Elicea, 10 mg 28 pcs.

Depression, Depressed mood, Phobias and panic attacks, Obsessive compulsive disorder

– Depressive episodes of any severity.

– Panic disorder with/without agoraphobia.

– Obsessive-compulsive disorder.

Indications

· Depressive episodes of any severity.

· Panic disorders with/without agoraphobia.

· Obsessive-compulsive disorder.

Pharmacological effect

antidepressant

Special instructions

Severe renal failure (creatinine clearance less than 30 ml/min), mania/hypomania, pharmacologically uncontrolled epilepsy, severe suicidal behavior, diabetes mellitus, liver cirrhosis, bleeding tendency, concomitant use with an MAO B inhibitor (selegiline), serotonergic drugs, drugs that lower the seizure threshold, lithium, tryptophan, drugs, containing St. John’s wort, anticoagulants for oral administration and drugs that affect blood clotting, drugs that can cause hyponatremia, drugs metabolized by the CYP2C19 isoenzyme, ethanol, when using electroconvulsive therapy (ECT), in elderly patients, during pregnancy, during breastfeeding.

Contraindicated in children and adolescents under 18 years of age (the effectiveness and safety of use have not been studied).

Elderly patients (over 65 years old)

It is recommended to use half the usually recommended dose (5 mg/day) and a lower maximum dose (10 mg/day).

Renal dysfunction

For mild to moderate renal failure (creatinine clearance more than 30 ml/min), no dose adjustment is required.

In severe renal failure (creatinine clearance less than 30 ml/min), Elitsey® should be prescribed with caution.

Liver dysfunction

For mild to moderate liver failure (class A or B on the Child-Pugh scale), the recommended initial dose during the first 2 weeks of treatment is 5 mg/day. Depending on the patient’s individual response, the dose may be increased to 10 mg/day. In severe liver failure (class C on the Child-Pugh scale), Elitsey® is prescribed under the close supervision of a physician.

Reduced activity of the CYP2C19 isoenzyme

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

When using drugs belonging to the SSRI therapeutic group, including escitalopram, the following should be considered:

Use in children and adolescents under 18 years of age

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 (with a predominance of aggressive behavior, confrontational behavior and irritation). If a decision is made to initiate antidepressant therapy based on clinical assessment, the patient should be closely monitored. In addition, there is insufficient data on long-term safety in children and adolescents regarding growth, maturation, cognitive and behavioral development.

Paradoxical anxiety

Some patients with panic disorder may experience increased anxiety when starting antidepressant treatment. This paradoxical reaction usually disappears within the first two weeks of treatment. To reduce the likelihood of an anxiogenic effect, low initial doses are recommended.

Convulsions

Escitalopram should be discontinued in the event of the primary development of convulsive seizures or in the event of an increase in their frequency (in patients with previously diagnosed epilepsy). SSRIs should not be used in patients with unstable epilepsy; 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 plasma glucose concentrations. Therefore, dose adjustments of insulin and/or oral hypoglycemic drugs may be required.

Suicide/suicidal ideation or clinical worsening

Depression is associated with an increased risk of suicidal ideation, 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 practice shows that in the early stages of recovery the risk of suicide may increase.

Other psychiatric conditions for which escitalopram is prescribed may also be associated with an increased risk of suicidal events and events. In addition, these conditions may be a comorbidity in relation to a depressive episode. When treating patients with other mental disorders, the same precautions should be taken as when treating patients with a depressive episode.

Patients with a history of suicidal behavior or patients with a significant level of suicidal thoughts before treatment are at greater risk for suicidal ideation or suicide attempts and should be closely monitored during treatment.

A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders found that there is an increased risk of suicidal behavior in patients under 25 years of age when taking antidepressants compared with placebo. Drug treatment of these patients, and in particular those at high risk for suicide, should be accompanied by careful monitoring, especially early in treatment and during dose changes.

Patients (and caregivers) should be warned to monitor for any signs of clinical worsening, suicidal behavior or ideation, or unusual changes in behavior, and to seek immediate medical advice if these symptoms occur.

