Escitalopram-SZ (Tablets) Instructions for Use

Marketing Authorization Holder

Severnaya Zvezda NAO (Russia)

Contact Information

SEVERNAYA ZVEZDA NAO (Russia)

ATC Code

N06AB10 (Escitalopram)

Active Substance

Escitalopram (Rec.INN registered by WHO)

Dosage Forms

	Escitalopram-SZ	Film-coated tablets, 10 mg: 10, 14, 20, 28, 30 or 42 pcs.
		Film-coated tablets, 20 mg: 10, 14, 20, 28, 30 or 42 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with a score on one side; the core of the tablet is white or almost white on the cross-section.

Excipients: microcrystalline cellulose 102, croscarmellose sodium (primellose), lactose monohydrate (lactopress) (milk sugar), low-substituted hypromellose (low-substituted hydroxypropylcellulose), colloidal silicon dioxide (aerosil), magnesium stearate.

Shell composition: hypromellose, polysorbate-80 (tween-80), talc, titanium dioxide (E171).

10 pcs. – contour cell blisters (1) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
10 pcs. – contour cell blisters (3) – cardboard packs.
14 pcs. – contour cell blisters (1) – cardboard packs.
14 pcs. – contour cell blisters (2) – cardboard packs.
14 pcs. – contour cell blisters (3) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – polymer bottles (1) – cardboard packs.

Film-coated tablets white or almost white, round, biconvex; the core of the tablet is white or almost white on the cross-section.

Excipients: microcrystalline cellulose 102, croscarmellose sodium (primellose), lactose monohydrate (lactopress) (milk sugar), low-substituted hypromellose (low-substituted hydroxypropylcellulose), colloidal silicon dioxide (aerosil), magnesium stearate.

Shell composition: hypromellose – 5.1 mg, polysorbate-80 (tween-80) – 2.12 mg, talc – 1.7 mg, titanium dioxide (E171) – 1.08 mg.

10 pcs. – contour cell blisters (1) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
10 pcs. – contour cell blisters (3) – cardboard packs.
14 pcs. – contour cell blisters (1) – cardboard packs.
14 pcs. – contour cell blisters (2) – cardboard packs.
14 pcs. – contour cell blisters (3) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – polymer bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Antidepressant

Pharmacological Action

Escitalopram is an antidepressant, an SSRI with high affinity for the primary binding site.

Escitalopram also binds to the allosteric site of the transporter protein with an affinity 1000 times lower. The allosteric modulation of the transporter protein enhances the binding of escitalopram at the primary binding site, leading to more complete inhibition of serotonin reuptake.

Escitalopram has no or very low ability to bind to a number of receptors, including serotonin 5-HT_1A, 5-HT₂ receptors, dopamine D₁ and D₂ receptors, α₁-, α₂-, β-adrenergic receptors, histamine H₁ receptors, muscarinic cholinergic receptors, benzodiazepine and opioid receptors.

Inhibition of serotonin reuptake is the only possible mechanism of action that explains the pharmacological and clinical effects of escitalopram.

In double-blind, placebo-controlled studies in healthy volunteers, the change from baseline in QTc (Fridericia’s correction) on ECG was 4.3 msec (90% confidence interval (CI): 2.2-6.4) at a dose of 10 mg/day and 10.7 msec (90% CI: 8.6-12.8) at a dose of 30 mg/day.

Clinical efficacy and safety

Severe depressive episodes

The efficacy of escitalopram in the acute treatment of severe depressive episodes was found in three out of four double-blind, placebo-controlled, short-term (8-week) studies.

During a long-term relapse prevention study, 274 patients who completed the initial 8-week open-label phase and received Escitalopram at a dose of 10 or 20 mg/day were randomized and subsequently received Escitalopram at the same dose or placebo for up to 36 weeks.

During this study, patients who continued to take Escitalopram experienced relapse after a longer period of time over the subsequent 36 weeks compared to those who received placebo.

