Escitalopram
JFDA label: Cipralex
- Suicidality and antidepressant drugs:
Mechanism of Action
Escitalopram is the S-enantiomer of the racemic derivative citalopram, which selectively inhibits the reuptake of serotonin with little to no effect on norepinephrine or dopamine reuptake. It has no or very low affinity for 5-HT1-7, alpha- and beta-adrenergic, D1-5, H1-3, M1-5, and benzodiazepine receptors. Escitalopram does not bind to or has low affinity for Na+, K+, Cl-, and Ca++ ion channels.
Indications
Off-label
- Hot flashes
- Obsessive-Compulsive disorder (OCD)
- Panic disorder
- Post-traumatic stress disorder
Contraindications
Source: Lexicomp
- Additional contraindications (not in US labeling): Known QT-interval prolongation or congenital long QT syndrome Absolute
- Hypersensitivity to escitalopram, citalopram, or any component of the formulation Absolute
- concurrent use of pimozide Absolute
- initiation of escitalopram in a patient receiving linezolid or intravenous methylene blue Absolute
- use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either escitalopram or the MAO inhibitor) Absolute
Adverse Reactions
Cardiac disorders (1)
Uncommon QT prolongation (dose-dependent)
Nervous system disorders (14)
Very Common drowsiness · Headache · Headache · insomnia
Common abnormal dreams · anorgasmia · Discontinuation syndrome · dizziness · Fatigue · lethargy · paresthesia · Somnolence / fatigue · yawning
Rare Serotonin syndrome
Renal and urinary disorders (3)
Very Common Ejaculatory disorder
Common Impotence · urinary tract infection
Metabolism and nutrition disorders (3)
Common Decreased libido · menstrual disease
Rare Hyponatraemia (SIADH)
Gastrointestinal disorders (12)
Very Common diarrhea · Nausea · Nausea
Common abdominal pain · constipation · decreased appetite · Diarrhoea · dyspepsia · flatulence · toothache · vomiting · Xerostomia
Skin and subcutaneous tissue disorders (1)
Common Diaphoresis
Musculoskeletal and connective tissue disorders (3)
Common back pain · Neck pain · shoulder pain
Psychiatric disorders (1)
Common Insomnia
Reproductive system and breast disorders (1)
Very Common Sexual dysfunction
Respiratory, thoracic and mediastinal disorders (4)
Common Flu-like symptoms · nasal congestion · rhinitis · sinusitis
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
Suicidal thinking/behavior
Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Escitalopram is not FDA approved for use in children
Bleeding risk
Use with caution in patients who are hemodynamically unstable. May impair platelet aggregation resulting in increased risk of bleeding events (including GI bleeding), particularly if used concomitantly with aspirin, NSAIDs, warfarin, or other anticoagulants. Bleeding related to SSRI or SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.
Cardiovascular effects
Use has been associated with dose-dependent QT interval prolongation with doses of 10 mg and 30 mg/day in healthy subjects (mean change from baseline: 4.3 msec and 10.7 msec, respectively); prolongation of QT interval and ventricular arrhythmia (including torsade de pointes) have been reported, particularly in females with preexisting QT prolongation or other risk factors (eg, hypokalemia, other cardiac disease).
CNS depression
Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
Fractures
Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).
Ocular effects
May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors
Serotonin syndrome
Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.
Sexual dysfunction
May cause or exacerbate sexual dysfunction.
SIADH and hyponatremia
SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium Disease-related concerns:
Cardiovascular disease
Patients with a recent history of MI or unstable heart disease were excluded from clinical trials; use with caution.
Hepatic impairment
Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.
Mania/hypomania
May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Escitalopram is not FDA approved for the treatment of bipolar depression.
Metabolic disease
Use with caution; limited data in patients with altered metabolism.
Renal impairment
Use with caution in patients with severe renal impairment.
Seizure disorders
Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism. Concurrent drug therapy issues:
Drug-drug interactions
Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:
CYP2C19 poor metabolizers
Escitalopram systemic exposure may be increased in CYP2C19 poor metabolizers.
