Escitalopram-vista
Ukraine
Table of Contents
INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ESCITALOPRAM-VISTA (ESCITALOPRAM VISTA)
Composition:
Active substance: escitalopram oxalate;
1 tablet contains escitalopram oxalate equivalent to 5 mg, 10 mg or 20 mg of escitalopram;
Excipients: potassium polacrilin; lactose monohydrate; microcrystalline cellulose1; sodium croscarmellose; potassium acesulfame (E950); neohesperidin dihydrochalcone; peppermint flavor; magnesium stearate; purified water2; concentrated hydrochloric acid.
1 Particle size requirements: retention on sieve #200 ≥ 45%.
2 The majority is removed during manufacturing.
Pharmaceutical form. Orodispersible tablets.
Main physicochemical properties:
5 mg tablets: white or almost white, round, flat tablets with bevelled edges and engraved "5" on one side;
10 mg tablets: white or almost white, round, flat tablets with bevelled edges and engraved "10" on one side;
20 mg tablets: white or almost white, round, flat tablets with bevelled edges and engraved "20" on one side.
Pharmacotherapeutic group.
Antidepressants. Selective serotonin reuptake inhibitors.
ATC code N06AB10.
Pharmacological properties.
Pharmacodynamics.
Escitalopram is a selective serotonin reuptake inhibitor (SSRI) characterized by high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter, although its affinity for this site is 1000-fold lower.
Escitalopram has no or very weak affinity for a number of receptors, including serotonin 5-HT1A, 5-HT2 receptors, dopamine D1 and D2 receptors, α1-, α2-, β-adrenergic receptors, histamine H1, muscarinic cholinergic, benzodiazepine, and opioid receptors.
Inhibition of 5-HT reuptake is the only plausible mechanism of action that can explain the pharmacological and clinical effects of escitalopram.
Pharmacodynamic effects.
In one double-blind, placebo-controlled ECG study in healthy subjects, QTc interval (corrected using Fridericia's formula) prolongation from baseline was 4.3 ms (90% CI: 2.2, 6.4) with escitalopram 10 mg/day and 10.7 ms (90% CI: 8.6, 12.8) with a dose higher than therapeutic—30 mg/day (see sections «Contraindications», «Special precautions», «Interaction with other medicinal products and other forms of interactions», «Adverse reactions», «Overdose»).
Clinical efficacy.
Major depressive episodes. The efficacy of escitalopram in the acute treatment of major depressive episodes was demonstrated in 3 out of 4 double-blind, placebo-controlled, short-term (8-week) studies. In a long-term relapse prevention study, 274 patients who responded to escitalopram treatment at a dose of 10 or 20 mg/day during an initial 8-week open-label phase were randomized to continue escitalopram at the same dose or switch to placebo for up to 36 weeks. In this study, patients continuing escitalopram had a statistically significantly longer time to relapse within the following 36 weeks compared to those receiving placebo.
Social anxiety disorder. Escitalopram was shown to be effective in the treatment of social anxiety disorder in three short-term (12-week) studies and in a 6-month relapse prevention study. In a 24-week dose-optimization study, efficacy of escitalopram was demonstrated at doses of 5, 10, and 20 mg.
Generalized anxiety disorder. Escitalopram at doses of 10 and 20 mg/day was effective in 4 out of 4 placebo-controlled studies.
According to pooled data from three studies with similar designs, involving a total of 421 patients receiving escitalopram and 419 patients receiving placebo, response to treatment was observed in 47.5% and 28.9% of patients, respectively, and remission occurred in 37.1% and 20.8% of patients, respectively. A sustained effect was observed from the first week of treatment.
The maintenance effect of escitalopram 20 mg/day was demonstrated in a 24–76-week randomized study on maintenance of treatment efficacy, which included 373 patients who responded to escitalopram during an initial 12-week open-label treatment period.
