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Lexapro
Classes
Selective Serotonin Reuptake Inhibitor Antidepressants, SSRIs
Administration
May administer escitalopram with or without food. If nausea occurs, administer after a meal.
Tablets: The 10 mg and 20 mg tablets are scored and may be cut in half if needed.
Oral solution: Measure dosage with a calibrated measuring device to ensure dose accuracy.
Adverse Reactions
pancreatitis / Delayed / Incidence not known
tardive dyskinesia / Delayed / Incidence not known
seizures / Delayed / Incidence not known
suicidal ideation / Delayed / Incidence not known
SIADH / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
hypertensive crisis / Early / Incidence not known
torsade de pointes / Rapid / Incidence not known
thrombosis / Delayed / Incidence not known
atrial fibrillation / Early / Incidence not known
stroke / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
visual impairment / Early / Incidence not known
ocular hypertension / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
spontaneous fetal abortion / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
serotonin syndrome / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known
persistent pulmonary hypertension of the newborn / Delayed / Incidence not known
neonatal abstinence syndrome / Early / Incidence not known
ejaculation dysfunction / Delayed / 12.0-12.0
constipation / Delayed / 3.0-5.0
impotence (erectile dysfunction) / Delayed / 2.0-2.0
dysphagia / Delayed / Incidence not known
akathisia / Delayed / Incidence not known
choreoathetosis / Delayed / Incidence not known
pseudoparkinsonism / Delayed / Incidence not known
dysarthria / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
migraine / Early / Incidence not known
myoclonia / Delayed / Incidence not known
dystonic reaction / Delayed / Incidence not known
nystagmus / Delayed / Incidence not known
amnesia / Delayed / Incidence not known
delirium / Early / Incidence not known
hostility / Early / Incidence not known
depression / Delayed / Incidence not known
hallucinations / Early / Incidence not known
psychosis / Early / Incidence not known
mania / Early / Incidence not known
confusion / Early / Incidence not known
hyponatremia / Delayed / Incidence not known
platelet dysfunction / Delayed / Incidence not known
hypoprothrombinemia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
bleeding / Early / Incidence not known
leukopenia / Delayed / Incidence not known
hematoma / Early / Incidence not known
hypertension / Early / Incidence not known
peripheral vasodilation / Rapid / Incidence not known
chest pain (unspecified) / Early / Incidence not known
phlebitis / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
palpitations / Early / Incidence not known
edema / Delayed / Incidence not known
dyspnea / Early / Incidence not known
blurred vision / Early / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hyperprolactinemia / Delayed / Incidence not known
priapism / Early / Incidence not known
urinary retention / Early / Incidence not known
dysuria / Early / Incidence not known
myasthenia / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
diabetes mellitus / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
hypokalemia / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known
osteopenia / Delayed / Incidence not known
withdrawal / Early / Incidence not known
growth inhibition / Delayed / Incidence not known
headache / Early / 24.0-24.0
nausea / Early / 15.0-18.0
drowsiness / Early / 6.0-13.0
insomnia / Early / 9.0-12.0
xerostomia / Early / 6.0-9.0
diarrhea / Early / 8.0-8.0
fatigue / Early / 5.0-8.0
libido decrease / Delayed / 3.0-6.0
hyperhidrosis / Delayed / 4.0-5.0
dizziness / Early / 5.0-5.0
rhinitis / Early / 5.0-5.0
dyspepsia / Early / 3.0-3.0
vomiting / Early / 3.0-3.0
lethargy / Early / 3.0-3.0
sinusitis / Delayed / 3.0-3.0
orgasm dysfunction / Delayed / 3.0-3.0
dental pain / Delayed / 2.0-2.0
abdominal pain / Early / 2.0-2.0
paresthesias / Delayed / 2.0-2.0
yawning / Early / 2.0-2.0
menstrual irregularity / Delayed / 2.0-2.0
flatulence / Early / Incidence not known
weight loss / Delayed / Incidence not known
pyrosis (heartburn) / Early / Incidence not known
gastroesophageal reflux / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
asthenia / Delayed / Incidence not known
nightmares / Early / Incidence not known
tremor / Early / Incidence not known
vertigo / Early / Incidence not known
restless legs syndrome (RLS) / Delayed / Incidence not known
paranoia / Early / Incidence not known
anxiety / Delayed / Incidence not known
irritability / Delayed / Incidence not known
emotional lability / Early / Incidence not known
restlessness / Early / Incidence not known
agitation / Early / Incidence not known
purpura / Delayed / Incidence not known
epistaxis / Delayed / Incidence not known
ecchymosis / Delayed / Incidence not known
syncope / Early / Incidence not known
malaise / Early / Incidence not known
fever / Early / Incidence not known
rash / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
flushing / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
nasal congestion / Early / Incidence not known
anosmia / Delayed / Incidence not known
cough / Delayed / Incidence not known
diplopia / Early / Incidence not known
mydriasis / Early / Incidence not known
tinnitus / Delayed / Incidence not known
dysmenorrhea / Delayed / Incidence not known
menorrhagia / Delayed / Incidence not known
increased urinary frequency / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
myalgia / Early / Incidence not known
back pain / Delayed / Incidence not known
Boxed Warning
Safety and efficacy of escitalopram have not been established in pediatric populations for any indication except for the treatment of major depressive disorder (MDD) in children and adolescents 12 years of age and older. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. No suicides occurred in any of the pediatric trials. Nevertheless, the need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of escitalopram may be necessary in patients with emerging suicidality or worsening depression. The potential for growth inhibition in pediatric patients should be monitored during SSRI therapy. Monitor height and weight periodically while the patient is receiving escitalopram. Data are inadequate to determine whether the chronic use of SSRIs causes long-term growth inhibition; however, decreased weight gain has been observed in children and adolescents receiving SSRIs. The mechanism of growth inhibition in children may be due to the suppression of growth hormone secretion, which is known to occur in adults taking SSRIs.
Common Brand Names
Lexapro
Dea Class
Rx
Description
Oral selective serotonin reuptake inhibitor (SSRI) antidepressant; an enantiomer of citalopram
Indicated in adults for major depression and generalized anxiety disorder and pediatric patients 12 and older for depression
Increased risk of suicidality during treatment initiation in pediatric and young adult patients
Dosage And Indications
10 mg PO once daily, initially. May increase the dose to 20 mg/day after at least 1 week if inadequate response and depending on tolerability. However, a fixed-dose trial failed to demonstrate a greater benefit of the 20 mg over 10 mg. Max: 20 mg/day. Periodically reassess the need for continued treatment.
10 mg PO once daily. Periodically reassess the need for continued treatment.
10 mg PO once daily, initially. May increase the dose to 20 mg/day after at least 3 weeks if inadequate response and depending on tolerability. However, a fixed-dose trial failed to demonstrate a greater benefit of the 20 mg over 10 mg. Max: 20 mg/day. Periodically reassess the need for continued treatment.
10 mg PO once daily, initially. May increase the dose to 20 mg/day as needed and tolerated after 1 week or more.
10 mg PO once daily.
10 mg PO once daily, initially. May increase the dose to 20 mg/day as needed and tolerated after 2 weeks or more.
Initiate at 5 mg/day PO for at least 1 week, then gradually titrate. Max: 20 mg/day PO. Periodically reassess the need for continued treatment. Data are limited. Results from 1 open-label, forced titration study (n = 28) suggest that escitalopram may be effective in treating some behavioral symptoms associated with autism such as irritability. The mean final dose was 11.1 mg/day PO. The response rate was 61%, with response defined as a 50% or greater reduction in the Aberrant Behavior Checklist (ABC)-Community Version Irritability score. Of the 5 patients who did not complete the 10-week study, 2 were responders but had significant continuing hyperactivity, 1 was a non-responder and had continuing obsessions and compulsions, and 2 had symptoms of disinhibition and aggression.
In one controlled trial of adult patients (up to 80 years of age) receiving escitalopram, citalopram, or placebo, escitalopram was initiated at 5 mg/day PO. At the end of the first week, the dose was increased to 10 mg/day. At the end of week 4, the dose could be increased to 20 mg/day based on response and tolerability. The proportion of patients with no panic attacks at study end was significantly higher in patients receiving escitalopram than placebo (50% vs. 38%). The relative panic attack frequency was statistically significant for escitalopram compared to placebo (-1.61 vs. -0.32). There were no statistical differences in either measurement between citalopram and placebo. Adverse events were similar to placebo for escitalopram; improvement in the escitalopram group began at week 4. According to the British Association for Psychopharmacology (BAP) evidence-based guidelines, all SSRIs are efficacious for the acute treatment of panic disorder. The relative effectiveness and tolerability of differing medications during long-term treatment is uncertain; however, double-blind studies indicate that continuing treatment from 12 to 52 weeks is associated with an increase in overall treatment response rates.
Doses of escitalopram ranging from 5 to 20 mg once daily PO were more effective than placebo during 12- and 24-weeks of treatment for social anxiety disorder (n = 839 patients). In the same study, 20 mg/day of escitalopram was significantly superior to 20 mg/day of paroxetine at week 24. According to the British Association for Psychopharmacology (BAP) evidence-based guidelines, escitalopram is among the antidepressants with proven efficacy. Relapse prevention studies have shown that there is a significant advantage for staying on active medication for up to 6 months in patients responding to acute treatment. A post-hoc analysis of clinical trials indicates that response is unlikely if there is no onset of clinical effect within the first 4 weeks of treatment.
