Escitalopram

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Oral:

Lexapro: 5 mg/5 mL (240 mL [DSC]) [contains methylparaben, propylene glycol, propylparaben; peppermint flavor]

Generic: 5 mg/5 mL (10 mL, 240 mL)

Tablet, Oral:

Lexapro: 5 mg

Lexapro: 10 mg, 20 mg [scored]

Generic: 5 mg, 10 mg, 20 mg

Pharmacology

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-HT_1-7, alpha- and beta-adrenergic, D_1-5, H_1-3, M_1-5, and benzodiazepine receptors. Escitalopram does not bind to or has low affinity for Na⁺, K⁺, Cl^-, and Ca⁺⁺ ion channels.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: ~20 L/k (Søgaard 2005)

Metabolism

Hepatic via CYP2C19 and 3A4 to S-desmethylcitalopram (S-DCT); S-DCT is metabolized to S-didesmethylcitalopram (S-DDCT) via CYP2D6; in vitro data suggest metabolites do not contribute significantly to the antidepressant effects of escitalopram

Excretion

Urine (8% as unchanged drug; S-DCT 10%)

Clearance:

Hepatic impairment: Decreased by 37%

Mild to moderate renal impairment: Decreased by 17%

Severe renal impairment (CrCl <20 mL/minute): No information available.

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 to 12 weeks after initiation of treatment.

Time to Peak

Escitalopram: Adolescents: 2.9 hours; Adults: ~5 hours

Half-Life Elimination

Mean: Adolescents: 19 hours; Adults: ~27 to 32 hours (increased ~50% in the elderly and doubled in patients with hepatic impairment)

Protein Binding

~56% to plasma proteins

Use in Specific Populations

Special Populations: Elderly

AUC and half-life increased ~50%.

Use: Labeled Indications

Major depressive disorder (unipolar): Acute and maintenance treatment of unipolar major depressive disorder (MDD)

Generalized anxiety disorder: Acute treatment of generalized anxiety disorder (GAD)

Use: Off Label

Binge eating disordercyes

Data from a limited number of patients studied suggest that escitalopram may be beneficial to improve weight loss, severity of illness, binge frequency, and binge days in patients with binge eating disorder Guerdjikova 2008.

Based on the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of eating disorders, escitalopram may be effective and is recommended in the management of binge eating disorder.

Body dysmorphic disorderc

Data from a limited number of patients studied suggest that escitalopram may be beneficial for the treatment of symptoms (including depression, insight, and psychosocial functioning) and prevention of relapse associated with body dysmorphic disorder Phillips 2016.

Bulimia nervosayes

Based on the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of eating disorders, SSRIs including fluoxetine and fluvoxamine are effective and recommended in the management of bulimia nervosa. Based on clinical experience some experts also recommend use of escitalopram as an alternative option for patients who do not respond to or tolerate fluoxetine Crow 2019.

Obsessive-compulsive disorder (OCD)ayes

Data from a randomized, double-blind, placebo-controlled trial and a relapse prevention trial support the use of escitalopram in the treatment of OCD Fineberg 2007, Stein 2007.

Based on the American Psychiatric Association guidelines for the treatment of obsessive-compulsive disorder and the World Federation of Societies of Biological Psychiatry guidelines for the treatment of anxiety disorders, obsessive-compulsive disorder, and posttraumatic stress disorder, selective serotonin reuptake inhibitors (SSRIs) such as escitalopram are first-line for the treatment of OCD.

Panic disorderbyes

Data from a double-blind, randomized, parallel-group, flexible-dose, placebo-controlled, multicenter study and an open-label trial support the use of escitalopram in the treatment of panic disorder Rampello 2006, Stahl 2003.

Based on the American Psychiatric Association guidelines for the treatment of panic disorder and the World Federation of Societies of Biological Psychiatry guidelines for the treatment of anxiety disorders, obsessive-compulsive disorder, and posttraumatic stress disorder, escitalopram is effective and recommended in the management of panic disorder.

Posttraumatic stress disorder (PTSD)cyes

Data from a limited number of patients suggest that escitalopram may be beneficial for the treatment of PTSD Qi 2017, Robert 2006.

Based on the

Premature ejaculationyes

According to the International Society for Sexual Medicine guidelines, SSRIs such as escitalopram are effective and recommended in the management of premature ejaculation; however, evidence supporting escitalopram is limited.

Premenstrual dysphoric disorderayes

Data from a randomized, placebo-controlled study support the use of escitalopram in the treatment of premenstrual dysphoric disorder during the luteal phase Eriksson 2008. Data from a small randomized, parallel-group, double-blind trial also suggest benefits for symptom-based dosing Freeman 2005.

