Each film-coated tablet contains 10 mg escitalopram (as 12.78 mg escitalopram oxalate).
The tablet can be divided into equal doses.
Excipients/Inactive Ingredients: The ingredients are lactose monohydrate, crospovidone, povidone K30, microcrystalline cellulose, pregelatinised maize starch and magnesium stearate in the tablet core and hypromellose, titanium dioxide (E171), lactose monohydrate, macrogol 3000 and triacetin in the film-coating.
Pharmacotherapeutic Group: antidepressants, selective serotonin reuptake inhibitors. ATC Code: N06AB10.
Pharmacology: Pharmacodynamics: Mechanism of action: Escitalopram is a selective inhibitor of serotonin (5-HT) re-uptake with high affinity for the primary binding site. It also binds to an allosteric site on the serotonin transporter, with a 1000 fold lower affinity.
Allosteric modulation of the serotonin transporter enhances binding of escitalopram to the primary binding site, resulting in more complete serotonin reuptake inhibition.
Escitalopram has no or low affinity for a number of receptors including 5-HT1A, 5-HT2, DA D1 and D2 receptors, α1-, α2-, β-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine, and opioid receptors.
The inhibition of 5-HT re-uptake is the only likely mechanism of action explaining the pharmacological and clinical effects of escitalopram.
Escitalopram is the S-enantiomer of the racemate (citalopram) and the enantiomer to which the therapeutic activity is attributed. Pharmacological studies have shown that the R-enantiomer is not inert but counteracts the serotonin-enhancing and consequent pharmacological properties of the S-enantiomer.
Pharmacokinetics: Absorption: Absorption is almost complete and independent of food intake. Mean time to maximum concentration (mean Tmax) is 4 hours after multiple dosing.
As with racemic citalopram, the absolute bioavailability of escitalopram is expected to be about 80%.
Distribution: The apparent volume of distribution (Vd,β/F) after oral administration is about 12 to 26 L/kg. The plasma protein binding is below 80% for escitalopram and its main metabolites.
Biotransformation: Escitalopram is metabolised in the liver to the demethylated and didemethylated metabolites. Both of these are pharmacologically active. Alternatively, the nitrogen may be oxidised to form the N-oxide metabolite. Both parent substance and metabolites are partly excreted as glucuronides.
Biotransformation of escitalopram to the demethylated metabolite is mediated primarily by CYP2C19. Some contribution by the enzymes CYP3A4 and CYP2D6 is possible.
Elimination: The elimination half-life (t½β) after multiple dosing is about 30 hours and the oral plasma clearance (Cloral) is about 0.6 L/min. The major metabolites have a significantly longer half-life. Escitalopram and major metabolites are assumed to be eliminated by both the hepatic (metabolic) and the renal routes, with the major part of the dose excreted as metabolites in the urine.
Linearity: There is linear pharmacokinetics. Steady-state plasma levels are achieved in about 1 week. Average steady-state concentrations of 50 nmol/L (range 20 to 125 nmol/L) are achieved at a daily dose of 10 mg.
Elderly patients (> 65 years): Escitalopram appears to be eliminated more slowly in elderly patients compared to younger patients. Systemic exposure (AUC) is about 50 % higher in elderly compared to young healthy volunteers (see Dosage & Administration).
Reduced hepatic function: In patients with mild or moderate hepatic impairment (Child-Pugh Criteria A and B), the half-life of escitalopram was about twice as long and the exposure was about 60% higher than in subjects with normal liver function (see Dosage & Administration).
Reduced renal function: With racemic citalopram, a longer half-life and a minor increase in exposure have been observed in patients with reduced kidney function (CLcr 10-53 ml/min). Plasma concentrations of the metabolites have not been studied, but they may be elevated (see Dosage & Administration).
Polymorphism: It has been observed that poor metabolisers with respect to CYP2C19 have twice as high a plasma concentration of escitalopram as extensive metabolisers. No significant change in exposure was observed in poor metabolisers with respect to CYP2D6 (see Dosage & Administration).
Treatment of major depressive episodes.
This product is intended for oral use.
Safety of daily doses above 20 mg has not been demonstrated.
Elicea is administered as a single daily dose and may be taken with or without food.
Major depressive episodes: Usual dosage is 10 mg once daily. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily.
Usually 2-4 weeks are necessary to obtain antidepressant response. After the symptoms resolve, treatment for at least 6 months is required for consolidation of the response.
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 (see Pharmacology: Pharmacokinetics under Actions).
Children and adolescents (<18 years): Elicea should not be used in the treatment of children and adolescents under the age of 18 years (see Precautions).
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 30 ml/min.) (see Pharmacology: Pharmacokinetics under Actions).
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 (see Pharmacology: Pharmacokinetics under Actions).
