Escitalopram asino

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Escitalopram Acino (Escitalopram 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;

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

20 mg tablets: white, round, biconvex film-coated tablets with a score line.

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATC code N06A B10.

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 does not bind at all or binds very weakly to a number of receptors, including serotonin 5-HT1A and 5-HT2 receptors, dopamine D1 and D2 receptors, α1-, α2-, β-adrenergic receptors, histamine H1 receptors, muscarinic cholinergic, benzodiazepine, and opioid receptors.

Inhibition of 5-HT reuptake is the sole plausible mechanism of action explaining 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 at a dose of 10 mg/day and 10.7 ms (90% CI: 8.6, 12.8) with a dose higher than therapeutic—30 mg/day (see sections "Contraindications", "Special Warnings and Precautions for Use", "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 receiving escitalopram at the same dose or placebo for up to 36 weeks. In this study, patients who continued receiving escitalopram had a statistically significantly longer time to relapse within 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 designs, 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, while 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 study on treatment maintenance efficacy, which included 373 patients who responded to the drug during an initial 12-week open-label treatment phase.

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 (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 with 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 of escitalopram is nearly complete and is not affected by 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 is approximately 12 to 26 L/kg. The bioavailability of escitalopram is approximately 80%. Protein binding of escitalopram and its main metabolites is less than 80%.

Biotransformation

Metabolism occurs in the liver to demethylated and didemethylated metabolites. Both are pharmacologically active. Nitrogen oxidation to form an N-oxide metabolite is also possible. Both the parent compound and metabolites are partially excreted as glucuronides. With repeated dosing, mean concentrations of the demethylated and didemethylated metabolites typically amount to 28–31% and < 5%, respectively, of escitalopram concentration. Biotransformation of escitalopram to the demethylated metabolite is primarily mediated by CYP2C19. Some contribution of CYP3A4 and CYP2D6 enzymes to this process is 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 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 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.

Elderly Patients

In patients aged 65 years and older, escitalopram is eliminated more slowly than in younger patients. Systemic exposure (AUC) in healthy elderly volunteers is approximately 50% higher than in young 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 (creatinine clearance [CrCl] 10–53 mL/min) receiving racemic citalopram, a longer elimination half-life and slightly increased exposure were observed. Plasma metabolite concentrations have not been studied but may be elevated (see section "Dosage and Administration").

Polymorphism

Patients with poor CYP2C19 metabolic function had twice the plasma concentration of escitalopram compared to patients with normal CYP2C19 function. No significant changes in exposure were observed with reduced CYP2D6 function (see section "Dosage and Administration").

Clinical characteristics

Indications

For the treatment of major depressive episodes, panic disorders with or without agoraphobia, social anxiety disorders (social phobia), generalized anxiety disorders, and 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, which may manifest with agitation, tremor, hyperthermia, and other symptoms (see section "Interaction with other medicinal products and other forms of interaction").

Combination of escitalopram with reversible inhibitors of monoamine oxidase A (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.

Concomitant use of escitalopram with medicinal products capable of prolonging the QT interval is contraindicated (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 MAOIs. Serious reactions have been reported in patients taking SSRIs in combination with non-selective irreversible MAOIs, as well as in patients who recently discontinued SSRI treatment and started MAOIs (see section "Contraindications"). In some cases, serotonin syndrome developed (see section "Adverse reactions"). 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 therapy. Non-selective irreversible MAOI therapy should not be initiated earlier than 7 days after discontinuation of escitalopram.

Reversible selective MAOI type A (moclobemide). Due to the risk of serotonin syndrome, the combination of escitalopram with the MAOI type A moclobemide is contraindicated (see section "Contraindications"). If combination therapy is deemed necessary, the lowest recommended doses should be used with enhanced clinical monitoring.

Reversible non-selective MAO inhibitor (linezolid). The antibiotic linezolid is a reversible non-selective MAO inhibitor and should not be administered to patients receiving escitalopram. If such a combination is necessary, the minimum doses of both medicinal products should be used under strict clinical supervision (see section "Contraindications").

Selective irreversible MAO inhibitor type B (selegiline). Combination with selegiline (an 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 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), and certain antihistamines (astemizole, hydroxyzine, mizolastine), is contraindicated.

