Esopram film-coated tablets 20 mg No. 30

Instructions for Esopram film-coated tablets 20 mg No. 30

Composition

active ingredient: escitalopram;

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

excipients: microcrystalline cellulose, colloidal anhydrous silica, talc, croscarmellose sodium, magnesium stearate;

shell: Opandry 03F2846 White: hypromellose 6cP, titanium dioxide (E 171), macrogol 600.

Dosage form

Film-coated tablets.

Main physicochemical properties:

Esopram 10 mg – white, oval, biconvex, film-coated tablets marked “E” on one side and with a breakline on the other and on both sides;

Esopram 20 mg are white, oval, biconvex, film-coated tablets marked "E" on one side and with a breakline on the other and on both sides.

Pharmacotherapeutic group

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATC code N06A B10.

Pharmacological properties

Pharmacodynamics.

Escitalopram is a selective serotonin (5-HT) reuptake inhibitor with high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter with 1000-fold lower affinity.

Escitalopram has no or very weak binding to receptors such as 5-HT1A, 5-HT2, dopamine D1 and D2 receptors, α1-, α2-, β-adrenergic receptors, histamine H1, muscarinic cholinergic, benzodiazepine and opiate receptors. Inhibition of 5-HT serotonin reuptake is only a possible mechanism of action that could explain the pharmacological and clinical effects of escitalopram.

Pharmacokinetics.

Absorption: Absorption is almost complete and independent of food intake. The mean time to reach maximum concentration (mean Tmax) is about 4 hours. The absolute bioavailability of escitalopram is expected to be 80%.

Distribution: The apparent volume of distribution (Vd, β/F) after oral administration is 12 to 26 l/kg. The binding of escitalopram and its major metabolites to plasma proteins is less than 80%.

Biotransformation. Escitalopram is metabolized in the liver to the biologically active demethylated and didemethylated metabolites. Nitrogen can also be oxidized to the N-oxide metabolite. Both metabolites and the parent compound are partially excreted as glucuronides. After multiple administration, the average concentration of demethylated and didemethyl metabolites is usually 28-31% and <5% of the concentration of escitalopram, respectively. Biotransformation of escitalopram to the demethylated metabolite occurs mainly with the help of cytochrome CYP2C19. Some participation of CYP3A4 and CYP2D6 enzymes is also possible.

Elimination. The elimination half-life (t½β) after multiple administration is about 30 hours. The plasma clearance after oral administration is 0.6 l/min. The main metabolites of escitalopram have a longer half-life. Escitalopram and its main metabolites are believed to be eliminated via the liver (metabolic pathway) and the kidneys. The majority is excreted as metabolites in the urine.

Escitalopram has linear kinetics. Steady-state concentrations are reached in approximately 1 week. The mean steady-state concentration of 50 nmol/l (range 20 to 125 nmol/l) is achieved with a daily dose of 10 mg.

Elderly patients (65 years and older)

Escitalopram is eliminated more slowly in elderly patients than in younger patients. Systemic exposure (AUC) in elderly subjects is approximately 50% higher than in young healthy volunteers.

Liver dysfunction

In patients with moderate or mild hepatic impairment (Child-Pugh class A and B), the half-life of escitalopram was almost doubled and exposure was approximately 60% higher than in subjects with normal hepatic function.

Kidney dysfunction

In patients with reduced renal function (CLcr 10–53 mL/min), an increase in the half-life of racemic citalopram and a slight increase in exposure were observed. Plasma concentrations of metabolites have not been studied, but an increase can be assumed.

Polymorphism: Insufficient activity of the CYP2C19 isoenzyme resulted in double the drug plasma concentrations compared to normal metabolism of escitalopram. Insufficient CYP2D6 isoenzyme did not result in significant changes in exposure.

Indication

Treatment:

major depressive episodes;

panic disorders with or without agoraphobia;

social anxiety disorders (social phobia);

generalized anxiety disorders;

obsessive-compulsive disorders.

Contraindication

Hypersensitivity to escitalopram or to any of the excipients included in the medicinal product;

simultaneous treatment with non-selective irreversible monoamine oxidase (MAO) inhibitors is contraindicated due to the risk of developing serotonin syndrome, which is manifested by agitation, tremor, hyperthermia, etc. Combined treatment with escitalopram and reversible MAO type A inhibitors (e.g. moclobemide) or reversible non-selective MAO inhibitors (linezolid) is also contraindicated due to the risk of developing serotonin syndrome;

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 receiving SSRIs in combination with non-selective, irreversible MAOIs and in patients who have recently stopped SSRIs and started taking an MAOI. In some cases, serotonin syndrome has been observed.