Elderly
Bioavailability and half-life are increased by 50% in the elderly. Dosage form specific issues:
Propylene glycol
Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP, 1997; Zar 2007). Other warnings/precautions:
Discontinuation syndrome
Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2-5 days after treatment discontinuation and last 7-14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).
Electroconvulsive therapy (ECT)
Use with caution; no clinical studies have assessed the combined use of escitalopram and electroconvulsive therapy; may increase the risks (eg, cognitive adverse effects) associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
Pregnancy & Lactation
Pregnancy
Caution
Reasonable safety profile in pregnancy; sertraline has more data
Lactation
Escitalopram and its metabolite are present in breast milk. The relative infant dose (RID) of escitalopram is ~3.9% and the RID of the metabolite is ~1.7% when calculated using average milk concentrations and compared to a weight-adjusted maternal dose of 10 to 20 mg/day. In general, breastfeeding is considered acceptable when the RID is Adverse effects have been reported in breastfeeding infants exposed to SSRIs including escitalopram in some studies (Hale 2010). Infants of mothers using psyc
Monitoring
| Clinical pearl | Mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; akathisia; signs/symptoms of serotonin syndrome |
|---|
Chemistry & Properties
| Formula | C20H21FN2O |
|---|---|
| Molecular weight | 324.4 g/mol |
| IUPAC name | (1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3H-2-benzofuran-5-carbonitrile |
| CAS | 128196-01-0 |
| PubChem CID | 146570 |
| InChIKey | WSEQXVZVJXJVFP-FQEVSTJZSA-N |
| logP | 3.81 (XLogP 3.2) |
| Polar surface area | 36.26 Ų |
| H-bond acceptors / donors | 3 / 0 |
| Drug-likeness (QED) | 0.84 |
| Lipinski violations | 0 |
SMILES
CN(C)CCC[C@@]1(c2ccc(F)cc2)OCc2cc(C#N)ccc21Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | Yes (logBB -0.37) |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2C19 | Substrate | — |
| CYP2D6 | Substrate | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 2)
| Target | Action | Affinity |
|---|---|---|
| SERT (SLC6A4) | Inhibitor | pIC50 9.0 |
| SERT (SLC6A4) | Inhibitor | pKd 8.7 |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Abarelix | major | |
| Abiraterone | major | |
| Alimemazine | major | |
| Anagrelide | major | |
| Apalutamide | major | |
| Arsenic trioxide | major | |
| Astemizole | major | |
| Bicalutamide | major | |
| Bosutinib | major | |
| Bupropion | major | |
| Cabozantinib | major | |
| Ceritinib | major | |
| Chloroquine | major | |
| Cisapride | major | |
| Clarithromycin | major | |
| Crizotinib | major | |
| Dasatinib | major | |
| Daunorubicin | major | |
| Daunorubicin (liposomal) | major | |
| Degarelix | major | |
| Dexfenfluramine | major | |
| Dextromethorphan | major | |
| Diethylpropion | major | |
| Dolasetron | major | |
| Doxepin | major | |
| Doxepin (topical) | major | |
| Doxorubicin | major | |
| Doxorubicin (liposomal) | major | |
| Encorafenib | major | |
| Entrectinib | major | |
| Enzalutamide | major | |
| Epirubicin | major | |
| Eribulin | major | |
| Erythromycin | major | |
| Fenfluramine | major | |
| Fingolimod | major | |
| Fluconazole | major | |
| Flutamide | major | |
| Gilteritinib | major | |
| Glasdegib | major |
Showing 40 of 100+.