Obsessive-compulsive disorder. In a randomized, double-blind clinical trial, escitalopram at a dose of 20 mg/day demonstrated superiority over placebo in the total score on the Y-BOCS (Yale-Brown Obsessive Compulsive Scale) after 12 weeks of treatment. At 24 weeks, advantages of escitalopram treatment were observed both at 10 mg/day and 20 mg/day compared to placebo.
The efficacy of escitalopram in preventing relapses was demonstrated at doses of 10 and 20 mg/day in patients who responded to escitalopram during a 16-week open-label period and were then included in a 24-week randomized, double-blind, placebo-controlled phase.
Pharmacokinetics.
Absorption is almost complete and independent of food intake. Maximum plasma concentration (Tmax) is reached within 4 hours after administration. As with racemic citalopram, the absolute bioavailability of escitalopram is expected to be approximately 80%.
Distribution. The apparent volume of distribution (Vd,β/F) after oral administration of escitalopram is approximately 12 to 26 L/kg. The bioavailability of escitalopram is approximately 80%. Protein binding of escitalopram and its main metabolites is less than 80%.
Biological transformation. Escitalopram is metabolized in the liver to demethylated and didemethylated metabolites. Both are pharmacologically active. Oxidation of nitrogen to form an N-oxide metabolite is also possible. Both the parent compound and metabolites are partially excreted as glucuronides. With repeated administration of escitalopram, mean concentrations of the demethylated and didemethylated metabolites typically amount to 28–31% and < 5% of escitalopram concentration, respectively. The biotransformation of escitalopram to the demethylated metabolite is primarily mediated by CYP2C19. Some involvement of CYP3A4 and CYP2D6 enzymes in this process is possible.
Elimination. The elimination half-life (t½β) of escitalopram is approximately 30 hours. Oral plasma clearance is approximately 0.6 L/min. The main metabolites have a longer half-life. Escitalopram and its main metabolites are eliminated via the liver (metabolic pathway) and kidneys. Most of the dose is excreted in urine as metabolites.
Linearity. The pharmacokinetics of escitalopram are linear. Steady-state concentrations are reached after approximately 1 week. Mean steady-state concentrations of 50 nmol/L (range: 20–125 nmol/L) are achieved with a daily dose of 10 mg. Elderly patients. In patients aged 65 years and older, escitalopram is eliminated more slowly than in younger patients. Systemic exposure (AUC) in healthy elderly volunteers is approximately 50% higher than in younger healthy volunteers (see section «Dosage and administration»).
Hepatic impairment. In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), elimination half-life was twice as long and exposure was 60% higher than in individuals with normal liver function (see section «Dosage and administration»).
Renal impairment. In patients with impaired renal function (creatinine clearance [CrCl] 10–53 mL/min), administration of racemic citalopram resulted in a longer elimination half-life and slightly higher exposure. Plasma concentrations of metabolites have not been studied but may be increased (see section «Dosage and administration»).
Polymorphism. Patients with poor CYP2C19 metabolic function had twice the plasma concentration of escitalopram compared to patients with normal CYP2C19 function. No significant changes in exposure were observed with reduced CYP2D6 function (see section «Dosage and administration»).
Clinical characteristics.
Indications.
For the treatment of major depressive episodes, panic disorders with or without agoraphobia, social anxiety disorders (social phobia), generalized anxiety disorders, and obsessive-compulsive disorders.
Contraindications.
Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
Concomitant use of non-selective irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of developing serotonin syndrome with agitation, tremor, hyperthermia, and other symptoms (see section "Interaction with other medicinal products and other forms of interaction").
The combination of escitalopram with reversible MAO-A inhibitors (e.g., moclobemide) or with the reversible non-selective MAO inhibitor linezolid is contraindicated due to the risk of serotonin syndrome (see section "Interaction with other medicinal products and other forms of interaction").
Escitalopram is contraindicated in patients with QT interval prolongation or congenital long QT syndrome.