Akathisia/psychomotor agitation

The use of SSRIs/SNRIs is associated with the development of akathisia, characterized by the development of subjectively unpleasant or depressing restlessness and the need for constant movement, often combined with an inability to sit or stand quietly. 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, occurs rarely with SSRIs and usually disappears when therapy is discontinued. Caution should be exercised when using escitalopram and other SSRIs in persons at risk of developing hyponatremia: elderly patients, patients with cirrhosis of the liver, and those taking drugs that can cause hyponatremia.

Bleeding

Cases of skin hemorrhages (ecchymosis and purpura) have been reported when taking SSRIs. Escitalopram should be used with caution in patients taking oral anticoagulants and medications that affect blood clotting, as well as in patients with a tendency to bleed.

Electroconvulsive therapy

Because clinical experience with the concomitant use of SSRIs and ECT is limited, caution should be used when escitalopram and ECT are used concomitantly.

Serotonin syndrome

The simultaneous use of escitalopram and MAO A inhibitors is not recommended due to the risk of developing serotonin syndrome. Escitalopram should be used with caution concomitantly with drugs that have serotonergic effects, such as sumatriptan or other triptans, tramadol and tryptophan. Patients taking escitalopram and other SSRIs concomitantly with serotonergic drugs have rarely 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.

Withdrawal syndrome after cessation of therapy

When stopping treatment, withdrawal syndrome is common, especially if treatment is stopped abruptly. In clinical studies, adverse events at treatment discontinuation occurred in approximately 25% of patients treated with escitalopram and in 15% of patients treated with placebo.

The risk of withdrawal 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 commonly reported reactions were dizziness, sensory disturbances (including paresthesia and electric shock), 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. These symptoms are usually mild to moderate, but may be severe in some patients.

Symptoms usually occur within the first few days after stopping treatment, but such symptoms have been extremely rarely reported in patients who accidentally missed taking the drug.

As a rule, these symptoms resolve on their own, usually within 2 weeks, although in some patients they can be prolonged (2-3 months or more). Therefore, when stopping treatment, it is recommended to gradually reduce the dose over several weeks or months in accordance with the patient’s condition.

Coronary heart disease (CHD)

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

QT prolongation

Escitalopram has been found to cause a dose-dependent prolongation of the QT interval. Cases of QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP), have been reported post-marketing, predominantly in female patients with hypokalemia or pre-existing QT prolongation, or other cardiac disease.

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

Electrolyte imbalances, such as hypokalemia and hypomagnesemia, increase the risk of developing malignant arrhythmias; these disturbances 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, it is necessary to stop therapy and perform an ECG.

Angle-closure glaucoma

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

Sexual dysfunction

SSRIs/SSRIs may cause symptoms of sexual dysfunction. There have been reports of long-term sexual dysfunction where symptoms continued despite discontinuation of SSRIs/SNRIs.

Special information on excipients

Elitsey® contains lactose, so it should not be used for the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Despite the fact that Elitsey® does not affect intellectual functions and psychomotor activity, it is not recommended to drive vehicles or machinery during the treatment period.

Active ingredient

Escitalopram

Composition

for 1 tablet 5 mg/10 mg/20 mg

Core:

Active ingredient:

Escitalopram oxalate 6.390 mg/12.780 mg/25.560 mg, equivalent to escitalopram 5.00 mg/10.00 mg/20.00 mg

Excipients:

Lactose monohydrate, crospovidone, povidone-K30, microcrystalline cellulose, pregelatinized starch, magnesium stearate

Film shell:

Opadry white 33G287071

1 Opadry white 33G28707: hypromellose 6cP, titanium dioxide (E171), lactose monohydrate, macrogol, triacetin

Pregnancy

Pregnancy

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

Animal studies of escitalopram have demonstrated reproductive toxicity.

Escitalopram should only be taken during pregnancy when absolutely necessary and after a careful benefit/risk assessment.

If escitalopram was continued during late pregnancy, especially in the third trimester, the newborn should be monitored. If escitalopram was continued until delivery or was stopped shortly before delivery, the newborn may develop withdrawal symptoms.

