.3) ].

NDC 51672-1348-1

8 fl oz

(240 mL)

Dispense the accompanying

Medication Guide to each patient.

Escitalopram

Oral Solution, USP

5 mg*/5 mL

Rx only

TARO

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

During marketing of escitalopram 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 oral solution. 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) ].

In a study in normal volunteers, escitalopram oral solution 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 oral solution therapy does not affect their ability to engage in such activities.

Symptoms associated with discontinuation of escitalopram oral solution 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 oral solution, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

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 oral solution is initiated or discontinued.

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

Do not start escitalopram oral solution 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 oral solution 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 oral solution 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 oral solution 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 oral solution 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) ].

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