Eliceya

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ELICEA (ELICEA)

Composition:

Active substance: escitalopram oxalate;

One orodispersible tablet contains 5 mg, 10 mg, or 20 mg of escitalopram in the form of escitalopram oxalate;

Excipients: polacrilin potassium, hydrochloric acid concentrated, lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, potassium acesulfame, neohesperidin dihydrochalcone, peppermint flavor (containing maltodextrin, modified starch, peppermint oil), magnesium stearate.

Pharmaceutical form. Orodispersible tablets.

Main physicochemical properties:

5 mg tablets: white to almost white, round, flat tablets with bevelled edges and engraved "5" on one side;

10 mg tablets: white to almost white, round, flat tablets with bevelled edges and engraved "10" on one side;

20 mg tablets: white to almost white, round, flat tablets with bevelled edges and engraved "20" on one side.

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors. ATC code N06AB10.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action

Escitalopram is a selective serotonin reuptake inhibitor (5-HT) with high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter with 1000-fold lower affinity.

Escitalopram has no or very weak affinity for a wide range of receptors, including 5-HT1A, 5-HT2, dopamine D1 and D2 receptors, α1-, α2-, β-adrenergic receptors, histamine H1, muscarinic cholinergic, benzodiazepine, and opioid receptors.

Inhibition of serotonin (5-HT) reuptake is considered the probable mechanism responsible for the pharmacological and clinical effects of escitalopram.

Pharmacodynamic Effects

In a double-blind, placebo-controlled ECG study in healthy volunteers, the change from baseline in QTc (corrected using Fridericia’s formula) was 4.3 msec (90% confidence interval: 2.2, 6.4) at a dose of 10 mg/day and 10.7 msec (90% confidence interval: 8.6, 12.8) at a supratherapeutic dose of 30 mg/day (see sections “Contraindications”, “Special Warnings and Precautions for Use”, “Interaction with Other Medicinal Products and Other Forms of Interaction”, “Adverse Reactions”, and “Overdose”).

Clinical Efficacy

Depression

The efficacy of escitalopram in the acute treatment of depression was demonstrated in three out of four double-blind, placebo-controlled, short-term (8-week) studies. In a long-term relapse prevention study, 274 patients who responded during an initial 8-week open-label treatment phase with escitalopram 10 or 20 mg/day were randomized to continue escitalopram at the same dose or switch to placebo for 36 weeks. During this study, patients continuing escitalopram had a significantly longer time to relapse over the 36-week period compared to those on placebo.

Social Anxiety Disorder

Escitalopram was effective in three short-term (12-week) studies and in patients who responded to treatment during a 6-month relapse prevention study in social anxiety disorder. A 24-week dose-finding study demonstrated efficacy with 5, 10, and 20 mg of escitalopram.

Generalized Anxiety Disorder

Escitalopram at doses of 10 and 20 mg/day was effective in four placebo-controlled studies. In pooled data from three studies of similar design involving 421 patients receiving escitalopram and 419 receiving placebo, improvement in clinical condition was observed in 47.5% and 28.9%, respectively, and remission rates were 37.1% and 20.8%, respectively. A sustained effect was observed from week 1.

Maintenance of efficacy with escitalopram 20 mg/day was demonstrated from week 24 to week 76 in a randomized, open-label, efficacy maintenance study involving 373 patients who responded to initial 12-week treatment.

Obsessive-Compulsive Disorder (OCD)

In a randomized, double-blind, 12-week clinical trial, a dose of 20 mg/day of escitalopram showed significantly greater efficacy compared to placebo, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). After 24 weeks, both 10 and 20 mg/day doses of escitalopram were superior to placebo.

Relapse prevention was demonstrated for 10 and 20 mg/day doses of escitalopram in patients who responded to escitalopram during a 16-week open-label phase and then entered a 24-week randomized, double-blind, placebo-controlled phase.

Animal studies with citalopram have shown reduced fertility and pregnancy indices, decreased number of implantations, and presence of abnormal spermatozoa at exposure levels significantly exceeding those in humans. There are no animal study data available for escitalopram regarding these aspects.

Pharmacokinetics

Absorption

Absorption is almost complete and independent of food intake. The median time to reach maximum concentration (median Tmax) is 4 hours after multiple dosing. As with racemic citalopram, the absolute bioavailability of escitalopram is expected to be approximately 80%.

