Each tablet contains Escitalopram oxalate 25.54 mg equivalent to escitalopram 20 mg.
Pharmacology: Pharmacodynamics: Antidepressants, selective serotonin reuptake inhibitors.
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.
Pharmacokinetics: Onset of action: Depression: The onset of action is within a week; however, individual response varies greatly and full response may not be seen until 8-12 weeks after initiation of treatment.
Distribution: 20 L/kg.
Protein binding: 56% to plasma proteins.
Metabolism: Hepatic via CYP2C19 and 3A4 to S-desmethylcitalopram (S-DCT); S-DCT is metabolized to S-didesmethylcitalopram (S-DDCT) via CYP2D6; in vitro data suggest metabolites do not contribute significantly to the antidepressant effects of escitalopram.
Half-life elimination: 27-32 hours (increased 50% in the elderly and doubled in patients with hepatic impairment).
Time to peak: Escitalopram 5 hours.
Major depressive episodes: For the acute and maintenance treatment of MDD in adults and in adolescents 12-17 years of age.
Generalized anxiety disorder: For the acute treatment of generalized anxiety disorder (GAD) in adults.
Panic disorder with or without agoraphobia.
Social anxiety disorder.
Escitalopram is administered as a single daily dose and may be taken with or without food.
Major depressive episodes: For the acute and maintenance treatment of MDD in adults. Usual dosage is 10 mg once daily. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily after a minimum of 1 week. Although efficacy has been established at dosages of 10 or 20mg once daily, no additional benefit was observed with the 20-mg dosage in a fixed-dose study.
For the acute management of major depressive disorder in adolescents 12-17 years of age, the recommended initial dosage of escitalopram is 10mg once daily. Efficacy has been established at dosages of 10-20mg daily in a flexible-dose study. If dosage is increased to 20mg daily, this should occur after a minimum of 3 weeks.
Generalized anxiety disorder: For the management of generalized anxiety disorder in adults, the recommended initial dosage of escitalopram is 10mg once daily. If no clinical improvement is apparent, dosage may be increased to 20mg daily after a minimum of 1 week.
Panic disorder with or without agoraphobia: An initial dose of 5 mg is recommended for the first week before increasing the dose to 10 mg daily. The dose may be further increased, up to a maximum of 20 mg daily, dependent on individual patient response.
Maximum effectiveness is reached after about 3 months. The treatment lasts several months.
Social anxiety disorder: Usual dosage is 10 mg once daily. Usually 2-4 weeks are necessary to obtain symptom relief. The dose may subsequently, depending on individual patient response, be decreased to 5 mg or increased to a maximum of 20 mg daily.
Social anxiety disorder is a disease with a chronic course, and treatment for 12 weeks is recommended to consolidate response. Long-term treatment of responders has been studied for 6 months and can be considered on an individual basis to prevent relapse; treatment benefits should be re-evaluated at regular intervals.
Social anxiety disorder is a well-defined diagnostic terminology of a specific disorder, which should not be confounded with excessive shyness. Pharmacotherapy is only indicated if the disorder interferes significantly with professional and social activities.
The place of this treatment compared to cognitive behavioural therapy has not been assessed. Pharmacotherapy is part of an overall therapeutic strategy.
Obsessive-compulsive disorder: Initial dosage is 10 mg once daily. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg daily.
As OCD is a chronic disease, patients should be treated for a sufficient period to ensure that they are symptom free.
Treatment benefits and dose should be re-evaluated at regular intervals.
Elderly patients (> 65 years of age): Initial dosage is 5 mg once daily. Depending on individual patient response the dose may be increased to 10 mg daily.
Children and adolescents (12-17 years): Major depressive disorder: Initial dosage – 10mg once daily. Dosage titration – If the dose is increased to 20mg this should occur a minimum of 3 weeks.
Reduced renal function: Dosage adjustment is not necessary in patients with mild or moderate renal impairment. Caution is advised in patients with severely reduced renal function (CLcr less than 20 ml/min).
Reduced hepatic function: An initial dose of 5 mg daily for the first two weeks of treatment is recommended in patients with mild or moderate hepatic impairment. Depending on individual patient response, the dose may be increased to 10 mg daily. Caution and extra careful dose titration is advised in patients with severely reduced hepatic function.
Poor metabolisers of CYP2C19: For patients who are known to be poor metabolisers with respect to CYP2C19, an initial dose of 5 mg daily during the first two weeks of treatment is recommended. Depending on individual patient response, the dose may be increased to 10 mg daily.