If the mother takes SSRIs/SNRIs (selective serotonin and norepinephrine reuptake inhibitors) in late pregnancy, the newborn may develop the following side effects: respiratory depression, cyanosis, apnea, seizure disorders, temperature fluctuations, feeding difficulties, vomiting, hypoglycemia, muscle hypertension, muscle hypotonia, hyperreflexia, tremor, increased neuro-reflex excitability, irritability, lethargy, constant crying, drowsiness and poor sleep. These symptoms may occur due to the development of withdrawal syndrome or serotonergic effects. In most cases, such complications occur within 24 hours after birth.

Evidence from epidemiological studies suggests that use of SSRIs during pregnancy, especially later in pregnancy, may increase the risk of developing persistent pulmonary hypertension of the newborn (PPHN). The observed risk was 5 cases per 1000 pregnancies. In the general population, there are 1-2 cases of PPHN per 1000 pregnancies.

Breastfeeding period

Escitalopram is expected to be excreted in breast milk, therefore breastfeeding is contraindicated during treatment with escitalopram. If it is necessary to use the drug Elicea®, breastfeeding should be discontinued.

Fertility

Evidence from animal studies has shown that some SSRIs may affect sperm quality. There are no animal studies on this aspect for escitalopram. Reports of the use of some SSRIs in humans have shown that the effects of these drugs on sperm quality are reversible. To date, no effect of escitalopram on human fertility has been observed.

Contraindications

Hypersensitivity to escitalopram and other components of the drug.
Concomitant use of non-selective irreversible monoamine oxidase inhibitors (MAO).
Simultaneous administration of reversible MAO A inhibitors (moclobemide), reversible non-selective MAO inhibitors (linezolid).
History of QT prolongation, including congenital long QT syndrome.
Concomitant use of drugs that prolong the QT interval (see section “Interaction with other drugs”).
Concomitant use of pimozide.
Children and adolescents under 18 years of age (the effectiveness and safety of use have not been studied).
Lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome (Elitsea® contains lactose).

Side Effects

Side effects most often develop in the 1st or 2nd week of therapy, then usually become less intense and occur less frequently as therapy is continued.

Listed below are the side effects that occur with drugs belonging to the SSRI class and were reported with escitalopram. Information is presented based on data from placebo-controlled clinical trials and spontaneous reports.

Frequencies are reported as: 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 unknown (incidence cannot be estimated from existing data).

Blood and lymphatic system disorders:

frequency unknown: thrombocytopenia.

Immune system disorders:

rarely: anaphylactic reactions.

Endocrine system disorders:

frequency unknown: insufficient secretion of antidiuretic hormone (ADH).

Metabolic and nutritional disorders:

often: decreased appetite, increased appetite, weight gain;

uncommon: weight loss;

frequency unknown: hyponatremia, anorexia1.

Mental disorders:

often: anxiety, restlessness, unusual dreams, decreased libido, anorgasmia (in women);

uncommon: bruxism, agitation, nervousness, panic attacks, confusion;

rarely: aggression, depersonalization, hallucinations;

frequency unknown: mania, suicidal thoughts, suicidal behavior2.

Nervous system disorders:

very often: headache;

often: insomnia, drowsiness, dizziness, paresthesia, tremor;

infrequently: disturbance of taste, sleep disturbance, fainting;

rarely: serotonin syndrome;

frequency unknown: dyskinesia, movement disorders, seizure disorders, psychomotor agitation/akathisia1.

Visual disorders:

uncommon: mydriasis (pupil dilation), visual impairment.

Hearing and labyrinth disorders:

uncommon: tinnitus (tinnitus).

Disorders of the heart and blood vessels:

uncommon: tachycardia;

rarely: bradycardia;

frequency unknown: prolongation of the QT interval on the electrocardiogram (ECG), ventricular arrhythmia, including ventricular tachycardia of the “pirouette” type, orthostatic hypotension.

Disorders of the respiratory system, chest and mediastinal organs:

often: sinusitis, yawning;

uncommon: nosebleeds.

Gastrointestinal disorders:

very often: nausea;

often: diarrhea, constipation, vomiting, dry mouth;

uncommon: gastrointestinal bleeding (including bleeding from the rectum).

Disorders of the liver and biliary tract:

frequency unknown: hepatitis, increased activity of “liver” enzymes in the blood plasma.

