Citapra

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT CYTAPRA (CITAPRA)

Composition:

Active substance: escitalopram;

1 tablet contains 12.78 mg of escitalopram oxalate, equivalent to 10 mg of escitalopram;

1 tablet contains 25.55 mg of escitalopram oxalate, equivalent to 20 mg of escitalopram;

Excipients: colloidal anhydrous silicon dioxide, lactose monohydrate, povidone, microcrystalline cellulose, sodium croscarmellose, talc, magnesium stearate, Opadry Y-1-7000 (hypromellose, titanium dioxide (E 171), polyethylene glycol 400).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

10 mg tablets: white, cylindrical, biconvex film-coated tablets with a score line, marked with the code «ES1»;

20 mg tablets: white, cylindrical, biconvex film-coated tablets with a score line, marked with the code «ES3».

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 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 prolongation (corrected according to Fridericia's formula) from baseline was 4.3 ms (90% CI: 2.2, 6.4) with a dose of 10 mg/day and 10.7 ms (90% CI: 8.6, 12.8) with a 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 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 a dose of 10 or 20 mg/day during the 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 and in a 6-month relapse prevention study. In a 24-week optimal dose 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, 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 study involving 373 patients who responded to the drug during the 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, advantages of escitalopram use were observed both at a dose of 10 mg/day and 20 mg/day compared to placebo.

The efficacy of escitalopram in preventing relapses was demonstrated 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 is 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, ß/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%.

Biological transformation. Metabolism occurs in the liver, forming demethylated and didemethylated metabolites. Both are pharmacologically active. Alternatively, nitrogen oxidation may occur, forming an N-oxide metabolite. Both the parent compound and metabolites are partially excreted as glucuronides. After repeated administration, mean concentrations of demethylated and didemethylated metabolites typically amount to 28–31% and <5% of escitalopram concentration, respectively. The biotransformation of escitalopram to the demethylated metabolite is mediated by cytochrome CYP2C19. Minor involvement of isoenzymes CYP3A4 and CYP2D6 in this process is possible.

Elimination. The elimination half-life (t½) of the drug is approximately 30 hours. Oral clearance (Cloral) is approximately 0.6 L/min. The main metabolites have a longer half-life. 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. 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 healthy young volunteers (see section «Dosage and administration»).

Hepatic impairment. In patients with mild to moderate hepatic dysfunction (Child-Pugh classes A and B), elimination half-life was twice as long and exposure 6% higher than in individuals with normal liver function (see section «Dosage and administration»).

Renal impairment. In patients with impaired renal function (creatinine clearance 10–53 mL/min), prolonged elimination half-life and slightly increased exposure were observed with racemic citalopram. Plasma metabolite concentrations have not been studied but may be elevated (see section «Dosage and administration»).

Polymorphism. Patients with poor metabolic function of CYP2C19 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;
• 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 developing serotonin syndrome with agitation, tremor, hyperthermia, and other symptoms (see section "Interaction with other medicinal products and other types of interactions").

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

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

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

Interaction with other medicinal products and other types of interactions.

Pharmacodynamic interactions

Contraindicated combinations

Non-selective irreversible MAOIs. 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 MAOI treatment (see section "Contraindications"). In some cases, serotonin syndrome developed (see section "Adverse reactions"). The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Treatment with escitalopram should not be initiated earlier than 14 days after discontinuation of irreversible MAOIs. Treatment with non-selective irreversible MAOIs should not be initiated earlier than 7 days after discontinuation of escitalopram.

Reversible selective MAO-A inhibitor (moclobemide). Due to the risk of serotonin syndrome, the 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 under careful clinical monitoring.

Non-selective reversible MAO inhibitor (linezolid). The antibiotic linezolid is a non-selective reversible MAO inhibitor and should not be prescribed to patients receiving escitalopram. If such a combination is necessary, minimal doses of both drugs should be used under strict clinical supervision (see section "Contraindications").

Selective irreversible 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 in combination with racemic citalopram.

QT interval prolongation. Pharmacokinetic and pharmacodynamic studies of combined use of escitalopram with other medicinal products that prolong the QT interval have not been conducted. An additive effect cannot be excluded when escitalopram is used concomitantly with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, antipsychotics (e.g., phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g., sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials including halofantrine), certain antihistamines (astemizole, hydroxyzine, mizolastine). Therefore, concomitant use of escitalopram with such medicinal products 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 co-administering with agents that may reduce the seizure threshold (e.g., 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 agents should be co-administered with caution.

