Estcitalopram-SZ, 10 mg 30 pcs

Pharmacotherapeutic group:Antidepressant

ATC code: N06AB10

Pharmacodynamics:

Escitalopram is an antidepressant selective serotonin reuptake inhibitor (SSRI) with minimal effect on neuronal reuptake of noradrenaline and dopamine. The mechanism of escitalopram’s (S-enantiomer of racemic citalopram) antidepressant effect is based on its ability to selectively block serotonin reuptake (5-hydroxytryptamine (5-HT)) by presynaptic membranes of brain neurons which determines its strengthening of serotoninergic action in central nervous system responsible for antidepressant effect and effectiveness for treatment of panic and social anxiety disorder.

Escitalopram compared to R-enantiomer (right-handed) has a 100 times more pronounced effect with respect to serotonin reuptake inhibition. Estcitalopram has no or very low affinity for serotonin (5-HT1-7) or other receptors including α1- α2- β-adrenoreceptors-dopamine (D1-5) m-cholinoreceptors-histamine (H1-3) muscarinic (M1-5) benzodiazepine and opioid receptors. Estcitalopram also does not bind or has low affinity for various ion channels including Na+ K+ C1+ and Ca2+ channels.

Pharmacokinetics:

The pharmacokinetics of escitalopram are linear and dose-dependent over a dose range of 10 to 30 mg/day with both single and multiple doses.

Intake

Intake of escitalopram is not dependent on food intake. Bioavailability is about 80%. Mean time to reach maximum plasma concentration (TCmax) is 4 hours after multiple administration.

Distribution

The estimated volume of distribution after oral administration is from 12 to 26 l/kg. When administered once daily, the steady-state plasma equilibrium concentration (Css) is reached after one week. The average equilibrium concentration is 50 nmol/L (20 to 125 nmol/L) at a daily dose of 10 mg. Binding to plasma proteins is about 56%.

Metabolism

Biotransformation of escitalopram occurs in the liver to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DCT) both metabolites are pharmacologically active. After multiple uses, the concentrations of the demethyl and didemethyl metabolites are usually 28-31% and less than 5%, respectively, of the concentration of escitalopram.

Escitalopram is at least 7 and 27 times more potent than S-DCT and S-DDCT, respectively, in inhibiting serotonin reuptake, indicating that the metabolites of escitalopram do not contribute significantly to the antidepressant effects of the drug. S-DCT and S-DCT also have no or very low affinity for serotonergic (5-HT1-7) or other receptors including α- and β-adrenoreceptor dopamine (D1-5) histamine (H1-3) muscarinic (M1-5) and benzodiazepine receptors. S-DCT and S-DDCT also do not bind to various ion channels including Nay K+Cl- and Ca2+ channels.

The metabolism of escitalopram to a demethylated metabolite occurs primarily via cytochrome P450 isoenzymes: CYP2C19 CYP3A4 and CYP2D6.

The elimination half-life (T1/2) after multiple administration is about 30 hours. Oral clearance (Cloral) is about 06 l/min. The major metabolites of escitalopram have a longer elimination half-life. Excitalopram and its major metabolites are excreted by the liver and most of them by the kidneys partially in the form of glucuronides.

In hepatic insufficiency

In patients with decreased hepatic function, the clearance of escitalopram is decreased by 37% and the half-life is doubled.

In patients with low activity of CYP2C19 isoenzyme, the concentration of escitalopram may be twice as high as in cases with high activity of this isoenzyme. No significant changes in drug concentrations have been observed in cases with low CYP2D6 isoenzyme activity.

In moderately severe renal failure, the clearance of escitalopram is reduced by 17%. There are no data on the pharmacokinetics of escitalopram in patients with severe renal impairment (creatinine clearance below 20 ml/min).

In the elderly (over 65 years), escitalopram is excreted slower than in younger patients. The amount of escitalopram in the systemic bloodstream (area under the concentration-time curve) and the elimination half-life are increased by approximately 50% in elderly patients.

Indications

Depressive episodes of any severity.

Panic disorder with/without agoraphobia.

Obsessive-compulsive disorder.

Active ingredient

Composition

1 tablet contains:

the active substance:

escitalopram oxalate 12.77 mg in terms of escitalopram – 10 mg;

excipients:

Microcrystalline cellulose 102 – 23.73 mg,

croscarmellose sodium (primellose) – 4.5 mg,

lactose monohydrate (lactopress) (milk sugar) – 100.0 mg,

low-substituted hyprolose (low-substituted hydroxypropyl cellulose) – 6.0 mg,

colloidal silicon dioxide (aerosil) – 1.5 mg,

magnesium stearate – 1.5 mg.