Obsessive-compulsive disorder

In a randomized, double-blind clinical study, the effect of escitalopram at a dose of 20 mg/day was compared with placebo based on scores on the Yale-Brown Obsessive Compulsive Scale at 12 weeks.

At 24 weeks, Escitalopram at doses of 10 and 20 mg/day showed higher results compared to placebo.

Relapse prevention was demonstrated with escitalopram at doses of 10 and 20 mg/day in patients whose treatment with escitalopram was successful during a 16-week open-label study and who participated in a 24-week randomized, double-blind, placebo-controlled study.

Pharmacokinetics

Absorption

The absorption of escitalopram is almost complete and independent of food intake.

T_max is 4 hours after multiple administration. The absolute bioavailability is about 80%, the same as for racemic citalopram.

Distribution

The apparent V_d after oral administration ranges from 12 to 26 L/kg.

The binding of escitalopram and its main metabolites to plasma proteins is less than 80%. C_ss is reached in about 1 week, the mean C_ss is 50 nmol/L (range 20 to 125 nmol/L) achieved at a daily dose of 10 mg.

Metabolism

Escitalopram is biotransformed in the liver to demethylated and didemethylated metabolites.

Both metabolites are pharmacologically active. Nitrogen can be oxidized to an N-oxide metabolite. The parent substance and its metabolites are partially excreted as glucuronides. After multiple administration, the mean concentrations of the demethylated and didemethylated metabolites are 28-31% and less than 5%, respectively, of the escitalopram concentration.

The biotransformation of escitalopram to the demethylated metabolite occurs mainly via the CYP2C19 isoenzyme, with possible minor involvement of the CYP3A4 and CYP2D6 isoenzymes.

Excretion

T_1/2 after multiple administration is about 30 hours.

The oral clearance (Cl_oral) is about 0.6 L/min. The main metabolites of escitalopram have a longer T_1/2. Escitalopram and its main metabolites are excreted by the liver (metabolic pathway) and kidneys, with most excreted as metabolites by the kidneys.

Linearity/non-linearity

The pharmacokinetics of escitalopram are linear.

Pharmacokinetics in special patient groups

Elderly patients. In elderly patients (≥65 years), Escitalopram is eliminated more slowly than in younger patients.

The amount of escitalopram in the systemic circulation, calculated by AUC, is 50% higher in elderly patients than in young healthy volunteers.

Renal impairment. When using racemic citalopram in patients with renal impairment (creatinine clearance 10-53 ml/min), a prolongation of T_1/2 and a slight increase in AUC were noted.

Plasma concentrations of metabolites have not been studied, but they may be elevated.

Hepatic impairment. In patients with mild or moderate hepatic impairment (Child-Pugh class A and B), the T_1/2 of escitalopram is approximately 2 times longer and the AUC is 60% greater than in patients with normal liver function.

Polymorphism (in individuals with low activity of CYP2C19 or CYP2D6 isoenzymes). In patients with low activity of the CYP2C19 isoenzyme, the plasma concentration of escitalopram may be 2 times higher than in patients with high activity of this isoenzyme.

No significant changes in the plasma concentration of escitalopram were found with low activity of the CYP2D6 isoenzyme.

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Indications

For use in adults aged 18 years and older

• Depressive episodes of any severity;
• Panic disorder with/without agoraphobia;
• Social anxiety disorder (social phobia);
• Generalized anxiety disorder;
• Obsessive-compulsive disorder.

ICD codes

Dosage Regimen

Orally, once a day, regardless of meals.

Depressive episodes

Usually prescribed 10 mg once a day.

Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day. The antidepressant effect usually develops after 2-4 weeks of treatment. After the symptoms of depression disappear, therapy should be continued for at least another 6 months to consolidate the effect obtained.

Panic disorder with/without agoraphobia

During the first week of treatment, a dose of 5 mg/day is recommended, which is then increased to 10 mg/day.

Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day. The maximum therapeutic effect is achieved approximately 3 months after the start of treatment. Therapy lasts for several months.

Social anxiety disorder (social phobia)

The recommended dose is 10 mg once a day.

Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day. Symptom relief usually develops 2-4 weeks after starting treatment. Social anxiety disorder is a chronic condition; to consolidate the response to therapy, it is recommended to continue treatment for 3 months.

To prevent relapse of the disease, the drug may be prescribed for 6 months or longer depending on the individual patient response. It is recommended to regularly evaluate the ongoing treatment.

Generalized anxiety disorder

The recommended dose is 10 mg once a day.

Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day. The recommended duration of the therapeutic course is 3 months to consolidate the response to therapy. Long-term use of the drug (6 months or longer) is allowed to prevent relapse of the disease. It is recommended to regularly evaluate the ongoing treatment.

Obsessive-compulsive disorder

Usually prescribed 10 mg once a day.

Depending on the individual patient response, the dose may subsequently be increased to a maximum of 20 mg/day. Since obsessive-compulsive disorder is a chronic condition, the course of treatment should be long enough to ensure complete relief from symptoms and last for at least 6 months. To prevent relapse, treatment for at least 1 year is recommended.

Special patient groups

Elderly patients (over 65 years) are recommended to use half the usual recommended dose (i.e., only 5 mg/day) and a lower maximum dose (10 mg/day).

For mild and moderate renal impairment, no dose adjustment is required. Patients with severe renal impairment (creatinine clearance below 30 ml/min) should be prescribed Escitalopram-SZ with caution.

For mild or moderate hepatic impairment (Child-Pugh class A or B), the recommended initial dose for the first 2 weeks of treatment is 5 mg/day.

Depending on the individual patient response, the dose may be increased to 10 mg/day. For severe hepatic impairment (Child-Pugh class C), the drug should be prescribed under close medical supervision.

The safety and efficacy of escitalopram in children aged 0 to 18 years have not been established to date. Escitalopram-SZ should not be used in children under 18 years of age (see section “Special Instructions”), as there is insufficient data from long-term safety studies of escitalopram use in children and adolescents regarding growth, maturation, and cognitive and behavioral development.

Reduced activity of the CYP2C19 isoenzyme

For patients with low activity of the CYP2C19 isoenzyme, the recommended initial dose for the first 2 weeks of treatment is 5 mg/day. Depending on the individual patient response, the dose may be increased to 10 mg/day.

Discontinuation of treatment

When discontinuing treatment with Escitalopram-SZ, the dose should be reduced gradually over 1-2 weeks to avoid the occurrence of withdrawal syndrome.

Adverse Reactions

Side effects most often develop in the first or second week of treatment and then usually become less intense and occur less frequently with continued therapy.

The frequency of side effects listed below was determined according to the following (WHO classification): very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000), very rare (<1/10000), frequency unknown (frequency cannot be estimated from available data).

Blood and lymphatic system disorders frequency unknown – thrombocytopenia.

Immune system disorders rare – anaphylactic reactions.

Endocrine disorders frequency unknown – inappropriate ADH secretion.

Metabolism and nutrition disorders common – decreased appetite, increased appetite, weight gain; uncommon – weight loss; frequency unknown – hyponatremia, anorexia¹.

Psychiatric disorders common – anxiety, restlessness, abnormal dreams, decreased libido, anorgasmia (in women); uncommon – bruxism, agitation, nervousness, panic attacks, confusion; rare – aggression, depersonalization, hallucinations; frequency unknown – mania, suicidal thoughts, suicidal behavior². Cases of suicidal thoughts and behavior have been reported during treatment with escitalopram and immediately after discontinuation of therapy.

Nervous system disorders very common – headache; common – insomnia, somnolence, dizziness, paresthesia, tremor; uncommon – taste disturbance, sleep disorder, syncope; rare – serotonin syndrome; frequency unknown – dyskinesia, movement disorders, seizure disorders, psychomotor agitation/akathisia¹.

Eye disorders uncommon – mydriasis, visual impairment.

Ear and labyrinth disorders uncommon – tinnitus.

Cardiac disorders uncommon – tachycardia; rare – bradycardia; frequency unknown – QT interval prolongation on ECG, ventricular arrhythmia, including torsades de pointes, orthostatic hypotension.