Per available studies, doses of 5 mg/day PO initially, titrated up to 10 to 20 mg/day per efficacy and tolerance, appear efficacious. In a small open-label study (n = 20), escitalopram was initiated at 5 mg/day PO, increased to 10 mg/day after the first week, and subsequently titrated in 5 mg increments up to a maximum of 20 mg/day based upon efficacy and tolerability.
†Indicates off-label use
Dosing Considerations
10 mg PO once daily is the recommended dose for patients with hepatic impairment.
Renal ImpairmentCrCl 20 mL/minute or more: No dosage adjustment is necessary.
CrCl less than 20 mL/minute: Specific guidelines for dosage adjustments are not available; use with caution.
Drug Interactions
Abciximab: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving abciximab. Monitor closely for signs and symptoms of bleeding.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Acetaminophen; Aspirin: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of dihydrocodeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue dihydrocodeine if serotonin syndrome is suspected. Additionally, concomitant use of dihydrocodeine with escitalopram may decrease dihydrocodeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease dihydrocodeine plasma concentrations and increase diydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to diydromorphine, and by CYP3A4. Escitalopram is a weak inhibitor of CYP2D6.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6.
Acetaminophen; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and escitalopram because of the potential risk of serotonin syndrome. Discontinue hydrocodone if serotonin syndrome is suspected. Additionally, concomitant use of hydrocodone with escitalopram may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of escitalopram could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Escitalopram is a weak inhibitor of CYP2D6.
Acetaminophen; Oxycodone: (Moderate) The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue the suspected drugs if serotonin syndrome is suspected and manage cliinically. There has been a case report of possible serotonin syndrome caused by the combination of oxycodone and selective serotonin reuptake inhbitors (SSRIs).
Adagrasib: (Major) Concomitant use of adagrasib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfentanil: (Moderate) If concomitant use of alfentanil and escitalopram is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Alfuzosin: (Moderate) Concomitant use of escitalopram and alfuzosin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Almotriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with escitalopram. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue escitalopram and almotriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Alteplase: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
Amiloride: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Amiodarone: (Major) Concomitant use of amiodarone and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with escitalopram. Amisulpride causes dose- and concentration- dependent QT prolongation. Escitalopram has been associated with a risk of QT prolongation and TdP.
Amitriptyline: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; consider a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the TCAs; elevated TCA concentrations may occur in some patients. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Amobarbital: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as clarithromycin, should be done with caution and close monitoring. In addition, escitalopram is metabolized by CYP3A4. Theoretically, clarithromycin may inhibit this enzyme and lead to elevated plasma levels of this SSRI. However, because escitalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease its clearance. (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with omeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase escitalopram concentrations by 51% to 94%, which may increase the risk for adverse effects.
Amphetamines: (Moderate) Coadministration of selective serotonin reuptake inhibitors (SSRIs) like escitalopram with amphetamines may increase the risk of serotonin syndrome. At high doses, amphetamines can increase serotonin release and act as serotonin agonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
Anagrelide: (Moderate) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as anagrelide, should be done with caution and close monitoring. In addition, platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Antithrombin III: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like antithrombin III. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Apixaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like apixaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Apomorphine: (Moderate) Concomitant use of escitalopram and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Aprepitant, Fosaprepitant: (Moderate) Use caution if escitalopram and aprepitant, fosaprepitant are used concurrently and monitor for an increase in escitalopram-related adverse effects for several days after administration of a multi-day aprepitant regimen. Escitalopram is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of escitalopram. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of escitalopram. Patients receiving both a CYP3A inhibitor plus escitalopram may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Additionally, consider taking steps to minimize the risk of QT/QTc interval prolongation and torsade de pointes (TdP), such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may increase aripiprazole exposure and risk for side effects and may increase the risk of QT/QTc prolongation and TdP in some patients. Aripiprazole is a CYP2D6 and CYP3A substrate; escitalopram is a moderate CYP2D6 inhibitor; both medications have been associated with QT interval prolongation.
Armodafinil: (Moderate) The plasma concentration of escitalopram, a CYP2C19 substrate, may be increased when administered concurrently with armodafinil, a CYP2C19 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Arsenic Trioxide: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as arsenic trioxide, should be done with caution and close monitoring.
Artemether; Lumefantrine: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as artemether; lumefantrine, should be done with caution and close monitoring. In addition, Aatemether; lumefantrine is an inhibitor and escitalopram is a substrate/inhibitor of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased escitalopram concentrations. (Moderate) Lumefantrine is an inhibitor and escitalopram is a substrate/inhibitor of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased escitalopram concentrations. Concomitant use warrants caution due to the potential for increased side effects.
Asenapine: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as asenapine, should be done with caution and close monitoring. In addition, escitalopram is a modest inhibitor of CYP2D6 and may decrease the clearance of atypical antipsychotics that are CYP2D6 substrates including asenapine. Decreased metabolism of these CYP2D6 substrates may lead to clinically important adverse reactions that are associated with antipsychotic use, such as extrapyramidal symptoms.
Aspirin, ASA: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Caffeine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Carisoprodol: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Dipyridamole: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Omeprazole: (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with omeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase escitalopram concentrations by 51% to 94%, which may increase the risk for adverse effects. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Aspirin, ASA; Oxycodone: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. (Moderate) The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue the suspected drugs if serotonin syndrome is suspected and manage cliinically. There has been a case report of possible serotonin syndrome caused by the combination of oxycodone and selective serotonin reuptake inhbitors (SSRIs).
Atazanavir; Cobicistat: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
Atenolol; Chlorthalidone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with escitalopram can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Azilsartan; Chlorthalidone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Azithromycin: (Major) Concomitant use of azithromycin and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Barbiturates: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Bedaquiline: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as bedaquiline, should be done with caution and close monitoring.
Belladonna; Opium: (Moderate) Escitalopram modestly inhibits metabolism via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via the same pathway, including opium.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Benzhydrocodone; Acetaminophen: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of benzhydrocodone and escitalopram because of the potential risk of serotonin syndrome. Discontinue benzhydrocodone if serotonin syndrome is suspected. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) According to the manufacturer of escitalopram, treatment initiation with escitalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than escitalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving escitalopram and requiring urgent treatment with IV methylene blue, escitalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Escitalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
Betrixaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like betrixaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Brimonidine; Timolol: (Minor) Escitalopram modestly inhibits the hepatic CYP2D6 isoenzyme. This can result in increased concentrations of drugs metabolized via the same pathway, including timolol.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Bumetanide: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Buprenorphine: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of escitalopram and buprenorphine is necessary. Escitalopram may cause QT interval prolongation and a risk for torsade de pointes (TdP); buprenorphine caused QT prolongation in some patients during clinical trials. In addition, concurrent use of opioids with other drugs that modulate serotonergic function, such as SSRIs, has resulted in serotonin syndrome in some cases. Patients should be carefully observed, particularly during treatment initiation and during dose adjustments. Discontinue the serotonergic medications if serotonin syndrome is suspected.
Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation, cautious use and close monitoring are advisable if concurrent use of escitalopram and buprenorphine is necessary. Escitalopram may cause QT interval prolongation and a risk for torsade de pointes (TdP); buprenorphine caused QT prolongation in some patients during clinical trials. In addition, concurrent use of opioids with other drugs that modulate serotonergic function, such as SSRIs, has resulted in serotonin syndrome in some cases. Patients should be carefully observed, particularly during treatment initiation and during dose adjustments. Discontinue the serotonergic medications if serotonin syndrome is suspected.
Buspirone: (Moderate) Coadministration of buspirone with escitalopram may increase the risk of serotonin syndrome. Buspirone has some serotonergic properties. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
Butabarbital: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Butalbital; Acetaminophen: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Butalbital; Acetaminophen; Caffeine: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6. (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6. (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates. (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation.
Cabotegravir; Rilpivirine: (Moderate) Concomitant use of escitalopram and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Cangrelor: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Capsaicin; Metaxalone: (Moderate) Concomitant use of selective serotonin reuptake inhibitors (SSRIs) and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Carvedilol: (Moderate) Monitor for signs of bradycardia or heart block if coadministration of carvedilol with escitalopram is necessary. Carvedilol is a CYP2C9 substrate and escitalopram is a CYP2C9 inhibitor. Concomitant use may enhance the beta-blocking properties of carvedilol resulting in further slowing of the heart rate or cardiac conduction.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with escitalopram is necessary. If escitalopram is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and escitalopram is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ceritinib: (Major) Avoid coadministration of ceritinib with escitalopram if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Escitalopram has also been associated with a risk of QT prolongation and torsade de pointes (TdP).
Chloramphenicol: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be increased when administered concurrently with chloramphenicol, a CYP2C19 and potent CYP3A4 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Chlordiazepoxide; Amitriptyline: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; consider a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the TCAs; elevated TCA concentrations may occur in some patients. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Chloroquine: (Major) Concomitant use of chloroquine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Chlorothiazide: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Chlorpheniramine; Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6.
Chlorpheniramine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of dihydrocodeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue dihydrocodeine if serotonin syndrome is suspected. Additionally, concomitant use of dihydrocodeine with escitalopram may decrease dihydrocodeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease dihydrocodeine plasma concentrations and increase diydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to diydromorphine, and by CYP3A4. Escitalopram is a weak inhibitor of CYP2D6.
Chlorpheniramine; Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and escitalopram because of the potential risk of serotonin syndrome. Discontinue hydrocodone if serotonin syndrome is suspected. Additionally, concomitant use of hydrocodone with escitalopram may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of escitalopram could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Escitalopram is a weak inhibitor of CYP2D6.
