escitalopram 10 mg tablet (generic lexapro)

Cautions

Contraindications

Concurrent or recent (i.e., within 2 weeks) therapy with a monoamine oxidase (MAO) inhibitor. At least 14 days should elapse between discontinuance of escitalopram and initiation of MAO inhibitor therapy and vice versa.(See Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions and also see Drug Interactions: Monoamine Oxidase Inhibitors.)

Concomitant use with pimozide.(See Drug Interactions: Antipsychotic Agents and Other Dopamine Antagonists.)

Known hypersensitivity to escitalopram, citalopram, or any ingredient in the formulation.

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric (see Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions) patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants. This risk may persist until clinically important remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term, placebo-controlled studies of antidepressants (i.e., selective serotonin-reuptake inhibitors [SSRIs] and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders. An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults older than 24 years of age and a reduced risk was observed in adults 65 years of age or older.

The US Food and Drug Administration (FDA) recommends that all patients being treated with antidepressants for any indication be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, also should be advised to monitor patients on a daily basis for the emergence of agitation, irritability, or unusual changes in behavior as well as the emergence of suicidality, and to report such symptoms immediately to a health-care provider.

Although a causal relationship between the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consequently, consideration should be given to changing the therapeutic regimen or discontinuing therapy in patients whose depression is persistently worse or in patients experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if such manifestations are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If a decision is made to discontinue therapy, taper escitalopram dosage as rapidly as is feasible but consider the risks of abrupt discontinuance.(See Discontinuance of Therapy, under Dosage and Administration: Dosage.) FDA also recommends that the drugs be prescribed in the smallest quantity consistent with good patient management, in order to reduce the risk of overdosage.

Other Warnings and Precautions

Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions

Potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with SSRIs, including escitalopram, and selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs) alone, but particularly with concurrent use of other serotonergic drugs (including serotonin [5-hydroxytryptamine; 5-HT] type 1 receptor agonists [''triptans'']), drugs that impair the metabolism of serotonin (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists. Manifestations of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea). In its most severe form, serotonin syndrome may resemble NMS, which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation in vital signs, and mental status changes. Patients receiving escitalopram should be monitored for the development of serotonin syndrome or NMS-like signs and symptoms.(See Contraindications and also see Drug Interactions.)

Concurrent or recent (i.e., within 2 weeks) therapy with MAO inhibitors intended to treat depression is contraindicated.(See Contraindications and also see Drug Interactions: Monoamine Oxidase Inhibitors.)

If concurrent therapy with escitalopram and a 5-HT₁ receptor agonist (triptan) is clinically warranted, the patient should be observed carefully, particularly during initiation of therapy, when dosage is increased, or when another serotonergic agent is initiated.

Concomitant use of escitalopram and serotonin precursors (e.g., tryptophan) is not recommended.

If signs and symptoms of serotonin syndrome or NMS occur, treatment with escitalopram and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, should be immediately discontinued and supportive and symptomatic treatment initiated.

Withdrawal of Therapy

Withdrawal symptoms, including dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures, have been reported upon discontinuance of escitalopram and other SSRIs and SNRIs, particularly when discontinuance of these drugs is abrupt. While these reactions are generally self-limiting, there have been reports of serious discontinuance symptoms. Therefore, patients should be monitored for such symptoms when discontinuing escitalopram therapy. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.(See Discontinuance of Therapy under Dosage and Administration: Dosage.)

If intolerable symptoms occur following dosage reduction or discontinuance of escitalopram, the previously prescribed dosage should be reinstituted until symptoms abate; dosage reductions may then be resumed at a more gradual rate.

Seizures

Although anticonvulsant effects of racemic citalopram have been observed in animal studies, escitalopram has not been systematically evaluated in patients with seizure disorders. Seizures have been reported in patients receiving escitalopram in clinical trials; therefore, as with other antidepressants, escitalopram therapy should be initiated with caution in patients with a history of seizure disorder.

Activation of Mania/Hypomania

Activation of mania and hypomania has occurred in patients receiving escitalopram or citalopram. Escitalopram should be used with caution in patients with a history of mania.

Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Secretion

Treatment with SNRIs and SSRIs, including escitalopram, may result in hyponatremia. In many cases, hyponatremia appears to be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium concentrations lower than 110 mEq/L have been reported. Geriatric individuals and patients receiving diuretics or who are otherwise volume depleted may be at greater risk of developing hyponatremia. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls; more severe and/or acute cases have been associated with hallucinations, syncope, seizures, coma, respiratory arrest, and death. Discontinuance of escitalopram should be considered and appropriate medical intervention should be initiated in patients with symptomatic hyponatremia.

Abnormal Bleeding

SNRIs and SSRIs, including escitalopram, may increase the risk of bleeding events. Concurrent use of aspirin, nonsteroidal anti-inflammatory agents (NSAIAs), warfarin, and other anticoagulants may add to this risk. Case reports and epidemiologic studies have demonstrated an association between the use of drugs that interfere with serotonin reuptake and the occurrence of GI bleeding. Bleeding events related to SNRI and SSRI use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. The manufacturers recommend that patients be advised of the risk of bleeding associated with the concomitant use of escitalopram and aspirin or other NSAIAs, warfarin, or other drugs that affect coagulation.(See Drug Interactions: Drugs Affecting Hemostasis.)

