Pronunciation: ES-sye-TAL-oh-pram OX-a-late
Class: SSRI

Trade Names

Lexapro
- Tablets 5 mg
- Tablets 10 mg
- Tablets 20 mg
- Solution, oral 5 mg per 5 mL

Cipralex (Canada)

Pharmacology

Inhibits the CNS neuronal uptake of serotonin, potentiating serotonergic activity.

Slideshow: Can Prescription Drugs Lead to Weight Gain?

Pharmacokinetics

Absorption

T _max is approximately 5 h. Absolute bioavailability is approximately 80%.

Distribution

Vd is approximately 12 L/kg. Approximately 56% is protein bound.

Metabolism

Metabolized in the liver to 2 metabolites (minimally active); CYP3A4 and CYP2C19 are involved in N-demethylation.

Elimination

The mean terminal half-life is approximately 27 to 32 h. Approximately 8% is recovered in urine as escitalopram and 10% as a metabolite. Cl is 600 mL/min (approximately 7% caused by renal Cl).

Special Populations

Renal Function Impairment

No dosage adjustment for patients with mild to moderate renal impairment. No data on patients with CrCl less than 20 mL/min.

Hepatic Function Impairment

Cl of escitalopram is decreased and half-life is prolonged in patients with reduced hepatic function.

Elderly

AUC and half-life increased approximately 50%.

Children

No dosage adjustment is needed in adolescent patients.

Gender

Pharmacokinetics similar in men and women.

Indications and Usage

Major depressive disorder (MDD); generalized anxiety disorder (GAD).

Unlabeled Uses

Panic disorder; posttraumatic stress disorder.

Contraindications

Concurrent use of MAOIs or within 14 days of discontinuing MAOI treatment; coadministration of pimozide; hypersensitivity to escitalopram or citalopram.

Dosage and Administration

Generalized Anxiety Disorder
Adults

PO Start with 10 mg once daily. Dosage may be increased to 20 mg once daily after 1 wk.

Major Depressive Disorder
Adults

PO Start with 10 mg once daily. The dose may be increased to 20 mg after 1 wk. However, 20 mg has not shown a clinical benefit over 10 mg.

Children 12 yr of age and older

PO Start with 10 mg once daily. The dose may be increased to 20 mg after 3 wk.

Elderly/Hepatic Function Impairment
Adults

PO 10 mg/day.

General Advice

• Do not coadminister with citalopram.
• Administer without regard to meals. Administer with food if GI upset occurs.
• Use dosing spoon, cup, or syringe to measure and administer prescribed dose of oral solution.
• Administer once daily in the morning or evening.
• Taper dose when discontinuing treatment.

Storage/Stability

Store at controlled room temperature (59° to 86°F).

Drug Interactions

5-HT ₁ agonists (eg, sumatriptan)

Risk of serotonin syndrome may be increased. If coadministration is clinically warranted, carefully observe the patient, particularly when starting treatment or during dose increases.

Alcohol

May potentiate the effects of alcohol; use of alcohol is not advised.

Aspirin, NSAIDs (eg, ibuprofen), warfarin

Risk of bleeding may be increased. Use with caution and carefully monitor the patient.

Beta-blockers (eg, metoprolol, propranolol)

Excessive beta-blockade (eg, bradycardia) may occur, increasing the risk of cardiac and CNS toxicity. Use with caution.

Buspirone, opioid analgesics (eg, meperidine), sibutramine, SNRIs (eg, duloxetine), St. John's wort, sympathomimetics (eg, amphetamine), tramadol

The risk of serotonin syndrome may be increased. Closely monitor patients. Serotonin syndrome requires immediate medical attention, including withdrawal of the serotonergic agent and supportive care.

Carbamazepine

Consider the possibility of decreased escitalopram serum concentrations and reduced efficacy. If an interaction is suspected, adjust the escitalopram dose as needed.

Cimetidine

Serum levels may be increased by cimetidine. The clinical importance is unknown. If an interaction is suspected, it may be necessary to adjust the escitalopram dose.

Citalopram

Escitalopram is the active isomer of racemic citalopram; do not coadminister these two agents.

CNS drugs

Use with caution.