St. John’s wort. Concomitant use of SSRIs and herbal preparations containing St. John’s wort may increase the frequency of adverse reactions.

Anticoagulants. Effects of anticoagulants may be altered when used concomitantly with escitalopram. If patients are taking oral anticoagulants, careful monitoring of the coagulation system is required 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 interactions with alcohol. However, combination with alcohol is not recommended.

Drugs causing hypokalemia/hypomagnesemia. Use with caution in combination with agents that cause hypokalemia/hypomagnesemia, as these conditions increase the risk of malignant arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions

Effect of other agents on escitalopram pharmacokinetics

Metabolism of escitalopram is primarily mediated by CYP2C19. CYP3A4 and CYP2D6 enzymes may also play a minor role in its metabolism. The metabolism of the main metabolite S-DCIT (demethylated 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 plasma escitalopram concentrations. Concomitant use of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) leads to a moderate (approximately 70%) increase in plasma escitalopram concentrations. Caution is advised when combining escitalopram with cimetidine. Dose adjustment may be necessary (see section "Special precautions for use").

Thus, caution is required when escitalopram is used 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 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 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 two CYP2D6 substrates.

In vitro studies have demonstrated that escitalopram may also cause slight inhibition of CYP2C19.

Caution is recommended when escitalopram is used 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. Es-citalopram should be discontinued if a patient experiences a first seizure or increased seizure frequency (in patients with established epilepsy diagnosis). SSRIs should be avoided in patients with unstable epilepsy, and close monitoring is required in patients with controlled epilepsy.

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

Diabetes mellitus. In patients with diabetes mellitus, treatment with SSRIs may alter glycaemic control. The dose 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 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 necessary at the beginning of treatment and when the dose is changed.

Patients and their 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 advice if such symptoms occur.

Akathisia / psychomotor agitation. The use of SSRIs/SSNRI 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 is most likely to occur during the first few weeks of treatment. Increasing the dose may worsen symptoms in patients who develop such reactions.

Hyponatremia. Hyponatremia, possibly related to impaired secretion of antidiuretic hormone (SIADH), has been reported rarely with SSRIs and usually resolves after discontinuation of therapy. SSRIs should be prescribed with caution in patients at risk (elderly patients, those with liver cirrhosis, or those receiving concomitant medications that can cause hyponatremia).

Bleeding. Skin bleeding, ecchymoses, and purpura may occur during SSRI treatment. SSRIs/SSNRIs may increase the risk of postpartum haemorrhage (see sections "Use in pregnancy or breast-feeding" 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 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 taking SSRIs together with serotonergic drugs. Escitalopram should be used with caution in combination with medicinal products having serotonergic activity. A combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. In such cases, the SSRI and the serotonergic agent 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 reactions during discontinuation occurred in approximately 25% of patients receiving escitalopram and in 15% of patients receiving placebo.

The risk of discontinuation symptoms depends on several factors, including duration of treatment and dose, 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 to moderate in severity and resolve within 2 weeks, although they may be more prolonged (2–3 months or longer) in some patients. Therefore, it is recommended to gradually discontinue escitalopram treatment 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"). There have been reports of persistent sexual dysfunction, where symptoms continued despite discontinuation of SSRIs/SNRIs.

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 arrhythmia, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in women, patients with hypokalaemia, and patients with pre-existing QT prolongation or other cardiac diseases (see sections "Contraindications", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", "Overdose", and "Pharmacodynamics").

Caution is recommended in patients with pronounced 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 starting escitalopram treatment.

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, 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 lactose. Therefore, it should not be used in patients with hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.

This medicinal product contains less than 23 mg of sodium (1 mmol) per tablet; i.e., it is practically sodium-free.

Use during pregnancy or breast-feeding.

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 using the medicinal product. Newborns of mothers who have taken escitalopram during pregnancy, especially in the third trimester, should be carefully monitored. Abrupt discontinuation of the drug 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 instability, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, apathy, 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 have shown that the use of SSRIs during pregnancy increases the risk of persistent pulmonary hypertension in the newborn (up to 5 cases per 1000 pregnancies, based on observational data). In the general population, 1 to 2 cases per 1000 pregnancies occur. Observational data indicate an increased risk (by < 2 times) of postpartum haemorrhage following exposure to SSRIs/SNRIs within one month before delivery (see sections "Adverse reactions" and "Special precautions for use").

