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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(es sye TAL oh pram)
Generic Available (U.S.)
No
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088620.pdf, must be dispensed with this medication.
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of major depressive disorder; generalized anxiety disorders (GAD)
Use: Unlabeled/Investigational
Treatment of mild dementia-associated agitation in nonpsychotic patients
Pregnancy Risk Factor
C
Pregnancy Considerations
Due to adverse effects observed in animal studies, escitalopram is classified as pregnancy category C. Escitalopram is distributed into the amniotic fluid. Limited data is available concerning the use of escitalopram during pregnancy. Nonteratogenic effects in the newborn following SSRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. An increased risk of low birth weight and lower Apgar scores have also been reported. Exposure to SSRIs after the twentieth week of gestation has been associated with persistent pulmonary hypertension of the newborn (PPHN). Adverse effects may be due to toxic effects of the SSRI or drug withdrawal without a taper. The long-term effects of in utero SSRI exposure on infant development and behavior are not known. Escitalopram is the S-enantiomer of the racemic derivative citalopram; also refer to the Citalopram monograph.Women treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued as compared to pregnant women who continue taking antidepressant medications. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. If treatment during pregnancy is required, consider tapering therapy during the third trimester in order to prevent withdrawal symptoms in the infant. If this is done and the woman is considered to be at risk of relapse from her major depressive disorder, the medication can be restarted following delivery, although the dose should be readjusted to that required before pregnancy. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (Yonkers, 2009).
Lactation
Enters breast milk/consider risk:benefit
Breast-Feeding Considerations
Escitalopram and its metabolite are excreted into breast milk. Limited data is available concerning the effects escitalopram may have in the nursing infant and the long-term effects on development and behavior have not been studied. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother. Escitalopram is the S-enantiomer of the racemic derivative citalopram; also refer to the Citalopram monograph.
Contraindications
Hypersensitivity to escitalopram, citalopram, or any component of the formulation; concomitant use with pimozide; concomitant use or within 2 weeks of MAO inhibitors
Warnings/Precautions
Boxed warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Escitalopram is not FDA approved for use in children <12 years of age.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Escitalopram is not FDA approved for the treatment of bipolar depression.
Concerns related to adverse effects:
• Anticholinergic effects: Relatively devoid of these side effects.
• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events (including GI bleeding), particularly if used concomitantly with aspirin, NSAIDs, warfarin, or other anticoagulants. Bleeding related to SSRI or SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.
• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
• Serotonin syndrome (SS)/neuroleptic malignant syndrome (NMS)-like reactions: SS and NMS-like reactions have occurred with serotonin/norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) when used alone, and particularly when used in combination with serotonergic agents (eg, triptans) or antidopaminergic agents (eg, antipsychotics). The diagnosis of SS can be made using the Hunter Serotonin Toxicity Criteria (Dunkley, 2003). Identification and differentiation of SS (eg, tremor, myoclonus, agitation) and more severe NMS-like reactions (eg, hyperthermia, muscle rigidity, autonomic instability, mental status changes) can be complex; monitor patients closely for either syndrome. Discontinue treatment (and any concomitant serotonergic and/or antidopaminergic agents) immediately if signs/symptoms arise.
• Sexual dysfunction: May cause or exacerbate sexual dysfunction.
• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L), predominately in the elderly. Hyponatremia is reversible with discontinuation of treatment. Volume depletion and/or concurrent use of diuretics likely increases risk.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.
• Renal impairment: Use with caution in patients with severe renal impairment.
• Seizure disorders: Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.
Concurrent drug therapy issues:
• Agents which lower seizure threshold: Concurrent therapy with other drugs which lower the seizure threshold.
• Anticoagulants/Antiplatelets: Use caution with concomitant use of aspirin, NSAIDs, warfarin, or other drugs that affect coagulation; the risk of bleeding may be potentiated.
• CNS depressants: Use caution with concomitant therapy.
