Escitam 10

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ESCITAM 10 (ESCITAM 10) ESCITAM 20 (ESCITAM 20)

Composition:

Active substance: escitalopram;

1 tablet contains 12.775 mg or 25.550 mg of escitalopram hydrogen oxalate equivalent to 10 mg or 20 mg of escitalopram;

Excipients: microcrystalline cellulose, sodium croscarmellose, talc, magnesium stearate, colloidal anhydrous silicon dioxide;

Film-coating suspension: hypromellose, titanium dioxide (E 171), polyethylene glycol 400 (macrogol 400).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical characteristics:

oval-shaped, film-coated tablets of white color, with engraving "E9CM" on one side and a break line with engraving "10" on the other side (the digit on both sides of the break line);

oval-shaped, film-coated tablets of white color, with engraving "E9CM" on one side and a break line with engraving "20" on the other side (the digit on both sides of the break line).

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATC code N06AB10.

Pharmacological Properties.

Pharmacodynamics.

Escitalopram is a selective serotonin reuptake inhibitor (SSRI) characterized by high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter, although its affinity for this site is 1000-fold lower.

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

Inhibition of serotonin (5-HT) reuptake is the only plausible mechanism of action that can explain the pharmacological and clinical effects of escitalopram.

Pharmacodynamic effects

In one double-blind, placebo-controlled study of ECG parameters in healthy subjects, QTc interval (corrected using Fridericia's formula) prolongation from baseline was 4.3 ms (90% CI: 2.2, 6.4) with escitalopram 10 mg/day and 10.7 ms (90% CI: 8.6, 12.8) with a dose higher than the therapeutic dose—30 mg/day (see sections «Contraindications», «Special precautions», «Interaction with other medicinal products and other forms of interaction», «Adverse reactions», «Overdose»).

Clinical efficacy

Major depressive episodes

The efficacy of escitalopram in the acute treatment of major depressive episodes was demonstrated in 3 out of 4 double-blind, placebo-controlled, short-term (8-week) studies. In a long-term relapse prevention study, 274 patients who responded to escitalopram treatment at doses of 10 or 20 mg/day during an initial 8-week open-label phase were randomized to continue escitalopram at the same dose or switch to placebo for up to 36 weeks. In this study, patients continuing escitalopram had a statistically significantly longer time to relapse within the following 36 weeks compared to those receiving placebo.

Social anxiety disorder

Escitalopram has been shown to be effective in the treatment of social anxiety disorder in three short-term (12-week) studies as well as in a 6-month relapse prevention study. Efficacy of escitalopram at doses of 5, 10, and 20 mg was demonstrated in a 24-week optimal dose study.

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 design, involving a total of 421 patients receiving escitalopram and 419 patients receiving placebo, treatment response was achieved in 47.5% and 28.9% of patients, 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 20 mg/day was demonstrated in a 24–76-week randomized maintenance-effect study involving 373 patients who responded to the drug during an initial 12-week open-label treatment period.

Obsessive-compulsive disorder

In a randomized, double-blind clinical trial, escitalopram at a dose of 20 mg/day demonstrated superiority over placebo in the total Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score 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 subsequently enrolled in a 24-week randomized, double-blind, placebo-controlled phase.

Pharmacokinetics.

Absorption is nearly complete and independent of food intake. Maximum plasma concentration (Tmax) is reached within 4 hours after administration. 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 ranges from 12 to 26 L/kg. The bioavailability of escitalopram is approximately 80%. Binding of escitalopram and its main metabolites to plasma proteins is not less than 80%.

Biological transformation

Metabolism occurs in the liver, forming demethylated and didemethylated metabolites. Both are pharmacologically active. Nitrogen may also be oxidized to form an N-oxide metabolite. Both metabolites and the parent compound are partially excreted as glucuronides. After repeated administration, 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 is mediated by the cytochrome CYP2C19. Minor contributions from CYP3A4 and CYP2D6 enzymes are possible.

Elimination

The elimination half-life (T½β) of the drug is approximately 30 hours. Oral clearance (Cloral) is approximately 0.6 L/min. The main metabolites have longer elimination half-lives. Escitalopram and its main metabolites are eliminated via the liver (metabolic pathway) and kidneys. The majority of the dose is excreted in urine as metabolites.

Linearity

The pharmacokinetics of escitalopram are linear. Steady-state concentration is 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.

