Feliz c

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FELIZ S

Composition:

Active substance: escitalopram;

One tablet contains escitalopram oxalate equivalent to escitalopram 10 mg;
Excipients: microcrystalline cellulose, sodium croscarmellose, povidone K-30, colloidal anhydrous silicon dioxide, talc, magnesium stearate, hydroxypropylmethylcellulose, polyethylene glycol 400, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: round, biconvex film-coated tablets, white to almost white, with a break line on both sides dividing the imprints «11» and «36» on one side and «10» on the other.

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 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 volunteers, QTc interval prolongation (corrected using Fridericia’s formula) from baseline was 4.3 ms (90% CI: 2.2; 6.4) with escitalopram 10 mg daily, and 10.7 ms (90% CI: 8.6; 12.8) with a supratherapeutic dose of 30 mg daily (see sections “Contraindications”, “Interaction with other medicinal products and other types of interactions”, “Special warnings and precautions for use”, “Overdose”, “Adverse reactions”).

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 mg or 20 mg daily during an initial 8-week open-label phase were randomized to continue escitalopram at the same dose or 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 demonstrated efficacy 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 mg, 10 mg, and 20 mg daily.

Generalized anxiety disorder.

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

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

The maintenance effect of escitalopram 20 mg daily 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 phase.

Obsessive-compulsive disorder.

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

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

Pharmacokinetics.

Absorption is nearly complete and is independent of food intake. Maximum plasma concentration (Tmax) is reached within 4 hours after administration.

As with racemic citalopram, the absolute bioavailability of escitalopram is expected to be approximately 80%.

Distribution.

The apparent volume of distribution (Vd,β/F) after oral administration 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, producing 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. With repeated dosing, mean concentrations of the demethylated and didemethylated metabolites typically amount to 28–31% and <5% of escitalopram concentration, respectively. The biotransformation of escitalopram to the demethylated metabolite is primarily mediated by CYP2C19. Some involvement of CYP3A4 and CYP2D6 enzymes in 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 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 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 elderly healthy volunteers is approximately 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 AUC 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 metabolite concentrations 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 use of non-selective irreversible monoamine oxidase inhibitors (MAO inhibitors), e.g. moclobemide, or the reversible non-selective MAO inhibitor linezolid, due to the risk of developing serotonin syndrome, which manifests as agitation, tremor, and hyperthermia (see section "Interaction with other medicinal products and other types of interactions"). Prolongation of the QT interval or congenital long QT syndrome. Concomitant use with medicinal products that prolong the QT interval and with pimozide. Escitalopram is contraindicated for concomitant use with medicinal products capable of prolonging the QT interval (see section "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Pharmacodynamic interactions.

Contraindicated combinations.

Non-selective irreversible MAO inhibitors.

Serious reactions have been reported in patients taking SSRIs in combination with non-selective irreversible MAO inhibitors, as well as in patients who recently discontinued SSRI treatment and started taking an MAO inhibitor. In some cases, serotonin syndrome developed. The combination of escitalopram with non-selective irreversible MAO inhibitors is contraindicated. Escitalopram treatment should be initiated no earlier than 14 days after discontinuation of an irreversible MAO inhibitor. Treatment with non-selective irreversible MAO inhibitors should not be initiated earlier than 7 days after stopping escitalopram.

Pimozide. The combination of pimozide and racemic citalopram resulted in an average QTc interval prolongation of approximately 10 msec. Due to the interaction between escitalopram and low doses of pimozide, and the enhanced adverse effects of the latter, concomitant use of these medicinal products is contraindicated.

Prolongation of the QT interval.

Pharmacokinetic and pharmacodynamic studies of escitalopram in combination with other medicinal products that increase the QT interval have not been conducted. A cumulative effect 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, neuroleptics (e.g., phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g., sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarial drugs including halofantrine), certain antihistamines (astemizole, mizolastine), is contraindicated.

Combinations requiring caution.

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. If combination therapy is necessary, treatment should be initiated with the minimum recommended doses and under careful clinical monitoring. Linezolid, an antibiotic, is not recommended for administration to patients taking escitalopram. If such a combination is necessary, treatment should be initiated at the minimum recommended dose with mandatory careful clinical monitoring.

Selegiline. Combination with selegiline (an irreversible MAO-B inhibitor) requires caution due to the risk of serotonin syndrome. There is experience with safe combination of selegiline at doses up to 10 mg daily with racemic citalopram.

