Escitalopram film-coated tablets 10 mg blister No. 30

Instructions Escitalopram film-coated tablets 10 mg blister No. 30

Composition

active ingredient: escitalopram;

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

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

Dosage form

Film-coated tablets.

Main physicochemical properties: film-coated tablets, white in color, round in shape, with a biconvex surface.

Pharmacotherapeutic group

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs).

ATX code N06A B10.

Pharmacological properties

Pharmacodynamics

Escitalopram is an antidepressant, a selective serotonin reuptake inhibitor, which determines the clinical and pharmacological effects of the drug. It has high affinity for the main binding site and the adjacent allosteric site of the serotonin transporter and has no or very weak ability to bind to some receptors, including serotonin 5-HT1A-, 5-HT2-receptors, dopamine D1- and D2-receptors, α1-, α2-, β-adrenergic receptors, histamine H1, muscarinic cholinergic, benzodiazepine and opiate receptors.

Escitalopram is the S-enantiomer of racemic citalopram with its own therapeutic activity. The R-enantiomer has been shown to be inert and to antagonize the serotonergic properties and corresponding pharmacological effects of the S-enantiomer.

Pharmacokinetics

Absorption is almost complete and independent of food intake. Maximum plasma concentration is reached 4 hours after administration. Bioavailability of escitalopram is approximately 80%. Protein binding of escitalopram and its main metabolites is below 80%. Metabolism occurs in the liver to demethylated and didemethylated metabolites. All of them are pharmacologically active. Biotransformation of escitalopram with the formation of the demethylated metabolite is carried out by cytochrome CYP2C19. Minor participation in the process of isoenzymes CYP3A4 and CYP2D6 is possible. The half-life (t½) of the drug is approximately 30 hours. Clearance (Cloral) when taken orally is approximately 0.6 l / min. The half-life is longer for the main metabolites. Escitalopram and its main metabolites are excreted by the liver (metabolic pathway) and kidneys. Most of the dose is excreted as metabolites in the urine. The kinetics of escitalopram are linear. Steady-state concentrations are reached after approximately 1 week.

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

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

In patients with reduced renal function, a longer half-life and slightly higher exposure were observed when racemic citalopram was administered. Plasma concentrations of metabolites have not been studied but may be increased.

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

Indication

Major depressive episodes;

panic disorders, including those with agoraphobia;

social anxiety disorders (social phobia);

generalized anxiety disorders;

obsessive-compulsive disorders.

Contraindication

Hypersensitivity to escitalopram or to other components of the drug;

simultaneous treatment with non-selective, irreversible monoamine oxidase inhibitors (MAOIs), as there is a risk of developing serotonin syndrome, manifested by agitation, tremor, and hyperthermia;

combination with reversible MAO-A inhibitors (e.g. moclobemide) or the reversible non-selective MAO inhibitor linezolid, as there is a risk of serotonin syndrome;

QT prolongation or congenital long QT syndrome;

simultaneous use with drugs that prolong the QT interval;

concomitant treatment with pimozide.

Interaction with other medicinal products and other types of interactions

Pharmacodynamic interactions

Contraindicated combinations

Non-selective, irreversible MAO inhibitors

Serious reactions have been reported in patients taking SSRIs in combination with a non-selective irreversible MAOI and in patients who have recently stopped taking SSRIs and started taking MAOIs. In some cases, serotonin syndrome has developed. The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Escitalopram treatment should be started 14 days after discontinuation of the irreversible MAOI. Treatment with non-selective irreversible MAOIs should be started no earlier than 7 days after discontinuation of escitalopram.

The combination of pimozide and racemic citalopram resulted in a mean prolongation of the QTc interval of approximately 10 ms. Due to the interaction of escitalopram with low doses of pimozide and increased side effects of the latter, the simultaneous use of these drugs is contraindicated.

Combinations requiring caution

Reversible selective MAO inhibitor type A (moclobemide)

Due to the risk of serotonin syndrome, the combination of escitalopram with the MAOI type A moclobemide is not recommended. If the need for this combination is proven, the minimum recommended doses should be prescribed initially and careful clinical monitoring should be carried out.

Treatment with escitalopram can be started no earlier than 1 day after stopping the reversible MAO inhibitor moclobemide.

The antibiotic linezolid is not recommended for use in patients taking escitalopram. If the combination is absolutely necessary, treatment should be initiated at the lowest recommended dose with close clinical monitoring.