Based on the International Society for Premenstrual Disorders auditable standards for diagnosis and management of premenstrual disorder, SSRIs are effective and recommended in the management of premenstrual dysphoric disorder Ismaili 2016.

Vasomotor symptoms associated with menopausebyes

Data from a randomized, double-blind, placebo-controlled trial support the use of escitalopram in the treatment of vasomotor symptoms (hot flashes) in peri- or postmenopausal women Carpenter 2012, Freeman 2011.

Based on the

Contraindications

Hypersensitivity to escitalopram, citalopram, or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either escitalopram or the MAO inhibitor); initiation of escitalopram in a patient receiving linezolid or intravenous methylene blue; concurrent use of pimozide

Canadian labeling: Additional contraindications (not in US labeling): Known QT-interval prolongation or congenital long QT syndrome

Dosage and Administration

Dosing: Adult

Note: Some experts suggest lower starting doses of 5 mg/day and lower titration increments of 5 mg in patients sensitive to adverse effects, particularly in patients with anxiety who are generally more sensitive to overstimulation effects (eg, anxiety, insomnia) with antidepressants (Hirsch 2018c; WFSBP [Bandelow 2012]).

Binge eating disorder (off-label use): Based on limited data: Oral: Initial: 10 mg once daily; may increase based on response and tolerability in 10 mg increments at intervals ≥1 week up to 30 mg/day (Guerdjikova 2008).

Body dysmorphic disorder (off-label use): Based on limited data: Oral: Initial: 10 mg once daily; may increase dose gradually based upon response and tolerability in increments of 10 mg at intervals of every 2 to 3 weeks to 30 mg/day by week 6 to 10 (Phillips 2016; Phillips 2019). Some experts suggest usual doses of 40 mg/day and that in some patients for optimal response doses up to 60 mg/day may be necessary; however, ECGs are recommended at every 10 mg dosing increment above 30 mg/day (eg, at 40 mg/day, 50 mg/day, 60 mg/day) and then as clinically indicated (Phillips 2019). Note: An adequate trial for assessment of effect in BDD is 12 to 16 weeks, including maximum tolerated doses for at least 3 to 4 of those weeks (Phillips 2019).

Bulimia nervosa (alternative agent) (off-label use): Based on limited data; recommendations based on expert opinion: Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability in increments of 10 mg at intervals ≥1 week. Maximum dose: 30 mg/day (Crow 2018).

Generalized anxiety disorder: Oral: Initial: 10 mg once daily; dose may be increased after ≥1 week based on response and tolerability to a maximum of 20 mg once daily.

Major depressive disorder (unipolar): Oral: Initial: 10 mg once daily; dose may be increased in 10 mg increments after ≥1 week based on response and tolerability up to a maximum dose of 20 mg once daily (according to the manufacturer's labeling); however, doses up to 30 mg/day are used in practice and may provide further benefit (Wade 2011).

Obsessive-compulsive disorder (OCD) (off-label use): Oral: Initial: 10 mg once daily; dose may be increased in 10 mg increments at intervals ≥1 week up to 40 mg once daily (Fineberg 2007; Shim 2011). Higher doses up to ~60 mg/day have been evaluated in open-label trials and may be considered in refractory patients; however, adverse effects may be increased (Rabinowitz 2008; Shim 2011). Note: An adequate trial for assessment of effect in OCD is considered to be ≥6 weeks at maximum tolerated dose (Issari 2016).

Panic disorder (off-label use): Oral: Initial: 5 mg once daily for 3 to 7 days, then increase dose to 10 mg once daily (APA 2009; Stahl 2003). May further increase at intervals ≥1 week to 20 mg once daily based on response and tolerability; mean dose in a clinical trial was ~10 mg once daily (Stahl 2003).

Posttraumatic stress disorder (off-label use): Oral: Initial: 10 mg once daily; may gradually increase dose (4-week intervals used in some trials) based on response and tolerability up to 40 mg once daily (Qi 2017; Robert 2006). Some experts suggest dose titrations of 5 to 10 mg increments every 1 to 4 weeks (Hirsch 2018c).

Premature ejaculation (off-label use): Based on limited data; recommendations based on expert opinion: Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability at intervals of ~3 to 4 weeks up to 20 mg once daily (Khera 2018).

Premenstrual dysphoric disorder (off-label use):

Continuous daily dosing regimen: Based on limited data; recommendations based on expert opinion: Oral: Initial: 5 to 10 mg once daily; over the first month, may increase dose based on response and tolerability to 20 mg once daily (Casper 2018).