Serotonergic agents. Concomitant use with serotonergic medicinal products (e.g., tramadol, sumatriptan, and other triptans) 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 medicinal products that lower the seizure threshold concomitantly, such as antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mephenoxalone, 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 used concomitantly with caution.

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

Anticoagulants. Effects of oral anticoagulants may change due to concomitant use with escitalopram. Patients taking oral anticoagulants require careful monitoring of the coagulation system before and after initiation of escitalopram.

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of bleeding.

Alcohol. Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interaction with alcohol. However, as with other psychoactive 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 may increase the risk of developing malignant arrhythmias.

Pharmacokinetic interactions.

Effect of other medicinal products on escitalopram pharmacokinetics.

The metabolism of escitalopram is primarily mediated by CYP2C19. Enzymes CYP3A4 and CYP2D6 may also be involved in metabolism, although to a lesser extent. The isoenzyme CYP2D6 is considered a partial catalyst in the metabolism of the main metabolite S-DCT (demethylated escitalopram).

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

Concomitant administration of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) increases the plasma concentration of escitalopram by approximately 70%.

Therefore, caution is required when using escitalopram concomitantly with CYP2C19 inhibitors (e.g., omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or with cimetidine. Dose reduction of escitalopram may be necessary when used concomitantly with the aforementioned medicinal products.

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

Caution is recommended when using escitalopram 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 central nervous system (CNS) acting medicinal products primarily metabolized by CYP2D6, such as antidepressants like desipramine, clomipramine, and nortriptyline, and antipsychotics such as risperidone, thioridazine, and haloperidol. Dose adjustment may be necessary. Combination with desipramine or metoprolol resulted in a twofold increase in plasma levels of these two medicinal products.

Caution is recommended when using this medicinal product concomitantly with medicinal products metabolized by CYP2C19.

Special precautions for use.

The special precautions mentioned below apply to the therapeutic group of SSRIs.

Paediatric population.

Escitalopram should not be used for the treatment of children. Suicidal behaviour (suicidal attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behaviour, and anger) have been observed more frequently in clinical trials among children receiving antidepressants compared to those receiving placebo. If treatment is nevertheless initiated based on clinical need, careful monitoring for the emergence of suicidal symptoms is required. Furthermore, long-term safety data on growth, maturation, and cognitive and behavioural development in the paediatric population are lacking.

Paradoxical anxiety. In some patients with panic disorders, increased anxiety may occur at the beginning of SSRI treatment. This paradoxical reaction usually resolves within two weeks of treatment. To reduce the likelihood of an anxiogenic effect, low initial doses are recommended.

Seizures. The medicinal product should be discontinued if a seizure occurs for the first time or if seizures increase in 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 (hypoglycaemia or hyperglycaemia). The dosage 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. Suicide risk may increase during the early stages of recovery. Other conditions for which escitalopram is used may also be associated with a risk of suicidal behaviour. Moreover, 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 have the highest risk of suicidal thoughts or 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 receiving 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 caregivers should be advised to monitor for any worsening of symptoms, suicidal behaviour or thoughts, and unusual changes in behaviour, and to seek immediate medical attention if these symptoms develop.

Akathisia. The use of SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) has been associated with the development of akathisia – a condition characterised 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 during the first few weeks of treatment. Increasing the dose may worsen symptoms in patients who develop such symptoms.

Hyponatraemia. Hyponatraemia, possibly related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), occurs rarely with SSRI use and usually resolves after discontinuation of therapy. SSRIs should be used with caution in patients at risk (elderly patients, patients with liver cirrhosis, or those taking concomitant medications that may cause hyponatraemia).

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

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 contraindicated due to the risk of serotonin syndrome.

Serotonin syndrome. Caution is advised when escitalopram is used concomitantly with serotonergic medicinal products such as sumatriptan or other triptans, tramadol, and tryptophan.

In patients taking SSRIs together with serotonergic medicinal products, serotonin syndrome may rarely develop. Symptoms suggestive of serotonin syndrome include 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 medicinal products containing St. John’s wort may lead to an increased frequency of adverse reactions.

Withdrawal symptoms. Withdrawal symptoms upon discontinuation of treatment, especially abrupt discontinuation, are common. In studies, adverse reactions occurred in approximately 25% of patients discontinuing escitalopram and in 15% of patients discontinuing placebo. The risk of withdrawal symptoms may depend on several factors, including duration and dose of treatment, and the speed of dose reduction. Dizziness, sensory disturbances (including paraesthesia, electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. These symptoms are usually mild to moderate in severity but may be severe in some patients. They typically occur within the first few days after discontinuation of treatment, although very rare reports exist of similar symptoms in patients who accidentally missed a dose. Withdrawal symptoms usually resolve within 2 weeks, but in some patients may persist longer (2–3 months or more). Therefore, it is recommended that escitalopram treatment be gradually discontinued by reducing the dose over several weeks or months, depending on the patient's condition.

