Escitalopram-ncs

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ESCITALOPRAM-NKS ESCITALOPRAM-NKS

Composition:

Active substance: escitalopram;

1 ml of solution contains escitalopram oxalate (25.56 mg), corresponding to escitalopram content of 20 mg.

1 drop contains 1 mg of escitalopram.

Excipients: propyl gallate, ethanol 96%, citric acid, sodium hydroxide, purified water.

Pharmaceutical form. Oral drops, solution.

Main physicochemical properties: clear liquid.

Pharmacotherapeutic group.

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs).

ATC code N06AB10.

Pharmacological Properties.

Pharmacodynamics.

Escitalopram is an antidepressant and a selective serotonin reuptake inhibitor (SSRI) with high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter with approximately 1000-fold lower affinity.

Escitalopram has either no or very weak affinity for a number of receptors, including 5-HT1A-, 5-HT2-, dopamine D1- and D2-receptors, α1-, α2-, β-adrenergic receptors, histamine H1, muscarinic cholinergic, benzodiazepine, and opioid receptors.

Inhibition of serotonin (5-HT) reuptake is considered the likely mechanism of action that may explain the pharmacological and clinical effects of escitalopram.

Pharmacokinetics.

Absorption is almost complete and is independent of food intake. The median time to reach maximum concentration (median Tmax) is approximately 4 hours. The absolute bioavailability of escitalopram is expected to be about 80%.

The apparent volume of distribution (Vd, β/F) after oral administration ranges from 12 to 26 L/kg. Plasma protein binding of escitalopram and its main metabolites is less than 80%.

Escitalopram is metabolized in the liver into demethylated and didemethylated metabolites. Both are pharmacologically active. Nitrogen may also be oxidized to form an N-oxide metabolite. Both metabolites and the parent compound are partially excreted as glucuronides. After repeated administration, the average concentrations of the demethyl and didemethyl metabolites are typically 28–31% and <5%, respectively, of the escitalopram concentration. The biotransformation of escitalopram to its demethylated metabolite occurs primarily via the cytochrome CYP2C19. Enzymes CYP3A4 and CYP2D6 may also play a minor role.

The elimination half-life (t1/2) after repeated dosing is approximately 30 hours. Oral plasma clearance is 0.6 L/min. The main metabolites of escitalopram have a longer half-life. Escitalopram and its main metabolites are considered to be eliminated via the liver (metabolic pathway) and kidneys. Most of the drug is excreted in urine as metabolites.

The pharmacokinetics of escitalopram are linear. Steady-state concentrations are reached after approximately 1 week. The mean steady-state concentration of 50 nmol/L (range 20–125 nmol/L) is achieved with a daily dose of 10 mg (10 drops).

Elderly patients (aged ≥65 years)

In elderly patients, escitalopram is eliminated more slowly than in younger individuals. Systemic exposure, measured by the pharmacokinetic parameter area under the curve (AUC), is about 50% higher in elderly patients compared to younger healthy volunteers.

Hepatic impairment

In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the half-life of escitalopram is nearly doubled, and exposure is 60% higher than in individuals with normal liver function.

Renal impairment

In patients with reduced renal function (CLcr 10–53 mL/min), an increased half-life of racemic citalopram and a slight increase in exposure have been observed. Plasma concentrations of metabolites have not been studied, but an increase may be expected.

In patients with poor activity of the CYP2C19 isoenzyme, plasma concentrations of the drug are doubled compared to those with normal escitalopram metabolism.

In patients with deficient CYP2D6 isoenzyme activity, no significant changes in exposure have been observed.

Clinical Characteristics.

Indications.

Treatment:

• 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 other components of the medicinal product.

Concomitant use of non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome, characterized by agitation, tremor, hyperthermia, and other symptoms (see section "Interaction with other medicinal products and other forms of interaction").

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

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

Escitalopram must not be used concomitantly with medicinal products that are capable of prolonging the QT interval (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Pharmacodynamic interactions

Contraindicated combinations

Non-selective irreversible MAO inhibitors

Serious reactions have been reported in patients taking SSRIs in combination with non-selective irreversible monoamine oxidase inhibitors (MAOIs), as well as in patients who have recently discontinued SSRIs and started MAOI treatment (see section "Contraindications"). In some cases, serotonin syndrome developed (see section "Adverse reactions"). Combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Escitalopram treatment should be initiated no 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, combination of escitalopram with the MAO-A inhibitor moclobemide is contraindicated (see section "Contraindications").

