Escitalopram-teva

INSTRUCTION for medical use of the medicinal product Escitalopram-Teva

Composition:

Active substance: escitalopram;

1 tablet contains escitalopram 5 mg, 10 mg, 15 mg, or 20 mg;

Excipients:
Core: microcrystalline cellulose, colloidal anhydrous silicon dioxide, sodium croscarmellose, stearic acid, magnesium stearate;
Coating: hypromellose, titanium dioxide (E 171), polyethylene glycol 400.

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties:

Escitalopram-Teva, 5 mg: white, round, biconvex, film-coated tablets with the imprint “5” on one side and smooth on the other side. No cracks or chips observed.

Escitalopram-Teva, 10 mg: white, round, biconvex, film-coated tablets with the imprint “10” on one side and a break line on the other side. No cracks or chips observed.

Escitalopram-Teva, 15 mg: white, round, biconvex, film-coated tablets with a break line on one side, imprint “S” to the left and “C” to the right of the break line, and imprint “15” on the other side, without visible cracks or chips.

The break line is not intended for dividing the tablet into two equal doses, but to facilitate swallowing.

Escitalopram-Teva, 20 mg: white, round, biconvex, film-coated tablets with a break line on one side, imprint “9” to the left and “3” to the right of the break line, and imprint “7463” on the other side, without visible cracks or chips. The tablet can be divided along the break line into two equal parts.

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATC code N06AB10.

Pharmacological properties.

Pharmacodynamics.

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

Escitalopram has no or very weak affinity for a number of receptors, including 5-HT1A, 5-HT2, dopamine D1 and D2 receptors, α1, α2, β-adrenergic receptors, histamine H1, muscarinic cholinergic, benzodiazepine, and opioid receptors.

Inhibition of serotonin (5-HT) reuptake is considered the likely mechanism of action that may explain the pharmacological and clinical effects of escitalopram.

Pharmacokinetics.

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

The apparent volume of distribution (Vd, β/F) after oral administration ranges from 12–26 L/kg. Plasma protein binding of escitalopram and its main metabolites is less than 80%.

Escitalopram is metabolized in the liver to demethylated and didemethylated metabolites. Both are pharmacologically active. Nitrogen may also be oxidized to form an N-oxide metabolite. Both metabolites and the parent compound are partially excreted as glucuronides. After repeated administration, the average concentrations of the demethyl and didemethyl metabolites are typically 28–31% and <5%, respectively, of escitalopram concentration. The biotransformation of escitalopram to its demethylated metabolite occurs primarily via the cytochrome CYP2C19. Enzymes CYP3A4 and CYP2D6 may also play a minor role.

The elimination half-life (t1/2) after repeated administration is approximately 30 hours. Oral plasma clearance is 0.6 L/min. The main metabolites of escitalopram have a longer elimination half-life. Escitalopram and its main metabolites are considered to be eliminated via hepatic (metabolic pathway) and renal routes. Most of the drug is excreted in urine as metabolites.

The pharmacokinetics of escitalopram are linear. Steady-state concentration is reached after approximately 1 week. The mean steady-state concentration of 50 nmol/L (range 20–125 nmol/L) is achieved with a daily dose of 10 mg.

Elderly patients (aged 65 years and older)

In elderly patients, escitalopram is eliminated more slowly than in younger patients. The systemic exposure, measured by the pharmacokinetic parameter "area under the curve" (AUC), is 50% higher in elderly patients compared to younger healthy volunteers.

Impaired liver function

In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the elimination half-life of escitalopram is nearly doubled, and exposure is 60% higher than in individuals with normal liver function.

Impaired renal function

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

In patients with poor CYP2C19 isoenzyme activity, plasma concentrations of the drug are doubled compared to those with normal escitalopram metabolism.

No significant changes in exposure have been observed in patients with deficient CYP2D6 isoenzyme activity.

Clinical characteristics.

Indications.

Treatment:

• Major depressive episodes;
• Panic disorders with/without agoraphobia;
• Social anxiety disorders (social phobia);
• Generalized anxiety disorders;
• Obsessive-compulsive disorders.

Contraindications.

Hypersensitivity to the active substance or to any other component of the medicinal product. Concomitant use with non-selective irreversible monoamine oxidase inhibitors (MAOIs) due to the risk of developing serotonin syndrome, which manifests as agitation, tremor, and hyperthermia.