Combinations requiring caution

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

Medicinal products that lower the seizure threshold. SSRIs may lower the seizure threshold. Caution is recommended when combining SSRIs with medicinal products that may reduce the seizure threshold (e.g., 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, concomitant administration of these medicinal products with escitalopram should be done with caution.

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

Anticoagulants. The effects of anticoagulants may be altered when used concomitantly with escitalopram. If patients are taking oral anticoagulants, careful monitoring of the coagulation system should be performed before and during escitalopram treatment (see section "Special precautions for use").

Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) 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 hypokalaemia/hypomagnesaemia. Caution should be exercised when using medicinal products capable of inducing hypokalaemia/hypomagnesaemia concomitantly, as this may increase the risk of developing malignant arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions

Effect of other agents on the pharmacokinetics of escitalopram

Escitalopram metabolism is primarily mediated by CYP2C19. Enzymes CYP3A4 and CYP2D6 may also play a minor role in its metabolism. The metabolism of the main metabolite S-DCT (desmethyl escitalopram) appears to be partially catalyzed by CYP2D6.

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

Concomitant use of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) caused a moderate (approximately 70%) increase in escitalopram plasma concentration. Caution should be exercised when combining escitalopram with cimetidine. Dose adjustment may be necessary (see section "Special precautions for use").

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

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 (desipramine, clomipramine, nortriptyline) and antipsychotics (risperidone, thioridazine, haloperidol). Dose adjustment may be necessary.

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

In vitro studies have demonstrated that escitalopram may also cause slight 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 class of selective serotonin reuptake inhibitors (SSRIs).

Paradoxical anxiety

Some patients with panic disorders may experience increased anxiety 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, a low initial dose is recommended (see section "Dosage and administration").

Seizures

Treatment with escitalopram should be discontinued if a patient develops a first seizure or increased seizure frequency (in patients with established epilepsy diagnosis). 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. If a manic state occurs, SSRIs should be discontinued.

Diabetes

In patients with diabetes mellitus, treatment with SSRIs may alter glycaemic control. The dose of insulin and/or oral hypoglycaemic agents may require adjustment.

Suicidality, 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 starting treatment are at the highest risk of suicidal thoughts or attempts and require close monitoring throughout treatment. A meta-analysis of clinical trials has shown an increased risk of suicidal behaviour in patients under 25 years of age treated with antidepressants compared to those receiving placebo. Close monitoring of high-risk patients is particularly important at the beginning of treatment and when the dose is changed.

Patients and their caregivers should be warned to monitor for any worsening of symptoms, suicidal behaviour or thoughts, and unusual changes in behaviour, and to seek immediate medical advice if such symptoms occur.

Akathisia / psychomotor agitation

The use of SSRIs / SNRIs (serotonin-norepinephrine reuptake inhibitors) 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 symptoms.

Hyponatraemia

Hyponatraemia, possibly related to impaired secretion of antidiuretic hormone, has been rarely reported during SSRI treatment and usually resolves after discontinuation of therapy. SSRIs should be used with caution in patients at risk (elderly patients, patients with hepatic cirrhosis, or those receiving concomitant medications that may cause hyponatraemia).

Bleeding

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

Electroconvulsive therapy (ECT)

Clinical experience with the 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.

Serotonin syndrome has been reported in isolated cases in patients receiving SSRIs together with other serotonergic drugs. Escitalopram should be used cautiously with other serotonergic agents. The combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. In such cases, treatment with the SSRI and the serotonergic agent should be discontinued immediately, and symptomatic treatment should be initiated.

St. John's wort

Concomitant use of SSRIs and herbal preparations containing St. John's wort 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 reactions during discontinuation occurred in approximately 25% of patients receiving escitalopram and in 15% of patients receiving placebo.

The risk of withdrawal symptoms may depend on several factors, including duration and dose of treatment, and the rate 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 commonly reported reactions. These symptoms are usually mild or moderate in severity, but may be severe in some patients. They typically occur within the first few days after discontinuation of treatment, although very rare reports of such symptoms have occurred in patients who accidentally missed a dose. Withdrawal symptoms usually resolve within 2 weeks, but may be prolonged (2–3 months or longer) in some patients. Therefore, it is recommended that treatment with escitalopram be gradually discontinued by reducing the dose over several weeks or months, depending on the patient's condition (see section "Dosage and administration").

