Elitsea

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ELICEA (ELICEA®)

Composition:

Active substance: escitalopram;

One film-coated tablet contains 5 mg, 10 mg or 20 mg of escitalopram as escitalopram oxalate;

Excipients: lactose monohydrate, crospovidone, povidone, microcrystalline cellulose, pregelatinized starch, magnesium stearate, hypromellose, titanium dioxide (E 171), macrogol 3000, triacetin.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

5 mg: white, round, biconvex, film-coated tablets with bevelled edges;

10 mg and 20 mg: white, oval, biconvex, film-coated tablets with a score line on one side. The 10 mg and 20 mg tablets can be divided into equal halves.

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

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Escitalopram is a selective serotonin reuptake inhibitor (SSRI) 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 number of receptors, including 5-HT1A, 5-HT2, dopamine D1 and D2, α1-, α2-, β-adrenergic, histamine H1, muscarinic cholinergic, benzodiazepine, and opioid receptors.

Inhibition of serotonin (5-HT) reuptake is considered the only plausible mechanism responsible for explaining 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 interval (corrected by Fridericia's formula) was 4.3 ms (90% CI: 2.2, 6.4) with a dose of 10 mg/day and 10.7 ms (90% CI: 8.6, 12.8) with a supratherapeutic dose of 30 mg/day (see sections «Contraindications», «Special precautions», «Interaction with other medicinal products and other forms of interaction», «Overdose», and «Adverse reactions»).

Clinical efficacy

Major depressive episodes

The efficacy of escitalopram in the treatment of depression during the acute phase 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 to treatment during the initial 8-week open-label phase with escitalopram 10 or 20 mg/day were randomly assigned to continue escitalopram at the same dose or switch to placebo for 36 weeks. During this study, patients continuing escitalopram had a statistically significantly longer time to relapse over the subsequent 36 weeks compared to those receiving placebo.

Social anxiety disorder

Escitalopram was effective in three short-term (12-week) studies as well as in a 6-month relapse prevention study. A 24-week dose-finding study demonstrated efficacy of 5, 10, and 20 mg escitalopram.

Generalized anxiety disorder

Escitalopram at doses of 10 and 20 mg/day was effective in 4 out of 4 placebo-controlled studies.

According to pooled data from three studies with similar designs, involving a total of 421 patients receiving escitalopram and 419 patients receiving placebo, response rates were 47.5% and 28.9%, respectively, and remission occurred in 37.1% and 20.8% of patients, respectively. A sustained effect was observed from the first week of treatment.

The maintenance effect of escitalopram at a dose of 20 mg/day was demonstrated in a 24–76-week randomized maintenance treatment study involving 373 patients who responded to the drug during the initial 12-week open-label treatment.

Obsessive-compulsive disorder

In a randomized, double-blind, clinical trial, escitalopram at a dose of 20 mg/day showed superiority over placebo in the total score of the Y-BOCS scale (Yale-Brown Obsessive Compulsive Scale) after 12 weeks of treatment. At 24 weeks, both 10 mg/day and 20 mg/day doses of escitalopram showed advantages over placebo.

The efficacy of the drug in preventing relapses was demonstrated for escitalopram at doses of 10 and 20 mg/day in patients who responded to escitalopram during a 16-week open-label period and were then included in a 24-week randomized, double-blind, placebo-controlled phase.

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 12–26 L/kg. The bioavailability of escitalopram is approximately 80%. Plasma protein binding of escitalopram and its main metabolites is less than 80%.

Biotransformation

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 the demethylated metabolite occurs primarily via the cytochrome CYP2C19. A possible contribution of CYP3A4 and CYP2D6 enzymes is also considered.

Elimination

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

Linearity

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

Patients of advanced age (> 65 years)

In elderly patients, escitalopram is eliminated more slowly than in younger patients. Systemic exposure (AUC) in elderly patients is 50% higher than in young healthy volunteers (see section «Dosage and administration»).

Hepatic impairment

In patients with mild to moderate hepatic dysfunction (Child-Pugh criteria A and B), the elimination half-life of escitalopram was nearly doubled and AUC was 60% higher than in individuals with normal liver function (see section «Dosage and administration»).

Renal impairment

In patients with reduced renal function (creatinine clearance (CLcr) 10–53 mL/min), an increased elimination half-life of racemic citalopram and a slight increase in AUC were observed. Plasma concentrations of metabolites were not studied, but an increase can be assumed (see section «Dosage and administration»).