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 (see Pharmacology: Pharmacokinetics under Actions).
Discontinuation symptoms seen when stopping treatment: Abrupt discontinuation should be avoided. When stopping treatment with escitalopram the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of discontinuation symptoms (see Precautions and Adverse Reactions).
Toxicity: In the majority of cases mild or no symptoms have been reported. Fatal cases of escitalopram overdose have rarely been reported with escitalopram alone; the majority of cases have involved overdose with concomitant medications. Doses between 400 and 800 mg of escitalopram alone have been taken without any severe symptoms.
Symptoms: Symptoms seen in reported 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, hyponatraemia).
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.
Hypersensitivity to the active substance or to any of the excipients.
Concomitant treatment with non-selective, irreversible monoamine oxidase inhibitors (MAO-inhibitors) (see Interactions).
Concomitant treatment with pimozide.
Suicidality in Children and Adolescents: Elicea should not be used in the treatment of children and adolescents under the age of 18 years. Suicide related behaviours (suicide attempt and suicidal thoughts), and hostility (predominately aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms.
Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders.
Anyone considering the use of an antidepressant in a child or adolescent for any clinical use must balance the risk of increased suicidality with the clinical need.
Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior.
Families and caregivers should be advised to closely observe the patient and to communicate with the prescriber.
The indication(s) approved in paediatric for the particular drug should be clearly stated / included.
The following special warnings and precautions apply to the therapeutic class of SSRIs (Selective Serotonin Re-uptake Inhibitors).
Seizures: Escitalopram should be discontinued in any patient who develops seizures. SSRIs should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be closely monitored. SSRIs should be discontinued if there is an increase in seizure frequency.
Mania: SSRIs should be used with caution in patients with a history of mania/hypomania. SSRIs should be discontinued in any patient entering a manic phase.
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycaemic control (hypoglycaemia or hyperglycaemia). Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
Other psychiatric conditions for which Elicea is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. In addition, there is a possibility of an increased risk of suicidal behavior in young adults.
Patients (and caregivers of patients) should be alerted about the need to monitor for the emergence of such events and to seek medical advice immediately if these symptoms present.
Akathisia/psychomotor restlessness: The use of SSRIs/SNRIs has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Hyponatraemia: Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported rarely with the use of SSRIs and generally resolves on discontinuation of therapy. Caution should be exercised in patients at risk, such as the elderly, cirrhotic patients or patients concomitantly treated with medications known to cause hyponatraemia.
Haemorrhage: There have been reports of cutaneous bleeding abnormalities, such as ecchymoses and purpura, with SSRIs. Caution is advised in patients taking SSRIs, particularly in concomitant use with oral anticoagulants, with medicinal products known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory medicinal products (NSAIDs), ticlopidine and dipyridamole) and in patients with known bleeding tendencies.
ECT (electroconvulsive therapy): There is limited clinical experience of concurrent administration of SSRIs and ECT, therefore caution is advisable.
Reversible, selective MAO A inhibitors: The combination of escitalopram with MAO A inhibitors is generally not recommended due to the risk of onset of a serotonin syndrome (see Interactions).
For information on concomitant treatment with non-selective, irreversible MAO-inhibitors see Interactions.
Serotonin syndrome: Caution is advisable if escitalopram is used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol and tryptophan.
In rare cases, serotonin syndrome has been reported in patients using SSRIs concomitantly with serotonergic medicinal products. A combination of symptoms, such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition. If this occurs treatment with the SSRI and the serotonergic medicinal product should be discontinued immediately and symptomatic treatment initiated.
St. John's wort: Concomitant use of SSRIs and herbal remedies containing St. John's wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see Interactions).
Discontinuation symptoms seen when stopping treatment: Discontinuation symptoms when stopping treatment are common, particularly if discontinuation is abrupt (see Adverse Reactions).
The risk of discontinuation symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity.
They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose.
Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that escitalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see "Discontinuation symptoms seen when stopping treatment" under Dosage & Administration).
Elicea contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on Ability to Drive and Use Machines: Although escitalopram has been shown not to affect intellectual function or psychomotor performance, any psychoactive medicinal product may impair judgement or skills. Patients should be cautioned about the potential risk of an influence on their ability to drive a car and operate machinery.
Pregnancy: For escitalopram only limited clinical data are available regarding exposed pregnancies.
Escitalopram should not be used during pregnancy unless clearly needed and only after careful consideration of the risk/benefit ratio.
Newborns should be observed if maternal use of escitalopram continues into the later stages of pregnancy, particularly in the third trimester. If escitalopram is used until or shortly before birth, discontinuation effects in the newborn are possible.
The following symptoms may occur in the neonate after maternal SSRI/SNRI use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either serotonergic effects or discontinuation symptoms. In a majority of instances the complications begin immediately or soon (<24 hours) after delivery.