Disorders of the skin and subcutaneous tissues:

often: increased sweating;

uncommon: urticaria, alopecia, skin rash, itching;

frequency unknown: ecchymosis, angioedema.

Musculoskeletal and connective tissue disorders:

often: arthralgia, myalgia.

Renal and urinary tract disorders:

frequency unknown: urinary retention.

Disorders of the genital organs and breast:

often: impotence, ejaculation disorders;

uncommon: menorrhagia, metrorrhagia;

frequency unknown: galactorrhea, priapism.

General disorders and disorders at the injection site:

often: weakness, hyperthermia;

uncommon: swelling.

1 Adverse events recorded with the use of drugs of the SSRI class.

2 Cases of suicidal thoughts and behavior have been reported while taking escitalopram and immediately after discontinuation of therapy.

QT prolongation

In the post-marketing period, cases of QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP), have been reported, primarily in female patients, with hypokalemia, or in patients with pre-existing QT prolongation or other cardiac disease.

Class effect

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

Withdrawal symptoms when stopping therapy

Cancellation of SSRI/SNRI drugs (especially abrupt) often leads to withdrawal syndrome. The most common symptoms include dizziness, sensory disturbances (including paresthesia and the sensation of current passing), sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremors, confusion, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances. As a rule, these effects are mild or moderate and disappear quickly, but in some patients they may occur in a more acute form and/or for a longer period of time. It is recommended to gradually discontinue the drug by reducing its dose.

Interaction

Pharmacodynamic interaction

Non-selective irreversible MAO inhibitors

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

The use of escitalopram simultaneously with non-selective irreversible MAO inhibitors is contraindicated. Escitalopram can be started 14 days after discontinuation of non-selective irreversible MAO inhibitors. Before starting to take non-selective irreversible MAO inhibitors, at least 7 days must pass after stopping taking escitalopram.

Reversible selective MAO A inhibitor (moclobemide)

Due to the risk of developing serotonin syndrome, it is not recommended to use escitalopram simultaneously with the MAO A inhibitor moclobemide. If taking such a combination of drugs is considered clinically necessary, it is recommended to start with the lowest possible doses, as well as to conduct constant 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 taking such a combination of drugs is considered clinically necessary, it is recommended to start with the lowest possible doses, as well as to conduct constant clinical monitoring of the patient’s condition.

Irreversible selective MAO B inhibitor (selegiline)

Due to the risk of developing serotonin syndrome, caution should be exercised when taking escitalopram concomitantly with the irreversible MAO B inhibitor selegiline.

Drugs that prolong the QT interval

Pharmacokinetic and pharmacodynamic studies of the use of escitalopram in combination with other drugs that prolong the QT interval have not been conducted. An additive effect of escitalopram and these drugs cannot be excluded. Therefore, the simultaneous use of escitalopram and drugs that prolong the QT interval, such as class IA and III antiarrhythmic drugs, antipsychotics (for example, phenothiazine derivatives, pimozide, haloperidol), tricyclic and tetracyclic antidepressants (amitriptyline, imipramine, maprotiline, etc.), selective serotonin reuptake inhibitors and the like antidepressants (for example, fluoxetine, venlafaxine, etc.), some antimicrobial drugs (macrolide antibiotics and their analogues, for example, erythromycin, clarithromycin, quinolone and fluoroquinolone derivatives: sparfloxacin, moxifloxacin, pentamidine), azole antifungals (ketoconazole, fluconazole), domperidone, ondansetron, drugs for the treatment of malaria, in particular halofantrine, some antihistamines (astemizole, mizolastine).

Serotonergic drugs

Concomitant use with serotonergic drugs (for example, tramadol, sumatriptan and other triptans) may lead to the development of serotonin syndrome.

Drugs that lower the seizure threshold

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

Lithium, tryptophan

Since increased effects have been reported when SSRIs are used concomitantly with lithium or tryptophan, caution is advised when using escitalopram concomitantly with these drugs.

St. John’s wort

The simultaneous use of SSRIs and drugs containing St. John’s wort may lead to an increase in the number of side effects.