Intermittent regimens:

Luteal phase dosing regimen: Oral: 5 to 10 mg once daily during the luteal phase of menstrual cycle (beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase dose to 20 mg once daily during the luteal phase (Casper 2018; Freeman 2005).

Symptom-onset dosing regimen: Oral: 5 to 10 mg once daily from the day of symptom-onset until a few days after the start of menses; over the first month, may increase dose based on response and tolerability to 20 mg once daily (Casper 2018; Freeman 2005).

Vasomotor symptoms associated with menopause (alternative agent) (off-label use): Note: Nonhormonal alternative in patients unable or unwilling to take estrogen (AACE [Goodman 2011]). Oral: Initial: 10 mg once daily, increase to 20 mg once daily after 4 weeks if symptoms not adequately controlled (Carpenter 2012; Freeman 2011; NAMS 2015).

Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower titration (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants (APA 2010; Hirsch 2019). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching antidepressants:Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, and pharmacodynamics), and the degree of symptom control desired (Hirsch 2018b; Ogle 2013; WFSBP [Bauer 2013]).

Switching to or from an MAOI:

Allow 14 days to elapse between discontinuing an MAOI and initiation of escitalopram.

Allow 14 days to elapse between discontinuing escitalopram and initiation of an MAOI.

Dosing: Geriatric

Major depressive disorder (unipolar); generalized anxiety disorder: Oral: 10 mg once daily; lower initial doses of 5 mg once daily have been suggested for depression (VA/DoD 2016).

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Pediatric

Depression: Oral:

Children <12 years: Limited data available; only one randomized, placebo-controlled trial has been published; efficacy was not demonstrated for children <12 years of age (Wagner 2006).

Children and Adolescents ≥12 years: Initial: 10 mg once daily; may be increased to 20 mg/day after at least 3 weeks.

Autism and Pervasive Developmental Disorders (PDD): Limited data available: Oral: Children and Adolescents 6 to 17 years: Initial: 2.5 mg once daily; may increase if needed to 5 mg/day after 1 week; may then increase at weekly intervals by 5 mg/day if needed and as tolerated; maximum dose: 20 mg/day. Dosing based on a prospective, 10-week, open-labeled, forced dose-titration trial of 28 children and adolescents 6 to 17 years of age (mean age: 10.4 years) (Owley 2005). Mean severity outcome scores showed significant improvement; mean final dose: 11.1 ± 6.5 mg/day (range: 0 to 20 mg/day); no significant correlation between final tolerated dose and weight was shown; 10 of 28 treated subjects could not tolerate a 10 mg/day dose.

Social anxiety disorder: Limited data available: Oral: Children and Adolescents 10-17 years: Initial: 5 mg once daily for 7 days, then 10 mg/day for 7 days; may then increase at weekly intervals by 5 mg/day if needed, based on clinical response and tolerability; maximum dose: 20 mg/day. Dosing based on a prospective, 12-week, open-labeled trial of 20 children and adolescents 10-17 years of age (mean age: 15 years) (Isolan 2007). At the end of the 12 weeks, 65% of patients met overall response criteria and all symptomatic and quality of life outcome measures showed significant improvements; mean final dose: 13 ± 4.1 mg/day.

Discontinuation of therapy: Consider planning antidepressant discontinuation for lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to antidepressant discontinuation (Hathaway 2018). Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of discontinuation syndromes (withdrawal) and allow for the detection of reemerging disease state symptoms (eg, relapse). Evidence supporting ideal taper rates after illness remission is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. After long-term (years) antidepressant treatment, WFSBP guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation. If intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Fenske 2009; Haddad 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of escitalopram.

Allow 14 days to elapse between discontinuing escitalopram and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Administration

Oral: Administer once daily (morning or evening), with or without food.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

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. Consider therapy modification

Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Alosetron; Ondansetron; Ramosetron. Monitor therapy

Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Monitor therapy

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Consider therapy modification

Blood Glucose Lowering Agents: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Brexanolone: Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Avoid combination

BuPROPion: May enhance the adverse/toxic effect of Escitalopram. Specifically, the risk for seizures and serotonin syndrome may be increased. Monitor therapy

BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

Cimetidine: May increase the serum concentration of Escitalopram. Monitor therapy

Citalopram: May enhance the antiplatelet effect of Escitalopram. Escitalopram may enhance the QTc-prolonging effect of Citalopram. Escitalopram may enhance the serotonergic effect of Citalopram. This could result in serotonin syndrome. Avoid combination

CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

CYP2C19 Inducers (Moderate): May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Monitor therapy

CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desmopressin: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

Doxepin-Containing Products: Escitalopram may enhance the QTc-prolonging effect of Doxepin-Containing Products. Escitalopram may enhance the serotonergic effect of Doxepin-Containing Products. This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

DULoxetine: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of DULoxetine. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of DULoxetine. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Monitor therapy

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Nicergoline. Monitor therapy

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination

Gilteritinib: Escitalopram may enhance the QTc-prolonging effect of Gilteritinib. Gilteritinib may diminish the therapeutic effect of Escitalopram. Management: Avoid use of this combination if possible. If use is necessary, monitor for reduced response to escitalopram and for QTc prolongation and arrhythmias. Patients with other risk factors may be at greater risk for these serious toxicities. Consider therapy modification

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Haloperidol: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures. Consider therapy modification

Hydroxychloroquine: Escitalopram may enhance the hypoglycemic effect of Hydroxychloroquine. Hydroxychloroquine may enhance the QTc-prolonging effect of Escitalopram. Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Avoid combination

Lofexidine: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. Lofexidine may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Lorcaserin: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Lumacaftor and Ivacaftor: May decrease the serum concentration of Escitalopram. Monitor therapy

Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. 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. Consider therapy modification

MetyroSINE: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Nefazodone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Exceptions: Diclofenac (Topical); Ibuprofen (Topical); Piroxicam (Topical). Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Omeprazole: May increase the serum concentration of Escitalopram. Management: Monitor for increased escitalopram toxicity with concomitant use of omeprazole. Recommendations for management of this interaction found in product labeling may differ by country. Consult appropriate labeling. Consider therapy modification

Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Ondansetron may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation or serotonin syndrome may be at even higher risk. Monitor therapy

Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: FentaNYL; Meperidine; TraMADol. Monitor therapy

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Pimozide. Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Gilteritinib. Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone; Lofexidine. Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Monitor therapy

Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Rasagiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Rasagiline. This could result in serotonin syndrome. Avoid combination

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Safinamide: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Use the lowest effective dose of SSRIs in patients treated with safinamide and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of other Selective Serotonin Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of other Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Exceptions: Citalopram; Dapoxetine; Vortioxetine. Monitor therapy

Selegiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Selegiline. This could result in serotonin syndrome. Avoid combination

Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Exceptions: TraMADol. Monitor therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Almotriptan; Eletriptan. Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Serotonin/Norepinephrine Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Exceptions: DULoxetine. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: Escitalopram may decrease the serum concentration of Simeprevir. Monitor therapy

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

TraMADol: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and seizures when these agents are combined. Monitor therapy

Tricyclic Antidepressants: May enhance the serotonergic effect of Escitalopram. Escitalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Exceptions: Doxepin (Systemic); Doxepin (Topical). Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Vortioxetine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Vortioxetine may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Monitor therapy

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Headache (24%), insomnia (7% to 14%), drowsiness (4% to 13%)

Gastrointestinal: Nausea (15% to 18%), diarrhea (6% to 14%)

Genitourinary: Ejaculatory disorder (9% to 14%)

1% to 10%:

Central nervous system: Fatigue (2% to 8%), dizziness (4% to 7%), anorgasmia (2% to 6%), abnormal dreams (3%), lethargy (3%), paresthesia (2%), yawning (2%)

Dermatologic: Diaphoresis (3% to 8%)

Endocrine & metabolic: Decreased libido (3% to 7%), menstrual disease (2%)

Gastrointestinal: Xerostomia (4% to 9%), constipation (3% to 6%), dyspepsia (2% to 6%), decreased appetite (3%), vomiting (3%), abdominal pain (2%), flatulence (2%), toothache (2%)

Genitourinary: Impotence (2% to 3%), urinary tract infection (children ≥2%)

Neuromuscular & skeletal: Neck pain (≤3%), shoulder pain (≤3%), back pain (children ≥2%)

Respiratory: Flu-like symptoms (5%), rhinitis (5%), sinusitis (3%), nasal congestion (children ≥2%)