Chlorpromazine: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as chlorpromazine, should be done with caution and close monitoring. In addition, escitalopram modestly inhibits CYP2D6. This can result in increased concentrations of drugs metabolized via the same pathway, including certain conventional antipsychotic agents (phenothiazines). Decreased metabolism of these CYP2D6 substrates may lead to arrhythmias or other clinically important adverse reactions associated with antipsychotic use such as sedation and extrapyramidal symptoms.
Chlorthalidone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Chlorthalidone; Clonidine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor for signs and symptoms of bleeding during concomitant magnesium salicylate and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
Cilostazol: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs), including escitalopram, due to platelet serotonin depletion. There may be an increased risk of a bleeding complication in patients receiving platelet inhibitors, such as cilostazol. Patients receiving this combination should be monitored for signs and symptoms of bleeding.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Avoid concomitant use of escitalopram and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Contraindicated) Due to the similarity in pharmacology of citalopram and escitalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Also, both citalopram and escitalopram have been associated with QT prolongation and torsade de pointes (TdP). It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
Clarithromycin: (Major) Escitalopram has been associated with QT prolongation. Coadministration with o
Clofazimine: (Moderate) Concomitant use of clofazimine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clomipramine: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered. Elevated concentrations of the tricyclic antidepressant may occur. Symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the tricyclic antidepressants. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Clopidogrel: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of escitalopram and clopidogrel. Selective serotonin reuptake inhibitors (SSRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with escitalopram and monitor for adverse reactions, inlcuding QT prolongation. If escitalopram is discontinued, monitor for lack of clozapine effect, and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine and increased risk of QT prolongation may occur during concurrent use. Clozapine is partially metabolized by CYP2D6 and has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Escitalopram is a moderate CYP2D6 inhibitor that has been associated with a risk of QT prolongation and TdP.
Cobicistat: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
Cocaine: (Major) Concomitant use of cocaine with drugs that have CNS serotonergic properties, such as SSRIs, could potentiate serotonin neurotransmission, and result in the serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving this combination should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions. Additionally, citalopram causes dose-dependent QT interval prolongation. Local anesthetics (e.g., cocaine) are associated with a possible risk for QT prolongation and according to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Codeine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6.
Codeine; Phenylephrine; Promethazine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6. (Moderate) Concomitant use of promethazine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Codeine; Promethazine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of codeine and escitalopram because of the potential risk of serotonin syndrome. Discontinue codeine if serotonin syndrome is suspected. Additionally, concomitant use of codeine with escitalopram may decrease codeine plasma concentrations resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of escitalopram could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Escitalopram is a weak inhibitor of CYP2D6. (Moderate) Concomitant use of promethazine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Crizotinib: (Major) Avoid coadministration of crizotinib with escitalopram due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Escitalopram has also been associated with a risk of QT prolongation and torsade de pointes (TdP).
Cyclobenzaprine: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of cyclobenzaprine with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, milnacipran and concurrent serotonergic agents should be discontinued.
Cyproheptadine: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as escitalopram. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine.
Dabigatran: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like dabigatran. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Dalteparin: (Moderate) Monitor for signs and symptoms of bleeding during concomitant low molecular weight heparin and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are coadministered with another anticoagulant.
Darifenacin: (Moderate) Escitalopram, a modest CYP2D6 inhibitor, may decrease the metabolism of darifenacin, a CYP2D6 substrate. Clinicians should monitor patients for increased anticholinergic effects; dosage adjustments of darifenacin may be necessary.
Darunavir; Cobicistat: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
Dasatinib: (Moderate) Concomitant use of escitalopram and dasatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Degarelix: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., degarelix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Delavirdine: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be increased when administered concurrently with delavirdine, a CYP2C19 and potent CYP3A4 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Desflurane: (Major) Concomitant use of escitalopram and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Desipramine: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered. Coadministration of escitalopram and desipramine, resulted in a 40% increase in Cmax and a 100% increase in AUC of desipramine. The clinical significance of the elevation in desipramine concentration is unknown. However, symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the tricyclic antidepressants. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Desmopressin: (Minor) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including SSRIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia, which may include monitoring serum sodium or electrolytes periodically. Ensure the patient is compliant with fluid restrictions and intake.
Desvenlafaxine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome, selective serotonin reuptake inhibitors (SSRIs) should generally not be administered with serotonin norepinephrine reuptake inhibitors like desvenlafaxine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Discontinuation symptoms have been reported when switching from other antidepressants to desvenlafaxine. It may be advisable to taper the previous antidepressant to minimize discontinuation symptoms.
Deutetrabenazine: (Moderate) Use escitalopram with caution in combination with deutetrabenazine. The risk of QT prolongation may be increased with coadministration of deutetrabenazine and escitalopram. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP).
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextromethorphan; Bupropion: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextromethorphan; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dextromethorphan; Quinidine: (Major) Concomitant use of quinidine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Dihydroergotamine: (Moderate) Use escitalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Diltiazem: (Minor) Escitalopram is metabolized by CYP3A4 and CYP2C19. Diltiazem can inhibit the metabolism of CYP 450 isoenzymes, including those that are responsible for the metabolism of escitalopram. Although clinical studies have not been done to determine the clinical significance of such an interaction, the potential for increased adverse effects and toxicity associated with elevated plasma levels of escitalopram theoretically exists.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with escitalopram can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Dipyridamole: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Disopyramide: (Major) Concomitant use of disopyramide and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Diuretics: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Dofetilide: (Major) Concomitant use of dofetilide and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolasetron: (Moderate) Concomitant use of escitalopram and dolasetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dolutegravir; Rilpivirine: (Moderate) Concomitant use of escitalopram and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Moderate) While both escitalopram and donepezil have been reported to cause cases of QT prolongation, the American Psychiatric Association and other experts recommend use of SSRIs including escitalopram in patients with Alzheimer's disease (who are treated with cholinesterase inhibitors) to treat depression, anxiety, or agitation. More study is needed to identify the most effective treatments in this challenging population. If use together is necessary, monitor heart rate and monitor patients for QT prolongation, unusual changes in mood or behaviors, and efficacy of combined treatment.
Donepezil; Memantine: (Moderate) While both escitalopram and donepezil have been reported to cause cases of QT prolongation, the American Psychiatric Association and other experts recommend use of SSRIs including escitalopram in patients with Alzheimer's disease (who are treated with cholinesterase inhibitors) to treat depression, anxiety, or agitation. More study is needed to identify the most effective treatments in this challenging population. If use together is necessary, monitor heart rate and monitor patients for QT prolongation, unusual changes in mood or behaviors, and efficacy of combined treatment.
Dorzolamide; Timolol: (Minor) Escitalopram modestly inhibits the hepatic CYP2D6 isoenzyme. This can result in increased concentrations of drugs metabolized via the same pathway, including timolol.
Doxepin: (Moderate) Monitor patients for signs and symptoms of serotonin syndrome during concomitant use of doxepin and escitalopram, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Doxercalciferol: (Moderate) Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors, including selective serotonin reuptake inhibitors (SSRIs), may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if SSRIs are coadministered with doxercalciferol.
Doxorubicin Liposomal: (Major) Avoid coadministration of escitalopram with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Escitalopram is a moderate CYP2D6 inhibitor and doxorubicin is a major substrate of CYP3D6. Concurrent use of CYP2D6 inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of escitalopram with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Escitalopram is a moderate CYP2D6 inhibitor and doxorubicin is a major substrate of CYP3D6. Concurrent use of CYP2D6 inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronedarone: (Contraindicated) Avoid concomitant use of escitalopram and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Droperidol: (Major) Concomitant use of droperidol and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Duloxetine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome, selective serotonin reuptake inhibitors (SSRIs) such as escitalopram should generally not be administered with serotonin norepinephrine reuptake inhibitors (SNRIs) such as duloxetine.
Dutasteride; Tamsulosin: (Moderate) Use caution if coadministration of escitalopram with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor.
Edoxaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like edoxaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Efavirenz: (Moderate) Concomitant use of escitalopram and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of escitalopram and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of escitalopram and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Elbasvir; Grazoprevir: (Moderate) Administering escitalopram with elbasvir; grazoprevir may result in elevated escitalopram plasma concentrations. Escitalopram is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eletriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with escitalopram. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and selective serotonin reuptake inhibitors (SSRIs). Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue escitalopram and eletriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Eliglustat: (Moderate) Concomitant use of escitalopram and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Close monitoring for antidepressant response and careful dose titrations of the antidepressant therapy is recommended during coadministration of selective serotonin reuptake inhibitors (SSRIs) and cobicistat. Concurrent use may result in elevated SSRI plasma concentrations. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. All SSRIs are substrates for the hepatic isoenzyme CYP2D6, while citalopram, escitalopram, and sertraline are also substrates for CYP3A4; cobicistat is an inhibitor of both CYP2D6 and CYP3A4.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of escitalopram and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of escitalopram and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Encorafenib: (Major) Concomitant use of encorafenib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Enoxaparin: (Moderate) Monitor for signs and symptoms of bleeding during concomitant low molecular weight heparin and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are coadministered with another anticoagulant.