Sexual dysfunction

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

Ischaemic heart disease

Due to limited clinical experience, caution is recommended when using the medicinal product in patients with ischaemic heart disease.

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 women, patients with hypokalaemia, and patients with pre-existing QT interval prolongation or other cardiac diseases (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 and in patients with recent acute myocardial infarction or decompensated heart failure.

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

In patients with stable cardiac disease, a thorough assessment of ECG parameters should be performed before initiating escitalopram treatment.

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

Closed-angle glaucoma

SSRIs, including escitalopram, may affect pupil size, leading to mydriasis. This mydriatic effect may narrow the angle of the eye, resulting in increased intraocular pressure and closed-angle glaucoma, particularly in predisposed 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) per tablet, 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 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, particularly in the third trimester, should be carefully monitored. Abrupt discontinuation of the drug during pregnancy should be avoided.

Newborns whose mothers have taken SSRIs/SNRIs in late pregnancy may experience symptoms such as respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, lethargy, persistent crying, somnolence, and sleep disturbances. These symptoms may be due to serotonergic effects or may represent withdrawal symptoms. In most cases, such complications occur immediately or shortly (within 24 hours) after delivery.

Epidemiological data suggest that the use of SSRIs during pregnancy may increase the risk of persistent pulmonary hypertension in newborns (up to 5 cases per 1000 pregnancies, according to observational data). In the general population, the incidence is 1 to 2 cases per 1000 pregnancies.

Breastfeeding. Since escitalopram is excreted in breast milk, breastfeeding is not recommended during treatment.

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

Fertility. Animal studies have shown that escitalopram may affect sperm quality. According to reports on the use of some SSRIs, the effect on sperm quality appears to be reversible. No effect on human fertility has been observed to date.

Ability to drive and use machines

Although escitalopram does not affect intellectual or psychomotor performance, any psychoactive drug may impair skills or the ability to think rationally. Patients should be warned about the potential effect on the 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 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 to the maximum of 20 mg.

Antidepressant effect usually occurs within 2–4 weeks. After symptom remission, treatment should be continued for at least 6 months to consolidate the therapeutic effect.

Panic Disorders, with or without Agoraphobia

A starting dose of 5 mg per day is recommended during the first week before increasing to 10 mg per day. The dose may subsequently be increased up to the maximum of 20 mg per day, depending on individual patient sensitivity.

Maximum therapeutic effect in panic disorders is achieved after 3 months. The duration of treatment lasts several months and depends on disease severity.

Social Anxiety Disorders (Social Phobia)

The usual dose is 10 mg once daily. Symptom relief generally requires 2–4 weeks of therapy. Thereafter, depending on individual patient response, the dose may be reduced to 5 mg or increased up to the maximum of 20 mg per day. Social anxiety disorder is a chronic condition, and treatment should be continued for 12 weeks to consolidate the effect.

Long-term treatment for 6 months has been shown to prevent relapse and may be prescribed individually; benefits of treatment 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 activities.

The value of this treatment compared to cognitive-behavioral therapy has not been assessed. Pharmacotherapy is one component of an overall treatment strategy for the patient.

Generalized Anxiety Disorders

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 has been studied for at least 6 months in patients receiving a dose of 20 mg per day; treatment benefits should be regularly evaluated (see section "Pharmacodynamics").

Obsessive-Compulsive Disorders (OCD)

The usual initial 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; 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 (see section "Pharmacodynamics").

Elderly Patients (aged 65 years and older)

The initial dose is 5 mg per day. Depending on individual sensitivity and severity of depression, the daily dose may be increased up to a maximum of 10 mg per day (see section "Pharmacokinetics").

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) (see section "Special Warnings and Precautions for Use").

Renal Impairment

No dosage adjustments are required in patients with mild to moderate renal impairment. Caution is advised when administering the drug to patients with severe renal impairment (creatinine clearance <30 mL/min) (see section "Pharmacokinetics").

Hepatic Impairment

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

Reduced CYP2C19 Isoenzyme Activity

For patients with low 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 (see section "Pharmacokinetics").