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

Gastrointestinal disorders very common – nausea; common – diarrhea, constipation, vomiting, dry mouth; uncommon – gastrointestinal bleeding (including rectal bleeding).

Hepatobiliary disorders unknown – hepatitis, increased serum liver enzymes.

Skin and subcutaneous tissue disorders common – hyperhidrosis; uncommon – urticaria, alopecia, rash, pruritus; frequency unknown – ecchymosis, angioedema.

Musculoskeletal and connective tissue disorders common – arthralgia, myalgia.

Renal and urinary disorders frequency unknown – urinary retention.

Reproductive system and breast disorders common – impotence, ejaculation disorder; uncommon – metrorrhagia, menorrhagia; frequency unknown – galactorrhea, priapism, postpartum hemorrhage (this adverse event is registered as a class effect for drugs of the SSRI/SNRI group (see section “Pregnancy and Lactation”)).

General disorders and administration site conditions common – asthenia, pyrexia; uncommon – edema.

¹ Adverse reactions reported with the use of SSRI class drugs.

²Cases of suicidal thoughts and behavior have been reported during treatment with escitalopram and immediately after discontinuation of therapy.

Description of selected adverse reactions

QT interval prolongation

In the post-marketing period, cases of QT interval prolongation and ventricular arrhythmia, including torsades de pointes, have been reported, mainly in female patients, with hypokalemia, or in patients with pre-existing QT interval prolongation or other heart disease.

Class Effect

Epidemiological studies involving patients aged 50 years and older have shown an increased risk of bone fractures in patients taking SSRIs and tricyclic antidepressants. The mechanism for this risk has not been established.

Discontinuation Syndrome upon Treatment Cessation

Discontinuation of SSRI/SNRI drugs (especially abrupt) often leads to the development of a discontinuation syndrome. The most frequently reported symptoms are dizziness, sensory disturbances (including paresthesia and electric shock sensation), sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances. Typically, these effects are mild to moderate and resolve quickly, but in some patients, they may be more acute and/or prolonged. It is recommended to discontinue the drug gradually by reducing its dose.

Contraindications

• Hypersensitivity to escitalopram and other components of the drug;
• Concomitant use of non-selective MAO inhibitors;
• Concomitant use of pimozide;
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• Age under 18 years (efficacy and safety of use have not been established).

With Caution

Severe renal impairment (creatinine clearance < 30 ml/min); mania/hypomania; pharmacologically uncontrolled epilepsy; significant suicidal behavior; diabetes mellitus; liver cirrhosis; bleeding tendency; narrow-angle glaucoma or history of glaucoma; concomitant use with MAO-A inhibitor (moclobemide) and MAO-B inhibitor (selegiline), serotonergic drugs, drugs that lower the seizure threshold, lithium, tryptophan, preparations containing St. John’s wort, oral anticoagulants and drugs affecting blood coagulation, drugs capable of causing hyponatremia, drugs biotransformed with the involvement of the CYP2C19 isoenzyme, ethanol; during electroconvulsive therapy (ECT); in elderly patients; during pregnancy; during breastfeeding.

Use in Pregnancy and Lactation

Pregnancy

There are limited clinical data on the use of escitalopram during pregnancy.

Animal studies of escitalopram have demonstrated reproductive toxicity.

Escitalopram-SZ should be used during pregnancy only in cases of extreme necessity and after careful benefit/risk assessment.

If the mother took escitalopram until late in pregnancy, especially in the third trimester, the newborn should be monitored. If escitalopram was continued until delivery or discontinued shortly before delivery, the newborn may develop discontinuation symptoms.

If the mother took SSRIs/SNRIs late in pregnancy, the following symptoms may occur in the newborn: respiratory depression, cyanosis, apnea, seizures, unstable temperature, feeding difficulties, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, drowsiness, poor sleep. These symptoms may be due to discontinuation syndrome or serotonergic overstimulation. In most cases, such complications occur within the first 24 hours after birth.