Elderly patients

In elderly patients (aged 65 years and older), escitalopram is eliminated more slowly than in younger patients. Systemic exposure (AUC) is 50% higher in elderly individuals compared to younger healthy volunteers (see section «Dosage and administration»).

Hepatic impairment

In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the elimination half-life was twice as long and exposure was 60% higher compared to individuals with normal liver function (see section «Dosage and administration»).

Renal impairment

In patients with reduced renal function (CLcr 10–53 mL/min), administration of racemic citalopram resulted in a longer elimination half-life and slightly increased exposure. Plasma concentrations of metabolites have not been studied but may be elevated (see section «Dosage and administration»).

Polymorphism

Patients with poor metabolic function of CYP2C19 had plasma concentrations of escitalopram twice as high as those with normal CYP2C19 function. No significant changes in exposure were observed with reduced CYP2D6 function (see section «Dosage and administration»).

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to escitalopram or to any of the excipients of the medicinal product; concomitant use of non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome with agitation, tremor, hyperthermia, etc. (see section "Interaction with other medicinal products and other forms of interactions"); combination of escitalopram with reversible 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 forms of interactions").

Escitalopram is contraindicated in patients with known QT interval prolongation or congenital long QT syndrome; escitalopram is contraindicated in combination with medicinal products known to prolong the QT interval (see section "Interaction with other medicinal products and other forms of interactions").

Interaction with other medicinal products and other forms 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, and in patients who have recently discontinued SSRIs and started treatment with MAO inhibitors (see section "Contraindications"). In some cases, serotonin syndrome developed (see section "Side effects"). Combination of escitalopram with non-selective irreversible MAO inhibitors is contraindicated. Treatment with escitalopram should be initiated no earlier than 14 days after discontinuation of an irreversible MAO inhibitor. Treatment with non-selective irreversible MAO inhibitors should not begin earlier than 7 days after stopping escitalopram.

Reversible selective MAO-A inhibitor (moclobemide).

Due to the risk of serotonin syndrome, combination of escitalopram with the MAO-A inhibitor moclobemide is contraindicated (see section "Contraindications"). If this combination is deemed necessary, treatment should begin with the lowest recommended doses and under careful clinical monitoring.

Reversible non-selective MAO inhibitor (linezolid).

The antibiotic linezolid is a reversible non-selective MAO inhibitor and therefore should not be used in patients receiving escitalopram. If combination is necessary, treatment should be initiated at the lowest doses and under close clinical supervision (see section "Contraindications").

Irreversible selective MAO-B inhibitor (selegiline).

Combination with selegiline (irreversible MAO-B inhibitor) requires caution due to the risk of serotonin syndrome.

Selegiline at doses up to 10 mg/day has been safely used concomitantly with racemic citalopram.

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 concomitantly with such medicinal products, an additive effect cannot be excluded. Therefore, concomitant use of escitalopram with medicinal products known to 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 such as halofantrine), and certain antihistamines (astemizole, hydroxyzine, mizolastine), is contraindicated.

Combinations requiring caution.

Serotonergic agents.

Concomitant use with serotonergic medicinal products, such as opioids (including tramadol) and triptans (including sumatriptan), may lead to serotonin syndrome.

Medicinal products that lower seizure threshold.

SSRIs may lower the seizure threshold. Caution is recommended when co-administering medicinal products that may reduce 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, co-administration of these medicinal products with escitalopram should be done with caution.

St. John’s wort (Hypericum perforatum).

Concomitant use of SSRIs and herbal preparations containing St. John’s wort may lead to an increased frequency of adverse reactions.

Anticoagulants.

Changes in the effects of oral anticoagulants may occur with concomitant use of escitalopram. In patients receiving oral anticoagulants, careful monitoring of the coagulation system is required before and during treatment with escitalopram (see section "Special precautions for use"). Concomitant use of nonsteroidal anti-inflammatory drugs may increase the risk of bleeding (see section "Special precautions for use").

Alcohol.

Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interactions with alcohol. However, combination with alcohol, as with other psychotropic medicinal products, is not recommended.

Medicinal products causing hypokalemia/hypomagnesemia.

Caution is required when co-administering medicinal products that cause hypokalemia/hypomagnesemia, as this increases the risk of serious arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions.

Effect of other medicinal products on the pharmacokinetics of escitalopram.

The metabolism of escitalopram is primarily mediated by CYP2C19, although CYP3A4 and CYP2D6 are also involved to a lesser extent. The isoenzyme 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 (approximately 50%) increase in plasma concentration of escitalopram.