Shell composition: hypromellose – 2.55 mg, polysorbate-80 (tween-80) – 1.06 mg, talc – 0.85 mg, titanium dioxide E 171 – 0.54 mg.

How to take, the dosage

Escitalopram-SZ is administered orally once daily regardless of meals.

Depressive episodes

Escitalopram-SS is usually prescribed 10 mg once daily. Depending on the patient’s individual response, the dose may be increased to a maximum of 20 mg/day. Antidepressant effect usually develops in 2-4 weeks after the start of treatment. After symptoms of depression have disappeared, it is necessary to continue therapy for at least another 6 months to consolidate the effect obtained.

Panic disorder with/without agoraphobia

For the first week of treatment, a dose of 5 mg/day is recommended and then increased to 10 mg/day. Depending on the individual response of the patient, the dose may be increased to a maximum of 20 mg/day. Maximum therapeutic effect is achieved about 3 months after the start of treatment. Therapy lasts for several months.

Obsessive-compulsive disorder

The dose is usually prescribed 10 mg once daily. Depending on the patient’s individual response, the dose may subsequently be increased to a maximum of 20 mg/day.

As obsessive-compulsive disorder is a disease with a chronic course, the course of treatment must be long enough to ensure complete relief from symptoms and must last for at least 6 months. At least 1 year of treatment is recommended to prevent relapses.

Use in special patient groups

Elderly patients (over 65 years of age)

Half the usual recommended dose (i.e., only 5 mg/day) and a lower maximum dose (10 mg/day) are recommended.

Decreased renal function

In mild to moderate renal impairment, no dose adjustment is required. In patients with significant renal impairment (CK values below 30 ml/min) Eszitalopram-SZ should be prescribed with caution.

Decreased liver function

In mild to moderate hepatic impairment (Child-Pugh grade A or B), the recommended starting dose for the first two 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 hepatic insufficiency (class C on the Child-Pugh scale) the drug is prescribed under close medical supervision.

Decreased CYP2C19 isoenzyme activity

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

Stopping treatment

When discontinuing Eszitalopram-SZ, the dose should be reduced gradually over 1-2 weeks to avoid the onset of withdrawal syndrome.

Interaction

Pharmacodynamic Interactions

Nonselective non-reversible MAOI inhibitors

The occurrence of serious adverse reactions has been reported. Serious adverse reactions have been reported with concomitant use of SSRIs and non-selective non-reversible MAO inhibitors, as well as with the initiation of MAO inhibitors in patients who had stopped taking SSRIs shortly before. In some cases, patients have developed serotonin syndrome.

Escitalopram should not be used concomitantly with non-selective non-reversible MAOI inhibitors. Administration of escitalopram may be started 14 days after discontinuation of irreversible MAO inhibitors. Before starting non-selective irreversible MAO inhibitors, it should be at least 7 days after discontinuation of escitalopram.

The reversible selective MAO A inhibitor (moclobemide)

Because of the risk of serotonin syndrome, it is not recommended to use escitalopram simultaneously with the MAO A inhibitor moclobemide. If this combination of drugs is deemed clinically necessary, it is recommended to start with the lowest possible dose, and to monitor the patient on an ongoing clinical basis. The use of escitalopram may be started at least one day after withdrawal of the reversible MAO A inhibitor moclobemide.

The irreversible MAO B inhibitor (selegiline)

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

Medications that prolong the QT interval

It is not appropriate to use with medications that prolong the QT interval such as antiarrhythmics (procainamide amiodarone, etc.) antipsychotics/neuroleptics (e.g. pimozide phenothiazine derivatives (chlorpromazine trifluoperazine thioridazine, etc.) butyrophenephene derivatives (e.g., pimozide).) butyrophenone derivatives (haloperidol droperidol, etc.) tricyclic and tetracyclic antidepressants (amitriptyline imipramine maprotiline, etc.) selective serotonin reuptake inhibitors and similar antidepressants (such as fluoxetine venlafaxine, etc.)) Antimicrobials (macrolide antibiotics and their analogues such as erythromycin clarithromycin; quinolone and fluoroquinolone derivatives: sparfloxacin moxifloxacin; pentamidine) azole antifungals (ketoconazole fluconazole) domperidone ondansetron because escitalopram in doses exceeding 20 mg per day can cause abnormal changes in electrical activity of the heart (QT interval prolongation on ECG) and lead to heart rhythm disturbances (including development of “pirouette” type arrhythmias) which can be fatal.

