Lexapro

>10%

Headache (24%)

Nausea (18%)

Ejaculation disorder (9-14%)

Somnolence (4-13%)

Insomnia (7-12%)

1-10%

Xerostomia (4-9%)

Constipation (3-6%)

Fatigue (2-8%)

Libido decrease (3-7%)

Anorgasmia (2-6%)

Flatulence (2%)

Toothache (2%)

Weight gain (1%)

Menstrual disorder (2%)

Neck/shoulder pain (3%)

Rhinitis (5%)

Flu-like syndrome (5%)

Ejaculation disorder (9-14%)

<1%

Arthralgia

Abdominal pain

Abnormal bleeding

Abnormal dreams

Allergy

Blurred vision

Bronchitis

Chest pain

Constipation

Decreased appetite

Decreased concentration

Disrupts platelets/hemostasis

Dizziness

Dyspepsia

Fever

Heartburn

Hot flashes

Impotence

Irritability

Jaw stiffness

Lethargy

Lightheadedness

Menstrual disorder

Hypertension

Palpitations

Migraine

Myalgia

Paresthesia

Rash

Sweating

Tinnitus

Tremor

Urinary frequency

Urinary tract infection

Vertigo

Vomiting

Yawning

Mechanism of Action

S-enantiomer of racemic citalopram; inhibits the reuptake of serotonin, with little or no effect on norepinephrine or dopamine reuptake

Absorption

Bioavailability: 80%

Peak plasma time: 3.5-6.5 hr

Distribution

Protein bound: 56%

Vd: 20 L/kg

Metabolism

CYP3A4, CYP2C19

Metabolites: Insignificant potency

Enzymes inhibited: CYP2D6

Elimination

Half-life: 27-32 hr

Dialyzable: No

Renal clearance: 42 mL/min

Total body clearance: 600 mL/min

Excretion: Urine (8%)

Take Lexapro exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. Your doctor will determine the best dose for you.

The recommended dosage of Lexapro is 10-20 mg a day. Exceptions include the elderly and patients with hepatic impairment, who should not take more than 10 mg a day. Both Generalized Anxiety Disorder (GAD) and Depression are considered chronic conditions, treatment is recommended for several months. The efficacy of Lexapro over long periods of time has not been studied, therefore consistent reevaluation of the treatment is recommended for longer periods of treatment.

Major Depressive Disorder

Acute and maintenance treatment of major depressive disorder.1 2 14 16 35 36

APA states that effectiveness of antidepressants is generally comparable between and within classes of medications, including SSRIs, SNRIs, TCAs, MAO inhibitors, and other antidepressants (e.g., bupropion, mirtazapine, trazodone).a Choose antidepressant based mainly on patient preference; nature of prior response to medication; safety, tolerability, and anticipated adverse effects; concurrent psychiatric and medical conditions; and specific properties of the medication (e.g., half-life, actions on CYP isoenzymes, other drug interactions).a For most patients, an SSRI, SNRI, mirtazapine, or bupropion is considered optimal.a Consult APA’s Practice Guidelines for the Treatment of Patients with Major Depressive Disorder for additional information.a

Generalized Anxiety Disorder

Management of generalized anxiety disorder.1

General

• Allow at least 2 weeks to elapse between discontinuance of an MAO inhibitor and initiation of escitalopram, and vice versa.1 29 (See Contraindications and also see Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions under Cautions.)

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.1 12 14 15 29 (See Worsening of Depression and Suicidality Risk under Cautions.)

• Sustained therapy may be required; monitor periodically for need for continued therapy.1

• Avoid abrupt discontinuance.1 29 Taper dosage gradually and monitor for withdrawal symptoms.1 29 If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage, then resume more gradual dosage reductions.1 29 (See Withdrawal of Therapy under Cautions.)

Administration

Oral Administration

Administer orally once daily (morning or evening) without regard to meals.1

Dosage

Available as escitalopram oxalate; dosage is expressed in terms of escitalopram.1 29

Escitalopram dosages of 10 mg daily appear to be comparable to racemic citalopram dosages of 40 mg daily.2

Pediatric Patients

Adolescents 12–17 years of age: Initially, 10 mg once daily.1 May be increased to 20 mg once daily after ≥3 weeks; efficacy established at dosages of 10–20 mg once daily in a flexible-dose study.1 36

Optimum duration not established; may require several months of therapy or longer.1 5

Adults

Initially, 10 mg once daily.1 29 May be increased to 20 mg once daily after ≥1 week; however, no additional therapeutic benefit with 20 mg once daily compared with 10 mg once daily.1 29

Optimum duration not established; may require several months of therapy or longer.1 5