Epidemiological study data suggest that the use of SSRIs/SNRIs during pregnancy, especially late in pregnancy, may increase the risk of persistent pulmonary hypertension of the newborn (PPHN). The observed risk was about 5 cases per 1000 pregnancies. In the general population, there are 1-2 cases per 1000 pregnancies.

Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage after the use of SSRI/SNRI drugs within one month prior to delivery.

Breastfeeding Period

Escitalopram is expected to be excreted in breast milk; therefore, breastfeeding is contraindicated during treatment with Escitalopram-SZ. If it is necessary to use Escitalopram-SZ, breastfeeding should be discontinued.

Fertility

Animal study data have shown that some SSRIs may affect sperm quality. There are no animal study data on this aspect for escitalopram. Reports on the use of some SSRIs in humans have shown that the effect of these drugs on sperm quality is reversible. No effect of escitalopram on human fertility has been observed to date.

Use in Hepatic Impairment

The drug should be used with caution in patients with liver cirrhosis.

In severe hepatic impairment (Child-Pugh class C), the drug should be used under strict medical supervision.

Use in Renal Impairment

The drug should be used with caution in patients with severe renal impairment (creatinine clearance less than 30 ml/min).

Pediatric Use

The use of the drug is contraindicated in children under 18 years of age.

Geriatric Use

The drug should be used with caution in patients over 65 years of age.

Special Precautions

The following should be considered when using drugs belonging to the SSRI therapeutic class, including Escitalopram.

Paradoxical Anxiety

Some patients with panic disorder may experience increased anxiety at the beginning of treatment with antidepressants. Such a paradoxical reaction usually disappears within the first 2 weeks of treatment. To reduce the likelihood of an anxiogenic effect, it is recommended to use low initial doses.

Seizures

Escitalopram should be discontinued if seizures develop for the first time or if their frequency increases (in patients with previously diagnosed epilepsy). SSRIs should not be used in patients with unstable epilepsy; patients with controlled seizures require careful monitoring.

Mania

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

Diabetes Mellitus

In patients with diabetes mellitus, treatment with escitalopram may alter blood glucose concentrations. Therefore, adjustment of insulin and/or oral hypoglycemic drug doses may be required.

Suicide/Suicidal Thoughts or Clinical Worsening of Depression

Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicidal events). This risk persists until significant remission occurs. Since improvement may not be observed during the first few weeks of therapy or even longer, patients should be closely monitored until their condition improves.

General clinical experience shows that the risk of suicide may increase during the early stages of recovery.

Other psychiatric conditions for which Escitalopram is prescribed may also be associated with an increased risk of suicidal events and phenomena. Furthermore, these conditions may be comorbid with a depressive episode. The same precautions should be observed when treating patients with other psychiatric disorders as when treating patients with a depressive episode.

Patients with a history of suicidal behavior or patients with a significant degree of suicidal ideation prior to treatment are at greater risk of suicidal thoughts or suicide attempts, so they should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed that there is an increased risk of suicidal behavior in patients under 25 years of age taking antidepressants compared with placebo. Drug treatment of these patients, and particularly patients at high risk of suicide, should be accompanied by careful monitoring, especially at the early stage of treatment and during dose changes.

Patients (and caregivers of patients) should be advised to monitor for any signs of clinical worsening, suicidal behavior or thoughts, and unusual changes in behavior, and to seek medical advice immediately if these symptoms appear.

Akathisia/Psychomotor Agitation

SSRI use is associated with the development of akathisia, characterized by subjectively unpleasant or distressing restlessness and a need to move constantly, often accompanied by an inability to sit or stand still. This most often occurs during the first few weeks of treatment. In patients with such symptoms, increasing the dose may lead to worsening.

Hyponatremia

Hyponatremia, possibly associated with impaired ADH secretion due to SSRI use, is rare and usually resolves upon discontinuation of therapy. Caution should be exercised when prescribing escitalopram and other SSRIs to individuals at risk of developing hyponatremia: the elderly, patients with liver cirrhosis, and those taking drugs that can cause hyponatremia.