Entrectinib: (Major) Concomitant use of entrectinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Eptifibatide: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Ergoloid Mesylates: (Moderate) Use escitalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Ergot alkaloids: (Moderate) Use escitalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Ergotamine: (Moderate) Use escitalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Ergotamine; Caffeine: (Moderate) Use escitalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Eribulin: (Major) Concomitant use of eribulin and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Erythromycin: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as erythromycin, should be done with caution and close monitoring. In addition, escitalopram is metabolized by CYP3A4. Theoretically, erythromycin may inhibit this enzyme and lead to elevated plasma levels of this SSRI. However, because escitalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease its clearance.
Eslicarbazepine: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be altered when administered concurrently with eslicarbazepine, a CYP2C19 inhibitor and CYP3A4 inducer. Because escitalopram is extensively metabolized by both CYP2C19 and CYP3A4, the outcome of the interaction is unpredictable. If these drugs are used together, monitor for reduced efficacy of escitalopram as well as escitalopram-associated adverse reactions.
Esomeprazole: (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with esomeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase dose-adjusted escitalopram concentrations by 82%, which may increase the risk for adverse effects.
Ethacrynic Acid: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression. (Moderate) Although escitalopram has not been shown to increase mental and motor skill impairments related to alcohol consumption, the combination of escitalopram and alcohol in depressed patients is not advised.
Felbamate: (Moderate) The plasma concentration of escitalopram, a CYP2C19 substrate, may be increased when administered concurrently with felbamate, a CYP2C19 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Fenfluramine: (Moderate) Use fenfluramine and escitalopram with caution due to an increased risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a weak inhibitor of CYP2C19. Concomitant use of fenofibric acid with CYP2C19 substrates, such as escitalopram, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of escitalopram during coadministration with fenofibric acid.
Fentanyl: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like fentanyl with serotonergic drugs, such as escitalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fingolimod: (Moderate) Concomitant use of escitalopram and fingolimod may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Flecainide: (Major) Concomitant use of escitalopram and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of flecainide, further increasing the risk of adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Flecainide is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor.
Fluconazole: (Moderate) Concomitant use of fluconazole and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoxetine: (Major) Due to the similarity in pharmacology of fluoxetine and escitalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Also, both fluoxetine and escitalopram have been associated with QT prolongation and torsade de pointes (TdP), which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
Fluphenazine: (Minor) Use escitalopram with caution in combination with fluphenazine. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Fluphenazine is associated with a possible risk for QT prolongation.
Fluvoxamine: (Major) Due to the similarity in pharmacology of fluvoxamine and escitalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Also, both fluvoxamine and escitalopram have been associated with QT prolongation and torsade de pointes (TdP), which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
Fondaparinux: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like fondaparinux. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Foscarnet: (Major) Concomitant use of escitalopram and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Fostemsavir: (Moderate) Concomitant use of escitalopram and fostemsavir may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering frovatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase of the SSRI or the addition of other serotonergic medications to an existing SSRI regimen. Discontinue the SSRI and frovatriptan and initiate symptomatic treatment if serotonin syndrome occurs.
Furosemide: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with escitalopram is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and escitalopram is a CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
Gemifloxacin: (Moderate) Concomitant use of escitalopram and gemifloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gemtuzumab Ozogamicin: (Moderate) Concomitant use of escitalopram and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gilteritinib: (Major) Avoid coadministration of escitalopram with gilteritinib if possible due to the potential for decreased response to escitalopram and additive QT prolongation. Gilteritinib inhibits human 5HT2B receptor or sigma nonspecific receptors, which may reduce the effects of drugs like escitalopram that target these receptors. In addition, both drug have been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with escitalopram due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP).
Goserelin: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., goserelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Granisetron: (Moderate) Concomitant use of escitalopram and granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Grapefruit juice: (Moderate) Interactions between citalopram and grapefruit juice have been documented. Grapefruit juice is an inhibitor of the cytochrome P450 isozyme 3A4, a metabolic enzyme utilized by escitalopram. Theoretically, elevated levels of escitalopram may occur. Until further information is available, clinicians should warn patients to avoid consumption of grapefruit juice while taking escitalopram.
Guaifenesin; Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and escitalopram because of the potential risk of serotonin syndrome. Discontinue hydrocodone if serotonin syndrome is suspected. Additionally, concomitant use of hydrocodone with escitalopram may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of escitalopram could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Escitalopram is a weak inhibitor of CYP2D6.
Halogenated Anesthetics: (Major) Concomitant use of escitalopram and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Moderate) Use escitalopram with caution in combination with haloperidol as concurrent use may increase the risk of QT prolongation and haloperidol-related adverse effects. Escitalopram is a moderate CYP2D6 inhibitor that has been associated with a risk of QT prolongation and torsade de pointes (TdP). Haloperidol is a CYP2D6 substrate; QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP2D6 inhibitors.
Heparin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like heparin. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Histrelin: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Homatropine; Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and escitalopram because of the potential risk of serotonin syndrome. Discontinue hydrocodone if serotonin syndrome is suspected. Additionally, concomitant use of hydrocodone with escitalopram may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of escitalopram could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Escitalopram is a weak inhibitor of CYP2D6.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Hydrocodone: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and escitalopram because of the potential risk of serotonin syndrome. Discontinue hydrocodone if serotonin syndrome is suspected. Additionally, concomitant use of hydrocodone with escitalopram may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of escitalopram could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Escitalopram is a weak inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and escitalopram because of the potential risk of serotonin syndrome. Discontinue hydrocodone if serotonin syndrome is suspected. Additionally, concomitant use of hydrocodone with escitalopram may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of escitalopram could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Escitalopram is a weak inhibitor of CYP2D6.
Hydrocodone; Pseudoephedrine: (Moderate) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of hydrocodone and escitalopram because of the potential risk of serotonin syndrome. Discontinue hydrocodone if serotonin syndrome is suspected. Additionally, concomitant use of hydrocodone with escitalopram may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of escitalopram could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If escitalopram is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Escitalopram is a weak inhibitor of CYP2D6.
Hydromorphone: (Moderate) Escitalopram modestly inhibits metabolism via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via the same pathway, including hydromorphone.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Contraindicated) According to the manufacturer of escitalopram, treatment initiation with escitalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than escitalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving escitalopram and requiring urgent treatment with IV methylene blue, escitalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Escitalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma. (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin.
Ibuprofen; Oxycodone: (Moderate) The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue the suspected drugs if serotonin syndrome is suspected and manage cliinically. There has been a case report of possible serotonin syndrome caused by the combination of oxycodone and selective serotonin reuptake inhbitors (SSRIs).
Ibutilide: (Major) Concomitant use of ibutilide and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with escitalopram, a CYP3A substrate, as escitalopram toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as iloperidone, should be done with caution and close monitoring. In addition, escitalopram is a modest inhibitor of CYP2D6 and may decrease the clearance of atypical antipsychotics that are CYP2D6 substrates including iloperidone. Decreased metabolism of these CYP2D6 substrates may lead to clinically important adverse reactions that are associated with antipsychotic use, such as extrapyramidal symptoms.
Imipramine: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered. Elevated concentrations of the tricyclic antidepressant may occur. Symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the tricyclic antidepressants. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Indapamide: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with escitalopram due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Escitalopram has been associated with a risk of QT prolongation and TdP.
Iobenguane I 123: (Major) Discontinue medications that decrease norepinephrine uptake, such as selective serotonin reuptake inhibitors (SSRIs), for at least 5 biological half-lives prior to iobenguane I 123 administration. Consider medication tapering or additional supportive therapy as appropriate to minimize the risk for precipitating SSRI withdrawal symptoms. Medications that decrease the uptake of norepinephrine can cause false negative imaging results. Increasing the dose of iobenguane I 123 will not overcome any potential uptake limiting effect of this medication.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with escitalopram may result in increased serum concentrations of escitalopram. Escitalopram is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
Isoflurane: (Major) Concomitant use of escitalopram and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isoniazid, INH: (Moderate) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs), such as escitalopram, should be approached with caution. Isoniazid is chemically related to iproniazid, a drug that was known to possess monoamine oxidase (MAO) inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with escitalopram, including serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be implemented.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs), such as escitalopram, should be approached with caution. Isoniazid is chemically related to iproniazid, a drug that was known to possess monoamine oxidase (MAO) inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with escitalopram, including serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be implemented. (Moderate) Escitalopram is metabolized by CYP3A4. Rifampin can induce the metabolism of escitalopram via induction of CYP3A4. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking rifampin.
Isoniazid, INH; Rifampin: (Moderate) Concurrent use of isoniazid and selective serotonin reuptake inhibitors (SSRIs), such as escitalopram, should be approached with caution. Isoniazid is chemically related to iproniazid, a drug that was known to possess monoamine oxidase (MAO) inhibiting activity. Although isoniazid does not inhibit mitochondrial MAO, it does appear to inhibit plasma MAO. Isoniazid may possess enough MAO inhibiting activity to produce clinical symptoms consistent with serotonergic excess when combined with escitalopram, including serotonin syndrome. If serotonin syndrome occurs, all serotonergic drugs should be discontinued and appropriate medical treatment should be implemented. (Moderate) Escitalopram is metabolized by CYP3A4. Rifampin can induce the metabolism of escitalopram via induction of CYP3A4. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking rifampin.
Itraconazole: (Moderate) Concomitant use of escitalopram and itraconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with escitalopram due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP).
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and escitalopram due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Ketoconazole is associated with a risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been reported postmarketing with escitalopram. Pharmacokinetic interactions are not expected based on studies with citalopram.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as clarithromycin, should be done with caution and close monitoring. In addition, escitalopram is metabolized by CYP3A4. Theoretically, clarithromycin may inhibit this enzyme and lead to elevated plasma levels of this SSRI. However, because escitalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease its clearance.