Initially, 10 mg once daily.29 Dosage may be increased to 20 mg once daily after ≥1 week.29

Not studied >8 weeks of therapy; periodically reevaluate need for therapy.1

Special Populations

Hepatic Impairment

10 mg once daily.1 29

Renal Impairment

No dosage adjustment required in patients with mild to moderate renal impairment; not studied in patients with severe renal impairment (Clcr <20 mL/minute).1 29

Geriatric Patients

10 mg once daily.1 29

• S-enantiomer of citalopram,1 an SSRI that occurs as a 50:50 racemic mixture of the R- and S-enantiomers.1 4

• At least 100-fold more potent as an inhibitor of serotonin (5-hydroxytryptamine [5-HT]) reuptake at presynaptic membranes and 5-HT neuronal firing rate than R-enantiomer and is twice as potent as racemic mixture.1 2 9

• Mechanism of action as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the CNS resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).1

• Highly selective; minimal effects on norepinephrine (NE) and dopamine (DA) neuronal reuptake and little or no affinity for α- or β-adrenergic, dopamine D1–5, histamine H1–3, GABA-benzodiazepine, muscarinic M1–5, or 5-HT1–7 receptors or various ion channels (e.g., calcium, chloride, potassium, sodium channels).1

In the U.S.

• Lexapro

Available Dosage Forms:

• Tablet
• Solution

Therapeutic Class: Antidepressant

Pharmacologic Class: Serotonin Reuptake Inhibitor

Take this medicine only as directed by your doctor to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor or pharmacist if you have any questions.

Escitalopram may be taken with or without food. If your doctor tells you to take it at a specific time, follow your doctor's instructions.

If you are using the oral liquid, shake the bottle well before measuring each dose. Use a marked measuring spoon, oral syringe, or medicine cup to measure each dose. The average household teaspoon may not hold the right amount of liquid.

You may have to take escitalopram for a month or longer before you begin to feel better.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (solution or tablets):
  • For depression:
    • Adults and children 12 years of age and older—10 milligrams (mg) once a day, taken either in the morning or evening. Your doctor may adjust your dose as needed. However, the dose is usually not more than 20 mg per day.
    • Older adults—10 mg once a day, taken either in the morning or evening.
    • Children younger than 12 years of age—Use and dose must be determined by your doctor.
  • For generalized anxiety disorder:
    • Adults—At first, 10 milligrams (mg) once a day, taken either in the morning or evening. Your doctor may adjust your dose as needed. However, the dose is usually not more than 20 mg per day.
    • Older adults—10 mg once a day, taken either in the morning or evening.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Major Depressive Disorder

Lexapro (escitalopram) 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.

Generalized Anxiety Disorder

Lexapro 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.

Human Experience

In clinical trials of escitalopram, there were reports of escitalopram overdose, including overdoses of up to 600 mg, with no associated fatalities. During the postmarketing evaluation of escitalopram, Lexapro 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.

Management of Overdose

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

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.

Mechanism of Action

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

Pharmacodynamics

In vitro and in vivo studies in animals suggest that escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate. Tolerance to a model of antidepressant effect in rats was not induced by long-term (up to 5 weeks) treatment with escitalopram. Escitalopram has no or very low affinity for serotonergic (5-HT1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5), 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.

Pharmacokinetics

The single- and multiple-dose pharmacokinetics of escitalopram are linear and dose-proportional in a dose range of 10 to 30 mg/day. Biotransformation of escitalopram is mainly hepatic, with a mean terminal half-life of about 27-32 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 2.2-2.5 times the plasma concentrations observed after a single dose. The tablet and the oral solution dosage forms of escitalopram oxalate are bioequivalent.

Absorption and Distribution

Following a single oral dose (20 mg tablet or solution) of escitalopram, peak blood levels occur at about 5 hours. Absorption of escitalopram is not affected by food.

The absolute bioavailability of citalopram is about 80% relative to an intravenous dose, and the volume of distribution of citalopram is about 12 L/kg. Data specific on escitalopram are unavailable.

The binding of escitalopram to human plasma proteins is approximately 56%.

Metabolism and Elimination

Following oral administrations of escitalopram, the fraction of drug recovered in the urine as escitalopram and S-demethylcitalopram (S-DCT) is about 8% and 10%, respectively. The oral clearance of escitalopram is 600 mL/min, with approximately 7% of that due to renal clearance.