Distribution

The apparent volume of distribution (Vd,β/F) after oral administration is approximately 12 to 26 L/kg. Protein binding of escitalopram and its main metabolites to plasma proteins is less than 80%.

Metabolism

Escitalopram is metabolized in the liver to demethylated and didemethylated metabolites. Both are pharmacologically active. Alternatively, the nitrogen may be oxidized to form an N-oxide metabolite. Both metabolites and the parent compound are partially excreted as glucuronides. After repeated administration, the average concentrations of the demethyl and didemethyl metabolites are typically 28–31% and <5% of escitalopram concentration, respectively. The biotransformation of escitalopram to its demethylated metabolite occurs primarily via the cytochrome CYP2C19. Enzymes CYP3A4 and CYP2D6 may also play a minor role.

Elimination

The elimination half-life (t½β) after repeated administration is approximately 30 hours. Oral plasma clearance (Cloral) is 0.6 L/min. The main metabolites of escitalopram have longer half-lives. Escitalopram and its main metabolites are believed to be eliminated via the liver (metabolic pathway) and kidneys, with the majority excreted as metabolites in urine.

The pharmacokinetics of escitalopram are linear. Steady-state plasma concentrations are reached after approximately 1 week. The average steady-state concentration of 50 nmol/L (range 20–125 nmol/L) is achieved with a daily dose of 10 mg.

Renal Impairment

In patients with reduced renal function (CLcr 10–53 mL/min), an increased half-life of racemic citalopram and a slight increase in exposure have been observed. Plasma metabolite concentrations have not been studied, but an increase can be expected (see section “Dosage and Administration”).

Hepatic Impairment

In patients with mild to moderate hepatic insufficiency (Child-Pugh criteria A and B), the half-life of escitalopram is nearly doubled and exposure is 60% higher compared to individuals with normal liver function (see section “Dosage and Administration”).

Geriatric Patients (>65 years)

In elderly patients, escitalopram appears to be eliminated more slowly than in younger patients. Systemic exposure (AUC) is 50% higher in elderly patients compared to younger healthy volunteers (see section “Dosage and Administration”).

Polymorphism

With reduced CYP2C19 isoenzyme activity, plasma concentrations of escitalopram were approximately doubled compared to normal metabolizers. With reduced CYP2D6 isoenzyme activity, no significant changes in exposure were observed (see section “Dosage and Administration”).

Clinical characteristics.

Indications.

• Treatment of major depressive episodes.
• Treatment of panic disorder with or without agoraphobia.
• Treatment of social anxiety disorder (social phobia).
• Treatment of generalized anxiety disorder.
• Treatment of obsessive-compulsive disorder.

Contraindications.

Hypersensitivity to escitalopram or to any other component of the medicinal product.

Concomitant use with non-selective irreversible monoamine oxidase inhibitors (MAO inhibitors) due to the risk of serotonin syndrome with agitation, tremor, hyperthermia (see section "Interaction with other medicinal products and other forms of interaction").

Combination of escitalopram with irreversible MAO-A inhibitors (e.g., moclobemide) or with the reversible non-selective MAO inhibitor linezolid due to the risk of serotonin syndrome (see section "Interaction with other medicinal products and other forms of interaction").

Known QT interval prolongation or congenital long QT syndrome.

Combination with medicinal products that prolong the QT interval (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Pharmacodynamic interactions

Contraindicated combinations

Irreversible non-selective MAO inhibitors

Serious reactions have been reported in patients taking SSRIs in combination with irreversible non-selective monoamine oxidase inhibitors (MAOIs), and in patients who recently discontinued SSRIs and started MAOI therapy (see section "Contraindications"). Cases of serotonin syndrome have occasionally occurred (see section "Adverse reactions").

Concomitant use of escitalopram with irreversible non-selective MAO inhibitors is contraindicated. Escitalopram treatment may be initiated only 14 days after discontinuation of irreversible MAO inhibitors. Treatment with irreversible non-selective MAO inhibitors may be initiated only 7 days after discontinuation of escitalopram.

Reversible selective MAO-A inhibitor (moclobemide)

Concomitant administration of escitalopram with the MAO-A inhibitor moclobemide is contraindicated due to the risk of serotonin syndrome (see section "Contraindications"). If use of this combination is considered necessary, the lowest recommended doses should be used under close medical supervision (see section "Contraindications").