Concomitant administration of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) increases the plasma concentration of escitalopram by approximately 70%. Caution is recommended when escitalopram is used concomitantly with cimetidine. Dose adjustment may be necessary (see section "Special precautions for use").

Therefore, caution is advised when using escitalopram concomitantly with CYP2C19 inhibitors (e.g., omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or with cimetidine, especially when prescribing the upper limit doses of escitalopram. Dose reduction of escitalopram may be required when used concomitantly with the above-mentioned medicinal products.

Effect of escitalopram on the pharmacokinetics of other agents.

Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution is recommended when escitalopram is used concomitantly with medicinal products that are primarily metabolized by this enzyme and have a narrow therapeutic index, such as flecainide, propafenone, and metoprolol (in heart failure), or with certain centrally acting agents primarily metabolized by CYP2D6, such as antidepressants (e.g., desipramine, clomipramine, nortriptyline) and antipsychotics (e.g., risperidone, thioridazine, haloperidol). Dose adjustment may be required.

Combination with desipramine or metoprolol has been shown to double plasma levels of these CYP2D6 substrates.

In vitro studies have demonstrated that escitalopram causes weak inhibition of CYP2C19. Caution is recommended when using escitalopram concomitantly with medicinal products metabolized by CYP2C19.

Special precautions for use.

The following special precautions apply to the therapeutic group of selective serotonin reuptake inhibitors (SSRIs).

Paradoxical anxiety.

In some patients with panic disorders, anxiety may increase at the beginning of treatment with antidepressants. This paradoxical reaction usually resolves within two weeks of treatment. To reduce the likelihood of anxiogenic effects, low initial doses are recommended (see section "Dosage and administration").

Seizures.

The medicinal product should be discontinued if a patient develops a first seizure or if seizures become more frequent (in patients with a confirmed diagnosis of epilepsy). SSRIs should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored.

Mania.

SSRIs should be used with caution in patients with a history of mania/hypomania. SSRIs should be discontinued if a manic state develops.

Diabetes mellitus.

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

Suicide, suicidal thoughts, or clinical worsening.

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

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

Patients with a history of suicidal behaviour prior to treatment initiation are at the highest risk of suicidal thoughts or suicide attempts and require close monitoring during treatment. A meta-analysis of clinical trials revealed an increased risk of suicidal behaviour among patients under 25 years of age taking antidepressants compared to those taking placebo.

Close monitoring of high-risk patients is particularly necessary at the beginning of treatment and when the dose is changed.

Patients and caregivers should be advised to monitor for any worsening of symptoms, suicidal behaviour or thoughts, and unusual changes in behaviour, and to seek immediate medical attention if these symptoms occur.

Akathisia/Psychomotor agitation.

The use of SSRIs/SSRIs is associated with the development of akathisia — a condition characterized by an unpleasant, distressing sense of restlessness and an urge to move, often accompanied by an inability to sit or stand still. This condition most commonly occurs within the first few weeks of treatment. Dose escalation may worsen symptoms in patients who develop such symptoms.

Hyponatremia.

Hyponatremia, possibly related to impaired secretion of antidiuretic hormone (ADH), occurs rarely during SSRI treatment and usually resolves after discontinuation of therapy. SSRIs should be used with caution in patients at risk (elderly patients, those with liver cirrhosis, or those receiving concomitant medications that may cause hyponatremia).

Bleeding.

Bleeding events (e.g., ecchymosis and purpura) may occur during SSRI treatment. SSRIs/SSRIs may increase the risk of postpartum haemorrhage (see sections "Use in pregnancy or breastfeeding", "Adverse reactions"). SSRIs should be used with caution in patients receiving concomitant anticoagulants and drugs affecting platelet function (e.g., atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, dipyridamole, and ticlopidine), as well as in patients with a predisposition to bleeding.

ECT (Electroconvulsive therapy).

Clinical experience with concomitant use of SSRIs and ECT is limited; 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 advised when escitalopram is used concomitantly with serotonergic agents such as triptans (including sumatriptan), opioids (including tramadol), and tryptophan. Rare cases of serotonin syndrome have been reported in patients taking SSRIs together with serotonergic drugs.

Escitalopram should be used cautiously in combination with medicinal products having serotonergic activity. A combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of serotonin syndrome.

If such a situation occurs, SSRIs and serotonergic agents should be discontinued immediately, and symptomatic treatment initiated.

St. John’s wort.

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

Withdrawal symptoms.

Withdrawal symptoms upon discontinuation of treatment, especially abrupt discontinuation, are common.