Withdrawal Symptoms upon Discontinuation

Abrupt discontinuation of the drug should be avoided. When stopping treatment with escitalopram, the dose should be gradually reduced over at least 1–2 weeks to minimize the risk of withdrawal symptoms (see sections "Special Warnings and Precautions for Use" and "Undesirable Effects"). If intolerable symptoms occur after dose reduction or discontinuation, re-institution of the previously prescribed dose may be considered. Thereafter, the physician may continue tapering 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 (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) have been observed more frequently in clinical trials among children and adolescents receiving antidepressants compared to those receiving placebo. If a clinical decision to prescribe is made, careful monitoring for the emergence of suicidal symptoms is essential.

Overdose

Toxicity. Clinical data on escitalopram overdose are limited. Many cases involve concomitant overdose with other drugs. Mild symptoms or asymptomatic overdose are most commonly observed. Reports of fatal outcomes following escitalopram overdose are extremely rare, and most cases involve concomitant overdose with other medications. Doses of escitalopram ranging from 400–800 mg have not caused severe symptoms.

Symptoms. Signs of escitalopram overdose are primarily related to 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 fluid/electrolyte imbalance (hypokalemia, hyponatremia).

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

In cases of overdose, ECG monitoring is recommended for patients with congestive heart failure/bradyarrhythmias, patients concurrently taking drugs that prolong the QT interval, and patients with impaired drug metabolism, such as those with hepatic impairment.

Adverse Reactions

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

Adverse reactions known for SSRIs and escitalopram, observed during placebo-controlled studies and post-marketing use, are listed below by system organ class and frequency. 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).

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

Immune system disorders: rare — anaphylactic reactions.

Endocrine disorders: frequency not known — disorders of antidiuretic hormone secretion, hyperprolactinemia.

Metabolism and nutrition disorders: common — decreased or increased appetite, weight gain; uncommon — weight loss; frequency not known — hyponatremia, anorexia^2.

Psychiatric disorders: common — anxiety, restlessness, abnormal dreams, decreased libido in males and females, anorgasmia in females; uncommon — bruxism, agitation, nervousness, panic attacks, confusion; rare — aggression, depersonalization, hallucinations; frequency not known — mania, suicidal thoughts, suicidal behaviour^1.

Nervous system disorders: very common — headache; common — insomnia, somnolence, dizziness, paraesthesia, tremor; uncommon — taste disturbance, sleep disorders, syncope; rare — serotonin syndrome; frequency not known — dyskinesia, movement disorders, seizures, psychomotor restlessness/akathisia^2.

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 system disorders: common — sinusitis, yawning; uncommon — epistaxis.

Gastrointestinal disorders: very common — nausea; common — diarrhoea, constipation, vomiting, dry mouth; uncommon — gastrointestinal haemorrhage (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, oedema.

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

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

Reproductive system and breast disorders: common — in males: ejaculation disorder, impotence; uncommon — in females: metrorrhagia, menorrhagia; frequency not known — galactorrhea, postpartum haemorrhage^3, in males — priapism.

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

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

^2 These adverse reactions are generally typical for SSRIs.

^3 These adverse reactions occurred during use of SSRIs/SSRIsN (see sections "Special Warnings and Precautions for Use" and "Use in Pregnancy and Lactation").

QT interval prolongation. During the post-marketing period, cases of QT interval prolongation and ventricular arrhythmia, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in women, patients with hypokalemia, and patients with pre-existing QT interval 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 effects of SSRIs. 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) is usually associated with 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, diarrhoea, 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 to gradually discontinue escitalopram treatment by dose reduction (see sections "Dosage and Administration" and "Special Warnings and Precautions for Use").

Reporting of suspected adverse reactions

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

Shelf life. 3 years.

Storage conditions. Store in a place inaccessible to children, in the original packaging, at a temperature not exceeding 25 °C.

Packaging. 10 tablets in a blister; 1, 3, or 6 blisters in a cardboard pack.

Prescription status. Prescription only.

Manufacturer: LLC "Pharma Start".

Manufacturer's address and location of business activity.
8 Vatslava Havela Boulevard, Kyiv, 03124, Ukraine.

Marketing Authorisation Holder:
LLC "ASINO UKRAINE".

Address of Marketing Authorisation Holder:
8 Vatslava Havela Boulevard, Kyiv, 03124, Ukraine.

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