Escitalopram must not be used concomitantly with medicinal products capable of prolonging the QT interval (see section "Interaction with other medicinal products and other forms of interaction").
Interaction with other medicinal products and other forms of interaction.
Pharmacodynamic interactions.
Contraindicated combinations.
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 MAOI treatment (see section "Contraindications"). In some cases, serotonin syndrome developed (see section "Adverse reactions"). The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Treatment with escitalopram should be initiated no earlier than 14 days after discontinuation of irreversible MAOIs. Treatment with non-selective irreversible MAOIs should not be initiated earlier than 7 days after discontinuation of escitalopram.
Combinations requiring caution
Reversible selective MAO-A inhibitor (moclobemide). Due to the risk of serotonin syndrome, the combination of escitalopram with the MAO-A inhibitor moclobemide is contraindicated (see section "Contraindications"). If this combination is deemed necessary, treatment should begin with the lowest recommended doses and intensified clinical monitoring should be applied. Reversible non-selective MAO inhibitor (linezolid). The antibiotic linezolid is a reversible non-selective MAO inhibitor and should not be administered to patients receiving escitalopram. If such a combination is necessary, minimal doses of both medicinal products should be used under close clinical supervision (see section "Contraindications").
Selective irreversible MAO-B inhibitor (selegiline). Combination with selegiline (an irreversible MAO-B inhibitor) requires caution due to the risk of serotonin syndrome.
Selegiline at doses up to 10 mg/day has been safely used concomitantly with racemic citalopram.
QT interval prolongation. Pharmacokinetic and pharmacodynamic studies on the combined use of escitalopram with other medicinal products that prolong the QT interval have not been conducted. When escitalopram is used concomitantly with such medicinal products, an additive effect cannot be excluded. Therefore, concomitant use of escitalopram with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmic agents, antipsychotics (e.g., phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g., sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarial agents including halofantrine), and certain antihistamines (astemizole, hydroxyzine, mizolastine), is contraindicated.
Serotonergic medicinal products. Concomitant use with serotonergic agents (e.g., tramadol, sumatriptan, and other triptans) may lead to serotonin syndrome.
MEDICINAL PRODUCTS THAT LOWER THE SEIZURE THRESHOLD. SSRIs may lower the seizure threshold. Caution is recommended when using medicinal products that may lower the seizure threshold concomitantly, such as: antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol.
Lithium, tryptophan. Since cases of enhanced effects have been reported with concomitant use of SSRIs and lithium or tryptophan, these medicinal products should be prescribed concomitantly with caution.
St. John’s wort. Concomitant use of SSRIs and herbal preparations containing St. John’s wort may increase the frequency of adverse reactions.
Anticoagulants. The effects of anticoagulants may change when used concomitantly with escitalopram. If patients are taking oral anticoagulants, careful monitoring of the blood coagulation system is required before and after the initiation of escitalopram (see section "Special precautions for use").
Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of bleeding (see section "Special precautions for use").
Alcohol. Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interactions with alcohol. However, as with other psychotropic medicinal products, combination with alcohol is not recommended.
MEDICINAL PRODUCTS CAUSING HYPOKALEMIA/HYPOMAGNESEMIA. Caution should be exercised when using medicinal products that may cause hypokalemia/hypomagnesemia concomitantly, as this increases the risk of developing malignant arrhythmias (see section "Special precautions for use").
Pharmacokinetic interactions.
Effects of other agents on the pharmacokinetics of escitalopram
The metabolism of escitalopram is primarily mediated by CYP2C19. CYP3A4 and CYP2D6 enzymes may also play a minor role in its metabolism. The metabolism of the main metabolite S-DCT (desmethyl escitalopram) appears to be partially catalyzed by CYP2D6.
Concomitant administration of escitalopram and omeprazole 30 mg once daily (a CYP2C19 inhibitor) results in a moderate (approximately 50%) increase in plasma escitalopram concentrations.