Selegiline

The combination with selegiline (an irreversible MAO type B inhibitor) requires caution due to the risk of serotonin syndrome.

QT prolongation

Pharmacokinetic and pharmacodynamic studies of escitalopram in combination with other drugs that increase the QT interval have not been conducted. A cumulative effect of escitalopram and these drugs cannot be excluded. Therefore, concomitant administration of escitalopram with drugs that prolong the QT interval, such as class IA and III antiarrhythmics, neuroleptics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobials (e.g. sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials, including halofantrine), certain antihistamines (astemizole, mizolastine), is contraindicated.

Serotonergic medications

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

Medications that lower the seizure threshold

SSRIs may lower the seizure threshold. Caution is advised with concomitant use of drugs that may lower the seizure threshold (e.g. antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion and tramadol).

Lithium, tryptophan

Since cases of enhanced effects have been reported with the combined use of SSRIs and lithium or tryptophan, it is recommended to prescribe these drugs concomitantly with caution.

Hypericum

Concomitant use of SSRIs and herbal remedies containing St. John's wort may lead to an increased incidence of adverse reactions.

Anticoagulants

The effects of anticoagulants may be altered by concomitant use with escitalopram. If patients are taking oral anticoagulants, careful monitoring of the blood coagulation system is necessary before and after the use of escitalopram.

Concomitant use of nonsteroidal anti-inflammatory drugs may increase the tendency to bleed.

Alcohol

Escitalopram does not interact with alcohol in a pharmacodynamic or pharmacokinetic manner. However, the combination with alcohol is undesirable.

Drugs causing hypokalemia/hypomagnesemia

Caution should be exercised when concomitantly using medicinal products that cause hypokalaemia/hypomagnesaemia, as the risk of developing malignant arrhythmias may be increased.

Pharmacokinetic interactions

Effect of other agents on the pharmacokinetics of escitalopram

The metabolism of escitalopram is mainly mediated by CYP2C19. CYP3A4 and CYP2D6 enzymes may also be involved in the metabolism, although to a lesser extent. The CYP2D6 isoenzyme is believed to be a partial catalyst for the metabolism of the main metabolite S-DCT (demethylated escitalopram).

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

Co-administration of escitalopram and cimetidine 400 mg twice daily (a moderately potent major enzyme inhibitor) results in a moderate (approximately 70%) increase in escitalopram plasma concentrations.

Therefore, caution should be exercised when prescribing the upper limit doses of escitalopram when co-administered with CYP2C19 inhibitors (e.g. omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and with cimetidine. A dose reduction of escitalopram may be necessary based on clinical judgment.

Effect of escitalopram on the pharmacokinetics of other drugs

Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is advised when escitalopram is co-administered with medicinal products that are primarily metabolised by this enzyme and have a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (in heart failure), or with certain central nervous system agents that are primarily metabolised by CYP2D6, e.g. antidepressants such as desipramine, clomipramine and nortriptyline, antipsychotics such as risperidone, thioridazine and haloperidol. Dose adjustment may be required.

Caution is recommended when used concomitantly with drugs metabolized by CYP2C19.

Application features

The following features of use apply to the therapeutic group of SSRIs.

Paradoxical anxiety.

Some patients with panic disorder may experience increased anxiety when starting SSRI treatment. This paradoxical reaction usually resolves within 2 weeks of treatment. To reduce the likelihood of anxiogenic effects, low initial doses are recommended.

Convulsive attacks.

Escitalopram should be discontinued if the patient develops a first seizure or if the seizure frequency increases (in patients with established epilepsy). SSRIs should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be closely monitored.

Mania.

SSRIs should be used with caution in patients with a history of mania/hypomania. If a manic state occurs, the SSRI should be discontinued.

Diabetes.

In patients with diabetes mellitus, treatment with SSRIs may alter glycemic control (hypoglycemia or hyperglycemia). Dosage of insulin and/or oral hypoglycemic agents may need to be adjusted.

Suicide or clinical deterioration.

Depression is associated with a risk of suicidal ideation, self-harm and suicide. This risk persists until sustained remission is achieved. As improvement may not occur within the first few weeks or more of treatment, patients should be closely monitored until improvement occurs. There is clinical evidence that the risk of suicide is increased in the early stages of recovery.

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

Patients with a history of suicidal behavior are at greatest risk of suicidal thoughts or attempts and require close monitoring during treatment. A meta-analysis of studies has found an increased risk of suicidal behavior among patients under 25 years of age who took antidepressants compared with those who took placebo. Close monitoring of high-risk patients is particularly necessary at the beginning of treatment and when changing the dosage.