In clinical trials, adverse effects upon discontinuation occurred in approximately 25% of patients taking escitalopram and in 15% of those taking placebo.

The risk of withdrawal symptoms may depend on several factors, including duration and dose of treatment, and the speed of dose reduction.

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, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. These symptoms are usually mild to moderate in severity but may be severe in some patients. They typically occur within the first few days after stopping treatment, although very rare reports describe similar symptoms in patients who accidentally missed a dose. Withdrawal symptoms usually resolve within two weeks, but in some patients may persist longer (2–3 months or more). Therefore, it is recommended to gradually discontinue escitalopram by tapering the dose over several weeks or months, depending on the patient's condition (see section "Dosage and administration").

Sexual dysfunction.

SSRIs/SSRIs may cause symptoms of sexual dysfunction (see section "Adverse reactions"). There have been reports of persistent sexual dysfunction, where symptoms continued after discontinuation of SSRI/SSRI treatment.

Ischaemic heart disease.

The medicinal product should be used with caution in patients with ischaemic heart disease due to limited clinical experience.

QT interval prolongation.

Escitalopram has been shown to cause dose-dependent QT interval prolongation. During the post-marketing period, cases of QT interval prolongation and ventricular arrhythmias, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in female patients with hypokalaemia or pre-existing QT prolongation, or other cardiac conditions (see sections "Contraindications", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", "Overdose", and "Pharmacodynamics").

The medicinal product 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.

In patients with stable cardiac disease, an ECG should be performed before starting treatment.

If signs of cardiac arrhythmia occur during treatment with escitalopram, treatment should be discontinued and an ECG performed.

Closed-angle glaucoma.

SSRIs, including escitalopram, may affect pupil size, leading to mydriasis. In turn, pupil dilation may narrow the anterior chamber angle and consequently increase intraocular pressure, potentially triggering closed-angle glaucoma, particularly in predisposed patients. Therefore, escitalopram should be used with caution in patients with closed-angle glaucoma or glaucoma, including a history thereof.

Excipients. This medicinal product contains less than 1 mmol sodium (23 mg), i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy.

Clinical data on the use of escitalopram in pregnant women are limited.

Animal studies have shown reproductive toxicity.

Escitalopram is contraindicated during pregnancy. The exception is when, after careful consideration of risks and benefits, a clear need for the medicinal product has been established.

Newborns whose mothers have taken escitalopram during pregnancy, particularly in the third trimester, should be carefully monitored. Abrupt discontinuation of the medicinal product during pregnancy should be avoided. Newborns whose mothers have taken SSRIs/SSRIs in late pregnancy may experience symptoms such as respiratory distress, cyanosis, apnoea, seizures, temperature fluctuations, feeding difficulties, vomiting, hypoglycaemia, arterial hypertension or hypotension, hyperreflexia, tremor, nervous agitation, irritability, apathy, persistent crying, somnolence, and sleep disturbances. These symptoms may arise either as a result of serotonergic effects or as signs of withdrawal syndrome.

In most cases, complications manifest immediately or shortly after birth (< 24 hours).

According to epidemiological data, the use of SSRIs during pregnancy may increase the risk of persistent pulmonary hypertension in the newborn to 5 cases per 1000 pregnancies. In the general population, 1 to 2 cases per 1000 pregnancies occur.

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

Breastfeeding period.

Since escitalopram passes into breast milk, women who are breastfeeding should not use the medicinal product.

Fertility.

Animal studies have shown that escitalopram may affect sperm quality. Reports on the use of certain SSRIs indicate that effects on sperm quality in humans are reversible. No effect on human fertility has been observed to date.

Ability to affect reaction speed when driving or operating machinery.

Overall, escitalopram does not affect intellectual functions or psychomotor reactions; however, it should be considered that any psychoactive agent may impair skills or the ability to think rationally. Patients should be warned about the potential risk of impaired ability to drive or operate machinery.

Dosage and Administration

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

Escitalopram is administered orally once daily to adults, independent of food intake.

Major Depressive Episode.

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

The antidepressant effect is usually observed within 2–4 weeks. After symptom remission, treatment should be continued for 6 months to consolidate the therapeutic effect.

Panic Disorder with or without Agoraphobia.

An initial dose of 5 mg per day is recommended during the first week, after which the dose may be increased to 10 mg per day. The dose may be further increased up to the maximum of 20 mg per day, depending on individual patient sensitivity.