Polymorphism

Patients with poor metabolic function of the CYP2C19 isoenzyme had plasma concentrations of the drug twice as high as those with normal CYP2C19 function. In patients with CYP2D6 deficiency, no significant changes in AUC were observed (see section «Dosage and administration»).

Clinical Characteristics.

Indications.

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

Contraindications.

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

Concomitant use with non-selective irreversible monoamine oxidase inhibitors (MAO inhibitors) is contraindicated due to the risk of serotonin syndrome, with symptoms such as agitation, tremor, hyperthermia, etc. (see section "Interaction with other medicinal products and other types of interactions").

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

Escitalopram is contraindicated in patients with known QT interval prolongation or congenital long QT syndrome.

Concomitant use of escitalopram with medicinal products capable of prolonging the QT interval is contraindicated (see section "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Pharmacodynamic interactions

Contraindicated combinations

Non-selective irreversible MAO inhibitors

Serious reactions have been reported in patients taking SSRIs in combination with non-selective irreversible MAO inhibitors, as well as in patients who recently discontinued SSRIs and started MAO inhibitor therapy (see section "Contraindications"). In some cases, serotonin syndrome occurred (see section "Adverse reactions").

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

Combinations requiring caution

Reversible selective MAO-A inhibitor (moclobemide)

Concomitant use of escitalopram with the MAO-A inhibitor moclobemide is contraindicated due to the risk of serotonin syndrome (see section "Contraindications"). If this combination is deemed 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 such a combination is considered necessary, the lowest recommended doses should be initiated 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. When escitalopram is used together with such agents, an additive effect cannot be excluded. Therefore, concomitant use of escitalopram with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, antipsychotics (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 during use

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 used concomitantly 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, these agents should be used concomitantly with caution.

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 effects of anticoagulants may be altered by concomitant use with escitalopram. Patients taking oral anticoagulants should have their coagulation system carefully monitored before and after starting escitalopram.

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

Alcohol

Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interaction with alcohol. However, as with other psychotropic medicinal products, concomitant intake of escitalopram with alcohol is not recommended.

MEDICINAL PRODUCTS CAUSING HYPOKALEMIA/HYPOMAGNESEMIA

Caution should be exercised when using medicinal products capable of causing hypokalemia/hypomagnesemia concomitantly, as this increases the risk of developing malignant arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions

Effect of other medicinal products on the pharmacokinetics of escitalopram

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 (desmethyl escitalopram).

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

Concomitant use of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) results in a moderate increase (approximately 70%) in escitalopram plasma concentration. Escitalopram should be used with caution in combination with cimetidine. Dose adjustment may be necessary (see section "Special precautions for use").

Therefore, caution is required when prescribing the upper limit doses of escitalopram concomitantly with inhibitors of cytochrome CYP2C19 (e.g., omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. Dose reduction of escitalopram may be necessary depending on clinical assessment.

Effect of escitalopram on the pharmacokinetics of other medicinal products

Escitalopram is an inhibitor of the CYP2D6 enzyme. Escitalopram should be prescribed with caution concomitantly with medicinal products whose metabolism is mediated by this enzyme, as well as with agents 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, such as antidepressants like desipramine, clomipramine, and nortriptyline; antipsychotics such as risperidone, thioridazine, and haloperidol. Dose adjustment may be necessary.

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

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

Special precautions for use.

The following special precautions apply to the therapeutic class of 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 suicidal 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 initiating such treatment, careful monitoring for emergence of suicidal symptoms is essential. Furthermore, there is no data available on long-term safety in children regarding growth, sexual maturation, and cognitive and behavioural development.

Paradoxical anxiety

In some patients with panic disorder, 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, a low initial dose is recommended (see section "Dosage and administration").

Seizures

Treatment with escitalopram should be discontinued if seizures occur for the first time or if there is an increase in seizure frequency (in patients with a prior diagnosis of epilepsy). SSRIs are not recommended for patients with unstable epilepsy, and close monitoring is required in 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 state develops.

Diabetes

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

Suicide/suicidal thoughts or worsening of clinical condition

Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide. This risk persists until a sustained remission is achieved. Since improvement may not occur during the first few weeks of treatment or longer, patients should be closely monitored until their condition improves. Clinically, the risk of suicide may increase in the early stages of recovery.