Sexual dysfunction. 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 coronary heart disease.

QT interval prolongation. Escitalopram has been shown to cause dose-dependent QT interval prolongation. Cases of QT interval prolongation and ventricular arrhythmia, including torsade de pointes, have been reported, primarily in female patients with hypokalaemia or pre-existing QT interval prolongation, or other cardiac diseases. The medicinal product should be used with caution in patients with marked bradycardia or those 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, an ECG should be reviewed before starting treatment. If signs of cardiac arrhythmia develop during escitalopram treatment, therapy should be discontinued and an ECG performed.

Closed-angle glaucoma. SSRIs, including escitalopram, may affect pupil size.

This mydriatic effect may potentially narrow the anterior chamber angle of the eye, thereby increasing intraocular pressure and triggering 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.

Important information on excipients.

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

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of escitalopram in pregnant women are limited. Escitalopram is contraindicated during pregnancy except in cases where a clear need for the medicinal product has been established after careful consideration of risks and benefits. Newborns of mothers who have taken escitalopram during pregnancy, particularly in the third trimester, should be carefully monitored. Abrupt discontinuation of the medicinal product during pregnancy should be avoided. Newborns of mothers who have taken SSRIs/SNRIs in late pregnancy may develop symptoms such as respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, arterial hypertension or hypotension, hyperreflexia, tremor, nervous irritability, lethargy, persistent crying, somnolence, and sleep disturbances. These symptoms may arise due to serotonergic effects or may represent withdrawal syndrome. In most cases, complications manifest immediately or shortly (<24 hours) after birth.

Epidemiological data have shown that the use of SSRIs during pregnancy may increase the risk of persistent pulmonary hypertension in the newborn (up to 5 cases per 1000 pregnancies). In the general population, the incidence is 1 to 2 cases per 1000 pregnancies. Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage after exposure to SSRIs/SNRIs within one month before delivery (see sections "Special precautions for use" and "Adverse reactions").

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

Fertility. Some SSRIs may affect sperm quality. Reports on the use of certain SSRIs have indicated that the effect on human 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 agent may impair skills or the ability to make prudent judgements. 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.

The medicinal product 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 a maximum of 20 mg.

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

Panic Disorder with or without Agoraphobia

An initial dose of 5 mg (administered in corresponding dosage form) once daily is recommended during the first week before increasing to 10 mg daily. The dose may subsequently be increased to a maximum of 20 mg daily, depending on individual patient sensitivity.

Maximum therapeutic effect in the treatment of panic disorders is achieved within 3 months. The duration of treatment is several months and depends on the severity of the disorder.

Social Anxiety Disorder (Social Phobia)

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.

Symptom improvement usually occurs within 2–4 weeks of treatment. 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 continued treatment should be regularly evaluated.

Generalized Anxiety Disorder

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

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 patient sensitivity, the dose may be increased up to 20 mg daily. OCD is a chronic condition; treatment should continue for a sufficient duration to ensure complete symptom remission, which may take several months or even 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 (administered in corresponding dosage form). Depending on individual sensitivity and severity of depression, the daily dose may be increased to a maximum of 10 mg daily.

Renal Impairment

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

Hepatic Impairment

The recommended initial dose for the first two weeks of treatment is 5 mg daily. Depending on individual patient response, the dose may be increased to 10 mg daily.

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 daily. Depending on individual patient response, the dose may be increased to 10 mg daily.

Discontinuation of Treatment

Abrupt discontinuation should be avoided. When stopping treatment with escitalopram, the dose should be gradually reduced over 1–2 weeks to minimize the risk of withdrawal symptoms. If adverse reactions occur after dose reduction or discontinuation, the previously prescribed dose may be reinstated. The physician may then continue tapering the dose more gradually.

Children

Antidepressants should not be used to treat children. Suicidal behavior (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) are more frequently observed in children and adolescents receiving antidepressants compared to those receiving placebo. If, based on clinical judgment, a decision is made to prescribe antidepressants, careful monitoring for the emergence of suicidal ideation is essential. There are no data on the long-term safety of antidepressants in children and adolescents regarding growth, sexual maturation, and cognitive and behavioral development.