The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Treatment with escitalopram should be initiated 14 days after discontinuation of the irreversible MAOI and at least one day after discontinuation of the reversible MAOI moclobemide. Treatment with non-selective irreversible MAOIs should be initiated no earlier than 7 days after discontinuation of escitalopram.

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 contraindicated. If the need for this combination is proven, the minimum recommended doses should be used initially with close clinical monitoring.

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

Reversible selective MAO inhibitor (linezolid)

The antibiotic linezolid (a reversible non-selective MAOI) should not be used in patients taking escitalopram. If the combination is proven necessary, the lowest recommended doses should be used initially and close clinical monitoring should be performed.

Selective irreversible MAO inhibitor type B (selegiline)

Caution should be exercised when used in combination with selegiline due to the risk of serotonin syndrome. There is experience of safe use of selegiline in doses up to 10 mg/day concomitantly with racemic citalopram.

QT-prolonging drugs

Pharmacokinetic and pharmacodynamic studies of escitalopram and QT-prolonging medicinal products have not been conducted. An additive effect of escitalopram and these medicinal products cannot be excluded. Therefore, the concomitant use of escitalopram with medicinal products that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (including phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobials, including sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials, especially halofantrine, certain antihistamines (including astemizole, mizolastine), is contraindicated.

Combinations requiring caution

Serotonergic drugs

Concomitant use with serotonergic drugs (e.g. opioids such as tramadol and buprenorphine; sumatriptan and other triptans) may lead to the development of serotonin syndrome.

Medications that lower the seizure threshold

SSRIs may lower the seizure threshold. Caution is advised when concomitantly using drugs that 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 when SSRIs are co-administered with lithium or tryptophan, caution is recommended when these drugs are co-administered.

Hypericum

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

Anticoagulants

The effects of anticoagulants may be altered by concomitant use with escitalopram. Patients taking oral anticoagulants should have their blood coagulation status monitored carefully before and after use of escitalopram.

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

Ethanol

Escitalopram has no pharmacodynamic or pharmacokinetic interaction with ethanol, but, as with other psychotropic drugs, concomitant administration of escitalopram with ethanol-containing drugs is not recommended.

Drugs that may cause hypokalemia/hypomagnesemia

Caution should be exercised when using escitalopram concomitantly with drugs that cause hyponatremia/hypomagnesemia, as the risk of developing malignant arrhythmias increases when taking such a combination of drugs (see section "Special warnings and precautions for use").

Pharmacokinetic interactions

Effect of other medicinal products on the pharmacokinetics of escitalopram

The metabolism of escitalopram occurs mainly with the participation of CYP2C19. To a lesser extent, CYP3A4 and CYP2D6 are involved in the metabolism. The CYP2D6 isoenzyme is considered to be a partial catalyst for the metabolism of the main metabolite S-DCT (demethylated escitalopram).

Concomitant use of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) causes a moderate increase (approximately 70%) in plasma escitalopram concentrations, which may require dose adjustment.

Therefore, caution should be exercised when escitalopram is co-administered with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. When co-administered with the above-mentioned drugs, a dose reduction of escitalopram may be required, depending on the side effects experienced.

Effect of escitalopram on the pharmacokinetics of other drugs

Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Caution is required when prescribing escitalopram simultaneously with drugs metabolized by this isoenzyme, as well as with drugs with a narrow therapeutic index, such as flecainide, propafenone, metoprolol (used in heart failure), or with drugs that act on the CNS and are mainly metabolized by CYP2D6, such as antidepressants - desipramine, clomipramine and nortriptyline; antipsychotics - risperidone, thioridazine or haloperidol. In these cases, dose adjustment may be required.

Concomitant use with desipramine (the main metabolite of imipramine) or metoprolol results in a two-fold increase in plasma levels of these two CYP2D6 substrates. Escitalopram causes weak inhibition of CYP2C19 in in vitro studies. Therefore, caution is recommended when co-administering medicinal products metabolised by CYP2C19.

Application features

The following special precautions apply to the entire therapeutic class of SSRIs.