• MAO inhibitors: Potential for severe reaction when used with MAO inhibitors; autonomic instability, coma, death, delirium, diaphoresis, hyperthermia, mental status changes/agitation, muscular rigidity, myoclonus, neuroleptic malignant syndrome features, and seizures may occur. Concomitant use is contraindicated.
• Serotonin syndrome/NMS-like reactions: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans), agents which reduce escitalopram's metabolism, or antidopaminergic agents (including antipsychotics). Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
Special populations:
• Elderly: Use caution in elderly patients; risk of hyponatremia and other adverse events may be increased. Bioavailability and half-life are increased by 50% in the elderly.
• Pediatrics: Safety and efficacy have not been established in children <12 years of age with major depressive disorder or in children <18 years with generalized anxiety disorder.
• Pregnancy: Use caution in pregnant patients; high doses of citalopram have been associated with teratogenicity in animals.
Other warnings/precautions:
• Electroconvulsive therapy (ECT): Use with caution; no clinical studies have assessed the combined use of escitalopram and electroconvulsive therapy; may increase the risks (eg, cognitive adverse effects) associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
• Withdrawal syndrome: May cause dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Upon discontinuation of escitalopram therapy, gradually taper dose. If intolerable symptoms occur following a decrease in dosage or upon discontinuation of therapy, then resuming the previous dose with a more gradual taper should be considered.
Adverse Reactions
>10%:
Central nervous system: Headache (24%), somnolence (6% to 13%), insomnia (9% to 12%)
Gastrointestinal: Nausea (15% to 18%)
Genitourinary: Ejaculation disorder (9% to 14%)
1% to 10%:
Central nervous system: Fatigue (5% to 8%), dizziness (5%), abnormal dreaming (3%), lethargy (3%), yawning (2%)
Endocrine & metabolic: Libido decreased (3% to 7%), anorgasmia (2% to 6%), menstrual disorder (2%)
Gastrointestinal: Xerostomia (6% to 9%), diarrhea (8%), constipation (3% to 5%), appetite decreased (3%), indigestion (3%), vomiting (3%), abdominal pain (2%), flatulence (2%), toothache (2%)
Genitourinary: Impotence (2% to 3%)
Neuromuscular & skeletal: Neck/shoulder pain (3%), paresthesia (2%)
Respiratory: Rhinitis (5%), sinusitis (3%)
Miscellaneous: Diaphoresis (4% to 5%), flu-like syndrome (5%)
<1%: Abdominal cramps, allergy, appetite increased, arthralgia, blurred vision, bronchitis, chest pain, concentration impaired, cough, fever, gastroenteritis, heartburn, hot flashes, hypertension, irritability, jaw stiffness, lightheadedness, limb pain, menstrual cramps, migraine, myalgia, nasal or sinus congestion, palpitation, rash, sinus headache, tinnitus, urinary frequency, urinary tract infection, weight gain
Postmarketing and/or case reports: Acute renal failure, aggression, agitation, agranulocytosis, akathisia, allergic reaction, alopecia, amnesia, anaphylaxis, anemia, anger, angioedema, anxiety, apathy, aplastic anemia, ataxia, atrial fibrillation, bilirubin increased, bradycardia, cardiac failure, cerebrovascular accident, choreoathetosis, confusion, delirium, delusion, depersonalization, depression aggravated, dermatitis, diabetes mellitus, diplopia, disorientation, DVT, dysarthria, dyskinesia, dysphagia, dyspnea, dystonia, dysuria, ecchymosis, edema, epistaxis, erythema multiforme, extrapyramidal symptoms, flushing, gait abnormal, GERD, GI hemorrhage, glaucoma, hallucination, hemolytic anemia, hepatic necrosis, hepatitis, hypercholesterolemia, hyper-/hypoglycemia, hypertensive crisis, hypoesthesia, hypokalemia, hyponatremia, hypotension, INR increased, leukopenia, liver enzymes increased, liver failure, malaise, menorrhagia, mood swings, muscle cramp, muscle stiffness, muscle weakness, mydriasis, myocardial infarction, myoclonus, nervousness, neuroleptic malignant syndrome, nightmares, nystagmus, orthostasis, pancreatitis, panic reaction, paranoia, Parkinsonism, phlebitis, photosensitivity, priapism, prolactinemia, prothrombin decreased, psychosis, pulmonary embolism, QT prolonged, rectal hemorrhage, restless legs, restlessness, rhabdomyolysis, seizures, serotonin syndrome, SIADH, spontaneous abortion, Stevens-Johnson syndrome, suicidal tendency, suicide attempt, syncope, tachycardia, tardive dyskinesia, thrombocytopenia, thrombocytopenic purpura (idiopathic), thrombosis, torsade de pointes, toxic epidermal necrolysis, tremor, urinary retention, urticaria, ventricular arrhythmia, ventricular tachycardia, vertigo, visual disturbance, weakness, weight loss, withdrawal syndrome