Lapatinib: (Moderate) Concomitant use of escitalopram and lapatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and selective serotonin reuptake inhibitors. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Lefamulin: (Major) Avoid coadministration of lefamulin with escitalopram as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP).
Lenvatinib: (Major) Concomitant use of lenvatinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Leuprolide: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Leuprolide; Norethindrone: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and escitalopram due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Ketoconazole is associated with a risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been reported postmarketing with escitalopram. Pharmacokinetic interactions are not expected based on studies with citalopram.
Levomilnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of levomilnacipran with other drugs that have serotonergic properties, such as selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, levomilnacipran and concurrent serotonergic agents should be discontinued.
Levorphanol: (Moderate) Escitalopram modestly inhibits metabolism via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via the same pathway, including levorphanol.
Linezolid: (Contraindicated) According to the manufacturer of escitalopram, treatment initiation with escitalopram is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than escitalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving escitalopram and requiring urgent treatment with linezolid, escitalopram should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Escitalopram may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with escitalopram can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Lithium: (Moderate) Coadministration of escitalopram and lithium may increase the risk for QT prolongation and serotonin syndrome. Lithium has been associated with QT prolongation and escitalopram also has this potential. Lithium is an effective augmenting agent to antidepressants in treatment-resistant depression; however, lithium has central serotonin-enhancing effects and may increase the risk of serotonin syndrome when combined with selective serotonin reuptake inhibitors (SSRIs) such as escitalopram. Inform patients of the possible increased risk and monitor for serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, serotonergic agents should be discontinued and symptomatic treatment should be initiated.
Lofexidine: (Moderate) Concomitant use of escitalopram and lofexidine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide: (Moderate) Concomitant use of loperamide and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lopinavir; Ritonavir: (Major) Concomitant use of lopinavir and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lorcaserin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including, selective serotonin reuptake inhibitors (SSRIs). Patients receiving this combination should be monitored for the emergence of serotonin syndrome or Neuroleptic Malignant Syndrome (NMS) like signs and symptoms.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Low Molecular Weight Heparins: (Moderate) Monitor for signs and symptoms of bleeding during concomitant low molecular weight heparin and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are coadministered with another anticoagulant.
Luliconazole: (Moderate) Theoretically, luliconazole may increase the side effects of escitalopram, which is a CYP2C19 and a CYP3A4 substrate. Monitor patients for adverse effects of escitalopram, such as GI effects or serotonin sydrome. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of escitalopram by decreasing its systemic exposure. If used together, a higher dose of escitalopram may be required to obtain the desired therapeutic effect. Do not exceed the recommended maximum dose. Escitalopram is a CYP3A and CYP2C19 substrate. Lumacaftor; ivacaftor is a strong inducer of CYP3A and has the potential to induce CYP2C19.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of escitalopram by decreasing its systemic exposure. If used together, a higher dose of escitalopram may be required to obtain the desired therapeutic effect. Do not exceed the recommended maximum dose. Escitalopram is a CYP3A and CYP2C19 substrate. Lumacaftor; ivacaftor is a strong inducer of CYP3A and has the potential to induce CYP2C19.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as escitalopram. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP).
Magnesium Salicylate: (Moderate) Monitor for signs and symptoms of bleeding during concomitant magnesium salicylate and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Maprotiline: (Moderate) Concomitant use of escitalopram and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mefloquine: (Moderate) Concomitant use of escitalopram and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Meperidine: (Moderate) If concomitant use of meperidine and escitalopram is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Metaxalone: (Moderate) Concomitant use of selective serotonin reuptake inhibitors (SSRIs) and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
Methadone: (Major) Coadministration may increase the risk of serotonin syndrome, QT prolongation, or torsade de pointes (TdP). Escitalopram has been associated with a risk of QT prolongation and TdP. The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is associated with an increased risk for QT prolongation and TdP, especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. In addition, both escitalopram and methadone have central serotonergic properties and serotonin syndrome is possible. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Contraindicated) According to the manufacturer of escitalopram, treatment initiation with escitalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than escitalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving escitalopram and requiring urgent treatment with IV methylene blue, escitalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Escitalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma.
Methohexital: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Methyclothiazide: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Methylene Blue: (Contraindicated) According to the manufacturer of escitalopram, treatment initiation with escitalopram is contraindicated in patients currently receiving intravenous (IV) methylene blue due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than escitalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving escitalopram and requiring urgent treatment with IV methylene blue, escitalopram should be discontinued immediately and methylene blue therapy initiated only if acceptable alternatives are not available and the potential benefits outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of methylene blue, whichever comes first. Escitalopram may be re-initiated 24 hours after the last dose of methylene blue. Results from an in vitro study indicate that methylene blue is a potent, reversible inhibitor of the monoamine oxidase type A enzyme (MAO-A). MAO-A is responsible for the metabolism of serotonin; therefore, concurrent use of an MAO-A inhibitor with a serotonergic agent may result in a clinically significant interaction. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent, in patients receiving SSRIs, serotonin/norepinephrine reuptake inhibitors, or clomipramine. It is not known if patients receiving other serotonergic psychiatric agents with IV methylene blue are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. One case describes a patient receiving citalopram who experienced agitation, restlessness, pupil dilation with sluggish response to light, myoclonic movements of the lower limbs, and brisk reflexes following an infusion of methylene blue, while another patient receiving paroxetine developed tachycardia, agitation, dystonia and abnormal eye movements. During a retrospective study of 193 surgical patients who had received a methylene blue injection, it was found that all 12 of the patients who experienced postoperative neurological sequelae had been taking a serotonin reuptake inhibitor preoperatively. One of the 12 patients experienced cardiopulmonary arrest and died. Of the remaining 181 patients who did not experience neurological sequelae, 8.8% were taking a serotonin reuptake inhibitor. Published interaction reports between IV methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and coma. Signs and symptoms of serotonin syndrome include fever, diaphoresis, shivering, myoclonus, tremor, tachycardia, diarrhea, nausea, headache, incoordination, mental status changes (e.g., agitation, confusion), hyperreflexia, seizures, and coma.
Methylergonovine: (Moderate) Use escitalopram and ergot alkaloids together with caution due to a potential for serotonin syndrome. Weakness, hyperreflexia, and incoordination have been reported rarely when ergot alkaloids or other serotonin agonists have been coadministered with SSRIs, which may be indicative of serotonin excess. If serotonin syndrome occurs, discontinue the offending agents and institute appropriate treatment.
Methylphenidate Derivatives: (Moderate) Caution should be observed when coadministering methylphenidate derivatives and the selective serotonin reuptake inhibitors (SSRIs). There are postmarketing reports of serotonin syndrome during concurrent use of methylphenidate derivatives with other serotonergic medications. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of some SSRIs and downward dose adjustment of the SSRI may be required in some patients. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome. If serotonin syndrome occurs, serotonergic agents should be discontinued and appropriate medical management should be implemented.
Metoclopramide: (Moderate) Concomitant use of metoclopramide and selective serotonin reuptake inhibitors (SSRIs) such as escitalopram may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary. In rare cases postmarketing, NMS-like symptoms, which may overlap with serotonin syndrome symptoms, have been reported with metoclopramide when used with serotonergic agents.
Metolazone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Metoprolol: (Minor) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with escitalopram. In a concomitant use study conducted in healthy volunteers, metoprolol peak and overall exposures were increased by 50% and 82%, respectively, however no clinically significant effects on blood pressure or heart rate were observed. Metoprolol is a CYP2D6 substrate and escitalopram is a CYP2D6 inhibitor.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. (Minor) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with escitalopram. In a concomitant use study conducted in healthy volunteers, metoprolol peak and overall exposures were increased by 50% and 82%, respectively, however no clinically significant effects on blood pressure or heart rate were observed. Metoprolol is a CYP2D6 substrate and escitalopram is a CYP2D6 inhibitor.
Metronidazole: (Moderate) Concomitant use of metronidazole and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mexiletine: (Moderate) Caution is recommended during the coadministration of escitalopram with drugs metabolized by CYP2D6, such as mexiletine. Limited in vivo data suggest a modest inhibitory effect of CYP2D6 by escitalopram, which may result in increased concentrations of CYP2D6 substrates.
Midostaurin: (Major) Concomitant use of midostaurin and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Concomitant use of mifepristone and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Milnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, concurrent use of milnacipran with other drugs that have serotonergic properties, such as the selective serotonin reuptake inhibitors (SSRIs), should generally be avoided. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, milnacipran and concurrent serotonergic agents should be discontinued.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and escitalopram may increase the risk of serotonin syndrome, QT prolongation, and torsade de pointes (TdP). Escitalopram has been associated with a risk of QT prolongation and TdP. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during use of mirtazapine, primarily after overdose or in patients with risk factors for QT prolongation (e.g., concurrent use of other medications associated with QT prolongation). Both mirtazapine and SSRIs such as escitalopram have central serotonin-enhancing effects, and case reports suggest that serotonin syndrome is possible. If serotonin syndrome occurs, all serotonergic agents should be discontinued, and appropriate medical treatment should be implemented.
Mitotane: (Moderate) Use caution if mitotane and escitalopram are used concomitantly, and monitor for decreased efficacy of escitalopram and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and escitalopram is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of escitalopram.
