escitalopram (Rx)

>10%

Headache (24%)

Nausea (15-18%)

Ejaculation disorder (9-14%)

Somnolence (4-13%)

Insomnia (7-12%)

1-10%

Xerostomia (4-9%)

Constipation (3-6%)

Fatigue (2-8%)

Diarrhea (8%)

Libido decrease (3-7%)

Anorgasmia (2-6%)

Indigestion (1-6%)

Rhinitis (5%)

Flu-like syndrome (5%)

Neck/shoulder pain (3%)

Decreased appetite (3%)

Vomiting (3%)

Sinusitis (3%)

Lethargy (3%)

Menstrual disorder (2%)

Flatulence (2%)

Toothache (2%)

Yawning (2%)

Menstrual disorder (1%)

Weight gain (1%)

Postmarketing Reports

Blood and lymphatic system disorders: Anemia, agranulocytosis, aplastic anemia, hemolytic anemia, idiopathic thrombocytopenia purpura, leukopenia, thrombocytopenia

Cardiac disorders: Atrial fibrillation, bradycardia, cardiac failure, myocardial infarction, tachycardia, torsades de pointes, ventricular arrhythmia, ventricular tachycardia

Ear and labyrinth disorders: Vertigo

Endocrine disorders: Diabetes mellitus, hyperprolactinemia, SIADH

Eye disorders: Angle closure glaucoma, diplopia, mydriasis, visual disturbance

Gastrointestinal disorder: Dysphagia, gastrointestinal hemorrhage, gastroesophageal reflux, pancreatitis, rectal hemorrhage

General disorders and administration site conditions: Abnormal gait, asthenia, edema, fall, feeling abnormal, malaise

Hepatobiliary disorders: Fulminant hepatitis, hepatic failure, hepatic necrosis, hepatitis

Immune system disorders: Allergic reaction, anaphylaxis

Investigations: Bilirubin increased, decreased weight, QT prolongation, hepatic enzymes increased, hypercholesterolemia, INR increased, prothrombin decreased

Metabolism and nutrition disorders: Hyperglycemia, hypoglycemia, hypokalemia, hyponatremia

Musculoskeletal and connective tissue disorders: Muscle cramp, muscle stiffness, muscle weakness, rhabdomyolysis

Nervous system disorders: Akathisia, amnesia, ataxia, choreoathetosis, cerebrovascular accident, dysarthria, dyskinesia, dystonia, extrapyramidal disorders, grand mal seizures (or convulsions), myoclonus, nystagmus, Parkinsonism, restless legs, seizures, syncope, tardive dyskinesia, tremor

Pregnancy, puerperium and perinatal conditions: Spontaneous abortion

Psychiatric disorders: Acute psychosis, aggression, agitation, anger, anxiety, apathy, completed suicide, confusion, depersonalization, depression aggravated, delirium, delusion, disorientation, feeling unreal, hallucinations (visual and auditory), mood swings, nervousness, nightmare, panic reaction, paranoia, restlessness, self-harm or thoughts of self-harm, suicide attempt, suicidal ideation, suicidal tendency

Renal and urinary disorders: Acute renal failure, dysuria, urinary retention

Reproductive system and breast disorders: Menorrhagia, priapism

Respiratory, thoracic and mediastinal disorders: Dyspnea, epistaxis, pulmonary embolism, pulmonary hypertension of the newborn

Skin and SC tissue disorders: Alopecia, angioedema, dermatitis, ecchymosis, erythema multiforme, photosensitivity reaction, Stevens Johnson syndrome, toxic epidermal necrolysis, urticaria

Vascular Disorders: Deep vein thrombosis, flushing, hypertensive crisis, hypotension, orthostatic hypotension, phlebitis, thrombosis

Contraindications

Hypersensitivity to escitalopram or citalopram

Pimozide

Monoamine oxidase inhibitors (MAOIs)

• Use of MAOIs intended to treat psychiatric disorders with escitalopram or within 14 days of discontinuation
• Use of escitalopram within 14 days of stopping an MAOI intended to treat psychiatric disorders
• Starting escitalopram in a patients being treated with MAOIs such as linezolid or IV methylene blue