Metabolism/Transport Effects
Substrate (major) of CYP2C19, 3A4; Inhibits CYP2D6 (weak)
Drug Interactions
Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Risk D: Consider therapy modification
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Alpha-/Beta-Blockers: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Alpha-/Beta-Blockers. Risk C: Monitor therapy
Analgesics (Opioid): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). This may cause serotonin syndrome. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
BusPIRone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Selective Serotonin Reuptake Inhibitors. Specifically those agents metabolized via CYP1A2, 2C, and/or 3A4 isoenzymes. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of CarBAMazepine. Specifically those SSRIs that inhibit CYP3A4 isoenzymes. Risk D: Consider therapy modification
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Risk D: Consider therapy modification
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
CloZAPine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of CloZAPine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Collagenase (Systemic): Antiplatelet Agents may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Desmopressin: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Dextromethorphan. Risk D: Consider therapy modification
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Management: When possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Glucosamine: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Haloperidol: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Haloperidol. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Iobenguane I 123: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Lithium: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Lithium. Risk C: Monitor therapy
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Macrolide Antibiotics: May decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Exceptions: Azithromycin; Azithromycin (Systemic); Spiramycin. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
Methadone: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Methadone. Fluvoxamine appears to be the only interacting SSRI. Risk D: Consider therapy modification
Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Risk D: Consider therapy modification
Mexiletine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Mexiletine. Risk D: Consider therapy modification
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
NSAID (COX-2 Inhibitor): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Risk D: Consider therapy modification
NSAID (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of an gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Risk D: Consider therapy modification
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Risk X: Avoid combination
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
RisperiDONE: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of RisperiDONE. Risk C: Monitor therapy
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
TraMADol: Selective Serotonin Reuptake Inhibitors may enhance the neuroexcitatory and/or seizure-potentiating effect of TraMADol. TraMADol may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk D: Consider therapy modification
Tricyclic Antidepressants: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, kava kava, and gotu kola (may increase CNS depression).
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Escitalopram is the S-enantiomer of the racemic derivative citalopram, which selectively inhibits the reuptake of serotonin with little to no effect on norepinephrine or dopamine reuptake. It has no or very low affinity for 5-HT1-7, alpha- and beta-adrenergic, D1-5, H1-3, M1-5, and benzodiazepine receptors. Escitalopram does not bind to or has low affinity for Na+, K+, Cl-, and Ca++ ion channels.
Pharmacodynamics/Kinetics
Onset of action: Depression: The onset of action is within a week; however, individual response varies greatly and full response may not be seen until 8-12 weeks after initiation of treatment.