Discontinuation symptoms seen when stopping treatment: Because withdrawal effects may occur with discontinuance of escitalopram and other SSRIs and selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), abrupt discontinuance should be avoided whenever possible. When escitalopram therapy is discontinued, the dosage should be reduced gradually and the patient monitored for possible withdrawal symptoms. If intolerable symptoms occur following dosage reduction or upon discontinuance of therapy, the drug may be reinstituted at the previously prescribed dosage. Subsequently, the clinician may continue decreasing the dosage, but at a more gradual rate. Withdrawal symptoms, including dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia such as electric shock sensations), sleep disturbances (including insomnia), anxiety, confusion, headache, lethargy, emotional instability, hypomania, tinnitus, and seizures are the most common reactions, particularly when discontinuance of these drugs is abrupt. While these reactions are generally self-limiting, there have been reports of serious discontinuance symptoms. Therefore, patients should be monitored for such symptoms when discontinuing escitalopram therapy. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.
MODE OF ADMINISTRATION: Escitalopram oxalate is administered orally once daily, in the morning or evening.
Toxicity: Escitalopram overdose are limited and may involve concomitant overdoses of other drugs. Doses between 400 and 800 mg of escitalopram alone have been taken without any severe symptoms.
Symptoms: Symptoms seen in overdose of escitalopram include symptoms mainly related to the central nervous system (ranging from dizziness, tremor, and agitation to rare cases of serotonin syndrome, convulsion, and coma), the gastrointestinal system (nausea/vomiting), and the cardiovascular system (hypotension, tachycardia, QT interval prolongation, and arrhythmia) and electrolyte/fluid balance conditions (hypokalaemia, hyponatremia).
Management: There is no specific antidote. Establish and maintain an airway, ensure adequate oxygenation and respiratory function. Gastric lavage and the use of activated charcoal should be considered. Gastric lavage should be carried out as soon as possible after oral ingestion. Cardiac and vital signs monitoring are recommended along with general symptomatic supportive measures.
ECG monitoring is advised in case of overdose in patients with congestive heart failure/ bradyarrhythmias, in patients using concomitant medications that prolong the QT interval, or in patients with altered metabolism, e.g. liver impairment.
Hypersensitivity to the active substance or to any of the excipients.
Concurrent or recent (i.e., within 2 weeks) therapy with a monoamine oxidase (MAO) inhibitor. At least 14 days should elapse between discontinuance of escitalopram and initiation of MAO inhibitor therapy and vice versa.
Concomitant use with pimozide.
Known hypersensitivity to escitalopram, citalopram.
The following special warnings and precautions apply to the therapeutic class of SSRIs (Selective Serotonin Reuptake Inhibitors).
Seizures: Use caution with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold.
Hyponatremia: May cause hyponatremia / SIADH (elderly at increased risk); volume depletion (diuretics may increase risk) may occur. Use caution in elderly patients; may be potentially inappropriate in patients with a history of falls or fractures, and may cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults.
Mania: Activation of mania and hypomania has occurred in patients receiving escitalopram or citalopram. Escitalopram should be used with caution in patients with a history of mania.
Abnormal bleeding: SNRIs and SSRIs, including escitalopram, may increase the risk of bleeding events. Concurrent use of aspirin, nonsteroidal anti-inflammatory agents (NSAIAs), warfarin, and other anticoagulants may add to this risk. Case reports and epidemiologic studies have demonstrated an association between the use of drugs that interfere with serotonin reuptake and the occurrence of GI bleeding. Bleeding events related to SNRI and SSRI use have ranged from ecchymosis, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.
ECT (electroconvulsive therapy): May increase the risks associated with electroconvulsive therapy.
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, TCA, 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]). Discontinue treatment (and concomitant serotonergic agent) immediately if signs / symptoms arise.
QT interval prolongation: Use has been associated with dose-dependent QT-interval prolongation with doses of 10mg and 30mg/day in healthy subjects; 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).
Renal or liver impairment: Use caution with severe renal impairment or liver impairment; concomitant CNS depressants.
Angle-Closure Glaucoma: May cause mild papillary 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.
Use in Children: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. This risk may persist until clinically important remission occurs. Recommended that all patients being treated with antidepressants for any indication be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.
Pregnancy: Category C.
The following symptoms may occur in the neonate after maternal SSRI/SNRI use in later stages of pregnancy: respiratory distress, cyanosis, apnea, seizures, temperature instability or fever, feeding difficulty, dehydration, excessive weight loss, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These symptoms could be due to either serotonergic effects or discontinuation symptoms.