Reversible non-selective MAO inhibitor (linezolid)

Concomitant use of escitalopram with the antibiotic linezolid is contraindicated in patients taking escitalopram. If use of this combination is considered necessary, the lowest recommended doses should be used under close medical supervision (see section "Contraindications").

Irreversible selective MAO-B inhibitor (selegiline)

Due to the risk of serotonin syndrome, combination of escitalopram with selegiline requires caution. For concomitant use with racemic citalopram, selegiline doses up to 10 mg/day are considered safe.

QT interval prolongation

Pharmacokinetic and pharmacodynamic studies of escitalopram in combination with other medicinal products that prolong the QT interval have not been conducted. A cumulative effect of escitalopram and these medicinal products cannot be excluded. Therefore, concomitant use of escitalopram with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, neuroleptics (e.g., phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g., sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials including halofantrine), certain antihistamines (astemizole, hydroxyzine, mizolastine), is contraindicated.

Combinations requiring caution

Serotonergic medicinal products

Concomitant use with serotonergic agents (e.g., opioids including tramadol, and triptans such as sumatriptan) may lead to serotonin syndrome (see section "Special precautions for use").

MEDICINAL PRODUCTS THAT LOWER SEIZURE THRESHOLD

SSRIs may lower the seizure threshold. Caution is required when escitalopram is co-administered with other agents that may lower the seizure threshold, such as antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol.

Lithium, tryptophan

Cases of enhanced effects have been reported with concomitant use of SSRIs and lithium or tryptophan; therefore, caution is recommended when SSRIs are used concomitantly with these agents.

St. John’s wort

Concomitant use of SSRIs and herbal preparations containing St. John’s wort (Hypericum perforatum) may increase the frequency of adverse reactions (see section "Special precautions for use").

Anticoagulants

The effect of anticoagulants may be altered by concomitant use with escitalopram. Patients receiving oral anticoagulants should have careful monitoring of coagulation parameters before and after starting escitalopram.

Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of bleeding (see section "Special precautions for use").

Alcohol

No pharmacodynamic or pharmacokinetic interaction between escitalopram and alcohol is expected. However, as with other psychotropic medicinal products, concomitant use of escitalopram with alcohol is not recommended.

MEDICINAL PRODUCTS CAUSING HYPOKALEMIA/HYPOMAGNESEMIA

Caution is warranted when medicinal products causing hypokalemia/hypomagnesemia are used concomitantly, as these conditions increase the risk of developing malignant arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions

Effect of other medicinal products on escitalopram pharmacokinetics

Escitalopram is metabolized primarily via CYP2C19. CYP3A4 and CYP2D6 may also be involved to a lesser extent. The enzyme CYP2D6 is considered a partial catalyst in the metabolism of the main metabolite S-DCT (demethylated escitalopram).

Concomitant administration of escitalopram and omeprazole 30 mg once daily (a CYP2C19 inhibitor) results in a moderate increase (approximately 50%) in plasma concentration of escitalopram.

Concomitant administration of escitalopram and cimetidine 400 mg twice daily (a moderately potent non-specific enzyme inhibitor) results in a moderate increase (approximately 70%) in plasma concentration of escitalopram. Escitalopram should be used with caution in combination with cimetidine. Dose adjustment may be necessary.

Therefore, escitalopram should be prescribed with caution when used concomitantly with inhibitors of cytochrome CYP2C19 (e.g., omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. Monitoring for adverse effects may necessitate a reduction in escitalopram dose (see section "Special precautions for use").

Effect of escitalopram on the pharmacokinetics of other medicinal products

Escitalopram is an inhibitor of the CYP2D6 enzyme. Escitalopram should be prescribed with caution when used concomitantly with medicinal products metabolized by this enzyme, and with medicinal products having a narrow therapeutic index, such as flecainide, propafenone, and metoprolol (used in heart failure), or with certain CNS-acting agents primarily metabolized by CYP2D6, e.g., antidepressants – desipramine, clomipramine, and nortriptyline; antipsychotics – risperidone, thioridazine, and haloperidol. Dose adjustment may be necessary.

Concomitant administration with desipramine or metoprolol results in a doubling of plasma levels of these CYP2D6 substrates.

In vitro studies have demonstrated that escitalopram may also cause weak inhibition of CYP2C19. Therefore, caution is recommended when prescribing medicinal products metabolized by CYP2C19 concomitantly with escitalopram.

Special precautions for use.

The special precautions apply to all selective serotonin reuptake inhibitors (SSRIs).