Concomitant use of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) led to a moderate (approximately 70%) increase in plasma escitalopram concentrations. Caution should be exercised when combining escitalopram with cimetidine. Dose adjustment may be necessary (see section "Special precautions for use").
Thus, caution is advised when using escitalopram concomitantly with CYP2C19 inhibitors (e.g., omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) and with cimetidine, particularly when prescribing the upper limit doses of escitalopram. Dose reduction of escitalopram may be required depending on clinical assessment.
Effects of escitalopram on the pharmacokinetics of other agents.
Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution is recommended when escitalopram is used concomitantly with medicinal products primarily metabolized by this enzyme and having a narrow therapeutic index, such as flecainide, propafenone, and metoprolol (in heart failure), or with certain centrally acting agents primarily metabolized by CYP2D6, such as antidepressants (e.g., desipramine, clomipramine, nortriptyline) and antipsychotics (e.g., risperidone, thioridazine, haloperidol). Dose adjustments may be required.
Combination with desipramine or metoprolol resulted in a doubling of plasma levels of these two CYP2D6 substrates.
In vitro studies have demonstrated that escitalopram may also cause slight inhibition of CYP2C19.
Caution is recommended when using escitalopram concomitantly with medicinal products metabolized by CYP2C19.
Special precautions for use.
The following special precautions apply to the therapeutic class of selective serotonin reuptake inhibitors (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 two weeks of treatment. To reduce the likelihood of an anxiogenic effect, a low initial dose is recommended (see section "Dosage and administration").
Seizures.
Esitalopram should be discontinued if a patient develops a first seizure or if seizures become more frequent (in patients with a confirmed diagnosis of 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 develops, SSRIs should be discontinued.
Diabetes mellitus.
In patients with diabetes mellitus, treatment with SSRIs may alter glycaemic control. The dose of insulin and/or oral hypoglycaemic agents may require adjustment.
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. Since improvement may not occur during the first few weeks of treatment or longer, patients should be carefully monitored until their condition improves. It is known that the risk of suicide may increase in the early stages of recovery.
Other conditions for which escitalopram is used may also be associated with a risk of suicidal behaviour. Moreover, such conditions may be comorbid with major depressive disorder. These warnings also apply to the treatment of patients with other psychiatric disorders.
Patients with a history of suicidal behaviour prior to treatment initiation are at the highest risk of suicidal thoughts or attempts and require close monitoring during treatment. A meta-analysis of clinical trials revealed an increased risk of suicidal behaviour in patients under 25 years of age treated with antidepressants compared to those receiving placebo. Close monitoring of high-risk patients is particularly necessary at the beginning of treatment and when dosage is changed.
Patients and their caregivers should be advised to monitor for any worsening of symptoms, suicidal behaviour or thoughts, or unusual changes in behaviour, and to seek immediate medical advice if such symptoms occur.
Akathisia / psychomotor agitation.
SSRI/SNRI use 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 be harmful in patients who develop such symptoms.
Hyponatraemia.
Hyponatraemia, possibly related to syndrome of inappropriate antidiuretic hormone secretion (SIADH), has been rarely reported with SSRIs and usually resolves upon discontinuation of therapy. SSRIs should be used with caution in patients at risk (elderly patients, those with hepatic cirrhosis, or those taking concomitant medications that may cause hyponatraemia).
Haemorrhage.
Skin bleeding, ecchymoses, and purpura may occur during SSRI treatment. SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections "Use in pregnancy or breastfeeding" and "Adverse reactions"). 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 non-steroidal anti-inflammatory drugs, dipyridamole, and ticlopidine), and in patients with a predisposition to bleeding.
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 not recommended due to the risk of serotonin syndrome.
Serotonin syndrome.