Serotonergic medications

The co-administration of serotonergic medications (e.g., tramadol sumatriptan and other triptans) may lead to serotonin syndrome.

Drugs that lower the seizure threshold

SSRIs may lower the seizure threshold. Caution is required with other medications that lower the seizure threshold (tricyclic antidepressants SSRIs antipsychotics (neuroleptics) – phenothiazine derivatives tioxanthene and butyrophenone – mefloquine bupropion and tramadol) concomitantly with escitalopram.

Lithium tryptophan

Because of reported cases of enhanced effects with concomitant use of SSRIs and lithium or tryptophan, caution is recommended when using escitalopram with these drugs.

St. John’s Wort

The concomitant use of SSRIs and preparations containing Hypericum sage (Hypericumperforatum) may result in increased side effects.

Anticoagulants and agents that affect blood clotting

Impaired clotting may occur with concomitant use of escitalopram with oral anticoagulants and medications that affect blood clotting (e.g., atypical neuroleptics and phenothiazine derivatives most tricyclic antidepressants acetylsalicylic acid and the non-steroidal anti-inflammatory drugs ticlopidine and dipyridamole). In such cases, careful monitoring of blood clotting is necessary at the beginning or end of therapy with escitalopram. Simultaneous use with nonsteroidal anti-inflammatory drugs may lead to increased bleeding.

Drugs causing hypokalemia/hypomagnesemia

Cautious concomitant use of drugs causing hypokalemia/hypomagnesemia is required because these conditions increase the risk of malignant arrhythmias.

Pharmacokinetic interaction

The effect of other drugs on the pharmacokinetics of escitalopram.

The metabolism of escitalopram mainly occurs with the participation of CYP2C19 isoenzyme. CYP3A4 and CYP2D6 isoenzymes may participate in metabolism to a lesser extent. The metabolism of the main metabolite, demethylated escitalopram, is apparently partially catalyzed by CYP2D6 isoenzyme.

The concomitant use of escitalopram and omeprazole (CYP2C19 isoenzyme inhibitor) leads to a moderate (about 50%) increase in plasma concentrations of escitalopram.

The simultaneous use of escitalopram and cimetidine (CYP2D6 CYP3A4 and CYP1A2 isoenzyme inhibitor) at a dose of 400 mg twice daily leads to increased (approximately 70%) plasma concentrations of escitalopram.

Hence, maximum possible doses of escitalopram should be used with CYP2C19 isoenzyme inhibitors (e.g., omeprazole fluoxetine fluvoxamine lansoprazole ticlopidine) and cimetidine with caution. Concomitant administration of escitalopram and the above drugs may require a reduction in the dose of escitalopram based on clinical evaluation.

The effect of escitalopram on the pharmacokinetics of other drugs

Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Caution is required with concomitant use of escitalopram and drugs metabolised with this isoenzyme and of low therapeutic index e.g. propafenone flecainide and metoprolol (if used in cardiac patients) or medical drugs mainly metabolised by CYP2D6 and affecting the central nervous system e.g. antidepressants: desipramine clomipramine nortriptyline or antipsychotic drugs: risperidone thioridazine haloperidol Dose adjustments may be necessary in these cases.

The simultaneous use of escitalopram and desipramine or metoprolol causes a twofold increase in concentrations of the latter two drugs.

Escitalopram may slightly inhibit the CYP2C19 isoenzyme. Therefore, caution is recommended when concomitant use of escitalopram and drugs metabolized by CYP2C19 isoenzyme.

Interaction with ethanol

Escitalopram has no pharmacodynamic or pharmacokinetic interaction with ethanol. However, as with other psychotropic medications, concomitant use of escitalopram and alcohol is not recommended.

Special Instructions

The use of the drug in children and adolescents under 18 years of age

Antidepressants should not be prescribed to children and adolescents under 18 years of age because of the increased risk of suicidal behavior (suicide attempts and suicidal ideation) of hostility (with a predominance of aggressive behavior of confrontation and irritation). If a decision is made based on a clinical assessment to initiate antidepressant therapy, the patient should be closely monitored.