Mobocertinib: (Major) Concomitant use of mobocertinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Modafinil: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be altered when administered concurrently with modafinil, a CYP2C19 inhibitor and CYP3A4 inducer. Because escitalopram is extensively metabolized by both CYP2C19 and CYP3A4, the outcome of the interaction is unpredictable. If these drugs are used together, monitor for reduced efficacy of escitalopram as well as escitalopram-associated adverse reactions.
Monoamine oxidase inhibitors: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
Morphine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like morphine with serotonergic drugs, such as escitalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Morphine; Naltrexone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like morphine with serotonergic drugs, such as escitalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Moxifloxacin: (Major) Concomitant use of moxifloxacin and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Naproxen; Esomeprazole: (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with esomeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase dose-adjusted escitalopram concentrations by 82%, which may increase the risk for adverse effects.
Naratriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering naratriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with escitalopram; adjust the nebivolol dose according to blood pressure response. Concomitant use may increase the exposure of nebivolol. Nebivolol is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor.
Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with escitalopram; adjust the nebivolol dose according to blood pressure response. Concomitant use may increase the exposure of nebivolol. Nebivolol is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor.
Nefazodone: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering drugs that have serotonergic properties such as nefazodone and escitalopram. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least one case report of serotonin syndrome from the concurrent use of nefazodone and a selective serotonin reuptake inhibitor (i.e., paroxetine) has been published. Additionally, when a 200 mg dose of nefazodone was administered to subjects who had been receiving fluoxetine for 1 week, there was an increased incidence of transient serotonin-related adverse events. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
Netupitant, Fosnetupitant; Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering palonosetron with other drugs that have serotonergic properties, such as escitalopram. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Nicardipine: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be increased when administered concurrently with nicardipine, a CYP2C19 and CYP3A4 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval, such as escitalopram. Nilotinib is a moderate inhibitor of CYP3A4 and escitalopram is a substrate of CYP3A4; administering these drugs together may result in increased escitalopram levels. If the use of escitalopram is necessary, hold nilotinib therapy. If these drugs are used together, consider an escitalopram dose reduction and monitor patients for toxicity (e.g., QT interval prolongation).
Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
Nortriptyline: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered. Elevated concentrations of the tricyclic antidepressant may occur. Symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the tricyclic antidepressants. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Ofloxacin: (Moderate) Concomitant use of ofloxacin and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Concomitant use of escitalopram and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Fluoxetine: (Major) Due to the similarity in pharmacology of fluoxetine and escitalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Also, both fluoxetine and escitalopram have been associated with QT prolongation and torsade de pointes (TdP), which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI. (Moderate) Concomitant use of escitalopram and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Samidorphan: (Moderate) Concomitant use of escitalopram and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and escitalopram is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and escitalopram may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If escitalopram is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Omeprazole: (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with omeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase escitalopram concentrations by 51% to 94%, which may increase the risk for adverse effects.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram. Rifabutin can induce the metabolism of escitalopram via induction of CYP3A4. Given the enzyme-inducing properties rifabutin, the possibility that the drug may increase the clearance of escitalopram should be considered if the 2 drugs are coadministered. (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with omeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase escitalopram concentrations by 51% to 94%, which may increase the risk for adverse effects.
Omeprazole; Sodium Bicarbonate: (Moderate) Monitor for an increase in escitalopram-related adverse effects, such as QT prolongation and serotonin syndrome, if concomitant use with omeprazole is necessary. An empiric escitalopram dosage reduction may be considered in patients with additional risk factors for adverse effects, such as age older than 60 years. Concomitant use has been observed to increase escitalopram concentrations by 51% to 94%, which may increase the risk for adverse effects.
Ondansetron: (Major) Concomitant use of ondansetron and escitalopram increases the risk of QT/QTc prolongation, torsade de pointes (TdP), and serotonin syndrome. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concomitant use is necessary, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, and monitor for serotonin syndrome.
Oritavancin: (Moderate) Coadministration of oritavancin and escitalopram may result in increases or decreases in escitalopram exposure and may increase side effects or decrease efficacy of escitalopram. Escitalopram is metabolized by CYP3A4 and CYP2C19. Oritavancin weakly induces CYP3A4, while weakly inhibiting CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy.
Osilodrostat: (Moderate) Concomitant use of escitalopram and osilodrostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Osimertinib: (Major) Concomitant use of osimertinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of oxaliplatin and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxycodone: (Moderate) The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue the suspected drugs if serotonin syndrome is suspected and manage cliinically. There has been a case report of possible serotonin syndrome caused by the combination of oxycodone and selective serotonin reuptake inhbitors (SSRIs).
Oxymorphone: (Moderate) Escitalopram modestly inhibits metabolis m via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via the same pathway, including oxymorphone.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking escitalopram due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis and serotonin syndrome. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension and serotonergic effects. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Escitalopram is a serotonergic drug that is associated with QT prolongation and TdP.
Pacritinib: (Major) Concomitant use of pacritinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Concomitant use of paliperidone and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering palonosetron with other drugs that have serotonergic properties, such as escitalopram. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Panobinostat: (Major) Concomitant use of panobinostat and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paroxetine: (Moderate) Monitor patients for an increase in paroxetine-related adverse reactions and signs and symptoms of serotonin syndrome during concomitant use of paroxetine and escitalopram, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor.
Pasireotide: (Moderate) Concomitant use of escitalopram and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Pazopanib: (Major) Because both pazopanib and escitalopram are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and escitalopram, a CYP3A4 substrate, may cause an increase in systemic concentrations of escitalopram. Use caution when administering these drugs concomitantly.
Pentamidine: (Major) Concomitant use of pentamidine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pentazocine: (Major) Because of the potential risk and severity of serotonin syndrome reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome occurs, discontinue the offending agent(s) and institute appropriate therapy.
Pentazocine; Naloxone: (Major) Because of the potential risk and severity of serotonin syndrome reactions, caution should be observed when administering selective serotonin reuptake inhibitors (SSRIs) with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome occurs, discontinue the offending agent(s) and institute appropriate therapy.
Pentobarbital: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Pentosan: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and pentosan, which has weak anticoagulant properties. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Perphenazine: (Minor) Use escitalopram with caution in combination with perphenazine as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Perphenazine; Amitriptyline: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; consider a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the TCAs; elevated TCA concentrations may occur in some patients. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). (Minor) Use escitalopram with caution in combination with perphenazine as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Phenelzine: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
Phenobarbital: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Phentermine: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) together with caution due to a potential for serotonin syndrome. Monitor weight, cardiovascular status, and for potential serotonergic adverse effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome when combined with serotonergic agents. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses and some large controlled clinical studies have allowed patients to start phentermine-based therapy for obesity along with their SSRI as long as the antidepressant dose had been stable for at least 3 months prior. Such therapy was generally well-tolerated, especially at lower phentermine doses. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies.
Phentermine; Topiramate: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) together with caution due to a potential for serotonin syndrome. Monitor weight, cardiovascular status, and for potential serotonergic adverse effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome when combined with serotonergic agents. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses and some large controlled clinical studies have allowed patients to start phentermine-based therapy for obesity along with their SSRI as long as the antidepressant dose had been stable for at least 3 months prior. Such therapy was generally well-tolerated, especially at lower phentermine doses. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies.
Pimavanserin: (Major) Concomitant use of pimavanserin and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Pimozide is contraindicated for use with selective serotonin reuptake inhibitors (SSRIs) due to an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is thought to be primarily metabolized through CYP3A4, and to a lesser extent, CYP1A2 and CYP2D6. Elevated plasma concentrations of pimozide occurring through inhibition of one or more of these isoenzymes by SSRIs can lead to QT prolongation, ventricular arrhythmias, and sudden death. Additionally, most SSRIs are also associated with QT prolongation, further increasing the risk of additive QT prolongation.
Pitolisant: (Major) Concomitant use of pitolisant and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking escitalopram due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP).
Posaconazole: (Moderate) Concomitant use of escitalopram and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Prasugrel: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving prasugrel. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Primaquine: (Moderate) Concomitant use of escitalopram and primaquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Primidone: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Procainamide: (Major) Concomitant use of procainamide and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Procarbazine: (Major) Procarbazine is a weak monoamine oxidase inhibitor (MAOI). Although procarbazine appears to be less likely than other MAOIs to produce serious drug interactions, clinicians should avoid the use of selective serotonin reuptake inhibitors (SSRIs) in patients receiving MAOIs. Fatalities have been reported when fluoxetine was administered to patients receiving MAOIs. Confusion, seizures, severe hypertension, and other, less severe symptoms have also been reported with this drug combination. Non-selective MAOIs inhibit both MAO types A and B. Since serotonin is metabolized by MAO type A, it is thought that this drug interaction may lead to serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of therapy with an SSRI except fluoxetine. At least 5 weeks should elapse between the discontinuation of fluoxetine therapy and commencement of MAOI therapy. This 5-week period is needed because of the long half-lives of fluoxetine and its principle metabolite norfluoxetine.
Prochlorperazine: (Minor) Use escitalopram with caution in combination with prochlorperazine as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Promethazine: (Moderate) Concomitant use of promethazine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dextromethorphan with escitalopram. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of promethazine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Concomitant use of escitalopram and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Avoid simultaneous use of propafenone and escitalopram with a CYP3A4 inhibitor. Propafenone is a CYP3A4 and a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor.