Children

Elitsea is contraindicated in children (under 18 years of age). In clinical trials, a higher incidence of suicidal behaviour (suicide attempts and thoughts) and hostility (predominantly aggression, oppositional behaviour and irritability) was observed in children treated with antidepressants compared to those receiving placebo. If clinical necessity requires such treatment, careful monitoring of the patient is essential to detect suicidal symptoms promptly. Furthermore, there is no data available on the long-term safety of the drug in children with regard to growth, sexual maturation, and cognitive and behavioural development.

Paradoxical anxiety

In some patients with panic disorder, symptoms of anxiety may worsen at the beginning of treatment with antidepressants. This paradoxical reaction usually resolves within the first two weeks of treatment. To reduce the likelihood of anxiogenic effects, it is recommended to initiate treatment with low starting doses (see section "Dosage and administration").

Seizures

Treatment with escitalopram should be discontinued if a patient develops seizures for the first time or experiences an increased frequency of seizures (in patients with a prior diagnosis of epilepsy). SSRIs are not recommended for patients with unstable epilepsy, and careful monitoring is required for patients with controlled epilepsy.

Mania

SSRIs should be used with caution in patients with a history of mania/hypomania. Treatment with SSRIs should be discontinued if a manic episode occurs.

Diabetes mellitus

In patients with diabetes mellitus, treatment with SSRIs may affect glycaemic control (hypoglycaemia or hyperglycaemia). Adjustment of insulin and/or oral hypoglycaemic agent doses may be necessary.

Suicide/suicidal thoughts or worsening of clinical condition

Suicide attempts are characteristic of individuals with depression, and the risk may persist until significant improvement occurs. Close monitoring of patients receiving antidepressants is essential, particularly during the first weeks of treatment until substantial improvement is achieved (as experience indicates an increased risk of suicide in the early stages of recovery).

Other psychiatric disorders for which Elitsea may be prescribed can also be associated with an increased risk of suicidal behaviour. Close monitoring of patients is required when treating other psychiatric disorders due to the potential co-occurrence of depression.

Due to the high risk of suicidal thoughts and behaviours during treatment, careful monitoring is necessary for patients with a history of such conditions or with significant levels of suicidal ideation prior to treatment initiation. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders demonstrated an increased risk of suicidal behaviour with antidepressants compared to placebo in patients under 25 years of age. Pharmacological treatment should be accompanied by careful monitoring of patients, especially those at increased risk, particularly at the beginning of treatment and after dose adjustments.

Patients and caregivers should be informed about the need to monitor for any clinical worsening, suicidal behaviour or thoughts, and unusual changes in behaviour. If such symptoms occur, medical help should be sought immediately if necessary.

Akathisia/psychomotor agitation

The use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) has been associated with the development of akathisia, characterized by a subjective feeling of unpleasant or anxious restlessness and an urge to move, often accompanied by an inability to sit or stand still. This is most commonly observed during the first weeks of treatment. Increasing the dose may be harmful in patients experiencing these symptoms.

Hyponatraemia

Cases of hyponatraemia, likely due to syndrome of inappropriate antidiuretic hormone secretion (SIADH), have been reported during SSRI treatment, which usually resolves upon discontinuation of therapy. The drug should be used with caution in patients at risk, such as elderly patients, patients with liver cirrhosis, or patients concurrently taking medications that may cause hyponatraemia.

Bleeding

Reports of skin bleeding, such as ecchymosis and purpura, have been received during SSRI use. SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections "Use during pregnancy or breastfeeding" and "Adverse reactions"). Therefore, caution is required when treating patients with a predisposition to bleeding, especially when used concomitantly with oral anticoagulants or drugs known to affect platelet function (e.g., atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, NSAIDs, ticlopidine, dipyridamole).

Electroconvulsive therapy (ECT)

There is currently limited clinical experience with combining SSRIs and electroconvulsive therapy; therefore, caution is recommended.

Serotonin syndrome

Caution is required when prescribing escitalopram in combination with medicinal products that have serotonergic effects, such as triptans (including sumatriptan), opioids (including tramadol), and tryptophan.

Cases of serotonin syndrome, a potentially life-threatening condition, have been reported in patients taking SSRIs together with serotonergic medicinal products (see section "Interaction with other medicinal products and other forms of interaction"). Symptoms may include agitation, tremor, myoclonus, and hyperthermia. In such cases, SSRIs and serotonergic medicinal products should be discontinued immediately, and symptomatic treatment should be initiated.