Bleeding

Cases of skin hemorrhages (ecchymosis and purpura) have been reported with SSRI use. Escitalopram should be used with caution in patients taking oral anticoagulants and drugs affecting blood coagulation, as well as in patients with a bleeding tendency.

The use of SSRI/SNRI drugs may increase the risk of postpartum hemorrhage (see sections “Pregnancy and Lactation”, “Adverse Reactions”).

Electroconvulsive Therapy (ECT)

Since clinical experience with the concomitant use of SSRIs and ECT is limited, caution should be exercised when using escitalopram concomitantly with ECT.

Serotonin Syndrome

Concomitant use of escitalopram and MAO-A inhibitors is not recommended due to the risk of serotonin syndrome.

Escitalopram should be used with caution concomitantly with drugs that have serotonergic effects, such as sumatriptan or other triptans, tramadol, and tryptophan. In rare cases, patients taking Escitalopram and other SSRIs concomitantly with serotonergic drugs have developed serotonin syndrome. Its development may be indicated by a combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia. If this occurs, concomitant treatment with SSRIs and serotonergic drugs should be discontinued immediately and symptomatic treatment initiated.

If concomitant treatment is clinically justified, careful monitoring of the patient is recommended, especially during therapy initiation and dose escalation.

Discontinuation Syndrome after Treatment Cessation

Discontinuation syndrome is common upon treatment cessation, especially if treatment is stopped abruptly. In clinical trials, adverse reactions upon treatment discontinuation were observed in approximately 25% of patients treated with escitalopram and 15% of patients receiving placebo.

The risk of discontinuation syndrome may depend on several factors, including the duration of therapy and the dose of the drug, as well as the rate of dose reduction. The most frequently reported reactions were dizziness, sensory disturbances (including paresthesia and electric shock sensation), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances. Usually, these symptoms are mild to moderate, but in some patients they may be severe.

Symptoms usually occur within the first few days after discontinuation, but there have been very rare reports of such symptoms in patients who accidentally missed a dose.

Typically, these symptoms resolve on their own, usually within 2 weeks, although in some patients they may be prolonged (2-3 months or more). Therefore, when discontinuing treatment, gradual dose reduction over several weeks or months is recommended, depending on the patient’s condition.

Coronary Artery Disease

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

Cases of QT Interval Prolongation

Escitalopram has been found to cause a dose-dependent prolongation of the QT interval. Post-marketing cases of QT interval prolongation and ventricular arrhythmia, including torsades de pointes, have been reported, predominantly in female patients, patients with hypokalemia or pre-existing QT prolongation, or other heart diseases.

Caution is required when using the drug in patients with significant bradycardia or in patients with a recent acute myocardial infarction or decompensated heart failure.

Electrolyte imbalances, such as hypokalemia and hypomagnesemia, increase the risk of malignant arrhythmias; these imbalances must be corrected before starting treatment with escitalopram.

In patients with stable coronary artery disease, an ECG should be performed before starting treatment.

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

Narrow-Angle Glaucoma

SSRIs, including Escitalopram, may affect pupil size, leading to mydriasis. This pupil-dilating effect has the potential to narrow the anterior chamber angle, leading to increased intraocular pressure and the development of narrow-angle glaucoma, especially in patients predisposed to this condition. Therefore, caution should be exercised when using escitalopram in patients with narrow-angle glaucoma or a history of glaucoma.

Sexual Dysfunction

SSRIs/SNRIs may cause symptoms of sexual dysfunction. There have been reports of persistent sexual dysfunction where symptoms continued after discontinuation of SSRIs/SNRIs.

Use in Children and Adolescents Under 18 Years

Antidepressants should not be prescribed to children and adolescents under 18 years of age due to an increased risk of suicidal behavior (suicide attempts and suicidal thoughts), hostility (predominantly aggressive behavior, confrontational tendencies, and irritability). If a decision is made based on clinical assessment to initiate treatment with antidepressants, the patient must be closely monitored. Furthermore, there are insufficient data on the long-term safety in children and adolescents regarding growth, maturation, and cognitive and behavioral development.