Combination therapy with escitalopram and reversible MAO-A inhibitors (e.g., moclobemide) or reversible non-selective MAOIs (e.g., linezolid) is contraindicated due to the risk of serotonin syndrome.

If prolonged QT interval or congenital long QT syndrome is known to be present in the patient, co-administration with medicinal products that prolong the QT interval is contraindicated.

Concomitant use with pimozide is contraindicated.

Interaction with other medicinal products and other forms of interaction.

Pharmacodynamic interactions.

Contraindicated combinations

Prolongation of QT interval

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

Non-selective irreversible MAOIs

Serious reactions have been reported in patients taking SSRIs in combination with non-selective irreversible MAOIs, as well as in patients who recently discontinued SSRIs and started therapy with such MAOIs. In some cases, serotonin syndrome occurred. Combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Escitalopram therapy may be initiated no sooner than 14 days after the last dose of an irreversible MAOI. Conversely, MAOI therapy may be started only 7 days after discontinuation of escitalopram.

The combination of pimozide and racemic citalopram has been associated with QT interval prolongation of approximately 10 msec. Due to the interaction between escitalopram and low doses of pimozide, and the potentiation of the latter's adverse effects, concomitant use of these drugs is contraindicated.

Reversible non-selective MAOI (linezolid)

The antibiotic linezolid is not recommended for administration to patients receiving escitalopram therapy. If such a combination is necessary, treatment should be initiated at the lowest recommended dose with mandatory close clinical monitoring.

Reversible selective MAOI type A (moclobemide)

Concomitant use of escitalopram with the reversible selective MAOI type A (moclobemide) is not recommended due to the risk of serotonin syndrome. If such a combination is necessary, treatment should be initiated at the lowest recommended dose with mandatory close clinical monitoring. Escitalopram therapy may be started no sooner than 1 day after discontinuation of the reversible MAOI moclobemide.

Irreversible selective MAO-B inhibitor (selegiline)

Due to the risk of serotonin syndrome, caution is required when using escitalopram concomitantly with selegiline. For concomitant use with racemic citalopram, selegiline doses up to 10 mg per day are considered safe.

Combinations requiring caution

Serotonergic medicinal products

Concomitant use with serotonergic medicinal products (e.g., opioids such as tramadol and buprenorphine; sumatriptan and other triptans) may lead to serotonin syndrome.

Medicinal products that lower the seizure threshold

SSRIs may lower the seizure threshold. Caution is required when co-administering escitalopram with other medicinal products that may lower the seizure threshold [e.g., antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, and butyrophenones), mefloquine, bupropion, and tramadol].

Lithium, tryptophan

Cases of enhanced serotonergic effect have been reported with the use of SSRIs in combination with lithium or tryptophan. Therefore, caution is recommended when using escitalopram concomitantly with these medicinal products, along with mandatory regular monitoring of lithium and tryptophan levels.

St. John’s wort

Concomitant use of escitalopram and herbal products containing St. John’s wort (Hypericum perforatum) may increase the frequency of adverse reactions; therefore, simultaneous administration is not recommended.

Anticoagulants and medicinal products affecting blood coagulation

Changes in the effects of anticoagulants may occur with concomitant use of escitalopram. Concomitant use of escitalopram and oral anticoagulants requires careful monitoring of blood coagulation parameters, especially before and after discontinuation of escitalopram. Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of bleeding.

Ethanol

Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interaction with ethanol. However, as with other psychotropic medicinal products, concomitant use of escitalopram with medicinal products containing ethanol is not recommended.

Medicinal products causing hypokalemia/hypomagnesemia

Caution is required when co-administering medicinal products that cause hypokalemia/hypomagnesemia, as this increases the risk of developing malignant arrhythmias.

Pharmacokinetic interactions.

Effect of other medicinal products on escitalopram pharmacokinetics

Escitalopram is metabolized primarily by CYP2C19, although CYP3A4 and CYP2D6 are also involved to a lesser extent. The isoenzyme CYP2D6 is considered a partial catalyst in the metabolism of the main metabolite S-DCT (demethylated escitalopram).

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

Concomitant administration of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) results in a moderate increase (approximately 70%) in plasma concentration of escitalopram.

Therefore, escitalopram should be used with caution when administered concomitantly with CYP2C19 inhibitors (e.g., omeprazole, esomeprazole, fluoxetine, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. When used concomitantly with the above-mentioned medicinal products, adverse effects may necessitate a reduction in escitalopram dosage.

