Escitam® asino

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ESCITAM® ACINO (ESCITAM ACINO)

Composition:

Active substance: escitalopram;

One tablet contains escitalopram oxalate (12.775 mg or 25.55 mg), equivalent to escitalopram 10 mg or 20 mg;

Excipients: microcrystalline cellulose, sodium croscarmellose, hydroxypropylmethylcellulose (hypromellose), colloidal anhydrous silicon dioxide, talc, magnesium stearate;

Coating Opadry II White: polyvinyl alcohol, titanium dioxide (E 171), polyethylene glycol (macrogol), talc.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

10 mg tablets: round, biconvex, film-coated white tablets with a score line;

20 mg tablets: round, biconvex, film-coated white tablets with a score 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 times 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 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 prolongation (corrected according to Fridericia's formula) from baseline was 4.3 ms (90% CI: 2.2, 6.4) with a 10 mg/day dose and 10.7 ms (90% CI: 8.6, 12.8) with a dose higher than therapeutic – 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 treatment of major depressive episodes during the acute phase 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 over the subsequent 36 weeks compared to those receiving placebo.

Social anxiety disorder

Escitalopram was 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. In a 24-week dose-optimization study, efficacy of escitalopram was demonstrated at doses of 5, 10, and 20 mg.

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 treated with escitalopram and 419 patients receiving placebo, response to treatment was observed 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 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 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 score on the Y-BOCS scale (Yale-Brown Obsessive Compulsive Scale) after 12 weeks of treatment. After 24 weeks, both 10 mg/day and 20 mg/day doses of escitalopram showed advantages over placebo.

The efficacy of the medicinal product in the prevention of 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 is almost complete and independent of food intake. Maximum plasma concentration 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%. Protein binding of escitalopram and its main metabolites to plasma proteins is less than 80%.

Biological transformation

Metabolites are formed in the liver, which are demethylated and didemethylated and are pharmacologically active. Alternatively, nitrogen oxidation may occur, forming an N-oxide metabolite. Both metabolites and the parent compound are partially excreted as glucuronides. After repeated administration, the average concentration of demethyl and didemethyl metabolites typically amounts to 28–31% and < 5%, respectively, of the escitalopram concentration. The biotransformation of escitalopram to the demethylated metabolite occurs primarily via cytochrome CYP2C19. Minor contributions from CYP3A4 and CYP2D6 isoenzymes are possible.

Elimination

The elimination half-life (T1/2β) of the drug is approximately 30 hours. Oral clearance (Cloral) is approximately 0.6 L/min. The main metabolites have longer 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) in elderly subjects is 50% higher than in younger healthy volunteers (see section «Dosage and administration»).

Hepatic impairment

In patients with mild to moderate hepatic dysfunction (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 CYP2C19 metabolic function had plasma escitalopram concentrations 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 treatment with 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 interaction"); 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 interaction").

Escitalopram is contraindicated in patients with known QT interval prolongation or congenital long QT syndrome; escitalopram is contraindicated together with medicinal products known to 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.

Non-selective irreversible MAO inhibitors.

Serious reactions have been reported in patients taking SSRIs in combination with non-selective irreversible MAOIs, and in patients who have recently discontinued SSRIs and started MAOIs (see section "Contraindications"). In some cases, serotonin syndrome developed. The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Escitalopram treatment should be initiated no earlier than 14 days after discontinuation of irreversible MAOI. Treatment with non-selective irreversible MAOIs should not be initiated earlier than 7 days after stopping escitalopram.

Reversible selective MAO-A inhibitor (moclobemide).

Due to the risk of serotonin syndrome, the combination of escitalopram with an MAO-A inhibitor such as moclobemide is contraindicated (see section "Contraindications"). If this combination is 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 therapy is necessary, treatment should be initiated at the lowest doses and under strict 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. An additive effect of concomitant use 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, antipsychotics (e.g., phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g., sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials such as halofantrine), 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 the development of serotonin syndrome.

Medicinal products that lower the seizure threshold.