Anticoagulants and agents affecting blood clotting

Bleeding disorders may occur when escitalopram is used concomitantly with oral anticoagulants and drugs that affect blood clotting (for example, atypical antipsychotics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs (NSAIDs), ticlopidine and dipyridamole). In such cases, careful monitoring of blood clotting parameters is necessary at the beginning or at the end of therapy with escitalopram. Concomitant use with NSAIDs may lead to an increase in bleeding.

Ethanol

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

Medicines that cause hypokalemia/hypomagnesemia

Caution is required when simultaneous use of drugs that cause the development of hypokalemia/hypomagnesemia, since these conditions increase the risk of developing malignant arrhythmias.

Pharmacokinetic interaction

Effect of other drugs on the pharmacokinetics of escitalopram

The metabolism of escitalopram is mainly carried out with the participation of the CYP2C19 isoenzyme. To a lesser extent, isoenzymes CYP3A4 and CYP2D6 may participate in metabolism. Metabolism of the main metabolite, demethylated escitalopram, appears to be partially catalyzed by the CYP2D6 isoenzyme.

The simultaneous use of escitalopram and omeprazole 30 mg 1 time per day (inhibitor of the CYP2C19 isoenzyme) leads to a moderate (approximately 50%) increase in the concentration of escitalopram in the blood plasma.

Co-administration of escitalopram and cimetidine 400 mg 2 times a day (an inhibitor of the isoenzymes CYP2D6, CYP3A4 and CYP1A2) leads to an increase (approximately 70%) in the concentration of escitalopram in the blood plasma.

Thus, the maximum possible dose of escitalopram should be used concomitantly with inhibitors of the CYP2C19 isoenzyme (for example, omeprazole, fluconazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and cimetidine. When taking escitalopram and the above drugs simultaneously, a dose reduction of escitalopram may be necessary based on clinical assessment.

Effect of escitalopram on the pharmacokinetics of other drugs

Escitalopram is an inhibitor of the CYP2D6 isoenzyme.

Caution must be exercised when simultaneous use of escitalopram and drugs that are metabolized by this isoenzyme and have a low therapeutic index, for example, flecainide, propafenone and metoprolol (in cases of use in heart failure) or drugs that are mainly metabolized through the CYP2D6 isoenzyme and act on the central nervous system, for example, antidepressants (desipramine, clomipramine, nortriptyline) or antipsychotic drugs (risperidone, thioridazine, haloperidol). In these cases, dose adjustment may be required.

The simultaneous use of escitalopram and desipramine or metoprolol leads to a twofold increase in the concentration of the latter two drugs.

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

Overdose

Toxicity

Data on overdose with escitalopram are limited, and many such cases have involved overdose with other drugs. In most cases, symptoms of overdose do not appear or are mild.

Cases of overdose of escitalopram (without taking other drugs) with a fatal outcome are rare, in most cases there is also an overdose of other drugs. When taking escitalopram in the dose range from 400 mg to 800 mg in monotherapy, no clinically significant symptoms of overdose occurred.

Symptoms

In case of an overdose of escitalopram, symptoms mainly occur from the central nervous system (from dizziness, tremor and agitation to rare cases of serotonin syndrome, convulsive disorders and coma), from the gastrointestinal tract (nausea/vomiting), from the cardiovascular system (arterial hypotension, tachycardia, prolongation of the QT interval and arrhythmia) and electrolyte imbalance (hypokalemia, hyponatremia).

Treatment

There is no specific antidote. Normal airway patency, oxygenation and ventilation of the lungs should be ensured. Gastric lavage should be performed and activated charcoal should be prescribed. Gastric lavage should be performed as soon as possible after taking the drug. It is recommended to monitor the performance of the heart and other vital organs and provide symptomatic and supportive therapy.

Clinical pharmacology

Pharmacodynamics

Escitalopram is an antidepressant, a selective serotonin reuptake inhibitor (SSRI) with high affinity for the primary binding site. Escitalopram also binds to the allosteric binding site of the transporter protein, with an affinity one thousand times lower. Allosteric modulation of the transporter protein enhances the binding of escitalopram at the primary binding site, resulting in more complete inhibition of serotonin reuptake.

