Escitalopram

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ESCITALOPRAM (ESCITALOPRAM)

Composition:

Active substance: escitalopram;

One tablet contains escitalopram oxalate equivalent to escitalopram 5 mg, or 10 mg, or 20 mg;

Excipients: microcrystalline cellulose, sodium croscarmellose, talc, colloidal anhydrous silicon dioxide, magnesium stearate, hypromellose, polyethylene glycol 400, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, round, biconvex film-coated tablets.

Pharmacotherapeutic group.

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs).

ATC code N06A B10.

Pharmacological properties.

Pharmacodynamics.

Escitalopram is an antidepressant and selective serotonin reuptake inhibitor, responsible for the clinical and pharmacological effects of the drug. It has high affinity for the primary binding site and the adjacent allosteric site of the serotonin transporter, and has no or very weak affinity for various 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.

Escitalopram is the S-enantiomer of racemic citalopram and possesses its own therapeutic activity. It has been demonstrated that the R-enantiomer is not inert, but counteracts the serotonergic properties and corresponding pharmacological effects of the S-enantiomer.

Pharmacokinetics.

Absorption is nearly complete and independent of food intake. Maximum plasma concentration is reached within 4 hours after administration. The bioavailability of escitalopram is approximately 80%. Protein binding of escitalopram and its main metabolites is less than 80%. Metabolism occurs in the liver, forming demethylated and didemethylated metabolites, all of which are pharmacologically active. The biotransformation of escitalopram into the demethylated metabolite is mediated by the cytochrome CYP2C19. A minor contribution of CYP3A4 and CYP2D6 isoenzymes to this process is possible. The elimination half-life (t½) of the drug is approximately 30 hours. Oral clearance (Cloral) is about 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 the urine as metabolites. The pharmacokinetics of escitalopram are linear. Steady-state concentration is achieved after approximately 1 week.

In elderly patients (aged 65 years and older), escitalopram is eliminated more slowly than in younger patients.

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

In patients with reduced renal function, administration of racemic citalopram resulted in a prolonged elimination half-life and slightly increased exposure. Plasma concentrations of metabolites have not been studied but may be elevated.

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 in patients with reduced CYP2D6 function.

Clinical Characteristics.

Indications.

• Major depressive episodes;
• Panic disorders, including with 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 with non-selective irreversible monoamine oxidase inhibitors (MAOIs), due to the risk of serotonin syndrome, which manifests as agitation, tremor, hyperthermia;

• Combination with reversible MAO-A inhibitors (e.g., moclobemide) or the reversible non-selective MAO inhibitor linezolid, due to the risk of serotonin syndrome;

• QT interval prolongation or congenital long QT syndrome;

• Concomitant use with medicinal products that prolong the QT interval;

• Concomitant treatment with pimozide.

Interaction with other medicinal products and other forms of interaction.

Pharmacodynamic interactions

Contraindicated combinations

Non-selective irreversible MAO inhibitors

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

Pimozide

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

Combinations requiring caution

Reversible selective MAO-A inhibitor (moclobemide)

Due to the risk of serotonin syndrome, the combination of escitalopram with the MAO-A inhibitor moclobemide is not recommended. If the necessity of this combination is established, treatment should be initiated with the lowest recommended doses and careful clinical monitoring is required.

Treatment with escitalopram may be initiated no earlier than 1 day after discontinuation of the reversible MAO inhibitor moclobemide.

Antibiotic linezolid is not recommended for administration to patients taking escitalopram. If such a combination is absolutely necessary, treatment should be initiated with 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.

QT interval prolongation

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, antimalarials including halofantrine), certain antihistamines (astemizole, mizolastine), is contraindicated.

Serotonergic medicinal products

Concomitant use with serotonergic agents (e.g., tramadol, sumatriptan, and other triptans) may lead to serotonin syndrome.