Interference with Cognitive and Motor Performance

In a study in healthy volunteers, escitalopram 10 mg daily did not impair intellectual function or psychomotor performance. However, because any psychoactive drug may impair judgment, thinking, or motor skills, caution patients about operating hazardous machinery, including driving a motor vehicle, until they are reasonably certain that the drug does not affect their ability to engage in such activities.

Concomitant Illnesses

Experience with escitalopram in patients with certain concomitant diseases is limited.(See Renal Impairment and see Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

Escitalopram has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable cardiovascular disease; such patients were generally excluded from clinical studies. The drug should be used with caution in patients with diseases or conditions that produce altered metabolism or hemodynamic responses.

Concomitant use of SSRIs and MAO inhibitors has been associated with serious, sometimes fatal, reactions, including hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes; these reactions have resembled serotonin syndrome or NMS. (See Contraindications and Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions and see also Drug Interactions: Monoamine Oxidase Inhibitors.)

Specific Populations

Pregnancy

Category C.

Some neonates exposed to serotonergic antidepressants (e.g., SSRIs, SNRIs) late in the third trimester of pregnancy have developed complications that have sometimes been severe and required prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in special-care nurseries. Such complications may arise immediately upon delivery and usually last several days or up to 2-4 weeks. Clinical findings reported in the neonates have included respiratory distress, cyanosis, apnea, seizures, temperature instability or fever, feeding difficulty, dehydration, excessive weight loss, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features appear to be consistent with either a direct toxic effect of serotonergic antidepressants or, possibly, a drug withdrawal syndrome. In some cases, the clinical picture was consistent with serotonin syndrome.

Infants exposed to SSRIs in late pregnancy may have an increased risk of persistent pulmonary hypertension of the newborn (PPHN), a rare heart and lung condition associated with substantial neonatal morbidity and mortality. Although several epidemiologic studies have suggested an increased risk of PPHN with SSRI use during pregnancy, other studies did not demonstrate a statistically significant association. The US Food and Drug Administration (FDA) states that it is currently unclear whether the use of SSRIs, including escitalopram, during pregnancy can cause PPHN and recommends that clinicians not alter their current clinical practice of treating depression during pregnancy.

For additional information on the management of depression in women prior to conception and during pregnancy, including treatment algorithms, clinicians may consult the joint American Psychiatric Association and American College of Obstetricians and Gynecologists guidelines (at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103063/pdf/nihms293836.pdf).

Lactation

Escitalopram is distributed into human milk. Because of the potential for serious adverse effects (e.g., excessive somnolence, decreased feeding, weight loss) in nursing infants, caution should be exercised and nursing infants should be observed for adverse reactions when escitalopram is administered to a nursing woman.

Pediatric Use

Safety and efficacy of escitalopram have not been established in pediatric patients younger than 12 years of age with major depressive disorder. Safety and effectiveness have been established in adolescents 12-17 years of age for the acute treatment of major depressive disorder. Although efficacy of escitalopram as maintenance therapy in adolescent patients with major depressive disorder has not been systematically evaluated, such efficacy can be extrapolated from adult data along with comparisons of pharmacokinetic parameters in adults and adolescent patients.(See Uses: Major Depressive Disorder.)

Safety and efficacy of escitalopram have not been established in pediatric patients younger than 18 years of age with generalized anxiety disorder.

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

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients younger than 19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials. These findings should be carefully considered when assessing potential benefits and risks of escitalopram in a child or adolescent for any clinical use.(See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

Geriatric Use

Approximately 6% of patients studied in clinical trials of escitalopram for major depressive disorder and generalized anxiety disorder were 60 years of age or older; geriatric patients in these trials received daily dosages of 10-20 mg daily. Experience in geriatric patients in these trials was insufficient to determine whether they respond differently from younger adults; however, increased sensitivity cannot be ruled out.

In 2 pharmacokinetic studies, the mean area under the plasma concentration-time curve (AUC) and elimination half-life of escitalopram were increased by approximately 50% in geriatric individuals compared with younger individuals and peak escitalopram concentrations were unchanged. Therefore, the manufacturers state that the recommended dosage of escitalopram in geriatric patients is 10 mg once daily.

SNRIs and SSRIs, including escitalopram, have been associated with clinically important hyponatremia in geriatric patients, who may be at greater risk for this adverse effect.(See Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Secretion under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults 65 years of age or older with antidepressant therapy compared with placebo.(See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

Renal Impairment

Escitalopram should be used with caution in patients with severe renal impairment (i.e., creatinine clearance less than 20 mL/minute).(See Dosage and Administration: Special Populations.)

Hepatic Impairment

In clinical studies, clearance of racemic citalopram was decreased by 37% and elimination half-life was doubled relative to that in patients with normal hepatic function. Dosage reduction is recommended for patients with hepatic impairment.(See Dosage and Administration: Special Populations.)

Common Adverse Effects

Adverse effects reported in approximately 5% or more of patients with generalized anxiety or major depressive disorder receiving escitalopram and with an incidence of at least twice that of placebo include insomnia, nausea, increased sweating, sexual dysfunction (ejaculation disorder [primarily ejaculatory delay], decreased libido, anorgasmia), fatigue, and somnolence.