St. John's wort

Concomitant use of SSRIs and herbal preparations containing St. John's wort (Hypericum perforatum) may increase the frequency of adverse reactions (see section "Interaction with other medicinal products and other forms of interaction").

Withdrawal symptoms observed upon discontinuation of treatment

Upon discontinuation of treatment (especially abrupt discontinuation), withdrawal symptoms usually occur (see section "Adverse reactions"). In clinical trials, adverse reactions associated with discontinuation were observed in approximately 25% of patients in the escitalopram group and in 15% of patients in the placebo group.

The risk of withdrawal symptoms depends on several factors, including duration and dose of therapy, and the gradualness of dose reduction. Most frequently reported adverse reactions include dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and restless dreams), agitation or anxiety, vomiting and/or nausea, tremor, confusion, increased sweating, headache, diarrhoea, tachycardia, emotional instability, irritability, and visual disturbances. Generally, these symptoms are mild or moderate, but in some patients, they may be more severe. Symptoms usually occur within the first few days after discontinuation, although very rarely they have been reported after missing just a single dose.

These symptoms are usually transient and resolve within 2 weeks, but in some individuals, they may persist for 2–3 months. In such cases, it is recommended to discontinue escitalopram gradually over several weeks to several months, depending on the patient's condition (see section "Dosage and administration. Withdrawal symptoms observed upon discontinuation of treatment").

Sexual dysfunction

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section "Adverse reactions"). Cases of persistent sexual dysfunction, where symptoms persisted despite discontinuation of SSRIs/SNRIs, have been reported.

Ischaemic heart disease

Due to limited clinical experience, caution is required when treating patients with ischaemic heart disease.

QT interval prolongation

Escitalopram has been shown to cause dose-dependent QT interval prolongation. Cases of QT interval prolongation and ventricular arrhythmias, including torsade de pointes, have been reported primarily in female patients with hypokalaemia or pre-existing prolonged QT interval, or other cardiac diseases. Caution is advised in patients with significant bradycardia, recent acute myocardial infarction, or decompensated heart failure.

Electrolyte imbalances, such as hypokalaemia and hypomagnesaemia, increase the risk of malignant arrhythmias and should be corrected prior to initiating escitalopram treatment.

An ECG should be performed before initiating treatment in patients with heart disease.

If cardiac arrhythmia occurs during escitalopram treatment, treatment should be discontinued and an ECG should be performed.

Closed-angle glaucoma

SSRIs, including escitalopram, may affect pupil size, leading to mydriasis. This mydriatic effect may narrow the angle of the eye, resulting in increased intraocular pressure and closed-angle glaucoma, particularly in predisposed individuals. Therefore, escitalopram should be used with caution in patients with glaucoma or a history of glaucoma.

Special warnings regarding excipients

The medicinal product should not be administered to patients with rare hereditary conditions such as galactose intolerance, congenital lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy

Clinical data on the use of escitalopram during pregnancy are limited. Animal studies have shown reproductive toxicity. Elitsea should be used during pregnancy only if clearly needed and only after careful evaluation of the benefit-risk ratio.

Newborns whose mothers have taken Elitsea during late pregnancy, especially in the third trimester, require monitoring. Abrupt discontinuation of the drug during pregnancy should be avoided. Newborns whose mothers have taken SSRIs/SNRIs during late pregnancy have shown respiratory distress syndrome, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, arterial hypertension, hypotension, hyperreflexia, tremor, nervous excitement, irritability, somnolence, persistent crying, lethargy, and sleep disturbances. These disturbances may be manifestations of serotonergic effects or withdrawal syndrome. In most cases, complications began immediately or shortly (<24 hours) after delivery.

Epidemiological data indicate that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk is approximately 5 cases per 1000 pregnancies. The frequency of PPHN in the general population is 1–2 cases per 1000 pregnancies.

Observational data suggest an increased risk (less than 2-fold) of postpartum haemorrhage following exposure to SSRIs/SNRIs within one month before delivery (see sections "Special precautions for use" and "Adverse reactions").

Breastfeeding

Escitalopram is expected to pass into breast milk; therefore, breastfeeding is recommended to be discontinued during treatment.

Fertility

Animal data have shown that citalopram may affect sperm quality. Human case reports with some SSRIs have demonstrated that the effect on sperm quality is reversible. No other effects on human fertility have been observed.

Ability to affect reaction speed when driving or operating machinery.