Medicinal products that lower seizure threshold

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

St. John’s wort (Hypericum perforatum)

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

Anticoagulants

Changes in anticoagulant effects may occur with concomitant use of escitalopram. If patients are taking oral anticoagulants, careful monitoring of the coagulation system before and during treatment with escitalopram is required.

Concomitant use of non-steroidal anti-inflammatory drugs may increase the risk of bleeding.

Alcohol

Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interactions with alcohol. However, 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 agents on the pharmacokinetics of escitalopram

The metabolism of escitalopram is primarily mediated by CYP2C19. Enzymes CYP3A4 and CYP2D6 may also be involved, 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 escitalopram plasma concentration.

Concomitant administration of escitalopram and cimetidine 400 mg twice daily (a moderately potent non-specific enzyme inhibitor) results in a moderate (approximately 70%) increase in escitalopram plasma concentration.

Therefore, caution is required when co-administering escitalopram with CYP2C19 inhibitors (e.g., omeprazole, fluconazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and 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 co-administering escitalopram 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 certain centrally acting agents primarily metabolized by CYP2D6, such as antidepressants (e.g., desipramine, clomipramine, nortriptyline), antipsychotics (e.g., risperidone, thioridazine, haloperidol). Dose adjustment may be required.

Combination with desipramine or metoprolol has led to a doubling of plasma levels of these agents.

Caution is recommended when co-administering escitalopram with medicinal products metabolized by CYP2C19.

Special precautions for use.

The following special precautions apply to the SSRI therapeutic group.

Paradoxical anxiety.

In some patients with panic disorders, anxiety may increase at the beginning of SSRI treatment. This paradoxical reaction usually resolves within 2 weeks of treatment. To reduce the likelihood of an anxiogenic effect, low initial doses are recommended.

Seizures.

Escitalopram should be discontinued if a patient experiences a first seizure or an increased frequency of seizures (in patients with a confirmed diagnosis of epilepsy). SSRIs should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored.

Mania.

SSRIs should be used with caution in patients with a history of mania/hypomania. 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). Dosage adjustments of insulin and/or oral hypoglycaemic agents may be required.

Suicidality 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. Clinically, the risk of suicide is known to increase in the early stages of recovery.

Other conditions for which escitalopram is indicated may also be associated with a risk of suicidal behaviour. Moreover, these conditions may be comorbid with major depressive disorder. These warnings are relevant when treating patients with other psychiatric disorders.

Patients with a history of suicidal behaviour are at the highest risk of developing suicidal thoughts or attempts and require careful monitoring during treatment. A meta-analysis of clinical trials revealed an increased risk of suicidal behaviour among 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 dosage adjustments are made.

Patients and their caregivers should be warned to monitor for any worsening of symptoms, suicidal thoughts or behaviour, or unusual changes in behaviour.

Akathisia.

The use of SSRIs/SSRI-Ns is associated with the development of akathisia—a distressing and unpleasant feeling of inner restlessness and a compelling need to move, often accompanied by an inability to sit or stand still. This condition most commonly occurs within the first few weeks of treatment. Increasing the dose may worsen symptoms in patients who develop such reactions.

Hypotension.

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

Bleeding.

The use of SSRIs may lead to bleeding events (ecchymosis and purpura). SSRIs should be prescribed with caution in patients with a predisposition to bleeding and in patients receiving anticoagulants or drugs affecting blood coagulation.

SSRIs/SSRI-Ns 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 not recommended due to the risk of serotonin syndrome.

Serotonin syndrome.

In patients taking SSRIs concomitantly with serotonergic agents, serotonin syndrome may rarely develop. Escitalopram should be used with caution when combined with medications having serotonergic activity. A combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of serotonin syndrome. If such a situation occurs, SSRIs and serotonergic agents should be discontinued immediately, and symptomatic treatment initiated.

St. John’s wort.

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

Withdrawal symptoms.

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

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, electric shock sensations), sleep disturbances (including insomnia, vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, excessive sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most frequently reported reactions. These symptoms are usually mild to moderate in severity, but may be severe in some patients. They typically occur within the first few days after discontinuation of treatment, although very rare reports have described such symptoms in patients who accidentally missed a dose.