Maximum therapeutic effect in panic disorder is achieved after 3 months. The duration of treatment is 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 of treatment. Depending on individual patient sensitivity, the dose may subsequently be reduced to 5 mg/day or increased up to the maximum of 20 mg/day.

Since social anxiety disorder is a chronic condition, treatment should be continued for 12 weeks to consolidate the achieved therapeutic effect.

Long-term treatment for up to 6 months has been shown to prevent relapse, taking into account individual disease manifestations; treatment efficacy should be regularly evaluated.

Social anxiety disorder is a clearly defined diagnostic term for a specific disorder and should not be confused with excessive shyness. Pharmacotherapy is indicated only when this disorder significantly impairs professional functioning and social activity.

The relative value of pharmacotherapy compared to cognitive-behavioral therapy has not been established. Pharmacotherapy is one component of an overall treatment strategy.

Generalized Anxiety Disorder.

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

Long-term treatment has been studied over 6 months in patients receiving a daily dose of 20 mg; treatment efficacy should be regularly evaluated.

Obsessive-Compulsive Disorder (OCD).

The usual initial dose is 10 mg once daily. Depending on individual patient sensitivity, the dose may be increased up to 20 mg per day. OCD is a chronic disorder; treatment should continue for a sufficient duration to ensure complete symptom remission, which may take several months or longer. The benefit of treatment and dosage should be regularly assessed (see section "Pharmacodynamics").

Elderly Patients (over 65 years of age).

The initial dose is 5 mg. Depending on individual sensitivity and severity of depression, the daily dose may be increased up to 10 mg per day (see section "Pharmacokinetics"). The efficacy of escitalopram in elderly patients with social anxiety disorder has not been evaluated.

Paediatric Population.

The medicinal product Escitam 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.

No dosage adjustments are required in patients with mild to moderate renal impairment. Escitalopram should be used with caution in patients with severe renal impairment (creatinine clearance < 30 mL/min) (see section "Pharmacokinetics").

Hepatic Impairment.

For patients with mild to moderate hepatic impairment, the recommended initial dose during the first two weeks of treatment is 5 mg per day. Depending on individual patient response, the dose may be increased to 10 mg per day. In patients with severe hepatic impairment, escitalopram should be used with caution and dose titration should be carefully performed (see section "Pharmacokinetics").

Reduced CYP2C19 Isoenzyme Activity.

For patients with poor CYP2C19 isoenzyme activity, the recommended initial dose during the first two weeks of treatment is 5 mg per day. Depending on individual patient response, the dose may be increased to 10 mg per day (see section "Pharmacokinetics").

Withdrawal Symptoms upon Discontinuation.

Abrupt discontinuation of treatment should be avoided. When stopping treatment with Escitam, the dose should be gradually reduced over 1–2 weeks to avoid possible withdrawal symptoms (see sections "Special Warnings and Precautions for Use" and "Undesirable Effects"). If intolerable symptoms occur after dose reduction or discontinuation, the previous dose may be reinstated. The physician may then continue to reduce the dose more gradually.

Children.

Antidepressants should not be used for the treatment of children and adolescents (under 18 years of age). Suicidal behavior (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) have been observed more frequently in children and adolescents treated with antidepressants compared to those receiving placebo. If, based on clinical judgment, a decision to prescribe antidepressants is made, careful monitoring for the emergence of suicidal symptoms is required.

Overdose.

Toxicity.

Data on escitalopram overdose are limited. Most cases involve concomitant overdose with other medicinal products. Symptoms have generally been mild or absent. Fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other drugs. Doses in the range of 400–800 mg escitalopram have not caused severe symptoms.

Symptoms.

Escitalopram overdose is primarily manifested by symptoms affecting the central nervous system (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizures, and coma), gastrointestinal tract (nausea/vomiting), cardiovascular system (hypotension, tachycardia, QT interval prolongation, arrhythmias), and electrolyte imbalances (hypokalemia, hyponatremia).

Treatment.

There is no specific antidote. Maintain adequate respiratory function and ensure proper oxygenation. Gastric lavage and activated charcoal may be used. Continuous monitoring of cardiac and vital functions is required, along with symptomatic and supportive treatment.

ECG monitoring is recommended in cases of overdose in patients with congestive heart failure/bradyarrhythmia, in patients concurrently taking drugs that prolong the QT interval, or in patients with impaired metabolism, such as those with hepatic impairment.

Adverse reactions.

Adverse reactions most commonly occur during the first or second week of treatment and usually their frequency and intensity gradually decrease with continued therapy.