Propranolol: (Minor) Escitalopram modestly inhibits the hepatic CYP2D6 isoenzyme. This can result in increased concentrations of drugs metabolized via the same pathway, including propranolol. Increased serum levels of the beta-blockers could result in reductions in cardioselectivity.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. (Minor) Escitalopram modestly inhibits the hepatic CYP2D6 isoenzyme. This can result in increased concentrations of drugs metabolized via the same pathway, including propranolol. Increased serum levels of the beta-blockers could result in reductions in cardioselectivity.
Protriptyline: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered. Elevated concentrations of the tricyclic antidepressant may occur. Symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the tricyclic antidepressants. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Quetiapine: (Major) Concomitant use of escitalopram and quietiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor patients for signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Quinidine: (Major) Concomitant use of quinidine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinine: (Moderate) The plasma concentration of escitalopram, a CYP2C19 and CYP3A4 substrate, may be increased when administered concurrently with quinine, a CYP2C19 and CYP3A4 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Quizartinib: (Major) Concomitant use of quizartinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Rabeprazole: (Moderate) The plasma concentration of escitalopram, a CYP2C19 substrate, may be increased when administered concurrently with rabeprazole, a CYP2C19 inhibitor. If these drugs are used together, monitor for escitalopram-associated adverse reactions.
Ranolazine: (Moderate) Concomitant use of escitalopram and ranolazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Rasagiline: (Major) It is recommended to avoid concurrent use of rasagiline and selective serotonin reuptake inhibitors (SSRIs). Severe CNS toxicity with hyperpyrexia has been reported during concurrent use of antidepressants and selective or non-selective MAOIs. During postmarketing use of rasagiline, non-fatal cases of serotonin syndrome have been reported during concomitant antidepressant administration. At least 2 weeks should elapse between stopping rasagiline treatment and beginning therapy with any SSRI. Conversely, when discontinuing an SSRI, it is advisable to wait the length of 4 to 5 half-lives of the individual agent being discontinued prior to initiation with rasagiline. At least 5 weeks should elapse between the discontinuation of fluoxetine therapy and initiation of rasagiline. If coadministration of rasagiline and fluvoxamine is required, do not exceed a rasagiline dose of 0.5 mg once daily. Rasagiline is primarily metabolized by CYP1A2; fluvoxamine is a strong CYP1A2 inhibitor. When rasagiline was administered with another strong CYP1A2 inhibitor, the AUC of rasagiline increased by 83%.
Relugolix: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Remifentanil: (Moderate) If concomitant use of remifentanil and selective serotonin reuptake inhibitors (SSRIs) is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Reteplase, r-PA: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
Ribociclib: (Major) Concomitant use of ribociclib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ribociclib; Letrozole: (Major) Concomitant use of ribociclib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Rifabutin: (Moderate) CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram. Rifabutin can induce the metabolism of escitalopram via induction of CYP3A4. Given the enzyme-inducing properties rifabutin, the possibility that the drug may increase the clearance of escitalopram should be considered if the 2 drugs are coadministered.
Rifampin: (Moderate) Escitalopram is metabolized by CYP3A4. Rifampin can induce the metabolism of escitalopram via induction of CYP3A4. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking rifampin.
Rilpivirine: (Moderate) Concomitant use of escitalopram and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Risperidone: (Moderate) Concomitant use of escitalopram and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Rivaroxaban: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and anticoagulants like rivaroxaban. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Rizatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering rizatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Some patients had used the combination previously without incident when serotonin syndrome occurred. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after the initiation of the SSRI or dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Romidepsin: (Moderate) Concomitant use of escitalopram and romidepsin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Safinamide: (Major) The concurrent use of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) is generally avoided; however, the manufacturer of safinamide recommends monitoring for serotonin syndrome and using the lowest effective dose of the SSRI during concurrent use. During clinical trial evaluation of safinamide, 1 case of serotonin syndrome occurred during co-administration with an SSRI. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Salsalate: (Moderate) The combined use of selective serotonin reuptake inhibitors (SSRIs) and aspirin, ASA or other salicylates which affect hemostasis may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. A cohort study in > 26,000 patients found that SSRI use alone increased the risk for serious GI bleed by 3.6-fold; when an SSRI was combined with aspirin the risk was increased by > 5-fold. The absolute risk of GI bleed from concomitant therapy with aspirin and a SSRI was low (20/2640 patients) in this cohort study and the clinician may determine that the combined use of these drugs is appropriate.
Saquinavir: (Major) Avoid concomitant use of saquinavir boosted with ritonavir with escitalopram. If use together is necessary, obtain a baseline ECG and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Escitalopram has also been associated with a risk of QT prolongation and torsade de pointes (TdP).
Secobarbital: (Moderate) Escitalopram is metabolized by CYP2C19 and CYP3A4. Barbiturates can induce the metabolism of various CYP 450 isoenzymes, including those involved in escitalopram metabolism. Although no clinical data are available to support a clinically significant interaction, escitalopram may need to be administered in higher doses in patients chronically taking barbiturates.
Selegiline: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
Selpercatinib: (Major) Concomitant use of selpercatinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sertraline: (Major) Due to the similarity in pharmacology of sertraline and escitalopram and the potential for serious adverse reactions, including serotonin syndrome, these selective serotonin reuptake inhibitors (SSRIs) should not be administered together. Also, both sertraline and escitalopram have been associated with QT prolongation, which could theoretically result in additive effects on the QT interval. It is advisable to monitor for signs and symptoms of serotonin syndrome during an overlapping transition from one SSRI to another SSRI.
Sevoflurane: (Major) Concomitant use of escitalopram and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Siponimod: (Major) Concomitant use of siponimod and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Concomitant use of escitalopram and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sorafenib: (Major) Concomitant use of sorafenib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of sotalol and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Spironolactone: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
St. John's Wort, Hypericum perforatum: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when coadministering escitalopram and St. John's Wort. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly during treatment initiation and dose increases. If serotonin syndrome occurs, serotonergic drugs should be discontinued and appropriate medical treatment should be initiated.
Sufentanil: (Moderate) Escitalopram modestly inhibits metabolism via the CYP2D6 pathway. Theoretically, this can result in increased concentrations of drugs metabolized via the same pathway, including sufentanil.
Sumatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sumatriptan; Naproxen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sumatriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sunitinib: (Moderate) Concomitant use of escitalopram and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tacrolimus: (Moderate) Concomitant use of escitalopram and tacrolimus may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tamsulosin: (Moderate) Use caution if coadministration of escitalopram with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 substrate and escitalopram is a moderate CYP2D6 inhibitor.
Tapentadol: (Moderate) If concomitant use of tapentadol and selective serotonin reuptake inhibitors (SSRIs) is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tedizolid: (Minor) Caution is warranted with the concurrent use of tedizolid and selective serotonin reuptake inhibitors (SSRIs) due to the theoretical risk of serotonin syndrome. Animal studies did not predict serotonergic effects; however, patients on concurrent SSRIs were excluded from clinical trials. Addtionally, tedizolid is an antibiotic that is also a weak reversible, non-selective MAO inhibitor and monoamine oxidase type A deaminates serotonin; therefore, coadministration theoretically could lead to serious reactions including serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid, which is structurally similar to tedizolid.
Telavancin: (Moderate) Concomitant use of escitalopram and telavancin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Tenecteplase: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
Terbinafine: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Thioridazine: (Contraindicated) Because of the potential for QT prolongation and torsade de pointes (TdP), concurrent use of phenothiazine antipsychotics such as thioridazine with escitalopram is contraindicated. In addition, thioridazine is a CYP2D6 substrate, and use with a modest CYP2D6 inhibitor, such as escitalopram, can result in increased plasma concentrations, further increasing the risk for cardiac or other phenothiazine-related side effects.
Thrombin Inhibitors: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and other drugs that affect coagulation like thrombin inhibitors. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Thrombolytic Agents: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
Ticagrelor: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving ticagrelor. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Ticlopidine: (Moderate) The plasma concentration of escitalopram, a CYP2C19 substrate, may be increased when administered concurrently with ticlopidine, a CYP2C19 inhibitor. In addition, platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., ticlopidine). Patients should be instructed to monitor for signs and symptoms of escitalopram-related adverse events and bleeding while taking an SSRI concurrently with ticlopidine and to promptly report any bleeding events to the practitioner.
Timolol: (Minor) Escitalopram modestly inhibits the hepatic CYP2D6 isoenzyme. This can result in increased concentrations of drugs metabolized via the same pathway, including timolol.
Tirofiban: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
Tolterodine: (Moderate) Use escitalopram with caution in combination with tolterodine as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Concomitant use of toremifene and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Torsemide: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with escitalopram is necessary. If escitalopram is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and escitalopram is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with escitalopram is necessary. If escitalopram is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and escitalopram is a CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tranylcypromine: (Contraindicated) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
Trazodone: (Major) Due to the risk of QT prolongation and torsade de pointes (TdP), the manufacturer of trazodone recommends avoiding use with other drugs that increase the QT interval. Escitalopram has been associated with a risk of QT prolongation and TdP. In addition, coadministration of trazodone and escitalopram may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue escitalopram and trazodone and initiate symptomatic treatment if serotonin syndrome occurs.