When using medications belonging to the therapeutic group of SSRIs, including escitalopram, the following should be considered. Paradoxical anxiety

Some patients with panic disorder may have increased anxiety at the beginning of antidepressant treatment. This paradoxical reaction usually disappears within the first two weeks of treatment. Low initial doses are recommended to reduce the likelihood of anxiogenic effects.

Epileptic seizures

Escitalopram should be discontinued in cases of primary development of seizures. Use is not recommended in patients with unstable epilepsy; in controlled seizures, close monitoring is necessary. If seizure frequency increases, SSRIs, including escitalopram, should be discontinued.

Mania

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

Diabetes

In patients with diabetes mellitus, treatment with escitalopram may alter blood glucose concentrations. Therefore, it may be necessary to adjust the doses of insulin and/or oral hypoglycemic drugs.

Suicidal/suicidal ideation and clinical worsening of depression

Depression is associated with an increased risk of suicidal ideation of self-harm and suicide (suicidal ideation). This risk persists until the onset of significant remission. Because improvement may not be seen for the first few weeks of therapy or even longer, patients should be monitored closely until improvement occurs.

Common clinical practice shows that in the early stages of recovery, there may be an increased risk of suicide.

Other psychiatric conditions for which escitalopram is prescribed may also be associated with an increased risk of suicidal events and phenomena. In addition, these conditions may be concomitant pathology with the depressive episode. When treating patients with other psychiatric disorders, the same precautions should be followed as when treating patients with a depressive episode.

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

Patients (and caregivers) should be cautioned to monitor for any clinical worsening of suicidal behavior or thoughts and unusual behavioral changes, and to seek medical advice immediately if these symptoms occur.

Akathisia/psychomotor agitation

The use of SSRIs is associated with the development of akathisia characterized by the development of subjectively unpleasant or depressing restlessness and a need for constant movement often combined with an inability to sit or stand still. This most often manifests itself during the first few weeks of treatment. In patients with these symptoms, increasing the dose may lead to worsening.

Hyponatremia

Hyponatremia possibly associated with impaired antidiuretic hormone (ADH) secretion on SSRIs is rare and usually disappears with discontinuation of therapy. Caution should be used when prescribing escitalopram and other SSRIs for individuals at risk for hyponatremia: older adults with cirrhosis and individuals taking medications that can cause hyponatremia.

Bleeding

In cases of skin bleeding (ecchymosis and purpura) have been reported while taking SSRIs. Caution is necessary when using escitalopram in patients taking oral anticoagulants and drugs that affect blood clotting and in patients who are prone to bleeding.

Electroconvulsive therapy

Because clinical experience with concomitant use of SSRIs and electroconvulsive therapy (ECT) is limited, caution should be exercised when using escitalopram and ECT concomitantly.

Serotonin syndrome

The combination of escitalopram and MAOA inhibitors is not recommended because of the risk of serotonin syndrome.

Escitalopram should be used with caution when taking medications with serotonergic effects such as sumatriptan or other triptans such as 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, myoclonus tremor and hyperthermia. If this occurs, concomitant treatment with SSRIs and serotoninergic drugs should be stopped immediately and symptomatic treatment should be initiated.

Ischemic Heart Disease

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

In cases of prolongation of the QT interval

. Excitalopram has been found to cause dose-dependent QT interval prolongation and ventricular arrhythmias including bidirectional tachycardia have been reported predominantly in female patients with hypokalemia or with pre-existing QT interval prolongation or other cardiovascular disease.

Patients with severe bradycardia after recent acute myocardial infarction or with uncompensated heart failure are advised to exercise caution when prescribing the drug.

Electrolyte disturbances such as hypokalemia and hypomagnesemia increase the risk of arrhythmias.

If escitalopram is prescribed for patients with chronic heart disease, an ECG should be done before starting treatment.

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

See withdrawal symptoms when discontinuing SSRI therapy

See withdrawal symptoms when discontinuing treatment are common especially if treatment is stopped abruptly.

In clinical studies, adverse events upon treatment discontinuation have been observed, but in 25% of patients receiving escitalopram and 15% of patients taking placebo.

The risk of treatment withdrawal may depend on several factors, including the duration of the dose during treatment as well as the rate of dose reduction. The most common reactions are dizziness sensory disturbances (including paresthesias and shocks) sleep disturbances (including insomnia and vivid dreams) agitation or restlessness nausea and/or vomiting confusion sweating headache diarrhea heart palpitations emotional instability irritability and visual disturbances. These symptoms are usually mild to moderate in severity, but in some patients they may become severe.