Adverse reactions typical for all SSRIs and escitalopram observed in placebo-controlled studies and clinical practice are listed by organ systems and frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), or frequency not known (cannot be estimated).

Blood and lymphatic system disorders: frequency not known – thrombocytopenia.

Immune system disorders: rare – anaphylactic reactions.

Endocrine system disorders: frequency not known – disturbances in antidiuretic hormone secretion, hyperprolactinemia.

Metabolism and nutrition disorders: common – decreased or increased appetite, weight gain; uncommon – weight loss; frequency not known – hyponatremia, anorexia².

Psychiatric disorders: common – anxiety, restlessness, abnormal dreams, decreased libido in both men and women, anorgasmia in women; uncommon – bruxism, agitation, nervousness, panic attacks, confusion; rare – aggression, depersonalization, hallucinations; frequency not known – mania, suicidal thoughts, suicidal behavior¹.

Nervous system disorders: very common – headache; common – insomnia, somnolence, dizziness, paraesthesia, tremor; uncommon – taste disturbances, sleep disorders, syncope; rare – serotonin syndrome; frequency not known – dyskinesia, movement disorders, seizures, psychomotor restlessness/akathisia².

Eye disorders: uncommon – mydriasis, blurred vision.

Ear and labyrinth disorders: uncommon – tinnitus.

Cardiac disorders: uncommon – tachycardia; rare – bradycardia; frequency not known – QT interval prolongation on electrocardiogram, ventricular arrhythmia, including torsade de pointes.

Vascular disorders: frequency not known – orthostatic hypotension.

Respiratory disorders: common – sinusitis, yawning; uncommon – epistaxis.

Gastrointestinal disorders: very common – nausea; common – diarrhea, constipation, vomiting, dry mouth; uncommon – gastrointestinal hemorrhage (including rectal bleeding).

Hepatobiliary disorders: frequency not known – hepatitis, changes in liver function tests.

Skin and subcutaneous tissue disorders: common – increased sweating; uncommon – rash, alopecia, urticaria, pruritus; frequency not known – bruising, edema.

Musculoskeletal and connective tissue disorders: common – arthralgia, myalgia.

Renal and urinary disorders: frequency not known – urinary retention.

Reproductive system and breast disorders: common – in men: ejaculation disorders, impotence; uncommon – in women: metrorrhagia, menorrhagia; frequency not known – in men: priapism; in women: galactorrhea, postpartum hemorrhage³.

General disorders: common – fatigue, pyrexia; uncommon – swelling.

¹ Cases of suicidal thoughts and behavior have been reported during escitalopram treatment or shortly after discontinuation.

² Such cases are known for the entire SSRI class.

³ Such cases have been reported for the therapeutic class of SSRIs or SNRIs (see sections "Special precautions", "Use during pregnancy or breastfeeding").

QT interval prolongation.

During the post-marketing period, cases of QT interval prolongation and ventricular arrhythmias, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in women, patients with hypokalemia, and patients with pre-existing QT prolongation or other cardiac diseases (see sections "Contraindications", "Special precautions", "Interaction with other medicinal products and other forms of interaction", "Overdose", and "Pharmacodynamics").

Class-specific effects. Epidemiological studies, conducted mainly in patients aged 50 years and older, have shown an increased risk of bone fractures associated with the use of SSRIs and tricyclic antidepressants. The mechanism of this phenomenon is unknown.

Withdrawal symptoms.

Discontinuation of SSRIs (especially abrupt discontinuation) usually leads to withdrawal symptoms. 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, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported symptoms. These symptoms are usually mild to moderate and transient; however, in some patients they may be severe and/or prolonged. Therefore, it is recommended to gradually discontinue escitalopram treatment by dose reduction (see sections "Dosage and administration", "Special precautions").

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after medicine authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

10 tablets per blister; 3 or 6 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LLC "Pharma Start" (packaging and repackaging from bulk supplied by Synthon Hispania, S.L., Spain).

Manufacturer's address and location of business activity.

8 Vatslava Havela Boulevard, Kyiv, 03124, Ukraine.

C/ Castello, No. 1, Pol. Las Salinas, Sant Boi de Llobregat, Barcelona, 08830, Spain.

In case of adverse effects or questions regarding the safety of the medicinal product, please contact the Pharmacovigilance Department of LLC "ASINO UKRAINE" at: 8 Vatslava Havela Boulevard, Kyiv, 03124, Tel/Fax: +38 044 281 2333.