Effect of escitalopram on the pharmacokinetics of other medicinal products

Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Caution is required when prescribing escitalopram concomitantly with medicinal products metabolized by this isoenzyme and having a narrow therapeutic index, such as flecainide, propafenone, metoprolol (in heart failure), or with CNS-acting drugs primarily metabolized by CYP2D6, such as antidepressants (e.g., desipramine, clomipramine, nortriptyline) and antipsychotics (e.g., risperidone, thioridazine, haloperidol). In such cases, dose adjustment may be necessary.

Concomitant administration with desipramine or metoprolol results in a doubling of plasma levels of these two CYP2D6 substrates. Escitalopram causes weak inhibition of CYP2C19 in in vitro studies; therefore, caution is recommended when co-prescribing medicinal products whose metabolism is mediated by CYP2C19.

Special precautions for use.

The special warnings and precautions listed below apply to the entire therapeutic class of SSRIs.

Paradoxical anxiety

Some patients with panic disorders may experience increased anxiety at the beginning of treatment with antidepressants. This paradoxical reaction usually resolves within the first two weeks of treatment. A low initial dose is recommended to reduce the likelihood of an anxiogenic effect.

Seizures

Treatment with escitalopram should be discontinued if a patient develops a seizure for the first time or experiences increased seizure frequency (in patients with established epilepsy). SSRIs should be avoided in patients with unstable epilepsy, and close monitoring is required in patients with controlled epilepsy.

Mania

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

Diabetes mellitus

In patients with diabetes mellitus, treatment with SSRIs may affect glycaemic control (hypoglycaemia or hyperglycaemia). Doses of insulin and/or oral hypoglycaemic agents may require adjustment.

Suicide, suicidal thoughts, or clinical worsening

Depression is associated with an increased risk of suicide, suicidal thoughts, and self-harm (suicidal behaviour). This risk persists until sustained remission is achieved. Since improvement may not occur during the first few weeks of treatment or longer, patients should be closely monitored until their condition improves. It is known that the risk of suicide may increase in the early stages of recovery.

Other psychiatric disorders for which escitalopram is used may also be associated with an increased risk of suicidal behaviour. These conditions may also be comorbid with major depressive disorder. Similar caution is required when treating other psychiatric disorders.

Due to the high risk of suicidal thoughts and behaviour during treatment, close monitoring is necessary for patients with a history of suicidal ideation or behaviour, or with significant levels of suicidal thinking before treatment initiation. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressant use in patients under 25 years of age compared to placebo. Pharmacological treatment should be accompanied by close monitoring of patients, especially those at increased risk, particularly at the beginning of treatment and after dose changes.

Patients (and their caregivers) should be warned to monitor for any worsening of symptoms, suicidal thoughts or behaviour, or unusual changes in behaviour, and to seek immediate medical advice if such symptoms occur.

Akathisia and psychomotor agitation

Use of SSRIs/SNRIs (selective serotonin and norepinephrine reuptake inhibitors) has been associated with the development of akathisia—a condition characterized by an unpleasant, distressing sense of restlessness and an urge 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 worsen symptoms in patients who develop such reactions.

Hyponatraemia

Cases of hyponatraemia have been reported during SSRI treatment, probably due to syndrome of inappropriate antidiuretic hormone secretion (SIADH), which usually resolves after discontinuation of therapy. Particular caution is required when treating patients at risk (elderly patients, patients with liver cirrhosis, or those receiving concomitant medications with hyponatraemia-inducing properties).

Bleeding

Skin haemorrhages, ecchymoses, and purpura may occur during SSRI treatment. SSRIs should be used with caution in patients receiving concomitant anticoagulants, drugs affecting platelet function (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid and NSAIDs, ticlopidine, and dipyridamole), and in patients with a predisposition to bleeding.

Use of SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections "Use during pregnancy or breastfeeding" and "Adverse reactions").

Electroconvulsive therapy (ECT)

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

Reversible selective MAO-A inhibitors

Combining escitalopram with MAO-A inhibitors is contraindicated due to the risk of serotonin syndrome.

Serotonin syndrome

Caution is required when escitalopram is used concomitantly with serotonergic agents such as sumatriptan or other triptans, opioids (e.g. tramadol and buprenorphine), and tryptophan.