These usually occur within the first few days of discontinuing treatment, with similar symptoms less commonly reported in patients who have accidentally missed a dose.

These symptoms are usually self-healing and usually go away within 2 weeks, although some people may have them for longer periods (2-3 months or more). Therefore, it is recommended that the dose of escitalopram be gradually reduced following withdrawal of treatment over a period of weeks or months, depending on the patient’s needs.

While using escitalopram, refrain from engaging in potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

– Hypersensitivity to escitalopram and other drug components;

– concomitant use with monoamine oxidase inhibitors (MAOIs) monoamine oxidase-A (MAOA) (e.g., moclobemide) or reversible non-selective MAOI inhibitors;

Patients with prolonged QT interval (congenital prolonged QT syndrome);

– concomitant use with medications that can prolong the QT interval (e.g. class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides).

– concomitant use of pimozide.

– lactose intolerance – glucose-galactose malabsorption deficiency;

– pregnancy and lactation;

– children under 18 years of age (efficacy and safety of use have not been confirmed).

Extended renal insufficiency (creatinine clearance less than 30 mL/min) manic disorders (including history) pharmacologically uncontrolled epilepsy depression with suicidal ideation and attempts (when taking the drug, the risk of suicidal ideation and suicidal behavior increases especially during the first few months of drug therapy or during dose changes) diabetes mellitus under 25 years of age (due to risk of suicidal behavior); age over 65 years of age coronary heart disease cirrhosis liver tendency to hemorrhage and bleeding hyponatremia CYP2C19 isoenzyme deficiency; simultaneous use with serotonergic drugs sumatriptan tramadol tryptophan fentanyl; drugs that lower the threshold of seizure readiness drugs lithium drugs drugs containing St. John’s wort; bupronion neuroleptics oral anticoagulants and drugs that affect blood clotting non-steroidal anti-inflammatory drugs drugs that can cause hyponatremia drugs metabolized with participation of CYP2C19 isoenzyme omeprazole cimetidine fluvoxamine desipramine metoprolol clomipramine nortriptyline haloperidol risperidone; electroconvulsive therapy.

Side effects

Side effects most commonly 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 (World Health Organization classification): Very common (≥ 1/10) common (≥ 1/100 to < 1/10) infrequent (≥ 1/1000 to < 1/100) rare (≥ 1/10000 to < 1/1000) very rare (< 1/10000) frequency unknown (incidence cannot be estimated from existing data).

Blood and lymphatic system disorders: incidence unknown – thrombocytopenia.

Immune system disorders: rare – anaphylactic reactions.

Endocrine system disorders: frequency is unknown – insufficient secretion of antidiuretic hormone (ADH).

Metabolic disorders and eating disorders: frequent – decreased appetite increased appetite increased weight; infrequent – weight loss; frequency unknown – hyponatremia anorexia.

Psychiatric: frequently – anxiety anxiety anxiety; unusual dreams decreased libido anorgasmia (in women); infrequent – bruxism agitation nervousness panic attacks confusion of consciousness; rarely – aggression depersonalization hallucinations; frequently unknown – mania suicidal thoughts suicidal behavior. Cases of suicidal thoughts and behavior have been reported while taking escitalopram and immediately after discontinuation of therapy.

Nervous system disorders: frequent – insomnia somnolence dizziness paresthesia tremor; infrequent – taste disorders sleep disturbances syncopal states; rare – serotonin syndrome; frequency unknown – dyskinesia motor disorders seizure disorders psychomotor agitation/ akathisia.

Oner organs of vision: infrequent – mydriasis (dilation of the pupil) visual disturbances; frequency unknown – closed-angle glaucoma.

Hearing organ and labyrinth disorders: infrequent – tinnitus (tinnitus).

Cardiovascular system: infrequent – tachycardia; rare – bradycardia; frequency unknown – prolongation of QT interval on electrocardiogram.

Cases of QT interval prolongation and ventricular arrhythmias including pirouette-type ventricular tachycardia predominantly in female patients with hypokalemia or pre-existing QT interval prolongation or other cardiovascular diseases have been reported. In double-blind, placebo-controlled ECG studies in healthy volunteers, the change from baseline QTc (corrected by the Friedericia formula) was 43 msec at the 10 mg/day dose and 107 msec at 30 mg/day.