If such combination is considered necessary, the lowest recommended doses should be used initially, with enhanced clinical monitoring.

Reversible non-selective MAO inhibitor (linezolid)

The antibiotic linezolid is a reversible non-selective MAO inhibitor and should not be administered to patients receiving escitalopram. If such combination is necessary, the lowest possible doses of both agents should be used under close 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 concomitantly with racemic citalopram.

QT interval prolongation

Pharmacokinetic and pharmacodynamic studies of escitalopram in combination with other medicinal products known to prolong 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 such as halofantrine), and certain antihistamines (astemizole, hydroxyzine, mizolastine), is contraindicated.

Combinations requiring caution

Serotonergic medicinal products

Concomitant use with serotonergic agents (e.g., opioids such as buprenorphine and tramadol) and triptans (including sumatriptan) may lead to serotonin syndrome (see section "Special precautions for use").

MEDICINAL PRODUCTS THAT LOWER SEIZURE THRESHOLD

SSRIs may lower the seizure threshold. Caution is recommended when co-administering with medicinal products that may lower 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 increase the frequency of adverse reactions (see section "Special precautions for use").

Anticoagulants

The effect 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 treatment (see section "Special precautions for use").

Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of bleeding (see section "Special precautions for use").

Alcohol

Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interactions with alcohol. However, as with other psychotropic medicinal products, combination with alcohol is not recommended.

MEDICINAL PRODUCTS CAUSING HYPOKALEMIA/HYPOmagnesemia

Caution is advised when using medicinal products that may cause hypokalemia/hypomagnesemia concomitantly, as this may increase the risk of developing malignant arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions

Effect of other medicinal products on escitalopram pharmacokinetics

Escitalopram metabolism is primarily mediated by CYP2C19. Enzymes CYP3A4 and CYP2D6 may also be involved to a lesser extent. The CYP2D6 isoenzyme 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. Caution is advised when combining escitalopram with cimetidine. Dose adjustment may be necessary.

Therefore, caution is required when administering escitalopram concomitantly with inhibitors of cytochrome CYP2C19 (e.g., omeprazole, esomeprazole, fluoxetine, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. When used concomitantly with the above-mentioned medicinal products, adverse effects may necessitate a reduction in escitalopram dose (see section "Special precautions for use").

Effect of escitalopram on the pharmacokinetics of other medicinal products

Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution is recommended when escitalopram is used concomitantly with medicinal products primarily metabolized by this enzyme and having a narrow therapeutic index, such as flecainide, propafenone, and metoprolol (in heart failure), or certain centrally acting agents primarily metabolized by CYP2D6, such as the antidepressants desipramine, clomipramine, and nortriptyline, and the antipsychotics risperidone, thioridazine, and 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 minor inhibition of CYP2C19.

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

Special precautions for use.

The following special precautions for use 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 the first two weeks of treatment. To reduce the likelihood of an anxiogenic effect, a low initial dose is recommended (see section "Dosage and administration").

Seizures

Treatment with escitalopram should be discontinued if a patient develops a first seizure or experiences increased seizure frequency (in patients with a confirmed diagnosis of epilepsy). 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 during treatment, SSRIs should be discontinued.

Diabetes

In patients with diabetes mellitus, treatment with SSRIs may affect glycaemic control (hypoglycaemia or hyperglycaemia). Dose adjustments of insulin and/or oral hypoglycaemic agents may be required.

Suicide, suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicide, suicidal thoughts, and self-harm (suicidal behaviour). 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 suicide risk may increase in the early stages of recovery.

Other psychiatric disorders for which escitalopram is used may also be associated with an increased risk of suicidal behaviour. These conditions may also be comorbid with major depressive disorder. Similar caution should be exercised when treating 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 careful monitoring throughout treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressant use in patients under 25 years of age compared to placebo. Pharmacological treatment should be accompanied by close monitoring of patients, especially those at increased risk, particularly at the beginning of treatment and after dose adjustments.

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

Akathisia and psychomotor agitation

The use of SSRIs/SNRIs (selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) has been associated with the development of akathisia – a condition characterized by a distressing, exhausting 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. Dose escalation may worsen symptoms in patients who develop such symptoms.

Hypotonic hyponatraemia

Cases of hyponatraemia have been reported during SSRI treatment, likely due to impaired secretion of antidiuretic hormone (SIADH), which usually resolves after discontinuation of therapy. Particular caution is required when treating patients at risk (elderly patients, patients with liver cirrhosis, or those receiving concomitant medications with hyponatraemic potential).

Bleeding

Skin haemorrhages, ecchymoses, and purpura may occur during SSRI treatment. SSRIs should be used with caution in patients receiving concomitant anticoagulants, medications affecting platelet function (e.g., atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid and NSAIDs, ticlopidine, and dipyridamole), and in patients with a predisposition to bleeding.

The use of SSRIs/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.

Serotonin syndrome

Caution is required when escitalopram is used concomitantly with serotonergic agents such as sumatriptan or other triptans, opioids (e.g., tramadol and buprenorphine), and tryptophan.

Cases of serotonin syndrome have been reported in patients taking SSRIs concomitantly with serotonergic drugs. Symptoms indicating the onset of this condition may include agitation, tremor, myoclonus, and hyperthermia. In such cases, escitalopram and the serotonergic drug should be discontinued immediately, and symptomatic treatment initiated.

St. John's wort

Concomitant use of SSRIs and herbal preparations containing St. John's wort (Hypericum perforatum) may increase the frequency of adverse reactions (see section "Interaction with other medicinal products and other forms of interaction").

Withdrawal symptoms

Upon discontinuation of treatment (especially abrupt discontinuation), withdrawal symptoms usually occur (see section "Adverse reactions"). During clinical trials, discontinuation-related adverse events were observed in approximately 25% of patients in the escitalopram group and 15% in the placebo group.

The risk of withdrawal symptoms depends on several factors, including duration of therapy, dose, and the gradualness 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 have been reported as the most common reactions. Generally, these symptoms are mild to moderate in severity, but may be severe in some patients. They usually occur within the first few days after discontinuation of treatment, although there have been isolated reports of such symptoms occurring after unintentional omission of a single dose. These symptoms are usually self-limiting and resolve within 2 weeks, although in some patients they may persist for a prolonged period (2–3 months or longer). In such cases, it is recommended to discontinue escitalopram gradually over several weeks to several 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.

Coronary heart disease

Due to limited clinical experience, caution is required when treating patients with coronary heart disease.

QT interval prolongation

Escitalopram has been shown to cause dose-dependent prolongation of the QT interval. During post-marketing surveillance, cases of QT interval prolongation and ventricular arrhythmias, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in women, patients with hypokalaemia, and patients with pre-existing QT prolongation or other cardiac diseases (see sections "Contraindications", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", "Overdose", and "Pharmacodynamics").

The drug should be used with caution 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 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 prior to initiating escitalopram treatment.

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

Closed-angle glaucoma

SSRIs, including escitalopram, may affect pupil size, resulting in mydriasis. In turn, pupil dilation may lead to narrowing of the anterior chamber angle and, consequently, increased intraocular pressure and triggering of closed-angle glaucoma, especially in predisposed patients. Therefore, escitalopram should be used with caution in patients with closed-angle glaucoma or a history of glaucoma.

The medicinal product contains a small amount of ethanol, less than 100 mg per dose. Each drop contains 4.7 mg of ethanol.

The preparation contains less than 1 mmol of sodium (23 mg) per dose, i.e., practically sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy

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

Animal studies have shown reproductive toxicity.

Escitalopram is contraindicated during pregnancy, except in cases where a careful evaluation of risks and benefits has clearly demonstrated the necessity of treatment. Newborns whose mothers have taken escitalopram during pregnancy, particularly during 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, nervous agitation, 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 newborns (up to 5 cases per 1000 pregnancies, according to observational data). In the general population, 1 to 2 cases per 1000 pregnancies occur.

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

Breastfeeding

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 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 influence 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 (20 drops) per day has not been established.

The medicinal product is administered orally once daily to adults, independent of food intake. It may be mixed with water, orange juice, or apple juice.

Turn the bottle upside down. If the drops do not flow, gently tap the bottle to initiate flow.

Major Depressive Episode.

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

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

Panic Disorder with or without Agoraphobia.

An initial dose of 5 mg (5 drops) per day is recommended during the first week of treatment, after which the dose may be increased to 10 mg (10 drops) per day. The dose may be further increased, depending on individual patient sensitivity, up to a maximum of 20 mg (20 drops) per day.