Overdose

Toxicity. Data on escitalopram overdose are limited. Most cases involve concomitant overdose with other medicinal products. The majority of cases have been associated with mild symptoms or asymptomatic overdose. Reports of fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other medicinal products. Ingestion of doses within the range of 400–800 mg of escitalopram has not resulted in severe symptoms.

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

Treatment. There is no specific antidote. Ensure airway patency, adequate oxygenation, and support respiratory function. Perform gastric lavage and administer activated charcoal. Gastric lavage should be performed as soon as possible after oral ingestion. Continuous monitoring of cardiac and vital functions is required, along with symptomatic and supportive treatment.

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

Adverse reactions.

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

Adverse reactions known for SSRIs and escitalopram, observed during placebo-controlled studies and in clinical practice, are listed below by system organ class 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).

System, organ, class	Frequency	Reaction
Blood and lymphatic system	Frequency unknown	Thrombocytopenia
Immune system	Rare	Anaphylactic reactions
Endocrine system	Frequency unknown	Disturbance of antidiuretic hormone secretion.
Metabolism and nutrition	Common	Decreased or increased appetite, weight gain.
	Uncommon	Weight loss.
	Frequency unknown	Hypotension, anorexia2
Psychiatric	Common	Anxiety, restlessness, abnormal dreams, decreased libido. Women: anorgasmia
	Uncommon	Bruxism, excitement, nervousness, panic attacks, confusion.
	Rare	Aggression, depersonalization, hallucinations
	Frequency unknown	Mania, suicidal thoughts, suicidal behavior1
Nervous system	Very common	Headache.
	Common	Insomnia, somnolence, dizziness, paresthesia, tremor
	Uncommon	Taste disturbance, sleep disorders, loss of consciousness.
	Rare	Serotonin syndrome
	Frequency unknown	Dyskinesia, movement disorders, seizures, psychomotor agitation/akathisia2
Eye organs	Uncommon	Pupil dilation, blurred vision
Ear and labyrinthine disorders	Uncommon	Tinnitus
Cardiovascular system	Uncommon	Tachycardia
	Rare	Bradycardia
	Frequency unknown	QT interval prolongation on electrocardiogram, ventricular arrhythmia including torsade de pointes, orthostatic hypotension
Respiratory, thoracic and mediastinal	Common	Sinusitis, yawning
	Uncommon	Nosebleeds
Gastrointestinal	Very common	Nausea
	Common	Diarrhea, constipation, vomiting, dry mouth
	Uncommon	Gastrointestinal hemorrhage (including rectal)
Hepatobiliary disorders	Frequency unknown	Hepatitis, changes in liver function tests
Skin and subcutaneous tissue	Common	Increased sweating
	Uncommon	Rash, alopecia, urticaria, pruritus
	Frequency unknown	Ecchymoses, edema
Musculoskeletal and connective tissue	Common	Arthralgia, myalgia
Renal and urinary	Frequency unknown	Urinary retention
Reproductive system and breast	Common	Men: ejaculation disorders, impotence
	Uncommon	Women: metrorrhagia, menorrhagia
	Frequency unknown	Galactorrhea. Men: priapism. Women: postpartum hemorrhage3
General disorders	Common	Fatigue, pyrexia
	Uncommon	Edema

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

2. Such cases are known for the entire SSRI drug class.

3. Cases have been reported for the therapeutic class of SSRIs or SNRI-SSRIs (see sections "Use in pregnancy or lactation", "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, in patients with hypokalemia, and in patients with pre-existing QT prolongation or other cardiac diseases (see sections "Pharmacodynamics", "Contraindications", "Interaction with other medicinal products and other forms of interactions", "Special precautions for use", "Overdose").

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

Withdrawal symptoms. Discontinuation of SSRI treatment (particularly abrupt discontinuation) usually 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, 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, but may be severe and/or prolonged in some patients. Therefore, it is recommended to gradually discontinue escitalopram treatment by dose reduction (see sections "Special precautions for use", "Dosage and administration").

Reporting suspected adverse reactions

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

Shelf life. 3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister pack, 1, 3 or 10 blisters in a cardboard package.

Prescription status. Prescription only.

Manufacturer. TORRENT PHARMACEUTICALS LTD.

Manufacturer's address and location of operations.

Indrad Plant, Vill. Indrad, Taluka Kadi, Dist. Mehsana Gujarat 382721, India.