Protein binding: ~56% to plasma proteins
Metabolism: Hepatic via CYP2C19 and 3A4 to an active metabolite, S-desmethylcitalopram (S-DCT; 1/7 the activity of escitalopram); S-DCT is metabolized to S-didesmethylcitalopram (S-DDCT; active; 1/27 the activity of escitalopram) via CYP2D6
Half-life elimination: Escitalopram: 27-32 hours; S-DCT: 59 hours
Time to peak: Escitalopram: ~5 hours; S-DCT: 14 hours
Excretion: Urine (Escitalopram: 8%; S-DCT: 10%)
Dosage
Oral:
Children ≥12 years: Major depressive disorder: Initial: 10 mg once daily; dose may be increased to 20 mg once daily after at least 3 weeks
Adults: Major depressive disorder, generalized anxiety disorder: Initial: 10 mg once daily; dose may be increased to 20 mg once daily after at least 1 week
Elderly: 10 mg once daily
Dosage adjustment in renal impairment:
Mild-to-moderate impairment: No dosage adjustment needed
Severe impairment: Clcr <20 mL/minute: Use with caution
Dosage adjustment in hepatic impairment: 10 mg once daily
Administration: Oral
Administer once daily (morning or evening), with or without food.
Monitoring Parameters
Mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; akathisia
Dietary Considerations
May be taken with or without food.
Patient Education
Avoid alcohol. May cause fatigue, dizziness, lightheadedness, insomnia, impaired concentration, headache, nausea, vomiting, loss of appetite, diarrhea, sexual dysfunction (reversible when drug is discontinued), muscle pain, dry mouth, or tremor. Report immediately any CNS changes, such as increased depression, confusion, impaired concentration, severe headache, insomnia, nightmares, irritability, acute anxiety, panic attacks, suicide ideation, persistent GI changes, chest pain or palpitations, blurred vision or vision changes, or unusual bleeding (eg, blood in stool, urine, or vomitus; unusual bruising or nosebleeds).
Geriatric Considerations
Bioavailability and half-life are increased by 50% in the elderly. The elderly are more prone to SSRI/SNRI-induced hyponatremia.
Additional Information
The tablet and oral solution dosage forms are bioequivalent. Clinically, escitalopram 20 mg is equipotent to citalopram 40 mg. Do not coadminister with citalopram.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and toothache. See Effects on Bleeding.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Although caution should be used in patients taking tricyclic antidepressants, no interactions have been reported with vasoconstrictors and escitalopram, a nontricyclic antidepressant which acts to increase serotonin; no precautions appear to be needed
Mental Health: Comment
The SSRIs as a class are generally considered to be safe and equally effective. Allow sufficient dose-response time (6-12 weeks). Differences lie in approved indications, receptor profiles, pharmacokinetics, and cytochrome P450 activity profile. Subtle differences exist in adverse effect profiles. All SSRIs have the potential to cause sexual dysfunction. Escitalopram is the s-isomer of citalopram and therefore, similar to citalopram. Among the SSRIs, escitalopram possesses the lowest effects on CYP isoenzymes.
Nursing: Physical Assessment/Monitoring
Monitor for signs of clinical worsening, suicide ideation, mania, hypomania, anxiety, or panic attacks. Taper dosage slowly when discontinuing.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral:
Lexapro®: 1 mg/mL (240 mL) [contains propylene glycol; peppermint flavor]
Tablet, oral:
Lexapro®: 5 mg
Lexapro®: 10 mg, 20 mg [scored]
Pricing: U.S. (www.drugstore.com)
Solution (Lexapro)
5 mg/5 mL (240): $169.99
Tablets (Lexapro)
5 mg (30): $99.99
10 mg (30): $109.99
20 mg (30): $109.99
References
American College of Obstetricians and Gynecologists, ACOG Practice Bulletin: Clinical Management Guidelines for Obstetricians-Gynecologists No. 92 April 2008 (Replaces Practice Bulletin Number 87, November 2007), “Use of Psychiatric Medications During Pregnancy and Lactation,” Obstet Gynecol, 2008, 111(4):1001-20.
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Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352:1112-20.
Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al, “Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn,” N Engl J Med, 2006, 354(6):579-87.
Dunkley EJ, Isbister GK, Sibbritt D, et al, “The Hunter Serotonin Toxicity Criteria: Simple and Accurate Diagnostic Decision Rules for Serotonin Toxicity,” QJM, 2003, 96(9):635-42.
Mahlberg R, Kunz D, Sasse J, et al, “Serotonin Syndrome With Tramadol and Citalopram,” Am J Psychiatry, 2004, 161(6):1129.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
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International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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