Cyproheptadine

May decrease the pharmacologic effect of escitalopram. If there is a decrease in the efficacy of escitalopram, consider discontinuing cyproheptadine.

Drugs metabolized by CYP2D6 (eg, desipramine)

Serum levels may be increased by escitalopram. Use with caution.

Ketoconazole

Plasma concentrations may be reduced by escitalopram, decreasing therapeutic effect of ketoconazole. Observe the clinical response of the patient.

Linezolid

The risk of serotonin syndrome may be increased. Because linezolid is an MAOI, allow at least 14 days after stopping linezolid before giving escitalopram.

Lithium

Serotonergic effects of escitalopram may be enhanced. Elevated lithium concentrations and neurotoxicity may occur. Use with caution. Monitor lithium plasma concentrations and adjust the lithium dose as needed.

L-tryptophan

The risk of symptoms related to central and peripheral toxicity (eg, agitation, dizziness, headache, restlessness, sweating) may be increased. Coadministration is not recommended.

MAOIs (eg, phenelzine)

Coadministration is contraindicated. Allow at least 14 days to elapse between discontinuing an MAOI and starting escitalopram. Similarly, allow at least 14 days after stopping escitalopram before starting an MAOI.

Methylene blue

Risk of neurologic adverse reactions, including serotonin syndrome, may be increased. Avoid concurrent use.

Omeprazole

Escitalopram plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Monitor the patient. If an interaction is suspected, it may be necessary to adjust the escitalopram dose.

Pimozide

Concurrent use is contraindicated with escitalopram.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension, palpitation (at least 1%); atrial fibrillation, bradycardia, cardiac failure, cerebrovascular accident, deep vein thrombosis, flushing, hypertensive crisis, hypotension, MI, orthostatic hypotension, phlebitis, QT prolongation, syncope, tachycardia, thrombosis, torsades de pointes, ventricular arrhythmia, ventricular tachycardia (postmarketing).

CNS

Headache (24%); insomnia (14%); somnolence (13%); fatigue (8%); decreased libido, dizziness (7%); abnormal dreaming, decreased appetite, lethargy (3%); paresthesia, yawning (2%); impaired concentration, increased appetite, irritability, light-headedness, migraine (at least 1%); abnormal gait, acute psychosis, aggression, akathisia, anger, asthenia, choreoathetosis, delirium, delusion, dysarthria, dyskinesia, dystonia, extrapyramidal disorder, fall, hypoesthesia, nightmare, NMS, paranoia, seizures, serotonin syndrome, tardive dyskinesia, tonic-clonic seizures, visual hallucinations (postmarketing).

Dermatologic

Increased sweating (8%); rash (at least 1%); erythema multiforme, necrolysis, photosensitivity, Stevens-Johnson syndrome, TEN, urticaria (postmarketing).

EENT

Rhinitis (5%); blurred vision, nasal congestion, tinnitus (at least 1%); diplopia, glaucoma, nystagmus (postmarketing).

Endocrine

Diabetes mellitus, hyperprolactinemia (postmarketing).

GI

Nausea (18%); diarrhea (14%); dry mouth (9%); constipation, indigestion (6%); vomiting (3%); abdominal pain, flatulence, toothache (2%); abdominal cramp, gastroenteritis, heartburn (at least 1%); GI hemorrhage, pancreatitis, rectal hemorrhage (postmarketing).

Genitourinary

Ejaculation disorder (14%); anorgasmia (6%); impotence (3%); menstrual disorder (2%); menstrual cramps, urinary frequency, UTI (at least 1%); acute renal failure, priapism, spontaneous abortion (postmarketing).

Hematologic-Lymphatic

Agranulocytosis, anemia, aplastic anemia, decreased prothrombin, ecchymosis, hemolytic anemia, idiopathic thrombocytopenia purpura, increased INR, leukopenia, thrombocytopenia (postmarketing).

Hepatic

Fulminant hepatitis, hepatic failure, hepatic necrosis, hepatitis (postmarketing).

Hypersensitivity

Allergic reaction, anaphylaxis, angioedema (postmarketing).

Metabolic-Nutritional

Increased weight (at least 1%); hyperglycemia, hypoglycemia, hypokalemia, hyponatremia, SIADH (postmarketing).