Lactation: It is expected that escitalopram will be excreted into human milk and breast-feeding is not recommended during treatment.
Fertility: Impact on human fertility has not been observed so far.
Undesirable effects are most frequent during the first or second week of treatment and usually decrease in intensity and frequency with continued treatment.
Tabulated list of undesirable effects: Undesirable effects known for SSRIs and also reported for escitalopram in either placebo-controlled clinical studies or as spontaneous post-marketing events are listed as follows by system organ class. (See table.)
Click on icon to see table/diagram/image
Class effects: In patients 50 years of age and older an increased risk of bone fractures in patients receiving SSRIs and TCAs were observed. The mechanism leading to this risk is unknown.
Discontinuation symptoms seen when stopping treatment: Discontinuation of SSRIs/SNRIs (particularly when abrupt) commonly leads to discontinuation symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when escitalopram treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see Dosage & Administration and Precautions).
Pharmacodynamic interactions: Contraindicated combinations: Non-selective MAOIs: Cases of serious reactions have been reported in patients receiving an SSRI in combination with a non-selective monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued SSRI treatment and have been started on such MAOI treatment (see Contraindications). In some cases, the patient developed serotonin syndrome (see Adverse Reactions).
Escitalopram is contraindicated in combination with non-selective, irreversible MAOIs. Escitalopram may be started 14 days after discontinuing treatment with an irreversible MAOI and at least one day after discontinuing treatment with reversible MAOI (RIMA), moclobemide. At least 7 days should elapse after discontinuing escitalopram treatment, before starting a non-selective MAOI.
Pimozide: Concomitant administration of escitalopram and pimozide is contraindicated.
Combinations requiring precautions for use: Reversible, selective MAO-A inhibitor (moclobemide): Due to the risk of serotonin syndrome, the combination of escitalopram with a MAO-A inhibitor such as moclobemide is not recommended. If the combination proves necessary, it should be started at the minimum recommended dosage and clinical monitoring is strongly recommended. Escitalopram may be started at least one day after discontinuing treatment with reversible MAOI (RIMA), moclobemide.
Selegiline: In combination with selegiline (irreversible MAO-B inhibitor), caution is required due to the risk of developing serotonin syndrome.
Serotonergic medicinal products: Co-administration with serotonergic medicinal products (e.g. tramadol, sumatriptan and other triptans) may lead to serotonin syndrome.
Medicinal products lowering the seizure threshold: SSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold (e.g antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), mefloquine, bupropion and tramadol).
Lithium, tryptophan: There have been reports of enhanced effects when SSRIs have been given together with lithium or tryptophan, therefore concomitant use of SSRIs with these medicinal products should be undertaken with caution.
St. John's wort: Concomitant use of SSRIs and herbal remedies containing St. John's wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see Precautions).
Haemorrhage: Altered anti-coagulant effects may occur when escitalopram is combined with oral anticoagulants. Patients receiving oral anticoagulant therapy should receive careful coagulation monitoring when escitalopram is started or stopped. Concomitant use of non-steriodal anti-inflammatory drugs (NSAIDs) may increase bleeding-tendency (see Precautions).
Alcohol: No pharmacodynamic or pharmacokinetic interactions are expected between escitalopram and alcohol. However, as with other psychotropic medicinal products, the combination with alcohol is not advisable.
Pharmacokinetic interactions: Influence of other medicinal products on the pharmacokinetics of escitalopram: The metabolism of escitalopram is mainly mediated by CYP2C19. CYP3A4 and CYP2D6 may also contribute to the metabolism although to a smaller extent. The metabolism of the major metabolite S-DCT (demethylated escitalopram) seems to be partly catalysed by CYP2D6.
Caution should be exercised at the upper end of dosage range of escitalopram when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. A reduction in the dose of escitalopram may be necessary based on clinical judgement.
Effect of escitalopram on the pharmacokinetics of other medicinal products: Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is recommended when escitalopram is co-administered with medicinal products that are mainly metabolised by this enzyme, and that have a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (when used in cardiac failure), or some CNS acting medicinal products that are mainly metabolised by CYP2D6, e.g. antidepressants such as desipramine, clomipramine and nortriptyline or antipsychotics like risperidone, thioridazine and haloperidol. Dosage adjustment may be warranted.
Caution is recommended in the co-administration of escitalopram and drugs metabolized by CYP2D6 (desipramine).
Caution is recommended with concomitant use of medicinal products that are metabolised by CYP2C19 (metoprolol).
Special Precautions for Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Do not store above 30 °C.
Store in the original package in order to protect from light and moisture.
Shelf-Life: 3 years.
N06AB10 - escitalopram ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.
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