Patients and their caregivers should be warned about the need to monitor for any worsening of condition, suicidal behavior or thoughts, and unusual behavior.

Akathisia.

The use of SSRIs/SNRIs has been associated with the development of akathisia, a condition characterized by an unpleasant, debilitating feeling of restlessness and a need to move, often accompanied by an inability to sit or stand still. This condition may most often occur during the first few weeks of treatment. Increasing the dose may be harmful in patients who develop these symptoms.

Hyponatremia.

Hyponatremia, possibly due to impaired antidiuretic hormone (ADH) secretion, occurs rarely with SSRIs and usually resolves after discontinuation of therapy. SSRIs should be used with caution in patients at risk (elderly, with cirrhosis of the liver, or concomitant treatment with drugs known to cause hyponatremia).

Hemorrhages.

When taking SSRIs, bleeding (ecchymosis and purpura) may develop. SSRIs should be prescribed with caution to patients with a tendency to bleeding, as well as to patients taking anticoagulants and drugs that affect blood clotting.

ECT (electroconvulsive therapy).

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

Reversible selective MAO inhibitors type A.

Combining escitalopram and MAO inhibitors is not recommended due to the risk of serotonin syndrome.

Serotonin syndrome.

In patients taking SSRIs concomitantly with serotonergic drugs, serotonin syndrome may develop in isolated cases. Escitalopram should be used with caution in combination with drugs that have serotonergic effects. The combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of serotonin syndrome. If such a situation occurs, SSRIs and serotonergic drugs should be urgently discontinued and symptomatic treatment should be prescribed.

Hypericum.

Concomitant use of SSRIs and herbal remedies containing St. John's wort may lead to an increased incidence of adverse reactions.

Withdrawal symptoms.

The risk of withdrawal symptoms may depend on several factors, including duration and dose, and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia, electric shock sensations), sleep disturbances (including insomnia, vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhoea, palpitations, emotional instability, irritability and visual disturbances are the most common reactions. These symptoms are usually mild to moderate in severity, but may be more severe in some patients. They usually occur within the first few days after discontinuation of treatment, but there have been very rare reports of such symptoms in patients who accidentally missed a dose.

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

Ischemic heart disease.

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

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

Caution is recommended in patients with marked bradycardia or in patients with recent acute myocardial infarction or uncompensated heart failure. Electrolyte disturbances such as hypokalemia and hypomagnesemia increase the risk of malignant arrhythmias and should be corrected before initiating treatment with escitalopram.

In patients with stable cardiac disease, an ECG should be reviewed before treatment is initiated. If signs of cardiac arrhythmia occur during treatment with escitalopram, therapy should be discontinued and an ECG should be performed.

Angle-closure glaucoma.

SSRIs, including escitalopram, can affect pupil size.

This mydriatic effect has the potential to narrow the anterior chamber angle, which in turn may lead to increased intraocular pressure and the development of angle-closure glaucoma, especially in predisposed patients. Escitalopram should therefore be used with caution in patients with angle-closure glaucoma or a history of glaucoma.

Use during pregnancy or breastfeeding

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

Escitalopram is contraindicated in pregnant women unless the need for the drug is clearly demonstrated after careful consideration of the risks and benefits. Careful observation of newborns whose mothers have taken escitalopram during pregnancy, especially in the third trimester, is recommended.

The following symptoms may occur in newborns whose mothers took SSRIs/SNRIs in the late stages of pregnancy: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, apathy, constant crying, drowsiness and difficulty sleeping. Such symptoms may develop either as a result of excessive serotonergic action or as withdrawal symptoms. In most cases, such complications occur immediately or shortly (up to 24 hours) after delivery.

Epidemiological data have shown 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 observational data). In the general population, the incidence is 1 to 2 cases per 1000 pregnancies.

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

Fertility

Animal data have shown that some SSRIs may affect sperm quality. Reports from some SSRIs in humans have shown that the effects on sperm quality are reversible. Effects on human fertility have not been observed to date.

Ability to influence reaction speed when driving vehicles or other mechanisms

Although escitalopram does not affect intellectual or psychomotor functioning, any psychoactive drug may impair skills or the ability to think rationally. Patients should be warned of the potential risk of impairment in driving or operating machinery.

Method of administration and doses

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

Depresan should be administered orally to adults once a day, regardless of meals.

Major depressive episode.