Musculoskeletal

Neck/shoulder pain (3%); arthralgia, jaw stiffness, limb pain, myalgia (at least 1%); myoclonus, rhabdomyolysis (postmarketing).

Respiratory

Sinusitis (3%); bronchitis, coughing, sinus congestion, sinus headache (at least 1%); dyspnea, epistaxis, pulmonary embolism (postmarketing).

Miscellaneous

Influenza-like symptoms (5%); allergy, chest pain, fever, hot flushes (at least 1%).

Precautions

Warnings Suicidality Compared with placebo, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for MDD and other psychiatric disorders. Appropriately monitor and closely observe patients of all ages who are started on antidepressant therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the prescriber.

Monitor Ensure that therapy is periodically reviewed to determine if it needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated. Monitor for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of therapy or at times of increases or decreases in dose. The following symptoms may represent precursors to suicidality and should be reported to the health care provider immediately if noted or suspected: aggressiveness, agitation, anxiety, hostility, hypomania, impulsivity, insomnia, irritability, mania, panic attacks, and psychomotor restlessness. Frequently assess patient for response to treatment.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established for treatment of GAD. Safety and effectiveness not established in children younger than 12 yr of age for the treatment of MDD.

Elderly

The number of elderly patients studied was insufficient to assess difference in safety and efficacy based on age. Greater sensitivity of some elderly patients cannot be ruled out.

Renal Function

Use with caution in patients with severe renal impairment.

Hazardous Tasks

May impair judgement, thinking, or motor skills.

Abnormal bleeding

Bleeding episodes have been reported in patients treated with drugs that interfere with serotonin reuptake.

Concomitant illness

Use with caution in patients with concurrent systemic illness.

Discontinuation

When discontinuing treatment, taper the dose to avoid adverse reactions. If treatment is to be discontinued or the dose reduced, gradually taper dose and monitor patient for withdrawal symptoms (eg, abnormal skin sensations, agitation, anxiety, confusion, dizziness, dysphoric mood, irritability, nausea, sweating). If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.

Hyponatremia

Cases of hyponatremia or SIADH have been reported.

Mania/Hypomania

May activate hypomania or mania.

Screening for bipolar disorder

Not indicated for bipolar depression. Therefore, prior to starting treatment in patients with depressive symptoms, determine if patient is at risk for bipolar disorder.

Seizures

Have been reported. Use with caution in patients with history of seizures.

Serotonin syndrome or NMS-like reactions

Life-threatening serotonin syndrome or NMS-like reactions may occur, particularly with coadministration of serotonergic drugs.

Overdosage

Symptoms

Acute renal failure (rare), coma, dizziness, ECG changes (including QTc prolongation and very rare cases of torsades de pointes), hypotension, insomnia, nausea, seizures, sinus tachycardia, somnolence, vomiting.

Patient Information

• Advise patient to read Medication Guide before starting therapy and with each refill.
• Advise patient that the medication is usually started at a low dose and then gradually increased until max benefit is obtained.
• Advise patient to take prescribed dose once daily, in the morning or evening, without regard to meals, but to take with food if stomach upset occurs.
• Advise patient, family, or caregiver to use dosing spoon, cup, or syringe to measure and administer prescribed dose of oral solution.
• Advise patient that it may take 1 to 4 wk to note improvement in symptoms and to continue with the prescribed therapy once improvement has been noted.
• Instruct patient to notify health care provider if symptoms do not appear to be getting better or are getting worse, or if bothersome adverse reactions (eg, changes in sexual function, diarrhea, drowsiness, headache, insomnia, nausea, nervousness, unusual sweating) occur.
• Advise patient being treated for depression, and family or caregiver of patient, to be alert for abnormal changes in mood or thinking and to report the following symptoms immediately to health care provider: agitation, anxiety, hostility or aggressiveness, impulsivity, irritability, panic attacks, suicidal thoughts or behavior.
• Advise patient that if medication needs to be discontinued, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
• Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Advise patient to avoid alcoholic beverages and other depressants while taking escitalopram.
• Advise patient that the drug may impair judgement, thinking, or reflexes, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

Copyright © 2009 Wolters Kluwer Health.