Escitalopram is metabolized to S-DCT and S-didemethylcitalopram (S-DDCT). In humans, unchanged escitalopram is the predominant compound in plasma. At steady state, the concentration of the escitalopram metabolite S-DCT in plasma is approximately one-third that of escitalopram. The level of S-DDCT was not detectable in most subjects. In vitro studies show that escitalopram is at least 7 and 27 times more potent than S-DCT and S-DDCT, respectively, in the inhibition of serotonin reuptake, suggesting that the metabolites of escitalopram do not contribute significantly to the antidepressant actions of escitalopram. S-DCT and S-DDCT also have no or very low affinity for serotonergic (5-HT1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5), and benzodiazepine receptors. S-DCT and S-DDCT also do not bind to various ion channels including Na+, K+, Cl-, and Ca++ channels.

In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram.

Population Subgroups

Age

Adolescents - In a single dose study of 10 mg escitalopram, AUC of escitalopram decreased by 19%, and Cmax increased by 26% in healthy adolescent subjects (12 to 17 years of age) compared to adults. Following multiple dosing of 40 mg/day citalopram, escitalopram elimination half-life, steady-state Cmax and AUC were similar in patients with MDD (12 to 17 years of age) compared to adult patients. No adjustment of dosage is needed in adolescent patients.

Elderly - Escitalopram pharmacokinetics in subjects ≥ 65 years of age were compared to younger subjects in a single-dose and a multiple-dose study. Escitalopram AUC and half-life were increased by approximately 50% in elderly subjects, and Cmax was unchanged. 10 mg is the recommended dose for elderly patients [see Dosage and Administration (2.3)].

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

Reduced hepatic function - Citalopram oral clearance was reduced by 37% and half-life was doubled in patients with reduced hepatic function compared to normal subjects. 10 mg is the recommended dose of escitalopram for most hepatically impaired patients [see Dosage and Administration (2.3)].

Reduced renal function - In patients with mild to moderate renal function impairment, oral clearance of citalopram was reduced by 17% compared to normal subjects. No adjustment of dosage for such patients is recommended. No information is available about the pharmacokinetics of escitalopram in patients with severely reduced renal function (creatinine clearance < 20 mL/min).

Drug-Drug Interactions

In vitro enzyme inhibition data did not reveal an inhibitory effect of escitalopram on CYP3A4, -1A2, -2C9, -2C19, and -2E1. Based on in vitro data, escitalopram would be expected to have little inhibitory effect on in vivo metabolism mediated by these cytochromes. While in vivo data to address this question are limited, results from drug interaction studies suggest that escitalopram, at a dose of 20 mg, has no 3A4 inhibitory effect and a modest 2D6 inhibitory effect. See Drug Interactions (7.18) for more detailed information on available drug interaction data.

You should not use Lexapro if you are allergic to escitalopram or citalopram (Celexa), or if:

• you also take pimozide or citalopram.

Do not use Lexapro within 14 days before or 14 days after you have used an MAO inhibitor. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.

Some medicines can interact with escitalopram and cause a serious condition called serotonin syndrome. Be sure your doctor knows if you also take stimulant medicine, opioid medicine, herbal products, or medicine for depression, mental illness, Parkinson's disease, migraine headaches, serious infections, or prevention of nausea and vomiting. Ask your doctor before making any changes in how or when you take your medications.

To make sure Lexapro is safe for you, tell your doctor if you have ever had:

• liver or kidney disease;

• seizures;

• low levels of sodium in your blood;

• heart disease, high blood pressure;

• a stroke;

• a bleeding or blood clotting disorder;

• bipolar disorder (manic depression); or

• drug addiction or suicidal thoughts.

Some young people have thoughts about suicide when first taking an antidepressant. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Taking an SSRI antidepressant during pregnancy may cause serious lung problems or other complications in the baby. However, you may have a relapse of depression if you stop taking your antidepressant. Tell your doctor right away if you become pregnant while taking Lexapro. Do not start or stop taking this medicine during pregnancy without your doctor's advice.

Escitalopram can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Lexapro should not be given to a child younger than 12 years old.

Take Lexapro exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take Lexapro with or without food. Try to take the medicine at the same time each day.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

It may take up to 4 weeks before your symptoms improve. Keep using Lexapro as directed and tell your doctor if your symptoms do not improve.

Do not stop using Lexapro suddenly, or you could have unpleasant withdrawal symptoms. Follow your doctor's instructions about tapering your dose.

Store at room temperature away from moisture and heat.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Common side effects of Lexapro include: diarrhea, drowsiness, ejaculatory disorder, headache, insomnia, nausea, and delayed ejaculation. Other side effects include: anorgasmia, constipation, dizziness, dyspepsia, fatigue, decreased libido, diaphoresis, and xerostomia. See below for a comprehensive list of adverse effects.