Elitsea has no effect or a negligible effect on the ability to drive or operate machinery. In general, escitalopram does not affect intellectual or psychomotor performance, but it should be noted that, as a psychotropic medicinal product, it may affect decision-making and abilities. Patients should be warned about the potential risk of impaired ability to drive or operate other mechanical devices.

Dosage and Administration

Administration

Elitsea should be administered as a single daily dose and taken without food. The mouth must be empty. Place the tablet on the tongue. It dissolves rapidly and can be swallowed without water. Orally disintegrating tablets are fragile and should be handled with care. Do not push the tablets through the foil blister, as this may damage the tablet. Do not handle the tablets with wet hands, as they may disintegrate.

To remove the tablet, follow these steps:

1. Hold the blister pack by the edge and carefully tear along the perforation to separate one section from the rest of the blister.
2. Pull back the edge of the foil and completely remove it.
3. Gently shake the tablet onto your hand.
4. Immediately place the tablet on the tongue.

Orally disintegrating tablets must not be divided into equal parts.

This dosage form is particularly suitable for patients who have difficulty swallowing conventional tablets or when liquid is not available.

Elitsea orally disintegrating tablets are bioequivalent to film-coated escitalopram tablets, with the same rate and extent of absorption. Elitsea has the same dosage and frequency of administration as film-coated tablets. Escitalopram orally disintegrating tablets may be used as an alternative to film-coated tablets.

The safety of doses above 20 mg per day has not been established.

Major Depressive Episodes

The usual dose is 10 mg once daily. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily.

Therapeutic effect typically develops within 2–4 weeks after initiation of treatment. After symptom remission, treatment should be continued for at least 6 months to consolidate the therapeutic response.

Panic Disorder with or without Agoraphobia

A dose of 5 mg is recommended during the first week of treatment, which should then be increased to 10 mg daily. Depending on individual patient response, the dose may subsequently be increased to a maximum of 20 mg daily.

Maximum efficacy is generally achieved within approximately 3 months. Treatment should continue for several months.

Social Anxiety Disorder (Social Phobia)

The usual dose is 10 mg once daily. Symptom improvement typically occurs within 2–4 weeks. Depending on individual patient response, the dose may subsequently be reduced to 5 mg or increased to a maximum of 20 mg daily.

Since social anxiety disorder is a chronic condition, a treatment duration of 12 weeks is recommended to consolidate the therapeutic effect. Long-term treatment has been studied in patients who responded to initial therapy over a period of 6 months and may be prescribed individually to prevent relapse. Therapeutic benefit should be regularly reassessed.

Social anxiety disorder has a clearly defined diagnostic classification and should not be confused with exaggerated shyness. Pharmacotherapy is indicated only for disorders that significantly impair professional and social functioning.

The efficacy of pharmacotherapy compared to cognitive-behavioral therapy has not been evaluated. Pharmacotherapy should be part of an overall therapeutic strategy.

Generalized Anxiety Disorder

The usual dose is 10 mg once daily. Depending on individual sensitivity, the dose may be increased up to a maximum of 20 mg daily.

Treatment should be continued for 3 months to consolidate the effect. Long-term treatment for 6 months has been shown to prevent relapse and may be prescribed individually; however, the benefits of continued treatment should be regularly evaluated.

Obsessive-Compulsive Disorder

The initial dose is 10 mg once daily. Depending on individual patient response, the dose may subsequently be increased to a maximum of 20 mg daily.

Since obsessive-compulsive disorder is a chronic condition, patients should be treated for a sufficient duration to ensure symptom remission. Therapeutic benefit and dosing should be regularly reassessed.

Elderly Patients (>65 years)

The initial dose is 5 mg once daily. Depending on individual patient response, the dose may subsequently be increased to 10 mg daily.

The efficacy of Elitsea in social anxiety disorder has not been studied in elderly patients.

Patients with Renal Impairment

Dose adjustment is not required in patients with mild to moderate renal impairment. Elitsea should be administered with caution in patients with severe renal impairment (creatinine clearance <30 mL/min).

Patients with Hepatic Impairment

In patients with mild to moderate hepatic impairment, the recommended initial dose for the first two weeks is 5 mg daily. Depending on individual patient response, the dose may subsequently be increased to 10 mg daily. Caution and careful dose titration are required in patients with severe hepatic impairment.