Excipients

Escitalopram-SZ contains lactose. Patients with rare hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product (see section “Contraindications”).

Escitalopram-SZ contains less than 1 mmol sodium per 10 mg and 20 mg dose, i.e., it is essentially sodium-free. This should be taken into account by patients on a sodium-restricted diet.

Effect on Ability to Drive and Operate Machinery

During the use of escitalopram, one should refrain from engaging in potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Overdose

Data on escitalopram overdose are limited, and in many such cases, there was also an overdose of other drugs. In most cases, symptoms of overdose are absent or mild.

Fatal cases of escitalopram overdose (without other drugs) are rare; in most cases, there is also an overdose of other drugs. When escitalopram was taken in the dose range of 400-800 mg as monotherapy, no clinically significant symptoms of overdose occurred.

Symptoms

Overdose with escitalopram mainly results in symptoms from the CNS (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizure disorders, and coma), GI tract (nausea/vomiting), cardiovascular system (hypotension, tachycardia, QT interval prolongation, and arrhythmia), and electrolyte imbalances (hypokalemia, hyponatremia).

Coma or fatal cases of escitalopram overdose are extremely rare; most of them involve simultaneous overdose with other medications. Ingestion of a dose within 400-800 mg of escitalopram did not cause severe symptoms.

Treatment

There is no specific antidote. Symptomatic and supportive treatment is provided: gastric lavage, administration of enterosorbents (particularly activated charcoal), ensuring a constant supply of fresh air, support of external respiratory function, adequate lung oxygenation. Monitoring of cardiovascular and respiratory functions is carried out along with general symptomatic and supportive treatment.

Drug Interactions

Pharmacodynamic Interactions

Non-selective irreversible MAO inhibitors

Serious adverse reactions have been reported with the concomitant use of SSRIs and non-selective irreversible MAO inhibitors, as well as when starting MAO inhibitors in patients who had recently discontinued SSRIs. In some cases, patients developed serotonin syndrome.

Concomitant use of Escitalopram with non-selective irreversible MAO inhibitors is contraindicated. Escitalopram may be started 14 days after discontinuation of irreversible MAO inhibitors. At least 7 days should elapse after stopping escitalopram before starting non-selective irreversible MAO inhibitors.

Reversible selective MAO-A inhibitor (moclobemide)

Due to the risk of serotonin syndrome, concomitant use of Escitalopram with the MAO-A inhibitor moclobemide is not recommended. If such a drug combination is deemed clinically necessary, it is recommended to start with the lowest possible doses and conduct continuous clinical monitoring of the patient’s condition. Escitalopram can be started at least 1 day after discontinuation of the reversible MAO-A inhibitor moclobemide.

Reversible non-selective MAO inhibitor (linezolid)

The antibiotic linezolid is a reversible non-selective MAO inhibitor and should not be used in patients receiving escitalopram therapy. If such a drug combination is deemed clinically necessary, it is recommended to start with the lowest possible doses and conduct continuous clinical monitoring of the patient’s condition.

Irreversible MAO-B inhibitor (selegiline)

Due to the risk of serotonin syndrome, caution is required when taking escitalopram concomitantly with the irreversible MAO-B inhibitor selegiline.

Medicinal Products that Prolong the QT Interval

Pharmacokinetic and pharmacodynamic studies on the use of escitalopram in combination with other medicinal products that prolong the QT interval have not been conducted. An additive effect of escitalopram and these medicinal products cannot be ruled out. Therefore, the concomitant use of escitalopram and medicinal products that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (e.g., phenothiazine derivatives, pimozide, haloperidol), tricyclic and tetracyclic antidepressants (amitriptyline, imipramine, maprotiline, etc.), SSRIs and similar antidepressants (e.g., fluoxetine, venlafaxine, etc.), some antimicrobials (macrolide antibiotics and their analogues, e.g., erythromycin, clarithromycin, quinolone and fluoroquinolone derivatives: sparfloxacin, moxifloxacin, pentamidine), azole antifungals (ketoconazole, fluconazole), domperidone, ondansetron, antimalarials, in particular, halofantrine, some antihistamines (astemizole, mizolastine), is contraindicated.