Children and adolescents

Suicidal behaviour (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were observed more frequently in clinical trials among children treated with antidepressants compared to those treated with placebo. If a decision to prescribe is made for clinical reasons, the patient should be closely monitored for suicidal symptoms. Furthermore, there are no data on the continued safety in children with regard to growth, puberty and cognitive and behavioural development. Therefore, the drug should not be used in the treatment of children and adolescents (under 18 years of age).

Paradoxical anxiety

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

Convulsive seizures

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, SSRIs should be discontinued.

Diabetes mellitus

In patients with diabetes mellitus, treatment with SSRIs may affect glycemic control (hypoglycemia or hyperglycemia). Dosage adjustments of insulin or oral hypoglycemic agents may be necessary.

Suicide, suicidal thoughts, or clinical worsening

Depression is associated with a risk of suicidal thoughts, 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 may be 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.

Therefore, such precautions are appropriate when treating patients with other mental disorders.

Patients with a history of suicidal behavior prior to initiation of treatment are at greatest risk of suicidal thoughts or attempts and require close monitoring during treatment. A meta-analysis of studies has shown an increased risk of suicidal behavior among patients under 25 years of age who received antidepressants compared with those who received 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 behavioral changes, and to seek immediate medical advice if they occur.

Akathisia/psychomotor agitation

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 is most likely to occur during the first few weeks of treatment. Increasing the dose may be harmful in patients who develop these symptoms.

Isolated cases of hyponatremia, presumably due to impaired antidiuretic hormone secretion, have been reported with SSRIs, which usually resolved after discontinuation of treatment. Particular caution is required when treating patients at risk, including the elderly, those with cirrhosis of the liver, and those taking concomitant medications that may cause hyponatremia.

Hemorrhages

Cutaneous hemorrhages such as ecchymosis and purpura have been reported with SSRIs. Caution should be exercised when using SSRIs, especially in combination with oral anticoagulants, drugs that affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs (NSAIDs), ticlopidine and dipyridamole), and in patients with a tendency to bleed.

The use of SSRIs/SNRIs may increase the risk of postpartum hemorrhage (see sections “Use during pregnancy or lactation” and “Adverse reactions”).

ECT (electroconvulsive therapy)

Clinical experience with the concomitant use of SSRIs and ECT is limited, so caution should be exercised.

Serotonin syndrome

Caution is required when prescribing escitalopram in combination with drugs that have serotonergic effects, such as sumatriptan and other triptans, opioids (tramadol and buprenorphine), and tryptophan.

Isolated cases of serotonin syndrome have been reported in patients receiving SSRIs and serotonergic medicinal products. Symptoms such as agitation, tremor, myoclonic seizures and hyperthermia may be indicative of the onset of this condition. In such cases, escitalopram and the serotonergic medicinal product should be discontinued immediately and symptomatic treatment initiated.

Hypericum

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

Withdrawal syndrome

Withdrawal symptoms are common when treatment is stopped (especially suddenly). In clinical trials, adverse events related to discontinuation of treatment were observed in approximately 25% of patients in the escitalopram group and 15% of patients in the placebo group.

The risk of withdrawal symptoms depends on many factors, including the duration and dose of therapy and the gradualness of dose reduction. The most commonly reported symptoms are dizziness, sensory disturbances (including paraesthesia, electric shock sensations), sleep disturbances (including insomnia and restless dreams), agitation or anxiety, vomiting/nausea, tremor, confusion, increased sweating, headache, diarrhoea, palpitations, emotional lability, irritability and visual disturbances. These symptoms are generally mild to moderate in severity, but may be severe in some patients. They usually occur within the first few days after discontinuation of treatment, although there have been isolated reports of such symptoms occurring after inadvertently missing only one dose. These symptoms are usually of limited duration and resolve within 2 weeks, although in some individuals they may be prolonged (2–3 months or more). In this case, it is recommended to discontinue escitalopram by gradually reducing the dose over a period of several weeks to several months, depending on the patient's condition.

Coronary heart disease

Due to limited clinical experience, caution is required when treating patients with coronary 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 torsades de pointes, have been reported in the post-marketing setting, predominantly in women with hypokalaemia or in patients with pre-existing QT prolongation or other cardiac disease.

Caution should be exercised when using the drug in patients with severe bradycardia and 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 starting treatment with escitalopram.

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

If signs of cardiac arrhythmia appear during the use of escitalopram, treatment should be discontinued and an ECG should be performed.

Angle-closure glaucoma

SSRIs, including escitalopram, may affect pupil size, resulting in mydriasis. This mydriatic effect may cause narrowing of the visual angle with subsequent increase in intraocular pressure and development of angle-closure glaucoma, especially in predisposed patients. Therefore, the drug should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.