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

The antidepressant effect usually occurs after 2-4 weeks. After the symptoms disappear, treatment should be continued for 6 months to consolidate the effect.

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

The maximum effect in the treatment of panic disorders is achieved after 3 months. The duration of treatment is several months and depends on the severity of the disease.

Social anxiety disorders (social phobia).

The usual dose is 10 mg once daily. Depending on the individual patient's response, it is recommended to increase the daily dose to a maximum of 20 mg per day.

Symptom relief usually occurs after 2-4 weeks of treatment. It is recommended to continue treatment for 3 months. Long-term treatment for 6 months should be prescribed to prevent relapse, taking into account individual manifestations of the disease; the effectiveness of treatment should be regularly assessed.

Generalized anxiety disorders.

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

It is recommended to continue treatment for 3 months. Long-term treatment for

6 months should be prescribed to prevent relapse, taking into account individual manifestations of the disease; the effectiveness of treatment should be regularly assessed.

Obsessive-compulsive disorder (OCD).

Prescribe 10 mg once daily. Depending on individual sensitivity, the dose may be increased to 20 mg daily. OCD is a chronic disease, treatment should last for a sufficient period to ensure complete resolution of symptoms, which may be several months or even longer.

Elderly patients (aged 65 and over).

The initial dose should be half the usual recommended dose. The recommended daily dose for the elderly is 5 mg. Depending on individual sensitivity and severity of depression, the daily dose may be increased to a maximum of 10 mg per day.

Kidney failure.

There are no restrictions in mild to moderate renal impairment. The drug should be used with caution in patients with severe renal impairment (creatinine clearance < 30 ml/min).

Decreased liver function.

The recommended starting dose for the first two weeks of treatment is 5 mg per day. Depending on the individual patient's response, the dose may be increased to 10 mg per day.

Reduced activity of the cytochrome isoenzyme CYP2C19.

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

Treatment discontinuation.

Treatment with Depresan should be discontinued gradually, reducing the dose over 1-2 weeks, to avoid a withdrawal reaction.

Children.

Depresan should not be used to treat children under 18 years of age. Suicidal behavior (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) were more frequently observed in studies among children and adolescents taking antidepressants compared to those taking placebo. If a decision to prescribe is nevertheless made for clinical reasons, careful monitoring for suicidal symptoms in the patient should be ensured.

There are no data on further safety for children regarding growth, puberty, cognitive and behavioral development.

Overdose

Toxicity. Clinical data on overdose with escitalopram are limited. Many cases have been caused by concomitant overdose with other drugs. In most cases, symptoms were mild or asymptomatic. Reports of fatal overdose with escitalopram are exceptional, most of them involving concomitant overdose with other drugs. Doses in the range of 400-800 mg of escitalopram have not caused any severe symptoms.

Symptoms: Escitalopram overdose is mainly manifested by symptoms from the central nervous system (from dizziness, tremor and agitation to rare cases of serotonin syndrome, seizures and coma), the gastrointestinal system (nausea, vomiting), the cardiovascular system (arterial hypotension, tachycardia, QT prolongation, arrhythmia) and electrolyte imbalance (hypokalemia, hyponatremia).

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

Adverse reactions

Adverse reactions are most often observed during the first or second week of treatment, and usually their frequency and intensity gradually decrease with continued treatment.

Adverse reactions that occurred with the use of SSRIs (selective serotonin reuptake inhibitors) and escitalopram are presented by organ system.

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

2 Such cases have occurred with the use of any SSRI.

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

Epidemiological studies, mainly in patients aged 50 years and older, have been reported to show an increased risk of bone fractures with the use of SSRIs, including escitalopram, and tricyclic antidepressants. The mechanism of this effect is unknown.

Withdrawal symptoms

Discontinuation of SSRI treatment (especially abrupt) usually leads to withdrawal 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, increased sweating, headache, diarrhoea, palpitations, emotional lability, irritability and visual disturbances are the most common reactions. These symptoms are usually mild to moderate in severity and transient, but may be severe and/or prolonged in some patients. Therefore, gradual discontinuation of escitalopram treatment by dose reduction is recommended.

Expiration date

3 years.

Storage conditions

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

Keep out of reach of children.

Packaging

10 tablets in a blister; 3 or 6 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

Limited Liability Company "Kharkiv Pharmaceutical Enterprise "People's Health".

Address

Ukraine, 61002, Kharkiv region, Kharkiv city, Kulykivska street, building 41.