Lactation: Escitalopram is distributed into human milk. Nursing infants should be observed for adverse reactions when escitalopram is administered to a nursing woman because of the serious adverse effects e.g., excessive somnolence, decreased feeding, weight loss.
Central nervous system:
Abnormal dreams, anorgasmia, dizziness, drowsiness, fatigue, headache, insomnia, lethargy, paresthesia, yawning.
Endocrine & metabolic:
Decreased libido, menstrual disease.
Abdominal pain, constipation, decreased appetite, diarrhea, dyspepsia, flatulence, nausea, toothache, vomiting, xerostomia.
Ejaculatory disorder, impotence, urinary tract infection (children).
Neuromuscular & skeletal:
Back pain (children), neck pain, shoulder pain.
Flu-like symptoms, nasal congestion (children), rhinitis, sinusitis.
Rare but important or life-threatening:
Such as abdominal cramps, abnormal gait, acute renal failure, aggressive behavior, agitated depression, alopesia, amnesia, anaphylaxis, and anemia.
Drugs affecting or metabolized by hepatic microsomal enzymes: Inhibitors or inducers of cytochrome P-450 (CYP) 3A4 (e.g., carbamazepine, ketoconazole, ritonavir, triazolam) and 2C19 isoenzymes: clinically important pharmacokinetic interaction unlikely since escitalopram is metabolized by multiple enzyme systems.
Substrates of CYP2D6 isoenzyme (e.g., desipramine, metoprolol): potential pharmacokinetic (increased peak plasma concentrations and AUC of the substrate) interactions. Use with caution.
Drugs affecting hemostasis: Pharmacokinetics of warfarin were not affected by racemic citalopram; however, prothrombin time increased by 5%. The effects of escitalopram have not been evaluated, and the clinical importance of this interaction is unknown.
Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or selective serotonin- and norepinephrine-reuptake inhibitor (SNRIs) were concurrently administered with warfarin or other anticoagulants.
Antipsychotic agents and other dopamine antagonists: Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) if used concurrently with antipsychotic agents or other dopamine antagonists. If signs and symptoms of serotonin syndrome or NMS occur, immediately discontinue treatment with escitalopram and any concurrently administered antidopaminergic or serotonergic agents and initiate supportive and symptomatic treatment.
5-HT1 Receptor agonists (Triptans): Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) if used concurrently with 5-HT1 Receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rzatriptan, sumatriptan, zolmitriptan). If concomitant use is clinically warranted, the patient should be observed carefully, particularly during treatment initiation, when dosage is increased, or when another serotonergic agent is initiated.
Monoamine oxidase inhibitors: Isoniazid: Potential pharmacologic interaction (potentially serious serotonin syndrome) when isoniazid, an antituberculosis agent that appears to have some MAO-inhibiting activity, is used concomitantly with escitalopram.
Linezolid: Linezolid, an anti-infective agent that is also a reversible MAO inhibitor, has been associated with drug interactions resulting in serotonin syndrome, including some associated with SSRIs. Because of this potential risk, linezolid generally should not be used in patients receiving escitalopram. Treatment with escitalopram should not be initiated in a patient receiving linezolid; when necessary, escitalopram may be started 24 hours after the last linezolid dose.
Alcohol: Concomitant use not recommended.
Cimetidine: Potential pharmacokinetic interaction (increased AUC and peak plasma concentrations of citalopram have been observed).
Citalopram: Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions).
CNS-active drugs: Potential pharmacologic interaction when given with other centrally acting drugs; use concomitantly with caution.
Digoxin: Pharmacokinetic interaction unlikely based on studies with racemic citalopram.
Lithium: Escitalopram is recommended that plasma lithium concentrations be monitored in patients concurrently receiving escitalopram and that lithium dosage be adjusted accordingly.
Ritonavir: Combined administration of a single 600-mg dose of ritonavir, a CYP3A4 substrate and potent inhibitor of CYP3A4, and escitalopram 20mg did not substantially affect the pharmacokinetics of either drug.
Sibutramine: Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions).
Theophylline: Pharmacokinetics of theophylline were not affected by racemic citalopram.
Store not exceeding 30°C.
N06AB10 - escitalopram ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.
FC tab 20 mg (white to off-white, circular, biconvex, having ML 61 debossed on one side, break line on opposite side and having notches on either ends of break line) x 2 x 14's.