SSRIs may lower the seizure threshold. Caution is recommended when using concomitantly with medicinal products that lower the seizure threshold, such as antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol.

Lithium, tryptophan.

Since cases of enhanced effects have been reported with concomitant use of SSRIs and lithium or tryptophan, these medicinal products should be prescribed concomitantly with caution.

Hypericum perforatum (St. John's wort).

Concomitant use of SSRIs and herbal preparations containing Hypericum perforatum may lead to an increased frequency of adverse reactions.

Anticoagulants.

Possible changes in the effects of oral anticoagulants may occur with concomitant use of escitalopram. Patients receiving oral anticoagulants require careful monitoring of the coagulation system before and after initiation of 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 interaction with alcohol. However, as with other psychotropic medicinal products, combination with alcohol 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 developing malignant arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions.

Effect of other agents on escitalopram pharmacokinetics. Escitalopram metabolism 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 (desmethyl 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) led to a moderate (approximately 70%) increase in plasma concentration of escitalopram. Caution is recommended when administering escitalopram concomitantly with cimetidine. Dose adjustment may be necessary (see section "Special precautions for use").

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

Effect of escitalopram on the pharmacokinetics of other agents. Escitalopram is an inhibitor of the CYP2D6 enzyme.

Caution is recommended when administering escitalopram concomitantly with medicinal products primarily metabolized by this enzyme and having 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 (desipramine, clomipramine, nortriptyline) and antipsychotics (risperidone, thioridazine, haloperidol). Dose adjustment may be necessary.

Combination with desipramine or metoprolol resulted in a two-fold increase in plasma levels of these two CYP2D6 substrates.

In vitro studies have demonstrated that escitalopram causes weak inhibition of CYP2C19. Caution is recommended when administering 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, increased anxiety may occur at the beginning of treatment with antidepressants. This paradoxical reaction usually resolves within two weeks of treatment. To reduce the likelihood of an anxiogenic effect, low initial doses are recommended (see section "Dosage and administration").

Seizures. The medicinal product should be discontinued if a patient experiences a first seizure or if seizures increase in frequency (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. Doses of insulin and/or oral hypoglycaemic agents may require adjustment.

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 few 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. Additionally, 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 studies using escitalopram revealed an increased risk of suicidal behaviour among patients under 25 years of age taking antidepressants compared to those receiving placebo. Close monitoring of high-risk patients is particularly necessary at the beginning of treatment and when dosage 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 such symptoms develop.

Akathisia/psychomotor restlessness. The use of SSRIs/SNRIs has been associated with the development of akathisia—a condition characterized by an unpleasant, distressing sense of restlessness and a compelling need to move, often accompanied by an inability to sit or stand still. This condition is most likely to occur during the first few weeks of treatment. Increasing the dose may worsen symptoms in patients who develop such reactions.

Hyponatraemia. Hyponatraemia, 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 cautiously in patients at risk (elderly patients, patients with hepatic cirrhosis, or those receiving concomitant medications that may cause hyponatraemia).

Bleeding. Skin bleeding (ecchymosis and purpura) may occur during SSRI treatment. SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections "Use in pregnancy or lactation" and "Adverse reactions"). SSRIs should be used cautiously in patients receiving concomitant anticoagulants or 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.

Electroconvulsive therapy (ECT). 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 medicinal products that have serotonergic activity, such as triptans (including sumatriptan), opioids (including tramadol), and tryptophan.

In patients taking SSRIs concomitantly with serotonergic medicinal products, serotonin syndrome may rarely develop. Escitalopram should be used cautiously with medicinal products having serotonergic activity. The development of serotonin syndrome may be indicated by a combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia. If such a situation occurs, SSRIs and serotonergic medicinal products should be discontinued immediately, and symptomatic treatment initiated.

St. John's wort. Concomitant use of SSRIs and herbal products containing St. John's wort may lead to an increased frequency of adverse reactions (see section "Interaction with other medicinal products and other forms of interaction").