Withdrawal symptoms usually resolve within 2 weeks, but may persist longer (2–3 months or more) in some patients. Therefore, it is recommended to gradually discontinue escitalopram treatment by tapering the dose over several weeks or months, depending on the patient's condition.

Ischaemic heart disease.

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

QT interval prolongation.

Escitalopram has been shown to cause dose-dependent QT interval prolongation. Cases of QT interval prolongation and ventricular arrhythmias, including torsade de pointes, have been reported, primarily in female patients with hypokalaemia, pre-existing QT prolongation, or other cardiac conditions.

The drug should be used with caution in patients with pronounced bradycardia or in 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.

An ECG should be reviewed before starting treatment in patients with stable cardiac disease. If signs of cardiac arrhythmia occur 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.

Sexual dysfunction.

SSRIs may cause symptoms of sexual dysfunction (see section "Adverse reactions"). Cases of persistent sexual dysfunction, with symptoms continuing despite discontinuation of SSRIs, have been reported.

Use during pregnancy or breastfeeding.

Clinical data on the use of escitalopram during pregnancy are limited.

Escitalopram is contraindicated during pregnancy, except in cases where a careful evaluation of risks and benefits has clearly established the necessity of treatment. Newborns whose mothers received escitalopram during pregnancy, particularly in the third trimester, should be carefully monitored.

Newborns whose mothers took SSRIs/SSRI-Ns during late pregnancy may develop symptoms such as respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, nervous agitation, irritability, apathy, persistent crying, somnolence, and sleep disturbances. These symptoms may arise either due to excessive serotonergic activity or as withdrawal symptoms. In most cases, such complications occur immediately or shortly (within 24 hours) after delivery.

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

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

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

Fertility

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

Ability to affect reaction speed when driving or operating machinery.

Although escitalopram does not affect intellectual or psychomotor performance, any psychoactive agent may impair skills or the ability to think rationally. Patients should be warned about the potential risk of impaired ability to drive or operate machinery.

Method of Administration and Dosage.

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

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

Major Depressive Episode.

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

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

Panic Disorder with or without Agoraphobia.

An initial dose of 5 mg daily is recommended during the first week, after which the dose may be increased 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 typically occurs within 2–4 weeks of treatment. Treatment should be continued for 3 months. Long-term treatment for 6 months is recommended to prevent relapse, taking into account individual disease manifestations; treatment efficacy should be regularly assessed.

Generalized Anxiety Disorder.

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

Treatment should be continued for 3 months. Long-term treatment for 6 months is recommended to prevent relapse, taking into account individual disease manifestations; treatment efficacy should be regularly assessed.

Obsessive-Compulsive Disorder (OCD).

Administer 10 mg once daily. Depending on individual patient sensitivity, the dose may be increased to 20 mg daily. OCD is a chronic condition, and treatment should continue for a sufficient duration to ensure complete symptom remission, which may take several months or longer.

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 to a maximum of 10 mg daily.

Renal Impairment.

No dosage adjustment is required in mild to moderate renal impairment. Exercise caution when administering the drug to 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 the individual patient's response, the dose may be increased to 10 mg daily.

Reduced Activity of Cytochrome Isoenzyme CYP2C19.

For patients with low CYP2C19 isoenzyme activity, the recommended initial dose for the first two weeks of treatment is 5 mg daily. Depending on the individual patient's response, the dose may be increased to 10 mg daily.

Discontinuation of Treatment.

Treatment should be discontinued gradually by reducing the dose over 1–2 weeks to avoid withdrawal reactions.

Children.

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

There are no data on the long-term safety of escitalopram in children regarding growth, sexual maturation, cognitive, and behavioral development.

Overdose.

Toxicity. Clinical data on escitalopram overdose are limited. Many cases involve concomitant overdose with other medications. In most cases, symptoms were mild or absent. Fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other drugs. Ingestion of doses within the range of 400–800 mg of escitalopram did not result in severe symptoms.