<1%, postmarketing, and/or case reports: Abdominal cramps, abnormal gait, acute renal failure, aggressive behavior, agitated depression, agitation, agranulocytosis, akathisia, alopecia, amnesia, anaphylaxis, anemia, angioedema, angle-closure glaucoma, anxiety, apathy, aplastic anemia, arthralgia, ataxia, atrial fibrillation, blurred vision, bradycardia, bronchitis, cardiac failure, cerebrovascular accident, chest pain, choreoathetosis, cough, deep vein thrombosis, delirium, delusions, depersonalization, dermatitis, diabetes mellitus, diplopia, dyskinesia, dysmenorrhea, dysphagia, dyspnea, dystonia, dysuria, ecchymoses, edema, epistaxis, erythema multiforme, extrapyramidal reaction, fever, flushing, gastroenteritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, hallucination, heartburn, hemolytic anemia, hepatic failure, hepatic necrosis, hepatitis, hot flash, hypercholesterolemia, hyperglycemia, hypermenorrhea, hyperprolactinemia, hypersensitivity reaction, hypertension, hypertensive crisis, hypoesthesia, hypoglycemia, hypokalemia, hyponatremia, hypoprothrombinemia, hypotension, immune thrombocytopenia, increased appetite, increased INR, increased liver enzymes, increased serum bilirubin, irritability, jaw tightness, lack of concentration, leukopenia, limb pain, migraine, myalgia, myasthenia, mydriasis, myocardial infarction, myoclonus, neuroleptic malignant syndrome (Stevens 2008), nightmares, nystagmus, orthostatic hypotension, palpitations, pancreatitis, panic, paranoia, Parkinsonian-like syndrome, phlebitis, priapism, prolonged Q-T interval on ECG, psychosis, pulmonary embolism, rectal hemorrhage, restless leg syndrome, rhabdomyolysis, seizure, serotonin syndrome, SIADH, sinus congestion, sinus headache, skin photosensitivity, skin rash, spontaneous abortion, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies, syncope, tachycardia, tardive dyskinesia, thrombocytopenia, thrombosis, tinnitus, torsades de pointes, toxic epidermal necrolysis, tremor, urinary frequency, urinary retention, urticaria, ventricular arrhythmia, ventricular tachycardia, vertigo, visual disturbance, weight gain, withdrawal syndrome

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 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 to 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 health care 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. 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 health care provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Bleeding risk: Use with caution in patients who are hemodynamically unstable. 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.
• Cardiovascular effects: Use has been associated with dose-dependent QT interval prolongation with doses of 10 mg and 30 mg/day in healthy subjects (mean change from baseline: 4.3 msec and 10.7 msec, respectively); prolongation of QT interval and ventricular arrhythmia (including torsades de pointes) have been reported, particularly in females with preexisting QT prolongation or other risk factors (eg, hypokalemia, other cardiac disease).
• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).
• Ocular effects: May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors
• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) 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:

• Cardiovascular disease: Patients with a recent history of MI or unstable heart disease were excluded from clinical trials; use with caution.
• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.
• Mania/hypomania: May 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.
• Metabolic disease: Use with caution; limited data in patients with altered metabolism.
• 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:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• CYP2C19 poor metabolizers: Escitalopram systemic exposure may be increased in CYP2C19 poor metabolizers.
• Elderly: Bioavailability and half-life are increased by 50% in the elderly.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).
• 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.

Monitoring Parameters

ECG (in patients at increased risk for QT-prolonging effects); electrolytes (potassium and magnesium concentrations at baseline and as clinically indicated); liver and renal function tests (baseline; as clinically indicated); serum sodium in at-risk populations (as clinically indicated); CBC (as clinically indicated); suicidal ideation (baseline and with dose changes).

Pregnancy

Pregnancy Considerations

Escitalopram crosses the placenta and is distributed into the amniotic fluid. An increased risk of teratogenic effects, including cardiovascular defects, may be associated with maternal use of escitalopram or other SSRIs; however, available information is conflicting. Nonteratogenic effects in the newborn following SSRI/SNRI 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. Symptoms may be due to the toxicity of the SSRIs/SNRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn (PPHN) has also been reported with SSRI exposure. 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.

Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of escitalopram may be altered. 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 health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy.

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Patient Education

What is this drug used for?

• It is used to treat low mood (depression).
• It is used to treat anxiety.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea
• Dizziness
• Diarrhea
• Constipation
• Dry mouth
• Trouble sleeping
• Sweating a lot
• Flu-like signs
• Headache
• Loss of strength and energy
• Fatigue
• Runny nose
• Yawning

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Depression like thoughts of suicide, anxiety, emotional instability, or confusion.
• Agitation
• Panic attacks
• Mood changes
• Behavioral changes
• Low sodium like headache, difficulty focusing, trouble with memory, confusion, weakness, seizures, or change in balance.
• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.
• Seizures
• Chills
• Sexual dysfunction
• Decreased sex drive
• Vision changes
• Eye pain
• Eye redness
• Eye edema
• Serotonin syndrome like dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea.
• Erection that lasts more than 4 hours
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.