Isolated cases of serotonin syndrome have been reported in patients taking SSRIs concomitantly with serotonergic drugs. Symptoms indicating the onset of this condition may include agitation, tremor, myoclonus, and hyperthermia. In such cases, escitalopram and the serotonergic drug should be discontinued immediately, and symptomatic treatment initiated.

St. John’s wort

Concomitant use of SSRIs and herbal preparations containing St. John’s wort (Hypericum perforatum) may increase the frequency of adverse reactions.

Withdrawal symptoms

Withdrawal symptoms usually occur when treatment is discontinued (especially abruptly). In clinical trials, adverse events associated with discontinuation were observed in approximately 25% of patients in the escitalopram group and 15% in the placebo group.

The risk of withdrawal symptoms depends on several factors, including duration of therapy, dose, and the gradualness of dose reduction. 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, excessive sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances have been reported as the most common reactions. 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, although isolated reports describe such symptoms after unintentionally missing only one dose. These symptoms are usually transient and resolve within 2 weeks, although in some patients they may persist for longer periods (2–3 months or more). In such cases, it is recommended to discontinue escitalopram gradually over 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 interval prolongation

Escitalopram has been shown to cause dose-dependent QT interval prolongation. During the post-marketing period, cases of QT interval prolongation, including torsades de pointes, have been reported, primarily in female patients with hypokalaemia or pre-existing QT prolongation or other cardiac diseases.

The drug should be used with caution in patients with marked bradycardia or those with recent acute myocardial infarction or uncompensated heart failure.

Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of malignant arrhythmias and should be corrected before initiating escitalopram treatment.

An ECG should be performed before starting treatment in patients with stable cardiac disease.

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

Alcoholic beverages should not be consumed during treatment with Escitalopram-Teva.

Angle-closure glaucoma

SSRIs, including escitalopram, may affect pupil size, resulting in mydriasis. This, in turn, may cause narrowing of the anterior chamber angle and, consequently, increased intraocular pressure and triggering of angle-closure glaucoma, especially in predisposed patients. Therefore, escitalopram should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.

Sexual dysfunction

Use of SSRIs/SNRIs may cause symptoms of sexual dysfunction. Reports of persistent sexual dysfunction have been documented, where symptoms persisted even after discontinuation of SSRIs/SNRIs.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of escitalopram during pregnancy are limited. In reproductive toxicity studies in animals, embryofetotoxic effects were observed without an increase in the frequency of developmental malformations. Escitalopram is contraindicated during pregnancy except in cases where a careful evaluation of risks and benefits clearly demonstrates the necessity of treatment. Newborns whose mothers received escitalopram during pregnancy, particularly in the third trimester, should be carefully monitored.

Treatment with the drug during pregnancy should not be stopped abruptly.

The following disturbances have been reported in newborns whose mothers took SSRIs/SNRIs late in pregnancy: respiratory distress syndrome, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, arterial hypertension, arterial hypotension, hyperreflexia, tremor, jitteriness, nervous agitation, irritability, somnolence, persistent crying, lethargy, and sleep difficulties. These disturbances may represent serotonergic effects or withdrawal syndrome. In most cases, complications began immediately or shortly (<24 hours) after delivery.

It has been reported that SSRI use during pregnancy may increase the risk of persistent pulmonary hypertension in newborns, with an estimated risk of approximately 5 cases per 1000 pregnancies, compared to 1–2 cases per 1000 pregnancies in the general population. Observational data suggest an increased risk (less than 2-fold) of postpartum haemorrhage after SSRI/SNRI use within one month before delivery (see sections "Special precautions for use" and "Adverse reactions").

Breastfeeding

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

Fertility

Animal studies have shown that some SSRIs may affect sperm quality. Reports on the use of some SSRIs indicate that effects on human sperm quality are reversible. No effect on human fertility has been observed to date.

Ability to influence reaction speed when driving or operating machinery.

Although it has been established that escitalopram does not affect cognitive functions or psychomotor performance, any psychoactive drug may impair the ability to think rationally or perform skilled tasks. Patients should be warned about the potential risk of impaired ability to drive or operate machinery.

Method of Administration and Dosage

The safety of doses exceeding 20 mg has not been demonstrated.

The medicinal product Escitalopram-Teva is administered orally once daily, independent of food intake.