Poor CYP2C19 Metabolizers

For patients known to be poor metabolizers of the CYP2C19 enzyme, the recommended initial dose for the first two weeks is 5 mg daily.

Depending on individual patient response, the dose may subsequently be increased to 10 mg daily.

Withdrawal Symptoms Observed upon Discontinuation

Abrupt discontinuation of this medication should be avoided. When stopping treatment, the dose of escitalopram should be gradually reduced over a period of at least 1–2 weeks to prevent discontinuation reactions (see sections "Special Warnings and Precautions for Use" and "Adverse Reactions"). If severe symptoms occur during dose reduction or after discontinuation, the previous dose may be reinstated. The physician may then continue tapering the dose more gradually.

Children

Elitsea should not be used in children (under 18 years of age).

Overdose

Toxicity

Clinical data on escitalopram overdose are limited, and in many cases, overdose involved concomitant medications. In most cases, symptoms were absent or mild. Fatalities following overdose with escitalopram alone have been reported rarely. Doses of escitalopram alone ranging from 400 to 800 mg have not resulted in severe symptoms.

Symptoms

Symptoms reported in cases of escitalopram overdose generally involved the central nervous system (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizures, and coma), gastrointestinal system (nausea/vomiting), cardiovascular system (hypotension, tachycardia, QT interval prolongation, and arrhythmias), as well as fluid and electrolyte imbalances (hypokalemia, hyponatremia).

Treatment

There is no specific antidote. Ensure airway patency and adequate oxygenation and ventilation. Gastric lavage and administration of activated charcoal should be considered. Gastric lavage should be performed as soon as possible after oral ingestion. Continuous monitoring of cardiovascular function and vital signs, together with general supportive and symptomatic measures, is recommended. ECG monitoring is advised in cases of overdose in patients with cardiac insufficiency and congestive symptoms/bradyarrhythmias, in patients taking concomitant medications that prolong the QT interval, or in patients with altered metabolism, e.g., due to hepatic impairment.

Adverse reactions.

Adverse reactions most commonly occur during the first and second week of treatment and become less intense over time, with their frequency decreasing during continued treatment.

The adverse effects typical for all SSRIs and escitalopram, observed during placebo-controlled studies and in clinical practice, are listed below by organ systems and frequency of occurrence.

Classification of frequency: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), or unknown (cannot be estimated from available data).

1Suicidal thoughts or behaviors were observed during escitalopram therapy or immediately after discontinuation of treatment (see section "Special precautions for use").

2These reactions have been reported for the class of SSRIs (selective serotonin reuptake inhibitors).

3This effect has been reported for the therapeutic class of SSRIs/SNRIs (serotonin and norepinephrine reuptake inhibitors) (see sections "Special precautions for use", "Use during pregnancy or breastfeeding").

Description of selected adverse reactions

Class effects

Epidemiological studies, primarily conducted in patients aged 50 years and older, have demonstrated an increased risk of bone fractures in patients taking SSRIs and tricyclic antidepressants. The mechanism leading to this risk is currently unknown.

Withdrawal symptoms observed upon discontinuation of treatment

Discontinuation of SSRIs/SNRIs (serotonin and norepinephrine reuptake inhibitors), especially abrupt discontinuation, frequently leads to withdrawal symptoms. The most commonly reported reactions include dizziness, sensory disturbances (paraesthesia and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, vomiting and/or nausea, tremor, confusion, excessive sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances. In general, these symptoms are mild to moderate in severity; however, in some patients they may be severe and/or prolonged. Therefore, if continued treatment with escitalopram is not required, discontinuation should be carried out gradually by tapering the dose.

QT interval prolongation

Cases of QT interval prolongation and ventricular arrhythmia, including torsade de pointes, have been reported during the post-marketing period, primarily in female patients with hypokalemia, pre-existing QT interval prolongation, or other cardiac diseases.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life.

3 years.

Storage conditions.

No special temperature storage conditions are required for this medicinal product.

Keep in the original packaging to protect from light and moisture.

Keep out of reach of children.

Packaging.

7 tablets in a blister; 4 or 12 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

KRKA, d.d., Novo mesto / KRKA, d.d., Novo mesto.

Genepharm SA / Genepharm SA.

Manufacturer's address and place of business.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia / Smarjeska cesta 6, 8501 Novo mesto, Slovenia.

18th km Marathonos Ave, Pallini Attiki, 15351, Greece / 18th km Marathonos Ave, Pallini Attiki, 15351, Greece.