Other psychiatric disorders for which escitalopram is used may also be associated with an increased risk of suicidal behaviour. These conditions may also be comorbid with major depressive disorder. These warnings also apply to the treatment of patients with other psychiatric disorders.

Due to the high risk of suicidal thoughts and behaviours during treatment, close monitoring is required in patients with a history of such conditions or with significant levels of suicidal ideation prior to treatment initiation. A meta-analysis of clinical trials revealed an increased risk of suicidal behaviour in patients under 25 years of age treated with antidepressants compared to those receiving placebo. Close monitoring of patients at increased risk is particularly necessary at the beginning of treatment and after dose adjustments.

Patients and caregivers should be warned to monitor for any clinical worsening, suicidal behaviour or thoughts, and unusual changes in behaviour. They should be advised to seek immediate medical help if such symptoms occur.

Akathisia/psychomotor agitation

Use of SSRIs/norepinephrine and serotonin reuptake inhibitors (SNRIs) has been associated with the development of akathisia, characterised by a subjective feeling of inner restlessness or anxiety 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. Dose increases may be harmful in patients experiencing such symptoms.

Hypotonic hyponatraemia

Cases of hyponatraemia, likely due to impaired secretion of antidiuretic hormone, have been reported during SSRI treatment. This condition usually resolves upon discontinuation of treatment. The drug should be used with caution in patients at risk, such as elderly patients, patients with liver cirrhosis, or patients concurrently taking medications capable of causing hyponatraemia.

Bleeding

Skin haemorrhages, ecchymoses, and purpura may occur during SSRI treatment. SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections "Use during pregnancy and breastfeeding", "Adverse reactions"). SSRIs should be used with caution in patients with a predisposition to bleeding, particularly when used concomitantly with anticoagulants or drugs affecting platelet function (e.g., atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs, ticlopidine, dipyridamole).

Electroconvulsive therapy (ECT)

There is limited clinical experience with combining SSRIs and ECT; therefore, caution is recommended.

Reversible, selective MAO-A inhibitors

Combining escitalopram with MAO-A inhibitors is not recommended due to the risk of serotonin syndrome.

Serotonin syndrome

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

Cases of serotonin syndrome have been reported in patients taking SSRIs concomitantly with serotonergic drugs (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 the serotonergic drug should be discontinued immediately, and symptomatic treatment 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 commonly occur (see section "Adverse reactions"). In clinical trials, discontinuation-related reactions were observed in approximately 25% of patients in the escitalopram group and 15% in the placebo group.

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

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

Sexual dysfunction

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

Ischaemic heart disease (IHD)

Due to limited clinical experience, caution is required when treating patients with IHD.

QT interval prolongation

Escitalopram has been shown to cause dose-dependent prolongation of the QT interval. Cases of prolongation of the QT interval and ventricular arrhythmias, including torsade de pointes, have been reported primarily in female patients with hypokalaemia or pre-existing QT prolongation, or other cardiac diseases. The drug should be used with caution in patients with marked 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 before initiating escitalopram treatment.

An ECG should be performed before initiating treatment in patients with heart disease. If cardiac arrhythmias occur during escitalopram treatment, treatment should be discontinued and an ECG performed.

Closed-angle glaucoma

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

Special warnings regarding excipients

Elitsea contains lactose. It should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding.

Pregnancy

Clinical data on the use of escitalopram during pregnancy are limited. Animal studies have shown reproductive toxicity. Escitalopram is contraindicated during pregnancy except in cases where a careful evaluation of risks and benefits has clearly demonstrated the necessity of treatment.

Newborns whose mothers have taken escitalopram during pregnancy, especially in the third trimester, should be closely monitored. Abrupt discontinuation of the drug during pregnancy should be avoided. In newborns whose mothers took SSRIs/SNRIs late in pregnancy, respiratory distress syndrome, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, lethargy, persistent crying, somnolence, and sleep disturbances have been reported. 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 suggest that the use of SSRIs during pregnancy may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Observational data indicate a risk of up to 5 cases per 1000 pregnancies. The background rate of PPHN in the general population is 1–2 cases per 1000 pregnancies.

Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI use within one month prior to delivery (see sections "Special precautions for use", "Adverse reactions").

Breastfeeding period

Since escitalopram passes into breast milk, breastfeeding should 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 effect on human fertility has been observed to date.

Ability to affect reaction speed when driving or operating machinery.