Triamterene: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Use escitalopram with caution in combination with trifluoperazine as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Trimipramine: (Moderate) Use tricyclic antidepressants (TCAs) and escitalopram together with caution as concurrent use may increase the risk of QT prolongation and serotonin syndrome; a decreased dosage of the TCA or the avoidance of concomitant SSRI therapy should be considered. Elevated concentrations of the tricyclic antidepressant may occur. Symptoms of toxicity, including seizures, have been reported when drugs from these 2 classes were used together. If serotonin syndrome is suspected, discontinue all serotonergic agents. Escitalopram is a moderate inhibitor of CYP2D6 that has been associated with a risk of QT prolongation and torsade de pointes (TdP). CYP2D6 is responsible for metabolism of many of the tricyclic antidepressants. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Triptorelin: (Moderate) Concomitant use of escitalopram and androgen deprivation therapy (i.e., triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tryptophan, 5-Hydroxytryptophan: (Major) Concurrent use of tryptophan and a selective serotonin reuptake inhibitor (SSRI) is not recommended. Since tryptophan is converted to serotonin, the use of tryptophan in patients receiving SSRIs could lead to serotonin excess and, potentially, serotonin syndrome. Discontinuation of tryptophan usually resolves symptoms.
Valerian, Valeriana officinalis: (Moderate) Substances that act on the CNS, including psychoactive drugs, may theoretically interact with valerian, Valeriana officinalis. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action. Persons taking medications such as SSRIs should discuss the use of herbal supplements with their health care professional prior to consuming these herbs. Patients should not abruptly stop taking their prescribed psychoactive medication.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Vandetanib: (Major) Concomitant use of vandetanib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Moderate) Concomitant use of vardenafil and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing syndrome of inappropriate antidiuretic hormone (SIADH), such as selective serotonin reuptake inhibitors. Use together may increase the pressor and antidiuretic effects of vasopressin.
Vemurafenib: (Major) Because both vemurafenib and escitalopram are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, concomitant use of vemurafenib and escitalopram may result in altered concentrations of escitalopram. Vemurafenib is a weak inhibitor of CYP2D6 and an inducer of CYP3A4. Escitalopram is a substrate of CYP3A4. Use caution and monitor patients for toxicity and efficacy.
Venlafaxine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome and QT prolongation, escitalopram, a selective serotonin reuptake inhibitor (SSRI) should generally not be administered with venlafaxine, a serotonin norepinephrine reuptake inhibitor (SNRI).
Vilazodone: (Major) Due to possible additive effects on serotonin concentrations, it is advisable to avoid combining selective serotonin reuptake inhibitors (SSRIs), such as escitalopram, with vilazodone. Interactions between serotonergic agents can lead to serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving vilazodone and escitalopram should be monitored for the emergence of serotonin syndrome, particularly during treatment initiation and during dosage increases. Vilazodone and escitalopram should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
Voclosporin: (Moderate) Concomitant use of escitalopram and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as clarithromycin, should be done with caution and close monitoring. In addition, escitalopram is metabolized by CYP3A4. Theoretically, clarithromycin may inhibit this enzyme and lead to elevated plasma levels of this SSRI. However, because escitalopram is metabolized by multiple enzyme systems, inhibition of one pathway may not appreciably decrease its clearance.
Vorapaxar: (Moderate) Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as selective serotonin reuptake inhibitors (SSRIs). Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion. In addition, fluoxetine and fluvoxamine are CYP3A4 inhibitors and coadministration with vorapaxar, a CYP3A4 substrate, may result in increased serum concentrations of vorapaxar. Increased exposure to vorapaxar may increase the risk of bleeding complications. Patients should be instructed to monitor for signs and symptoms of bleeding while taking a SSRI with vorapaxar and to promptly report any bleeding events.
Voriconazole: (Moderate) Administer voriconazole with caution in combination with escitalopram due to additive QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Escitalopram has been associated with a risk of QT prolongation and TdP.
Vorinostat: (Moderate) Concomitant use of escitalopram and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vortioxetine: (Major) Due to similarity of pharmacology and the potential for additive adverse effects, including serotonin syndrome, vortioxetine should generally not be co-administered with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
Warfarin: (Moderate) Advise patients of the increased bleeding risk associated with the concomitant use of escitalopram and warfarin. Carefully monitor patients receiving warfarin therapy if escitalopram is initiated or discontinued. Although the pharmacokinetics of warfarin were unaffected by citalopram, prothrombin time was increased by 5%; the clinical significance is unknown. Case reports and epidemiological studies have demonstrated an association between use of drugs that interfere with serotonin reuptake and gastrointestinal bleeding.
Ziprasidone: (Major) Concomitant use of ziprasidone and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Zolmitriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering zolmitriptan with selective serotonin reuptake inhibitors (SSRIs). Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists ("triptans") and SSRIs. Inform patients of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after initiation of SSRI treatment or any dose increases. Discontinue serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
How Supplied
Escitalopram/Lexapro Oral Sol: 5mg, 5mL
Escitalopram/Lexapro Oral Tab: 5mg, 10mg, 20mg
Maximum Dosage
20 mg/day PO.
Geriatric10 mg/day PO.
Adolescents20 mg/day PO.
Children12 years: 20 mg/day PO.
6 to 11 years: Safety and efficacy have not been established; however, doses up to 20 mg/day PO have been used for anxiety and pervasive developmental disorders.
1 to 5 years: Safety and efficacy have not been established.
Safety and efficacy have not been established.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
Escitalopram, an SSRI, is the the S-enantiomer of the SSRI citalopram. Escitalopram is at least 100-fold more potent than the R-enantiomer of citalopram with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate, but a clinical benefit over citalopram or other SSRIs has not been shown. The precise antidepressant effect of SSRIs is not fully understood, but involves selective serotonin reuptake blockade at the neuronal membrane, which enhances the actions of serotonin (5-HT). Initially, SSRIs increase availability of serotonin in the somatodendritic area through serotonin reuptake blockade at the serotonin transport pump. During long-term administration of SSRIs, serotonin autoreceptors are down-regulated and desensitized, allowing the neuron to increase serotonin release in the axon terminal synapses and increase its neuronal impulses. Because of the delay in therapeutic response to SSRIs, it is theorized that the change in the balance of serotonin receptors over time is an important mechanism of effect. The therapeutic action of SSRIs in treating anxiety disorders is thought to occur from potent central serotonin reuptake blockade, although the exact mechanism is unknown. SSRIs have less sedative, anticholinergic, and cardiovascular effects than do tricyclic antidepressants due to dramatically decreased binding to histaminergic, muscarinic, and alpha-adrenergic receptors. The metabolites of escitalopram do not appear to contribute to the pharmacologic activity of the drug.
Pharmacokinetics
Escitalopram is administered orally. Pharmacokinetic parameters are similar to citalopram. Manufacturer-sponsored pharmacokinetic studies suggest that 20 mg of escitalopram is bioequivalent to 40 mg of citalopram; however, head-to-head therapeutic interchange studies have not been performed. The volume of distribution of citalopram is 12 L/kg; data are not available for escitalopram. Dosing is linear and proportional in a range of 10 to 30 mg/day. The binding of escitalopram to plasma proteins is clinically insignificant. Hepatic metabolism of escitalopram is the primary route for biotransformation. In vitro studies indicate CYP3A4 and CYP2C19 are the main isozymes involved in N-demethylation of escitalopram. Due to metabolism by more than one isozyme, genetic polymorphism or concurrent use of CYP450 inhibitors is unlikely to have a large effect of net metabolic clearance. S(+)-desmethylcitalopram is the primary metabolite. In the plasma at steady state, the concentration of the primary metabolite is one-third that of the parent compound. S(+)-didesmethylcitalopram is a secondary metabolite. Both primary and secondary metabolites have minimal biological activity in humans. Renal excretion of escitalopram is similar to citalopram with 8% excreted as the unchanged drug and 10% excreted as S(+)-desmethylcitalopram. The elimination half-life of escitalopram is roughly 27 to 32 hours and that of S(+)-desmethylcitalopram (inactive) is 59 hours.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6, CYP3A4, CYP2C19
Escitalopram is extensively metabolized by 2C19 and 3A4. Because it is metabolized by multiple isoenzymes, inhibition of a single enzyme, such as CYP3A4, may not significantly decrease escitalopram clearance. No clinically significant effect on the pharmacokinetics of escitalopram was observed in drug interaction studies with the strong CYP3A4 inhibitors ritonavir and ketoconazole, suggesting that drug interactions with other CYP3A4 inhibitors and escitalopram are unlikely. In vitro data indicate that escitalopram does not inhibit 1A2, 2C19, 2C9, 2E1, and 3A4. In vivo data suggest a modest inhibitory effect on CYP2D6.
The absolute bioavailability of citalopram is roughly 80%; however, data are not available for escitalopram. The tablet and the oral solution dosage forms are bioequivalent. The absorption of escitalopram is not affected by food. Peak concentrations occur about 5 hours after a single 20 mg dose. Peak concentrations of the major metabolite, S(+)-desmethylcitalopram occurred in 14 hours. Steady-state concentrations are achieved in roughly 1 week. Clinical trials suggest that a significant onset of antidepressant activity may occur by the end of the first or second week of treatment.
Pregnancy And Lactation
Available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage from the use of escitalopram during pregnancy. There are risks to the mother associated with untreated depression (e.g., relapse) and a potential risk due to SSRI exposure of persistent pulmonary hypertension of the newborn (PPHN). Some neonates exposed to SSRIs late in the third trimester have experienced poor neonatal adaptation resulting in complications requiring prolonged hospitalization, respiratory support, and tube feeding upon delivery. Symptoms have included 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 direct SSRI toxicity, serotonin syndrome, or a drug discontinuation syndrome. Data from published observational studies have also reported that exposure to SSRIs, particularly in the month before obstetric delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to escitalopram; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry/antidepressants or by calling 1-866-961-2388.