Registered Products (35)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Exopex | Tablet as Oxalate 5 mg | 30 tab | Al-Taqqadom Pharmaceutical Industries | 6.380 |
| Exopex 5mg ODT | Orodispersible Tablet 5 mg | 30 ODT | AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN | 6.380 |
| Selixa | Tablet 10 mg | 30 tab | SANA PHARMACEUTICAL INDUSTRY/JORDAN | 7.320 |
| cipralex | Tablet as Oxalate 5 mg | 28 tab | Abu Sharef Medical Stores | 7.740 |
| Depralex | Tablet 10 mg | 28 tab | Sukhtian Group | 7.810 |
| Zetaprix | Tablet 10 mg | 28 tab pack varies | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 8.360 |
| Zetaprix | Tablet 10 mg | 30 tab pack varies | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 8.360 |
| Jorex | Tablet 10 mg | 30 tab | JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN | 8.510 |
| Cibramine | Tablet 10 mg | 28 tab | Dar Al Dawa Development and Investment Co Ltd/Jordan | 8.780 |
| Purlex | Tablet (as Oxalate) 5 mg | 30 tab | Hikma Pharmaceuticals Co.Ltd/Jordan | 8.780 |
| Ecipharm | Tablet 10 mg | 30 tab | Pharma International Company/ Jordan | 9.410 |
| Exopex 10mg F.C tab | Film-Coated Tablet as Oxalate 10 mg | 30 tab pack varies | Al-Taqqadom Pharmaceutical Industries | 9.410 |
| Ezura 10mg F.C Tab | Film-Coated Tablet 10 mg | 30 tab | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 9.410 |
| Purlex | Tablet (Oxalate) 10 mg | 30 tab | Hikma Pharmaceuticals Co.Ltd/Jordan | 9.410 |
| Zelax | Tablet 10 mg | 30 tab | JORDAN SWEDEN MEDICAL&STERILE.CO(JOSWE)/JORDAN | 9.410 |
| Cipralex | Tablet as Oxalate 10 mg | 28 tab | Abu Sharef Medical Stores | 9.760 |
| Ezura | Solution 0.307 g/240 ml | 240 MILLILITER | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 10.000 |
| Exopex 10mg ODT | Orodispersible Tablet 10 mg | 30 ODT | AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN | 10.460 |
| Selixa | Tablet 20 mg | 30 tab | SANA PHARMACEUTICAL INDUSTRY/JORDAN | 12.000 |
| Depralex | Tablet 20 mg | 28 tab | Sukhtian Group | 12.810 |
| Jorex | Tablet 20 mg | 30 tab | JORDAN RIVER PHARMA.IND(JORIVER)/JORDAN | 13.960 |
| Zetaprix | Tablet 20 mg | 30 tab | THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN | 15.520 |
| Exopex | Tablet as Oxalate 15 mg | 30 tab | Al-Taqqadom Pharmaceutical Industries | 15.690 |
| Exopex 15mg ODT | Orodispersible Tablet 15 mg | 30 ODT | AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN | 15.690 |
| EXOPEX 20mg ODT | Orodispersible Tablet 20 mg | 30 ODT | AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN | 17.150 |
| Exopex 20mg F.C Tab | Film-Coated Tablet as Oxalate 20 mg | 30 tab pack varies | Al-Taqqadom Pharmaceutical Industries | 17.150 |
| Cibramine | Tablet 20 mg | 28 tab | Dar Al Dawa Development and Investment Co Ltd/Jordan | 17.340 |
| Ecipharm | Tablet 20 mg | 30 tab | Pharma International Company/ Jordan | 18.960 |
| Cipralex | Tablet as Oxalate 15 mg | 28 tab | Abu Sharef Medical Stores | 19.020 |
| Ezura 20mg F.C tab | Film-Coated Tablet 20 mg | 30 tab | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 21.070 |
| Purlex | Tablet (Oxalate) 20 mg | 30 tab | Hikma Pharmaceuticals Co.Ltd/Jordan | 21.070 |
| Zelax | Tablet 20 mg | 30 tab | Jordan Sweden Medical & Sterilization Co. | 21.070 |
| Cipralex | Tablet as Oxalate 20 mg | 28 tab | Abu Sharef Medical Stores | 21.850 |
| Exopex 10mg F.C tab | Film-Coated Tablet as Oxalate 10 mg | 1000 tab pack varies | Al-Taqqadom Pharmaceutical Industries | 266.620 |
| Exopex 20mg F.C Tab | Film-Coated Tablet as Oxalate 20 mg | 1000 tab pack varies | Al-Taqqadom Pharmaceutical Industries | 485.920 |