Sexual dysfunction

The use of SSRIs/SNRIs may cause symptoms of sexual dysfunction. There have been reports of long-term sexual dysfunction, where symptoms persist even after discontinuation of SSRIs/SNRIs.

Use during pregnancy or breastfeeding

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

In reproductive toxicity studies conducted in rats with escitalopram, embryofetotoxic effects were observed, but without an increase in the incidence of malformations.

Escitalopram should not be administered to pregnant women unless clearly necessary after a careful assessment of the risks and benefits. Careful monitoring of newborns whose mothers have taken escitalopram during pregnancy, especially in the third trimester, is recommended. If the drug is used during pregnancy, abrupt discontinuation of treatment should also be avoided.

Newborns whose mothers took selective serotonin reuptake inhibitors (SSRIs)/selective serotonin norepinephrine reuptake inhibitors (SSRIs) in late pregnancy may experience the following symptoms: respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, breastfeeding problems, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, shaking, nervousness, irritability, apathy, constant crying, drowsiness and sleep disturbances. Such symptoms may develop either as a result of excessive serotonergic action or as withdrawal symptoms. In most cases, manifestations of 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: the risk was approximately 5 cases per 1000 pregnancies, the risk in the general population is 1-2 cases per 1000 pregnancies. Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage after the use of SSRIs/NSAIDs during the month before delivery (see sections “Special instructions for use” and “Adverse reactions”).

Breast-feeding

It is assumed that escitalopram passes into breast milk. Therefore, it is recommended to stop breastfeeding during treatment.

Fertility

Animal data have shown that some SSRIs may affect sperm quality. Data from humans using some SSRIs suggest that these effects on sperm quality are reversible. No effects on human fertility have been identified to date.

Ability to influence reaction speed when driving vehicles or other mechanisms

Although escitalopram has been shown not to affect mental function or psychomotor performance, any psychotropic drug may impair the ability to think clearly or to perform tasks. Patients should be warned of the potential risk of impairment when driving or operating machinery.

Method of administration and doses

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

Esopram is administered orally to adults once a day, regardless of meals.

Major depressive episodes. Usually prescribed 10 mg 1 time per day. 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 usually 6 months in order to consolidate the effect.

Panic disorder with or without agoraphobia. An initial dose of 5 mg (to be used in the appropriate dosage) per day is recommended for the first week, before increasing to 10 mg per day. The dose may then be increased to a maximum of 20 mg per day, depending on the individual patient's response.

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 disorder (social phobia). Usually prescribed 10 mg 1 time per day. Depending on the individual sensitivity of the patient, 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 prevents relapse and may be prescribed based on individual disease manifestations; the benefits of treatment should be regularly assessed. Social anxiety disorder has a well-defined diagnostic terminology for a specific disease, which should not be confused with hypertrophic shyness. Pharmacotherapy is indicated only for a disorder that significantly affects the professional and social activity of a person. The effectiveness of such treatment compared with cognitive behavioral therapy has not been studied. Pharmacotherapy should be part of an overall therapeutic strategy.

Generalized anxiety disorders. Usually prescribed 10 mg 1 time per day. 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 to consolidate the effect.

;Obsessive-compulsive disorder (OCD). Usually prescribed 10 mg 1 time per day. Depending on individual sensitivity, the dose may be increased to a maximum of 20 mg per day. OCD is a chronic disease, treatment should last a sufficient period to ensure complete disappearance of symptoms. The benefit of treatment and the correctness of the dosage should be regularly assessed.

Elderly patients (aged 65 years and over)

The recommended daily dose for the elderly is 5 mg (to be used in the appropriate dosage). Depending on individual sensitivity and severity of depression, the daily dose may be increased to 10 mg per day.

The effectiveness of escitalopram in the treatment of social anxiety disorder in the elderly has not been studied.

Kidney failure

In the presence of mild to moderate renal insufficiency, no dose adjustment is required. The drug should be used with caution in patients with severe renal insufficiency (creatinine clearance <30 ml/min).

Decreased liver function

For patients with mild to moderate hepatic impairment, the recommended starting dose during the first two weeks of treatment is 5 mg per day. Depending on the individual patient response, the dose may be increased to 10 mg per day. Escitalopram should be used with particular caution in patients with severe hepatic impairment, with careful dose titration.

Patients with reduced CYP2C19 activity

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.