Vascular aspects: frequency unknown – orthostatic hypotension.

Respiratory system of the chest and mediastinum: frequent – sinusitis yawning; infrequent – nasal bleeding.

Gastrointestinal tract: very common – nausea; common – diarrhea constipation vomiting dry mouth; infrequent – gastrointestinal bleeding (including rectal bleeding).

Hepatic and biliary tract disorders: unknown – hepatitis impairment of liver function parameters.

Skin and subcutaneous tissue: common – increased sweating; infrequent – urticaria alopecia rash itching; frequency unknown – ecchymosis angioedema.

Skeletal, muscular and connective tissue: often – arthralgia myalgia.

Renal and urinary tract disorders: frequency unknown – urinary retention.

Reproductive system and the mammary gland: often – impotence impaired ejaculation; infrequent – metrorrhagia (uterine bleeding) menorrhagia; frequency unknown – galactorrhea priapism.

General disorders and disorders at the site of administration: frequent – weakness hyperthermia; infrequent – edema.

Impact on the results of laboratory and instrumental studies: frequently – change of laboratory indexes of liver function – hyponatremia and electrocardiogram changes (prolongation of QT interval – extension of QRS complex – change of S-T segment and T wave).

The abrupt withdrawal of drugs from the group of selective norepinephrine and serotonin reuptake inhibitors often leads to withdrawal syndrome. The most common effects are dizziness sensory disturbances (including paresthesias and current sensations) sleep disturbances (including insomnia and intense dreaming) agitation or anxiety nausea and/or vomiting Tremors confusion increased sweating headache diarrhea heart palpitations emotional instability irritability visual disturbances. These effects are usually mild to moderate and pass quickly, but in some patients they may be more severe and/or last longer. Gradual withdrawal of the drug by reducing the dose is recommended.

Class effect

In epidemiologic studies involving patients aged 50 years and older, an increased risk of bone fractures has been reported in patients receiving selective serotonin reuptake inhibitors and tricyclic antidepressants. The mechanism leading to this risk is unknown.

Overdose

Symptoms

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

Coma or fatal cases of overdose with escitalopram are extremely rare most of them include simultaneous overdose with other drugs. Taking a dose between 400 and 800 mg of escitalopram did not cause severe symptoms.

Treatment

There is no specific antidote. Symptomatic and supportive treatment: gastric lavage administration of enterosorbents (in particular activated charcoal) provision of a constant supply of fresh air support of external respiration function adequate oxygenation of the lungs. Monitor cardiovascular and respiratory system function along with general symptomatic and supportive treatment. Forced diuresis hemodialysis and hemosorption are not effective. The outcome is favorable.

Pregnancy use

Pregnancy use

Escitalopram should not be administered to pregnant women unless the potential clinical benefit outweighs the theoretical risk due to insufficient data on efficacy and safety in pregnant women.

In a study of reproductive toxicity of escitalopram in rats, embryopheletotoxicity was observed but no increase in birth defects was found. If administration of escitalopram continued into late pregnancy, especially in the third trimester, the newborn should be monitored.

If administration of escitalopram continued until delivery or was discontinued shortly before delivery, the newborn may develop withdrawal syndrome.

If the mother takes selective serotonin reuptake inhibitors or selective serotonin and noradrenaline reuptake inhibitors late in pregnancy, the following side effects may develop in the newborn: Persistent pulmonary hypertension respiratory depression cyanosis apnea seizure disorders temperature spikes difficulty feeding vomiting hypoglycemia muscle hypotonia hyperreflexia tremor increased neuroreflex excitability irritability lethargic sleep persistent crying sleepiness poor sleep. These symptoms may occur due to the development of withdrawal syndrome or serotoninergic effects. In most cases, such complications occur within 24 hours after birth.

Epidemiologic evidence suggests that use of selective serotonin reuptake inhibitors or selective serotonin and noradrenaline reuptake inhibitors during pregnancy, particularly in the later stages, may increase the risk of sustained pulmonary hypertension in newborns with a rate of up to 5 per 1000, with a rate in the general population of 1-2 per 1000.

The use during breastfeeding

Escitalopram and its metabolites penetrate into breast milk so the drug is contraindicated in breastfeeding. If it is necessary to use the drug, breastfeeding should be stopped.

Similarities