Major Depressive Episode

The usual dose is 10 mg daily. Depending on individual patient response, the dose may be increased to the maximum of 20 mg daily. The antidepressant effect usually develops within 2–4 weeks after initiation of treatment. After disappearance of depressive symptoms, treatment should be continued for at least 6 months to consolidate the therapeutic effect.

Panic Disorders with or without Agoraphobia

A dose of 5 mg daily is recommended during the first week of treatment, which is then increased to 10 mg daily. Depending on individual patient response, the dose may subsequently be increased up to the maximum of 20 mg daily.

Maximum therapeutic effect is achieved approximately within 3 months. Treatment continues for several months.

Social Anxiety Disorders

The usual dose is 10 mg daily. Symptom relief usually develops within 2–4 weeks. Depending on individual patient response, the dose may subsequently be reduced to 5 mg daily or increased up to the maximum of 20 mg daily. Since social anxiety disorder is a chronic condition, the minimum recommended duration of treatment to consolidate the achieved effect is 12 weeks. To prevent relapses, the medicinal product may be prescribed for up to 6 months, depending on individual patient response. Therapeutic benefit should be regularly evaluated.

Social anxiety disorder has clearly defined diagnostic criteria for a specific condition and should not be confused with exaggerated shyness. Pharmacotherapy is indicated exclusively for the disorder that significantly affects a person's professional and social functioning. The efficacy of such treatment compared to cognitive behavioral therapy has not been studied. Pharmacotherapy should be part of an overall therapeutic strategy.

Generalized Anxiety Disorders

The recommended initial dose is 10 mg daily. Depending on individual patient response, the dose may subsequently be increased up to the maximum of 20 mg daily. Treatment should be continued for at least 3 months. Long-term use of the medicinal product (6 months) at a dose of 20 mg daily is permitted to prevent relapses. Therapeutic benefit and dosage should be regularly evaluated.

Obsessive-Compulsive Disorder (OCD)

The usual dose is 10 mg daily. Depending on individual sensitivity, the dose may be increased up to 20 mg daily. OCD is a chronic disorder; treatment should continue for a sufficient period to ensure complete symptom remission, which may take several months or longer. Therapeutic benefit and dosage should be regularly assessed.

Elderly Patients (aged 65 years and older)

Initial dose: 5 mg daily. Depending on individual patient response, the dose may be increased to 10 mg daily. The lowest effective dose should be used.

The efficacy of Escitalopram-Teva in elderly patients with social anxiety disorder has not been studied.

Renal Impairment

Dose adjustment is not required in patients with mild to moderate renal impairment. The medicinal product should be administered with caution in patients with severe renal impairment (CLcr less than 30 ml/min).

Hepatic Impairment

In patients with mild to moderate hepatic impairment, the recommended initial dose for the first two weeks is 5 mg daily. Depending on individual patient response, the dose may subsequently be increased to 10 mg daily. Caution and careful dose titration are required in patients with severe hepatic impairment.

Reduced CYP2C19 Isoenzyme Activity

For patients known to have low CYP2C19 isoenzyme activity, the recommended initial dose of Escitalopram-Teva for the first two weeks is 5 mg daily. Depending on individual patient response, the dose may subsequently be increased to 10 mg daily.

Discontinuation Symptoms after Stopping Treatment

Abrupt discontinuation of this medication should be avoided. The dose of escitalopram should be gradually reduced over 1–2 weeks to minimize potential discontinuation symptoms. If discontinuation symptoms occur during dose tapering, the previous prescribed dose may be reinstated. The physician may then continue to reduce the dose, but more gradually.

Children

Antidepressants are contraindicated for the treatment of children (under 18 years of age). Suicidal behavior (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) have been observed more frequently in children and adolescents taking antidepressants compared to those receiving placebo. If a decision to prescribe is made for clinical reasons, careful monitoring for the emergence of suicidal symptoms in the patient is required.

Furthermore, there are no data on the long-term safety in children and adolescents regarding growth, sexual maturation, and cognitive and behavioral development.

Overdose

Toxicity. Data on escitalopram overdose are limited and, in many cases, involve concomitant overdose with other medicinal products. In most cases, symptoms were mild or absent. Fatal cases following escitalopram overdose have been reported rarely, and most such cases involved concomitant overdose with other medicinal products. Single doses of escitalopram alone of 400–800 mg did not cause severe symptoms.