Generally, escitalopram does not affect intellectual or psychomotor performance, but as a psychotropic medicinal product, it may influence decision-making and skills. Patients should be warned about the potential risk of impaired ability to drive or operate machinery.

Dosage and Administration

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

Elitsea should be administered once daily, independent of food intake.

Major Depressive Episode

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

Therapeutic effect usually 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 may 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 achieved within approximately 3 months. Treatment duration lasts several months and depends on disease severity.

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 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 therapeutic response. Long-term use in patients who responded to treatment has been studied for up to 6 months and may be considered, depending on individual patient response, to prevent relapse. The therapeutic benefit of continued treatment should be regularly evaluated.

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

The efficacy of this treatment compared to cognitive-behavioral therapy has not been evaluated. Pharmacological treatment should be part of an overall patient management strategy.

Generalized Anxiety Disorder

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

Long-term treatment has been studied for at least 6 months in patients receiving a daily dose of 20 mg; the benefits of treatment should be regularly assessed.

Obsessive-Compulsive Disorder (OCD)

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 OCD is a chronic disorder, patients should be treated for a sufficient duration to ensure symptom remission, which may take several months or longer. The therapeutic benefit and dosing should be regularly evaluated (see section "Pharmacodynamics").

Elderly Patients (over 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 (see section "Pharmacokinetics").

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

Pediatric Population

Escitalopram should not be used for the treatment of children and adolescents (under 18 years of age) (see section "Special Warnings and Precautions for Use").

Renal Impairment

Dose adjustment is not required in patients with mild to moderate renal impairment. The drug should be used with caution in patients with severe renal impairment (CLcr < 30 mL/min) (see section "Pharmacokinetics").

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. In patients with severe hepatic impairment, the drug should be used with caution and dose titration should be carefully performed.

Reduced CYP2C19 Activity

For patients known to have reduced CYP2C19 enzyme activity, 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 (see section "Pharmacokinetics").

Withdrawal Symptoms 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 minimize discontinuation reactions (see sections "Special Warnings and Precautions for Use" and "Adverse Reactions"). If intolerable symptoms occur during dose reduction or after treatment discontinuation, the previous dose may be reinstated. Subsequently, the physician may continue tapering the dose, but more gradually.

Children

The drug should not be used for the treatment of children and adolescents (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 of escitalopram alone have been rarely reported; in most such cases, overdose involved concomitant medications. Single doses of escitalopram ranging from 400 to 800 mg have not caused 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), the gastrointestinal system (nausea/vomiting), the cardiovascular system (hypotension, tachycardia, QT interval prolongation, and arrhythmias), as well as fluid and electrolyte imbalances (hypokalemia, hyponatremia).

Treatment

There is no specific antidote. Supportive care and maintenance of airway patency, respiratory function, and adequate oxygenation are essential. Gastric lavage and 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, combined with general symptomatic and supportive measures, is recommended. ECG monitoring is recommended in cases of overdose in patients with congestive heart failure/bradyarrhythmias, patients taking concomitant medications that prolong the QT interval, or patients with altered metabolism, such as those with hepatic impairment.

Adverse reactions.

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

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

Frequency is defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), or frequency not known (cannot be estimated from available data).

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

2These reactions have been reported for the class of SSRIs.

3This reaction has been reported for the therapeutic class of SSRIs/SNRIs (see sections "Special precautions", "Use in pregnancy or lactation").

QT interval prolongation

Cases of QT interval prolongation and ventricular arrhythmia, including torsade de pointes, have been reported during the post-marketing period, predominantly in women, in patients with hypokalemia, and in patients with pre-existing QT interval prolongation or other heart diseases (see sections "Pharmacodynamics", "Contraindications", "Interaction with other medicinal products and other forms of interactions", "Special precautions", "Overdose").

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, 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. Generally, these symptoms are mild to moderate, but in some patients they may be severe and/or prolonged. Therefore, when continued treatment with escitalopram is not required, discontinuation should be carried out gradually by tapering the dose (see sections "Special precautions", "Dosage and administration").

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should 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.

Store at a temperature not exceeding 30 °C in the original packaging to protect from light and moisture.

Keep out of the reach of children.

Packaging.

7 tablets in a blister, 4, 8, or 14 blisters in a carton.

10 tablets in a blister, 3, 6, or 9 blisters in a carton.

Prescription category.

Prescription only.

Manufacturer.

KRKA, d.d., Novo mesto, Slovenia.

Manufacturer's address and location of its operations.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia.