Escitodar®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Esцитodar® (Escitodar)

Composition:

Active substance: escitalopram;

One orodispersible tablet contains escitalopram oxalate 12.775 mg, equivalent to escitalopram 10 mg, or escitalopram oxalate 25.55 mg, equivalent to escitalopram 20 mg;

Excipients: potassium polacrilin, hydrochloric acid concentrated, lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, potassium acesulfame, neohesperidin dihydrochalcone, peppermint flavor, magnesium stearate.

Pharmaceutical form. Orodispersible tablets.

Main physicochemical properties:

10 mg dosage: tablets from white to almost white, round-shaped, flat surface, beveled edges, with engraving “10” on one side.

20 mg dosage: tablets from white to almost white, round-shaped, flat surface, beveled edges, with engraving “20” on one side.

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 only 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 ECG study in healthy subjects, the change from baseline in QTc interval (corrected using Fridericia's formula) was 4.3 ms (90% CI: 2.2, 6.4) with escitalopram 10 mg/day and 10.7 ms (90% CI: 8.6, 12.8) with a supratherapeutic dose of 30 mg/day.

Major Depressive Episodes

The efficacy of escitalopram in the treatment of major depressive episodes during the acute phase was demonstrated in three out of four double-blind, placebo-controlled, short-term (8-week) studies. In a long-term relapse prevention study, 274 patients who had responded positively to escitalopram treatment at doses of 10 mg/day or 20 mg/day during an initial 8-week open-label phase were randomized to continue on the same dose of escitalopram or switch to placebo for up to 36 weeks. In this study, the time to relapse was statistically significantly longer over the subsequent 36 weeks in patients continuing escitalopram compared to those receiving placebo.

Social Anxiety Disorder

Escitalopram was shown to be effective in the treatment of social anxiety disorder in three short-term (12-week) studies as well as in a six-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.

Generalized Anxiety Disorder

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

According to pooled data from three studies with similar design, in which 421 patients received escitalopram and 419 received placebo, positive response to treatment was observed in 47.5% and 28.9% of patients, respectively, and remission occurred in 37.1% and 20.8% of patients, respectively. A sustained effect was observed from the first week of treatment.

The maintenance effect of escitalopram at a dose of 20 mg daily was demonstrated in a 24–76-week randomized maintenance treatment study involving 373 patients who had responded positively to the drug during an initial 12-week open-label treatment phase.

Obsessive-Compulsive Disorder

In a randomized, double-blind clinical trial, escitalopram at a dose of 20 mg daily demonstrated superiority over placebo in the total score on the Y-BOCS (Yale-Brown Obsessive Compulsive Scale) after 12 weeks of treatment. After 24 weeks, advantages of escitalopram treatment were observed both at 10 mg/day and 20 mg/day compared to placebo.

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

Pharmacokinetics

Absorption is nearly complete and is independent of food intake. Maximum plasma concentration is reached within 4 hours after administration. As with racemic citalopram, the absolute bioavailability of escitalopram is approximately 80%.

Distribution

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

Biotransformation

Metabolism occurs in the liver, producing 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 multiple dosing, the average concentrations of the demethyl and didemethyl metabolites are typically 28–31% and <5% of escitalopram concentration, respectively. The biotransformation of escitalopram to its demethylated metabolite is mediated by the cytochrome CYP2C19. Minor contributions from CYP3A4 and CYP2D6 isoenzymes are possible.

Elimination

The elimination half-life (t½) of the drug is approximately 30 hours. Oral clearance is approximately 0.6 L/min. The main metabolites have longer half-lives. Escitalopram and its main metabolites are eliminated via the liver (metabolic pathway) and kidneys. The majority of the dose is excreted in urine as metabolites.

Linearity

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

Elderly Patients (aged 65 years and older)

In patients aged 65 years and older, escitalopram is eliminated more slowly than in younger patients. Systemic exposure, measured by the pharmacokinetic parameter AUC (area under the curve), is 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), t½ was twice as long and exposure was 60% higher compared to individuals with normal liver function.

Renal Impairment

In patients with reduced renal function (creatinine clearance 10–53 mL/min), administration of racemic citalopram resulted in a longer elimination half-life and slightly higher exposure. Plasma concentrations of metabolites have not been studied but may be increased.

Polymorphism

Patients with poor metabolic function of CYP2C19 had plasma concentrations of escitalopram twice as high as patients with normal CYP2C19 function. No significant changes in exposure were observed with reduced CYP2D6 function.

Clinical characteristics.

Indications.

For the treatment of major depressive episodes, panic disorders with or without agoraphobia, social anxiety disorders (social phobia), generalized anxiety disorders, and obsessive-compulsive disorders.

Contraindications.

Hypersensitivity to escitalopram or to any of the excipients of the medicinal product.

Concomitant use with non-selective irreversible monoamine oxidase inhibitors (MAOIs) — due to the risk of developing serotonin syndrome, which manifests as agitation, tremor, hyperthermia, and other symptoms.

Combination therapy with escitalopram and reversible MAO-A inhibitors (e.g., moclobemide) or reversible non-selective MAO inhibitors (e.g., linezolid) — due to the risk of developing serotonin syndrome.

Concomitant use with medicinal products that prolong the QT interval; known QT interval prolongation or congenital long QT syndrome.

Interaction with other medicinal products and other forms of interaction.

Pharmacodynamic interactions

Non-selective irreversible MAOIs

Serious reactions have been reported in patients taking SSRIs in combination with non-selective irreversible MAOIs, and in patients who recently discontinued SSRI treatment and initiated MAOI therapy (see section "Contraindications"). Contraindicated combinations In some cases, serotonin syndrome developed (see section "Adverse reactions"). The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Treatment with escitalopram should be initiated no earlier than 14 days after discontinuation of irreversible MAOI. Treatment with non-selective irreversible MAOIs should not be initiated earlier than 7 days after discontinuation of escitalopram.

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 contraindicated (see section "Contraindications"). If this combination is deemed 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 a 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 (an irreversible MAO-B inhibitor) requires caution due to the risk of serotonin syndrome.

Selegiline at doses up to 10 mg/day has been safely used concomitantly with racemic citalopram.

MEDICINAL PRODUCTS THAT PROLONG THE QT INTERVAL

Pharmacokinetic and pharmacodynamic studies of the combined use of escitalopram with other medicinal products that prolong the QT interval have not been conducted. When escitalopram is used concomitantly with such agents, an additive effect cannot be excluded. Therefore, concomitant use of escitalopram with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, antipsychotics (e.g., phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g., sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials such as halofantrine), and certain antihistamines (astemizole, hydroxyzine, 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 THE SEIZURE THRESHOLD

SSRIs may lower the seizure threshold. Caution is recommended when combining with agents that may lower the seizure threshold, such as 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, these agents should be co-administered 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.

Anticoagulants

The effects of anticoagulants may be altered when used concomitantly with escitalopram. If patients are taking oral anticoagulants, careful monitoring of the coagulation system should be performed before and during treatment with escitalopram (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, concomitant use with alcohol is not recommended.

MEDICINAL PRODUCTS THAT INDUCE HYPOKALEMIA/HYPOMAGNESEMIA

Caution should be exercised when using medicinal products that may induce hypokalemia/hypomagnesemia concomitantly, as this increases the risk of developing malignant arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions

Effect of other agents on the pharmacokinetics of escitalopram

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

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

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

Therefore, caution is warranted when escitalopram is used concomitantly with CYP2C19 inhibitors (e.g., omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or with cimetidine, particularly when high-dose escitalopram is prescribed. Dose reduction of escitalopram may be required based on clinical assessment.

Effect of escitalopram on the pharmacokinetics of other agents

Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution is recommended when escitalopram is used concomitantly with medicinal products that are primarily metabolized by this enzyme and have a narrow therapeutic index, such as flecainide, propafenone, and metoprolol (in heart failure), or with certain centrally acting agents primarily metabolized by CYP2D6, such as antidepressants (e.g., desipramine, clomipramine, nortriptyline) or antipsychotics (e.g., risperidone, thioridazine, haloperidol). Dose adjustment may be required.

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

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

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

Special precautions for use

The special precautions described below generally apply to the therapeutic class of SSRIs.

Paradoxical anxiety

Some patients with panic disorders may experience increased anxiety at the beginning of treatment with antidepressants. This paradoxical reaction usually resolves within two weeks of treatment. A low starting dose is recommended to reduce the likelihood of an anxiogenic effect.

Seizures

Escitalopram should be discontinued if a patient experiences a first seizure or increased seizure frequency (in patients with established epilepsy diagnosis). SSRIs should generally 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

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

Suicide, suicidal thoughts, or clinical worsening

Depression is associated with a risk of suicidal thoughts, self-harm, and suicide (suicidal behaviour). This risk persists until a sustained remission is achieved. Since improvement may not occur during the first few weeks of treatment or longer, patients should be closely monitored until their condition improves. It is known that the risk of suicide may increase in the early stages of recovery.

Other conditions for which escitalopram is used may also be associated with a risk of suicidal behaviour. Additionally, these conditions may be accompanied by major depressive disorder. These warnings also apply to the treatment of patients with other psychiatric disorders.

Patients with a history of suicidal behaviour prior to starting treatment are at the highest risk of suicidal thoughts or suicide attempts and require close monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour in patients under 25 years of age compared to placebo. Close monitoring of high-risk patients is particularly necessary at the beginning of treatment and when the dose is changed.

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

Akathisia

Treatment with SSRIs/SSRI-NRIs has been associated with the development of akathisia—a state characterized by an unpleasant, distressing sensation of inner restlessness and a compelling need to move, often accompanied by an inability to sit or stand still. This condition is most likely to occur during the first few weeks of treatment. Increasing the dose may worsen symptoms in patients who develop such reactions.

Hyponatraemia

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

Bleeding

Skin haemorrhages, ecchymoses, and purpura may occur during SSRI treatment. SSRIs/SSRI-NRIs may increase the risk of postpartum haemorrhage. SSRIs should be used with caution in patients receiving concomitant anticoagulants or drugs affecting platelet function (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, dipyridamole, and ticlopidine), and in patients with a predisposition to bleeding.

Electroconvulsive therapy (ECT)

Clinical experience with the concomitant use of SSRIs and ECT is limited; therefore, caution is recommended in prescribing and administration.

Reversible, selective MAO-A inhibitors

Combining escitalopram with MAO-A inhibitors is not recommended due to the risk of serotonin syndrome.

Serotonin syndrome

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

Cases of serotonin syndrome have been reported in patients taking SSRIs concomitantly with serotonergic drugs. Escitalopram should be used with caution in combination with medicinal products having serotonergic activity. The combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. In such cases, SSRIs and the serotonergic agent should be discontinued immediately, and symptomatic treatment should be initiated.

St. John’s wort

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

Discontinuation symptoms

Discontinuation symptoms upon stopping treatment, particularly abrupt discontinuation, are common. In clinical trials, adverse reactions during discontinuation occurred in approximately 25% of patients treated with escitalopram and in 15% of patients receiving placebo.

The risk of discontinuation symptoms depends on several factors, including duration of treatment, dose, and rate of dose reduction. Dizziness, sensory disturbances (e.g. paraesthesia, electric shock sensations), sleep disturbances (e.g. insomnia, 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 or moderate but may be severe in some patients. They typically occur within the first few days after stopping treatment, although rare reports describe similar symptoms in patients who accidentally missed a dose. These discontinuation symptoms usually resolve within two weeks, but may persist longer (2–3 months or more) in some patients. Therefore, it is recommended to gradually discontinue escitalopram by tapering the dose over several weeks or months, depending on the patient’s condition.

Sexual dysfunction

The use of SSRIs/SSRI-NRIs may lead to symptoms of sexual dysfunction. Cases of persistent sexual dysfunction, where symptoms persist even after discontinuation of SSRIs/SSRI-NRIs, have been reported.

Ischaemic heart disease

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

QT interval prolongation

Escitalopram has been shown to cause dose-dependent QT interval prolongation. During the post-marketing period, cases of QT interval prolongation and ventricular arrhythmias, including torsades de pointes, have been reported, primarily in female patients with hypokalaemia, pre-existing QT prolongation, or other cardiac conditions.

The medicinal product should be used with caution in patients with marked bradycardia, or in patients with recent acute myocardial infarction or uncompensated heart failure.

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

An ECG should be performed before starting treatment in patients with stable cardiac disease.

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

Angle-closure 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, potentially triggering angle-closure glaucoma, especially in predisposed patients. Therefore, escitalopram should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.

Use during pregnancy or breastfeeding

Pregnancy

Clinical data on the use of escitalopram in pregnant women are limited.

Embryo-fetotoxic effects have been observed in animal studies with escitalopram. Escitalopram is contraindicated during pregnancy except in cases where a careful evaluation of risks and benefits clearly justifies its use. Close monitoring of newborns whose mothers received escitalopram during pregnancy, particularly in the third trimester, is recommended. The use of the medicinal product during pregnancy should not be stopped abruptly.

Newborns of mothers who took SSRIs/SSRI-NRIs in late pregnancy may develop symptoms such as respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, apathy, persistent crying, somnolence, and sleep disturbances. These symptoms may result from excessive serotonergic activity or may represent withdrawal symptoms. Such complications usually occur immediately or shortly after delivery (within 24 hours).

Epidemiological data indicate that the use of SSRIs during pregnancy increases the risk of persistent pulmonary hypertension in the newborn: up to 5 cases per 1000 pregnancies, according to epidemiological observations, compared to 1–2 cases per 1000 in the general population.

Breastfeeding

Since escitalopram passes into breast milk, breastfeeding is not recommended during treatment. Observational data suggest an increased risk (less than 2-fold) of postpartum haemorrhage after SSRI or SSRI-NRI use within one month before delivery.

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 drug may impair skills or the ability to think rationally. Patients should be warned of the potential risk to their ability to drive or operate machinery.

Dosage and Administration

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

Ezcitodar® should be administered orally once daily in 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 be continued for at least 6 months to consolidate the therapeutic effect.

Panic Disorder, with or without Agoraphobia

An initial dose of 5 mg escitalopram* per day is recommended for the first week before increasing to 10 mg daily. The dose may then be increased, depending on individual patient sensitivity, up to a maximum of 20 mg daily.

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 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.

Since social anxiety disorder is a chronic condition, the minimum recommended treatment duration to consolidate response is 12 weeks. To prevent relapse, the medication may be continued for up to 6 months, depending on individual patient response. The therapeutic benefit of treatment should be regularly assessed.

Social anxiety disorder is a clearly defined diagnostic entity and should not be confused with exaggerated shyness. Pharmacotherapy is indicated only for the disorder significantly impairing professional and social functioning. The efficacy of this treatment compared to cognitive-behavioral therapy has not been studied. Pharmacotherapy should be part of an overall therapeutic strategy.

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.

Long-term treatment for 6 months has been shown to prevent relapse and may be individually prescribed. The therapeutic benefit and dosage should be regularly reviewed.

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, and treatment should continue for a sufficient duration to achieve complete symptom remission, which may take several months or longer. The therapeutic benefit and dosage should be regularly reviewed.

Elderly Patients (aged 65 years and older)

The initial dose is 5 mg escitalopram* daily. Depending on individual sensitivity and severity of depression, the daily dose may be increased to a maximum of 10 mg daily. The efficacy of Ezcitodar® in elderly patients with social anxiety disorder has not been studied.

Pediatric Population

Ezcitodar® should not be used to treat children and adolescents (under 18 years of age).

Renal Impairment

Dose adjustment is not required in patients with mild to moderate renal impairment. Caution is advised in patients with severe renal impairment (creatinine clearance < 30 mL/min).

Hepatic Impairment

For patients with mild to moderate hepatic impairment, the recommended initial dose for the first two weeks of treatment is 5 mg escitalopram* daily. Depending on individual patient response, the dose may be increased to 10 mg daily. In patients with severe hepatic impairment, caution is required in dosing, and careful dose titration is necessary.

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

Discontinuation Symptoms upon Treatment Cessation

Abrupt discontinuation of this medication should be avoided. The dose of escitalopram should be gradually reduced over 1–2 weeks to minimize the risk of discontinuation symptoms. If discontinuation symptoms occur during dose tapering, the previous dose may be reinstated. The physician may then continue to reduce the dose, but more gradually.

* Use the medicinal product with the appropriate escitalopram dosage strength.

Children

Antidepressants are contraindicated for the treatment of children under 18 years of age. Suicidal behavior (suicidal attempts and suicidal ideation) and hostility (predominantly 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 the medicinal product is made based on clinical judgment, careful monitoring for the emergence of suicidal symptoms is essential.

Overdose

Toxicity. Clinical data on escitalopram overdose are limited. Most cases involve concomitant overdose with other medicinal products. Mild symptoms or asymptomatic overdose are commonly observed. Reports of fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other medications. Escitalopram doses of 400–800 mg have not caused severe symptoms.