Discontinuation symptoms. Discontinuation symptoms upon stopping treatment, especially abrupt discontinuation, are common. In clinical trials, adverse effects occurred in approximately 25% of patients discontinuing escitalopram and in 15% of those discontinuing placebo. The risk of discontinuation 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, excessive sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most frequently reported reactions. These symptoms are usually mild to moderate in severity, but may be severe in some patients. Symptoms typically emerge within the first few days after discontinuation, although very rare reports describe similar symptoms in patients who accidentally missed a dose. Discontinuation symptoms usually resolve within two weeks, but may persist longer (2–3 months or more) in some patients. Therefore, it is recommended to gradually discontinue escitalopram by reducing the dose over several weeks or months, depending on the patient's condition (see section "Dosage and administration").

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

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

QT interval prolongation. Escitalopram has been shown to cause dose-dependent prolongation of the QT interval. In 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, or in patients with recent acute myocardial infarction or uncompensated 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 prior to treatment initiation, an ECG should be reviewed.

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

Closed-angle glaucoma. SSRIs, including escitalopram, may affect pupil size, resulting in mydriasis. In turn, pupil dilation may lead to narrowing of the anterior chamber angle and, consequently, increased intraocular pressure and precipitation of 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.

Excipients. This medicinal product contains less than 1 mmol of 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.

The medicinal product Escitam® Asino is contraindicated during pregnancy, except in cases where, after careful evaluation of risks and benefits, the necessity of treatment has been clearly established.

Newborns whose mothers have taken Escitam® Asino during pregnancy, particularly in the third trimester, should be carefully monitored. Abrupt discontinuation of the medicinal product during pregnancy should be avoided.

In newborns whose mothers have taken SSRIs/SNRIs during late pregnancy, the following symptoms may occur: respiratory distress, cyanosis, apnoea, seizures, temperature fluctuations, feeding difficulties, vomiting, hypoglycaemia, hypertension or hypotension, hyperreflexia, tremor, nervous agitation, irritability, apathy, persistent crying, somnolence, and sleep disturbances. These symptoms may arise due to either serotonergic effects or may represent signs of withdrawal syndrome. In most cases, complications manifest immediately or shortly (<24 hours) after delivery.

Epidemiological data have shown that SSRI use during pregnancy may increase the risk of persistent pulmonary hypertension in the newborn (up to 5 cases per 1000 pregnancies). In the general population, 1 to 2 cases per 1000 pregnancies occur.

Lactation. Since escitalopram passes into breast milk, breastfeeding is not recommended during treatment.

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

Fertility. Some SSRIs may affect sperm quality. Reports on the use of certain SSRIs have shown that effects on human sperm quality are reversible. Effects on human fertility have not been observed.

Ability to drive and use machines.

In general, escitalopram does not affect intellectual functions or psychomotor performance, but it should be considered that any psychoactive drug may impair skills or the ability to perform tasks requiring sound judgment. Patients should be warned about the potential risk of impaired ability to drive or operate machinery.

Method of Administration and Dosage

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

Escitalopram should be 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 to a maximum of 20 mg.

Antidepressant effect usually occurs 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 subsequently be increased to a 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 the severity of the condition.

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 response, the dose may subsequently be reduced to 5 mg/day or increased to a maximum of 20 mg/day.

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

Long-term treatment for 6 months is recommended to prevent relapse, taking into account individual disease manifestations; treatment efficacy should be regularly assessed.

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

The role of pharmacotherapy relative to cognitive-behavioral therapy has not been evaluated. Pharmacological treatment is one component of an overall treatment 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 per day.

Long-term treatment for 6 months is recommended to prevent relapse, considering individual disease manifestations; treatment efficacy should be regularly assessed.

Obsessive-Compulsive Disorder (OCD).

The usual dose is 10 mg once daily. Depending on individual sensitivity, the dose may be increased to 20 mg per day. OCD is a chronic condition, and 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 evaluated.

Elderly Patients (aged 65 years and older).

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

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

Pediatric Population.