Breast-feeding. Since escitalopram passes into breast milk, breast-feeding is not recommended during treatment.

Fertility. Animal studies have shown that some SSRIs may affect sperm quality. Reports on the use of some SSRIs in humans have indicated that the effect on sperm quality is 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 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.

The medicinal product 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 up 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 disorder with or without agoraphobia. During the first week, an initial dose of 5 mg per day is recommended before increasing to 10 mg per day. Subsequently, the dose may be increased up to the maximum of 20 mg per day, depending on individual patient sensitivity.

Maximum therapeutic effect in panic disorder treatment is achieved within 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. Usually, 2–4 weeks of therapy are required to alleviate symptoms. 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 therapeutic effect.

Long-term treatment for 6 months has been shown to prevent relapse and may be prescribed individually; the 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 and social functioning.

The relative efficacy of pharmacotherapy compared to cognitive-behavioral therapy has not been evaluated. Pharmacotherapy is one component of a comprehensive 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.

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

Obsessive-compulsive disorder (OCD). The usual dose is 10 mg once daily. Depending on individual sensitivity, the dose may be increased up 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.

Elderly patients (aged 65 years and older). The initial dose should be half the usual recommended dose. The recommended daily dose for elderly patients is 5 mg. Depending on individual sensitivity and severity of depression, the daily dose may be increased up to a maximum of 10 mg per day.

Renal impairment. No dosage adjustments are required in patients with mild to moderate renal impairment. The medicinal product should be used with caution in patients with severe renal impairment (creatinine clearance < 30 mL/min).

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.

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.

Discontinuation of treatment. When discontinuing treatment, the dose should be gradually reduced over 1–2 weeks to avoid possible withdrawal symptoms.

Children

Antidepressants are contraindicated for use in children. Suicidal behavior (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) have been observed more frequently in children and adolescents receiving antidepressants compared to those receiving placebo in clinical trials. If, based on clinical judgment, a decision to prescribe the medicinal product 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 medicinal products. Most reported cases have been associated with mild symptoms or asymptomatic overdose. Fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other medications. Doses of escitalopram ranging from 400–800 mg have not caused severe symptoms.

Symptoms. Signs of escitalopram overdose primarily include effects on 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, arrhythmia), and fluid/electroly imbalance (hypokalemia, hyponatremia).

Treatment. There is no specific antidote. Ensure adequate respiratory function and provide adequate oxygenation. 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 medicinal products 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 treatment.

Adverse reactions of SSRIs and escitalopram observed in placebo-controlled studies and during post-marketing use are listed below by system organ classes and frequency in the table. 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 the available data).

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

2 Such cases have been observed with drugs of the SSRI class.

3 Cases have been reported for the therapeutic class of SSRIs or SNRI-SSRIs (see sections "Use during pregnancy or breastfeeding", "Special precautions for use").

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 interval prolongation or other cardiac diseases (see sections "Contraindications", "Special precautions for use", "Interaction with other medicinal products and other forms of interaction", "Overdose", and "Pharmacodynamics").

Class effects. Epidemiological studies have demonstrated an increased risk of bone fractures associated with the use of SSRIs and tricyclic antidepressants, particularly in patients aged 50 years and older. The mechanism leading to this increased risk is currently unknown.

Withdrawal symptoms. Discontinuation of SSRIs (especially abrupt discontinuation) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paresthesia 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 in severity and transient; however, they may be severe and/or prolonged in some patients.

Therefore, it is recommended to gradually reduce the dose when discontinuing escitalopram (see sections "Dosage and administration" and "Special precautions for use").

Reporting suspected adverse reactions. Reporting of suspected adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua .

Shelf life. 30 months.

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

Keep out of reach of children.

Packaging. Film-coated tablets, 10 mg or 20 mg; 7 tablets per blister; 4 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer. LABORATORIOS CINFA S.A. / LABORATORIOS CINFA S.A.

Manufacturer's address and location of operations.

Poligono Industrial Areta Carretera Olaz Chipi 10, Huarte, 31620, Spain / Poligono Industrial Areta Carretera Olaz Chipi 10, Huarte, 31620, Spain.