Discontinuation of treatment

Abrupt discontinuation of treatment should be avoided.

When stopping treatment with Esopram, the dose should be gradually reduced over 1–2 weeks to avoid withdrawal reactions. If withdrawal symptoms occur during the dose reduction period or after stopping treatment, it may be necessary to return to the previously prescribed dose. Your doctor may then continue to reduce the dose, but more gradually.

Children.

The drug is contraindicated for the treatment of children (under 18 years of age). Suicidal behavior (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) were observed more frequently in children treated with antidepressants than in those treated with placebo. If a decision to prescribe is made for clinical reasons, the patient should be closely monitored for suicidal symptoms. In addition, there are no data on the subsequent safety in children with regard to growth, puberty, and 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 absent or mild. Reports of fatal outcomes from overdose with escitalopram are exceptional, most of them involving concomitant overdose with other drugs. Single doses of escitalopram in doses of 400-800 mg have not caused any severe symptoms.

Symptoms: Signs of escitalopram overdose mainly manifest themselves from the central nervous system (from dizziness, tremor and agitation to rare cases of serotonin syndrome, convulsions 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. It is necessary to establish and maintain a patent airway, ensure adequate oxygenation and respiratory function. Gastric lavage should be performed as soon as possible after oral administration of the drug and activated charcoal should be used. Continuous monitoring of cardiovascular function and vital signs is recommended, in combination with general symptomatic supportive measures.

Side effects

Side effects occur most often during the first or second week of treatment and, as a rule, the manifestations decrease with continued treatment.

Adverse reactions common to all SSRIs and escitalopram, observed in placebo-controlled studies and in clinical practice, are listed below by organ system and frequency.

Frequency classification: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000) or unknown (cannot be estimated from the available data).

Blood and lymphatic system disorders Not known: thrombocytopenia.

Immune system disorders: Rare: anaphylactic reactions.

Endocrine system: Not known: impaired secretion of antidiuretic hormone.

Nutritional and metabolic disorders: Common: decreased or increased appetite, weight gain. Uncommon: weight loss. Not known: hyponatremia, anorexia2.

Nervous system disorders: Very common: headache. Common: insomnia, somnolence, dizziness, paraesthesia, tremor. Uncommon: taste disturbance, sleep disturbance, syncope. Rare: serotonin syndrome. Not known: dyskinesia, movement disorders, convulsions, psychomotor restlessness/akathisia2.

On the part of the organs of vision. Uncommon: mydriasis, visual impairment.

Hearing disorders: Uncommon: tinnitus.

Cardiac disorders: Uncommon: tachycardia. Rare: bradycardia. Not known: ventricular arrhythmia, including torsades de pointes, QT prolongation (occurred predominantly in female patients with hypokalaemia or pre-existing QT prolongation or other cardiac disease).

Vascular disorders Not known: orthostatic hypotension.

Respiratory system disorders: Common: sinusitis, yawning. Uncommon: nosebleed.

Gastrointestinal disorders: Very common: nausea. Common: vomiting, diarrhoea, constipation, dry mouth. Uncommon: gastrointestinal bleeding (including rectal bleeding).

Hepatobiliary system: Not known: hepatitis, changes in liver function tests.

Skin and subcutaneous tissue disorders: Common: increased sweating. Uncommon: skin rash, alopecia, urticaria, pruritus. Not known: bruising, angioedema.

Musculoskeletal system: Common: arthralgia, myalgia.

Renal and urinary disorders: Not known: urinary retention.

Reproductive system and breast disorders: Common: men: ejaculation disorders, impotence. Uncommon: women: metrorrhagia, menorrhagia. Not known: galactorrhea; men: priapism; women: postpartum hemorrhage3.

General disorders: Common: fatigue, pyrexia. Uncommon: edema.

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

2 Such cases are known for the entire class of SSRIs.

3This event has been reported for the SSRI/SNRI therapeutic class as a whole (see sections “Special warnings and precautions for use”, “Use during pregnancy or lactation”).

Specific effects of drugs belonging to the SSRI class

Available data suggest that patients aged 50 years and older are at increased risk of bone fractures when taking SSRIs and tricyclic antidepressants. The mechanism for this is unknown.

Withdrawal symptoms

Discontinuation of SSRI/SNRI 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 in some patients they may be severe and/or prolonged. Therefore, gradual discontinuation of escitalopram treatment by dose reduction is recommended (see section 4.4).

QT prolongation

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