Escitalopram should not be used for the treatment of children and adolescents under 18 years of age.

Renal Impairment.

Dose adjustment is not 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).

Hepatic Impairment.

For patients with mild to moderate hepatic impairment, the recommended initial dose for 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, caution is required in dosing, and careful dose titration is necessary.

Reduced CYP2C19 Isoenzyme Activity.

For patients with poor CYP2C19 isoenzyme activity, the recommended initial dose for 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.

Withdrawal Symptoms upon Discontinuation.

Abrupt discontinuation should be avoided. When stopping treatment with Escitam® Asino, the dose should be gradually reduced over 1–2 weeks to avoid potential withdrawal symptoms (see sections "Special Warnings and Precautions for Use" and "Adverse Reactions"). If withdrawal symptoms occur during gradual dose reduction, the previous prescribed dose may be reinstated. The physician may then continue to reduce the dose, but 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) are observed more frequently in clinical trials among children and adolescents taking 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 ideation is required.

Overdose.

Toxicity. Data on escitalopram overdose are limited. Most cases involve concomitant overdose with other medicinal products. Generally, symptoms are mild or absent. Fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other medicinal products. Ingestion of doses in the range of 400–800 mg of escitalopram has not caused any severe symptoms.

Symptoms. Escitalopram overdose primarily manifests with symptoms affecting 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, arrhythmias), and electrolyte imbalances (hypokalemia, hyponatremia).

Treatment. There is no specific antidote. Maintenance of adequate respiratory function and appropriate oxygenation should be ensured. Gastric lavage and activated charcoal may be used. Continuous cardiac and vital function monitoring, along with symptomatic and supportive treatment, is recommended.

ECG monitoring is recommended in cases of overdose in patients with congestive heart failure/bradyarrhythmia, in patients concurrently taking medicinal products 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 decrease in frequency and intensity with continued therapy.

Adverse reactions observed with SSRIs as a class and with escitalopram in placebo-controlled studies and clinical practice are listed below by system organ class and frequency: 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).

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

Immune system disorders: rare – anaphylactic reactions.

Endocrine system disorders: frequency not known – syndrome of inappropriate 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 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 disturbance, sleep disorder, syncope; rare – serotonin syndrome; frequency not known – dyskinesia, movement disorders, convulsions, 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).

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, swelling.

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 disorder, impotence; uncommon – in women: metrorrhagia, menorrhagia; frequency not known – galactorrhea, postpartum hemorrhage³, in men: priapism.

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

¹ Suicidal thoughts and behavior have been reported during escitalopram treatment or shortly after discontinuation.

² These events are known for the entire SSRI class.

³ These events have been reported for the therapeutic class of SSRIs or SNRIs (see sections "Special Warnings and Precautions for Use", "Use During Pregnancy or Breastfeeding").

QT interval prolongation. Cases of QT interval prolongation and ventricular arrhythmia, including polymorphic ventricular tachycardia (torsade de pointes), have been reported in the post-marketing period, primarily in women, patients with hypokalemia, and patients with pre-existing QT prolongation or other cardiac diseases (see sections "Contraindications", "Special Warnings and Precautions for Use", "Interaction with Other Medicinal Products and Other Forms of Interaction", "Overdose", and "Pharmacodynamics").

Class-specific effects. Epidemiological studies, primarily in patients aged 50 years and older, have shown an increased risk of bone fractures associated with the use of SSRIs, including escitalopram, 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, excessive sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. These symptoms are usually mild to moderate and transient, but in some patients they may be severe and/or prolonged. Therefore, it is recommended that escitalopram treatment be gradually discontinued by dose tapering (see sections "Dosage and Administration", "Special Warnings and Precautions for Use").

Reporting suspected adverse reactions.

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

Shelf life. 3 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; 1, 3, or 6 blisters per cardboard pack.

Prescription status. Prescription only.

Manufacturer. LLC "Pharma Start", Ukraine.

Manufacturer's address and location of business activity.

8 Vatslava Havela Boulevard, Kyiv, 03124, Ukraine.