Maximum therapeutic effect in panic disorder 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 (10 drops) once daily. Symptom improvement typically occurs within 2–4 weeks of treatment. Subsequently, depending on individual patient response, the dose may be reduced to 5 mg (5 drops) or increased up to the maximum dose of 20 mg (20 drops) per day.

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 evaluated.

Generalized Anxiety Disorder.

The initial dose is 10 mg (10 drops) once daily. Depending on individual sensitivity, the dose may be increased up to a maximum of 20 mg (20 drops) per day.

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 evaluated.

Obsessive-Compulsive Disorder (OCD).

The usual dose is 10 mg (10 drops) once daily. Depending on individual sensitivity, the dose may be increased up to 20 mg (20 drops) 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 (5 drops). Depending on individual sensitivity, the dose may be increased up to a maximum of 10 mg (10 drops) per day.

Renal Impairment.

No dose adjustment is required in mild to moderate renal impairment. The drug 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 (5 drops) per day. Depending on individual patient response, the dose may be increased to 10 mg (10 drops) 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 (5 drops) per day. Depending on individual patient response, the dose may be increased to 10 mg (10 drops) per day.

Withdrawal Symptoms after Discontinuation.

Abrupt discontinuation of the drug should be avoided. When stopping escitalopram treatment, the dose should be gradually reduced over at least 1–2 weeks to minimize the risk of withdrawal symptoms (see sections "Special Warnings and Precautions for Use" and "Adverse Reactions"). If intolerable symptoms occur after dose reduction or discontinuation, consideration should be given to resuming the previously prescribed dose. The physician may then continue tapering the dose, but more gradually.

Children.

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

Furthermore, there are no data on the long-term safety in children and adolescents regarding growth, sexual maturation, and cognitive and behavioral development.

Overdose.

Toxicity.

Clinical data on escitalopram overdose are limited. Many cases involve concomitant overdose with other medicinal products. In most cases, symptoms were mild or absent. Reports of fatal outcomes following escitalopram overdose are rare and mostly involved 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. Supportive care is required, including maintenance of airway patency, respiratory function, and adequate oxygenation. Gastric lavage and administration of activated charcoal should be performed as soon as possible after oral ingestion. Continuous monitoring of cardiovascular function and vital signs, combined with general symptomatic and supportive measures, is recommended.

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

Adverse reactions.

Adverse reactions most commonly occur during the first and second weeks of treatment and subsequently become less intense, with their frequency decreasing during continued treatment.

The adverse reactions known for SSRIs and escitalopram, observed during placebo-controlled studies and post-marketing experience, are listed below by system organ class and frequency. Frequency is defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), or frequency not known (cannot be estimated from available data).

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

2Such cases are known for the entire class of SSRIs.

3These cases have been reported for the therapeutic class of SSRIs or SNRIs (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 prolongation or other cardiac diseases (see sections "Contraindications", "Special precautions for use", "Interaction with other medicinal products and other types of interactions", "Overdose", and "Pharmacodynamics").

Class-specific effects of SSRIs

Epidemiological studies, conducted primarily in patients aged 50 years and older, have demonstrated an increased risk of bone fractures in patients receiving selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. The mechanism leading to this increased risk is currently unknown.

Withdrawal symptoms upon abrupt discontinuation

Discontinuation of SSRIs/SNRIs (especially abrupt) 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, excessive sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances have been reported as the most common reactions. These symptoms are usually mild to moderate in severity and resolve spontaneously, but in some patients they may be severe and/or prolonged. Therefore, it is recommended to gradually discontinue escitalopram by tapering the dose (see sections "Dosage and administration", "Special precautions for use").

Reporting suspected adverse reactions

Reporting of adverse reactions after drug authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, 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.

2 years.

Shelf life after opening: 8 weeks at a temperature not exceeding 25 °C in a tightly closed bottle.

Storage conditions.

The medicinal product does not require special storage conditions. Store in a place inaccessible to children.

Packaging.

15 mL in a dark glass bottle with a dropper cap and child-resistant closure; 1 bottle in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Shanel Medical Limited Company

Manufacturer's address and location of its business operations.

Dublin Road, Lochrea, H62 FH90, Ireland.

Marketing authorization holder.

LLC "NKS-PHARM"

Address of the marketing authorization holder.

01103, Ukraine, Kyiv, Mykhaila Boichuka St., 6, office 103.