Symptoms. Signs of escitalopram overdose include central nervous system effects (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizures, and coma), gastrointestinal symptoms (nausea, vomiting), cardiovascular effects (hypotension, tachycardia, QT interval prolongation, arrhythmias), and fluid/electrolyte imbalances (hypokalemia, hyponatremia).

Treatment. There is no specific antidote. Maintain adequate respiratory function and ensure proper oxygenation. Gastric lavage and activated charcoal may be considered. Continuous monitoring of cardiac and vital functions, along with symptomatic and supportive treatment, is recommended.

In cases of overdose, ECG monitoring is recommended for patients with congestive heart failure/bradyarrhythmia, those taking concomitant medications that prolong the QT interval, or those with metabolic disorders such as 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 during continued treatment.

Below are adverse reactions of SSRIs and escitalopram observed during placebo-controlled clinical trials and post-marketing experience.

All adverse reactions are listed by organ systems. Frequency is defined according to the following categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

Eye disorders: uncommon — pupillary dilation, blurred vision.

Ear and labyrinth disorders: uncommon — tinnitus.

Respiratory, thoracic and mediastinal disorders: common — sinusitis, yawning; uncommon — epistaxis.

Gastrointestinal disorders: very common — nausea; common — diarrhea, constipation, vomiting, dry mouth; uncommon — gastrointestinal hemorrhage (including rectal).

Hepatobiliary disorders: frequency not known — hepatitis, changes in liver function tests.

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

Endocrine disorders: frequency not known — syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Metabolism and nutrition disorders: common — decreased or increased appetite, weight gain; uncommon — weight loss; frequency not known — hyponatremia, anorexia².

Nervous system disorders: very common — headache; common — insomnia, somnolence, dizziness, paraesthesia, tremor; uncommon — taste disturbance, sleep disorders, syncope; very rare — serotonin syndrome; frequency not known — dyskinesia, movement disorders, seizures, psychomotor agitation/akathisia².

Psychiatric disorders: common — anxiety, restlessness, abnormal dreams, decreased libido in males and females, anorgasmia in females; uncommon — bruxism, agitation, nervousness, panic attacks, confusion; very rare — aggression, depersonalization, hallucinations; frequency not known — mania, suicidal thoughts, suicidal behavior¹.

Cardiac disorders: uncommon — tachycardia; very rare — bradycardia; frequency not known — QT interval prolongation on electrocardiogram, ventricular arrhythmias including torsades de pointes, orthostatic hypotension.

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

Immune system disorders: very rare — anaphylactic reactions.

Skin and subcutaneous tissue disorders: common — increased sweating; uncommon — rash, alopecia, urticaria, pruritus; frequency not known — ecchymosis, angioneurotic edema.

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

Reproductive system and breast disorders: common — in males: ejaculation disorder, impotence; uncommon — in females: metrorrhagia, menorrhagia; frequency not known — galactorrhea, in males: priapism, in females: postpartum hemorrhage³.

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

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

² These cases relate to the entire SSRI class.

³ These cases relate to the therapeutic class of SSRIs or SNRIs.

QT interval prolongation

During the post-marketing period, cases of QT interval prolongation, ventricular arrhythmias including torsades de pointes, have been reported, primarily in female patients with hypokalemia or pre-existing QT prolongation or other cardiac conditions.

Class-specific effects of SSRIs

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

Discontinuation symptoms following cessation of treatment

Discontinuation of SSRIs (particularly abrupt discontinuation) usually leads to discontinuation symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, excessive sweating, headache, diarrhea, palpitations, emotional lability, irritability, and visual disturbances are the most commonly reported reactions. These symptoms are usually mild to moderate and transient; however, in some patients they may be severe and/or prolonged. Therefore, it is recommended that escitalopram treatment be gradually discontinued by dose tapering.

Reporting of suspected adverse reactions

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

Shelf life. 3 years.

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

Keep out of reach and sight of children.

Packaging. 15 tablets in a blister; 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. GenePharm S.A.

Pharmapas S.A.

Manufacturer's address and place of business.

18 Km Meresonos Avenue, Pallini, 153 51, Greece.

28 Oktobriou 1, Agia Barbara, 123 51, Greece.

Marketing Authorization Holder. JSC "Pharmaceutical Company "Darnitsa".

Address of the Marketing Authorization Holder. 13 Borispilska Street, Kyiv, 02093, Ukraine.