Symptoms. Signs of escitalopram overdose generally involve the CNS (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizures, and coma), gastrointestinal system (nausea, vomiting), cardiovascular system (hypotension, tachycardia, QT interval prolongation, arrhythmia), as well as fluid and electrolyte imbalances (hypokalemia, hyponatremia).

Treatment. There is no specific antidote. Supportive care and maintenance of airway patency, respiratory function, and adequate oxygenation are required. Gastric lavage and administration of activated charcoal should be performed as soon as possible after oral ingestion. Continuous monitoring of cardiovascular function and vital signs, combined with general symptomatic and supportive measures, is recommended.

In cases of overdose, ECG monitoring is recommended in patients with congestive heart failure/bradyarrhythmia, in patients concurrently taking medicinal products that prolong the QT interval, or in patients with impaired metabolism, e.g., hepatic impairment.

Adverse Reactions

Adverse reactions most commonly occur during the first and second weeks of treatment and subsequently become less intense, with their frequency decreasing during continued treatment.

The adverse effects typical for all SSRIs and escitalopram, observed during placebo-controlled studies and post-marketing use, are listed below by organ systems and frequency of occurrence.

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 frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders. Frequency not known: thrombocytopenia.

Immune system disorders. Rare: anaphylactic reactions.

Endocrine disorders. Frequency not known: disturbance in antidiuretic hormone secretion.

Metabolism and nutrition disorders. Common: decreased or increased appetite, weight gain. Uncommon: weight loss. Frequency not known: hyponatremia, anorexia².

Psychiatric disorders. Common: anxiety, restlessness, abnormal dreams, decreased libido in both men and women, anorgasmia in women. Uncommon: bruxism, agitation, nervousness, panic attacks, confusion. Rare: aggression, depersonalization, hallucinations. Frequency not known: mania, suicidal thoughts, suicidal behaviour¹.

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

Eye disorders. Uncommon: mydriasis, blurred vision.

Ear and labyrinth disorders. Uncommon: tinnitus.

Cardiac disorders. Uncommon: tachycardia. Rare: bradycardia. Frequency not known: ventricular arrhythmia, including torsade de pointes, QT interval prolongation on ECG, orthostatic hypotension.

Respiratory disorders. Common: sinusitis, yawning. Uncommon: epistaxis.

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

Hepatobiliary disorders. Frequency not known: hepatitis, changes in liver function tests.

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

Musculoskeletal and connective tissue disorders. Common: arthralgia, myalgia.

Renal and urinary disorders. Frequency not known: urinary retention.

Reproductive system and breast disorders. Common: in men: ejaculation disorders, impotence. Uncommon: in women: metrorrhagia, menorrhagia. Frequency not known: galactorrhea; in men: priapism; in women: postpartum haemorrhage³.

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

¹Cases of suicidal ideation or behaviour have been observed both during treatment with escitalopram and immediately after discontinuation of therapy.

²These adverse reactions have been reported for the SSRI class of drugs as a whole.

³This adverse reaction has been reported for the SSRI/SSRIN class of drugs as a whole (see sections "Special precautions for use", "Use during pregnancy or breastfeeding").

QT interval prolongation

During the post-marketing period, cases of QT interval prolongation, including torsade de pointes arrhythmia, have been reported, primarily in female patients with hypokalaemia or pre-existing QT interval prolongation or other cardiac conditions.

Class-specific effects of SSRIs

Epidemiological studies, mainly conducted in patients aged 50 years and older, have shown an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism of this phenomenon is unknown.

Withdrawal symptoms upon discontinuation

Discontinuation of SSRIs/SSRINs (especially abrupt discontinuation) 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, excessive sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances have been reported as the most common reactions. These symptoms are usually mild to moderate and transient; however, in some patients they may be severe and/or prolonged. Therefore, it is recommended to gradually discontinue escitalopram by reducing the dose over several weeks or months, depending on the patient's condition.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25°C, in the original packaging to protect from light and moisture, and in a place inaccessible to children.

Packaging.

Tablets 5 mg or 15 mg: 14 tablets in a blister; 2 blisters per carton.

Tablets 10 mg or 20 mg: 14 tablets in a blister; 2 blisters per carton; or 10 tablets in a blister; 3 or 9 blisters per carton.

Prescription status. Prescription only.

Manufacturer. Teva Operations Poland Sp. z o.o.

Manufacturer's address and place of business.

80 Mogilska Street, 31-546 Kraków, Poland.