Serotonergic Medicinal Products

Concomitant use with serotonergic medicinal products (e.g., tramadol, buprenorphine, sumatriptan and other triptans) may lead to the development of serotonin syndrome.

Medicinal Products that Lower the Seizure Threshold

SSRIs may lower the seizure threshold. Caution is advised when using other medicinal products that lower the seizure threshold concomitantly with escitalopram (tricyclic antidepressants, SSRIs, mefloquine, bupropion and tramadol, antipsychotic drugs (neuroleptics) – phenothiazine derivatives, thioxanthene and butyrophenone).

Lithium, Tryptophan

Since cases of enhanced effects have been reported with the concomitant use of SSRIs and lithium or tryptophan, caution is recommended when using escitalopram concomitantly with these drugs.

St. John’s Wort

Concomitant use of SSRIs and preparations containing St. John’s wort (Hypericum perforatum) may lead to an increase in the number of adverse reactions.

Anticoagulants and Drugs Affecting Blood Coagulation

Impaired blood coagulation may occur with the concomitant use of escitalopram with oral anticoagulants and medicinal products affecting blood coagulation (e.g., atypical antipsychotics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and NSAIDs, ticlopidine and dipyridamole). In such cases, careful monitoring of blood coagulation is necessary when initiating or finishing therapy with escitalopram. Concomitant use with NSAIDs may lead to an increased number of bleeding cases.

Ethanol

Escitalopram does not interact pharmacodynamically or pharmacokinetically with ethanol. However, as with other psychotropic medicinal products, the concomitant use of escitalopram and ethanol is not recommended.

Medicinal Products Causing Hypokalemia/Hypomagnesemia

Caution should be exercised with the concomitant use of medicinal products that cause the development of hypokalemia/hypomagnesemia, as these conditions increase the risk of malignant arrhythmias.

Pharmacokinetic Interaction

Effect of Other Medicinal Products on the Pharmacokinetics of Escitalopram

The metabolism of escitalopram occurs primarily with the participation of the CYP2C19 isoenzyme. The CYP3A4 and CYP2D6 isoenzymes may be involved to a lesser extent. The metabolism of the main metabolite – demethylated escitalopram – is apparently partially catalyzed by the CYP2D6 isoenzyme.

Concomitant use of escitalopram and omeprazole (an inhibitor of the CYP2C19 isoenzyme) at a dose of 30 mg once daily leads to a moderate (approximately 50%) increase in the plasma concentration of escitalopram.

Concomitant administration of escitalopram and cimetidine (an inhibitor of the CYP2D6, CYP3A4, and CYP1A2 isoenzymes) at a dose of 400 mg twice daily leads to an increase (approximately 70%) in the plasma concentration of escitalopram.

Thus, the maximum possible doses of escitalopram should be used with caution concomitantly with inhibitors of the CYP2C19 isoenzyme (e.g., omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and cimetidine. When escitalopram is used concomitantly with the aforementioned drugs, a dose reduction of escitalopram may be required based on clinical assessment.

Effect of Escitalopram on the Pharmacokinetics of Other Medicinal Products

Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Caution should be exercised when using escitalopram concomitantly with medicinal products metabolized by this isoenzyme and having a narrow therapeutic index, for example, flecainide, propafenone, and metoprolol (in cases of use for heart failure) or drugs primarily metabolized via CYP2D6 and acting on the CNS, for example, antidepressants (desipramine, clomipramine, nortriptyline) or antipsychotic drugs (risperidone, thioridazine, haloperidol). In these cases, dose adjustment may be required.

Concomitant use of escitalopram and desipramine or metoprolol leads to a twofold increase in their plasma concentration.

Escitalopram may slightly inhibit the CYP2C19 isoenzyme. Therefore, caution is recommended when using escitalopram concomitantly with medicinal products metabolized by the CYP2C19 isoenzyme.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.