Escitalopram has no or very weak ability to bind to a number of receptors, including serotonin 5-HT1A, 5-HT2 receptors, dopamine D1 and D2 receptors, α1-, α2-, β-adrenergic receptors, H1-histamine, m-cholinergic receptors, benzodiazepine and opioid receptors.

5-HT reuptake inhibition is the only possible mechanism of action that explains the pharmacological and clinical effects of escitalopram.

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

Clinical effectiveness

Severe depressive episodes

Escitalopram was found to be effective in the acute treatment of severe depressive episodes in three of four double-blind, placebo-controlled, short-term (8-week) studies. In the long-term relapse prevention study, 274 patients who completed the initial 8-week open-label phase of the study and received escitalopram at a dose of 10 or 20 mg per day were randomized to receive escitalopram at the same dose or placebo for a maximum of 36 weeks. During this study, patients who continued to take escitalopram did not experience a relapse for a longer period of time in the subsequent 36 weeks compared with those who took placebo.

Obsessive-compulsive disorder

In a randomized, double-blind clinical trial, escitalopram 20 mg daily was compared with placebo based on Yale-Brown Obsessive Compulsive Scale scores at 12 weeks. After 24 weeks, escitalopram at a dose of 10 and 20 mg per day showed superior results compared to placebo.

Relapse prevention was demonstrated with escitalopram 10 and 20 mg daily in patients treated with escitalopram in a 16-week open-label study who participated in a 24-week randomized, double-blind, placebo-controlled study.

Pharmacokinetics

Suction

Asorption is almost complete and does not depend on the time of food intake. The average time to reach maximum plasma concentration (TCmax) is 4 hours after repeated use. The absolute bioavailability of escitalopram is about 80%, similar to racemic citalopram.

Distribution

The apparent volume of distribution (Vd, β/F) after oral administration ranges from 12 to 26 l/kg. The binding of escitalopram and its main metabolites to plasma proteins is below 80%. The kinetics of escitalopram is linear. Equilibrium concentration (Css) is reached after approximately 1 week, average Css – 50 nmol/l (from 20 to 125 nmol/l) is achieved with a daily dose of 10 mg.

Metabolism

Escitalopram is metabolized in the liver to demethylated and didemethylated metabolites. Both metabolites are pharmacologically active. Nitrogen can be oxidized to the N-oxide metabolite. The main substance and its metabolites are partially excreted in the form of glucuronides. After repeated use, the average concentrations of demethylated and didemethylated metabolites are 28-31% and less than 5% (respectively) of the concentration of escitalopram. Biotransformation of escitalopram into a demethylated metabolite occurs mainly with the help of the CYP2C19 isoenzyme, with some participation of the CYP3A4 and CYP2D6 isoenzymes possible.

Withdrawal

The half-life (T1/2) after repeated use is about 30 hours.

Oral clearance (Cloral) is 0.6 l/min. The main metabolites of escitalopram have a longer T1/2. Escitalopram and its main metabolites are excreted by the liver (metabolic pathway) and kidneys, most of them are excreted as metabolites by the kidneys.

Special patient groups

Elderly patients (over 65 years old)

In elderly patients (over 65 years of age), escitalopram is eliminated more slowly than in younger patients. The amount of escitalopram in the systemic circulation, calculated using the pharmacokinetic indicator area under the concentration-time curve (AUC), in elderly patients is 50% greater than in young healthy volunteers.

Liver dysfunction

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

Impaired kidney function

When using racemic citalopram in patients with renal failure (creatinine clearance (CC) 10-53 ml/min), a prolongation of T1/2 and a slight increase in AUC are observed. Concentrations of metabolites in blood plasma have not been studied, but they may be increased.

Polymorphism (in individuals with low activity of CYP2C19 or CYP2D6 isoenzymes)

In patients with low activity of the CYP2C19 isoenzyme, the concentration of escitalopram in the blood plasma may be 2 times higher than in patients with high activity of this isoenzyme. No significant changes in the concentration of escitalopram in the blood plasma were detected with low activity of the CYP2D6 isoenzyme.

Storage conditions

At a temperature not exceeding 25 ºС, in the original packaging.

Keep out of the reach of children.

Shelf life

3 years.

Do not use the drug after the expiration date.

Manufacturer

KRKA dd Novo Mesto, Slovenia