Symptoms. Escitalopram overdose primarily manifests with symptoms affecting the central nervous system (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizures, and coma), gastrointestinal system (nausea, vomiting), cardiovascular system (arterial hypotension, tachycardia, QT interval prolongation, arrhythmia), and electrolyte imbalances (hypokalemia, hyponatremia).

Treatment. There is no specific antidote. Maintain adequate respiratory function and ensure appropriate oxygenation. Perform gastric lavage as soon as possible. Activated charcoal may be used. Continuous monitoring of vital functions is required, along with symptomatic and supportive treatment.

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 reported with SSRIs (selective serotonin reuptake inhibitors) and escitalopram are listed by organ systems.

Cardiovascular system			Tachycardia	Bradycardia	ECG QT interval prolongation, ventricular arrhythmia, including torsade de pointes
Blood and lymphatic system					Thrombocytopenia
Nervous system	Headache	Insomnia, drowsiness, dizziness, paraesthesia, tremor	Disturbance of taste, sleep disorders, loss of consciousness	Serotonin syndrome	Dyskinesia, movement disorders, seizures, psychomotor agitation/akathisia2
Eye disorders			Mydriasis, blurred vision
Ear and labyrinth disorders			Tinnitus
Respiratory system		Sinusitis, yawning	Nosebleeds
Gastrointestinal system	Nausea	Diarrhea, constipation, vomiting, dry mouth	Gastrointestinal hemorrhage (including rectal)
Renal and urinary system					Urinary retention
Skin and subcutaneous tissue		Increased sweating	Urticaria, alopecia, rash, pruritus		Ecchymosis, swelling
Musculoskeletal disorders		Arthralgia, myalgia
Endocrine system					Disorders of antidiuretic hormone secretion
Metabolism and nutrition		Decreased or increased appetite, weight gain	Weight loss		Hyponatremia, anorexia2
Vascular					Orthostatic hypotension
Immune system				Anaphylactic reactions
Hepatobiliary disorders					Hepatitis, changes in liver function tests
Reproductive system and breast		Men: ejaculation disorder, impotence	Women: metrorrhagia, menorrhagia		Postpartum hemorrhage3, galactorrhea Men: priapism
Psychiatric disorders		Anxiety, nervousness, dysphoria, agitation, abnormal dreams, decreased libido in men and women. Women: anorgasmia	Bruxism, excitement, restlessness, panic attacks, confusion	Aggression, depersonalization, hallucinations	Mania, suicidal thoughts and behavior1
General disorders		Fatigue, pyrexia	Edema

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

2 Such cases occurred during the use of any SSRIs.

3 This phenomenon has been documented for the therapeutic class of SSRIs/SSRIsN (see sections "Special precautions for use" and "Use during pregnancy or breastfeeding").

Cases of QT interval prolongation and ventricular arrhythmia, including torsade de pointes, have been reported, occurring predominantly in female patients with hypokalemia or pre-existing QT interval prolongation, or other cardiac diseases.

Epidemiological studies, primarily in patients aged 50 years and older, have shown an increased risk of bone fractures associated with the use of SSRIs, including escitalopram, and tricyclic antidepressants. The mechanism of this phenomenon is unknown.

Withdrawal symptoms

Discontinuation of SSRIs (especially abrupt discontinuation) usually leads to the emergence of 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 discontinue escitalopram treatment by dose reduction.

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

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

Prescription status.

Prescription only.

Manufacturer.

Limited Liability Company "Kharkiv Pharmaceutical Enterprise "Zdorov'ya Narodu".

Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and place of business.

Ukraine, 61002, Kharkiv region, city of Kharkiv, Kuilikivska Street, 41.

(Limited Liability Company "Kharkiv Pharmaceutical Enterprise "Zdorov'ya Narodu")

Ukraine, 08301, Kyiv region, city of Boryspil, Shevchenka Street, 100.

(Limited Liability Company "FARMEKS GROUP")