Cautions

Conflicting evidence regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn, or PPHN (see Pregnancy)

In neonates exposed to SNRIs/SSRIs late in third trimester: risk of complications such as feeding difficulties, irritability, and respiratory problems

Prior to initiating treatment, screen patients for any personal or family history of bipolar disorder, mania, or hypomania

Caution with seizure disorder, bipolar mania, severe renal impairment; not FDA approved for the treatment of bipolar depression

SNRIs/SSRIs have been associated with the development of SIADH; hyponatremia has been reported rarely

Activation of mania/hypomania reported in a small proportion of patients with major affective disorders treated with citalopram and other marketed drugs effective in treatment of major depressive disorder

May worsen psychosis in some patients and precipitate a shift to mania or hypomania in patients with bipolar disorder

Consider changing therapeutic regimen, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors

Risk of hyponatremia

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

Bone fractures are associated with antidepressant therapy; consider the possibility of a fracture in patients with unexplained bone pain, swelling, or bruising

Prescribe the smallest quantity of tablets consistent with good patient care and alert family or caregiver to monitor for emergence of suicidality and associated behaviors (anxiety, agitation, panic attacks, insomnia, hostility, akathisia, impulsivity, irritability)

SSRIs/SNRIs increase risk of abnormal bleeding (further increased if concomitant aspirin, NSAIDs or anticoagulants, or hemorrhagic diathesis)

Prolongation of QT interval and ventricular arrhythmias reported, especially in female patients with preexisting QT prolongation or other risk factors

Risk of cognitive and motor function impairment; use caution when operating heavy machinery

Use with caution in patients with history of seizure disorders or conditions predisposing to seizures including brain damage and alcoholism

May cause or exacerbate sexual dysfunction

Gradually taper dose before discontinuation; abrupt discontinuation may cause dysphoric mood, dizziness, sensory disturbances, agitation, confusion, anxiety, headache, insomnia, tinnitus, seizures, irritability

Drug interaction overview

• Escitalopram is a CYP3A4 and CYP2C19 substrate
• Risk of serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with SSRIs and SNRIs both when taken alone, but especially when coadministered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort); if symptoms occur, discontinue therapy and initiate supportive treatment; if concomitant use of escitalopram with other serotonergic drugs is clinically warranted, be aware of the increased risk for serotonin syndrome, particularly during treatment initiation and dose increases
• May impair platelet aggregation that can result in increased risk of bleeding events including GI bleeding especially if taken concomitantly with aspiring, warfarin, or NSAIDs
• Owing to primary CNS effects, caution when coadministered with other centrally acting drugs
• Did not potentiate cognitive and motor effects of alcohol in a clinical trial; however, as with other psychotropic medications, alcohol is not recommended

Pregnancy

There are no adequate and well-controlled studies in pregnant women; therefore, use during pregnancy only if the potential benefit justifies the potential risk to the fetus

In some cases, the clinical picture is consistent with serotonin syndrome

Effect on labor and delivery in humans is unknown

Neonates exposed to escitalopram and other SSRIs/SNRIs

• Neonates exposed to SSRIs/SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding
• Such complications can arise immediately upon delivery
• Reported clinical findings include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying
• These features are consistent with toxic effects of SSRIs and SNRIs or, possibly, drug discontinuation syndrome

Lactation

Escitalopram is excreted in human breast milk

Limited data from women taking 10-20 mg escitalopram showed that exclusively breast-fed infants receive a ~3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram

Caution should be exercised and breastfeeding infants should be observed for adverse reactions when administered to a nursing woman

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

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

Absorption

Peak plasma time: 5 hr (single 20-mg dose)

Bioavailability: 80% (IV citalopram)

Distribution

Protein bound: 56%

Vd: 12 L/kg (citalopram)

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%)

Oral Administrationº

Administer once daily, in the morning or evening, with or without food

Storage

Store at 20-25ºC (68-77ºF); excursions permitted to 15-30°C (59-86ºF)