Caution is advised when escitalopram is used concomitantly with serotonergic agents such as sumatriptan or other triptans, tramadol, and tryptophan. Cases of serotonin syndrome have been reported in patients taking SSRIs concomitantly with serotonergic drugs. Escitalopram should be used with caution in combination with serotonergic agents. The combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of serotonin syndrome. In such cases, SSRIs and the serotonergic agent should be discontinued immediately, and symptomatic treatment should be initiated.
St. John’s wort.
Concomitant use of SSRIs and herbal preparations containing St. John’s wort may increase the frequency of adverse reactions (see section "Interaction with other medicinal products and other forms of interaction").
Discontinuation symptoms.
Discontinuation symptoms upon stopping treatment, especially abrupt discontinuation, are common. In clinical trials, adverse reactions during discontinuation occurred in approximately 25% of patients receiving escitalopram and in 15% of patients receiving placebo. The risk of discontinuation symptoms may depend on several factors, including duration and dose of treatment, and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia, electric shock sensations), sleep disturbances (including insomnia, vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. These symptoms are usually mild to moderate in severity but may be severe in some patients. They typically occur within the first few days after discontinuation, although very rare reports have described such symptoms in patients who accidentally missed a dose. These discontinuation symptoms usually resolve within 2 weeks, but may be prolonged (2–3 months or longer) in some patients. Therefore, it is recommended to gradually discontinue escitalopram treatment by reducing the dose over several weeks or months, depending on the patient's condition (see section "Dosage and administration").
Sexual dysfunction.
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section "Adverse reactions"). There have been reports of persistent sexual dysfunction, where symptoms continued despite discontinuation of SSRIs/SNRIs.
Ischaemic heart disease.
Due to limited clinical experience, caution is recommended when using escitalopram in patients with ischaemic heart disease.
QT interval prolongation.
Escitalopram has been shown to cause dose-dependent QT interval prolongation. In the post-marketing period, cases of QT interval prolongation and ventricular arrhythmias, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in women, patients with hypokalaemia, and patients with pre-existing QT prolongation or other cardiac diseases (see sections "Contraindications", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", "Overdose", and "Pharmacodynamics").
Escitalopram should be used with caution in patients with marked bradycardia and in patients with recent acute myocardial infarction or decompensated heart failure.
Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of malignant arrhythmias and should be corrected before initiating escitalopram treatment.
In patients with stable cardiac disease, a thorough ECG evaluation should be performed before initiating escitalopram treatment.
If signs of cardiac arrhythmia occur during escitalopram treatment, the drug should be discontinued and an ECG should be performed.
Closed-angle glaucoma.
SSRIs, including escitalopram, may affect pupil size, leading to mydriasis. This mydriatic effect may potentially narrow the angle of the eye, resulting in increased intraocular pressure and closed-angle glaucoma, particularly in predisposed patients. Therefore, escitalopram should be used with caution in patients with closed-angle glaucoma or a history of glaucoma.
Important information about excipients.
Aspartame. A derivative of phenylalanine, which may be harmful to patients with phenylketonuria.
Lactose. If a patient has been diagnosed with intolerance to certain sugars, they should consult their physician before taking this medicinal product.
Use during pregnancy or breastfeeding.
Pregnancy. Clinical data on the use of escitalopram in pregnant women are limited. Animal studies have shown reproductive toxicity.
Escitalopram is contraindicated during pregnancy, except in cases where a careful evaluation of risks and benefits clearly indicates the necessity of escitalopram treatment. Newborns whose mothers have taken escitalopram during pregnancy, especially in the third trimester, should be carefully monitored. Abrupt discontinuation of escitalopram during pregnancy should be avoided. Newborns whose mothers have taken SSRIs/SNRIs in late pregnancy may experience symptoms such as respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, lethargy, persistent crying, somnolence, and sleep disturbances. These symptoms may be due to serotonergic effects or may represent discontinuation symptoms. In most cases, such complications occur immediately or shortly (within 24 hours) after delivery.
Epidemiological data indicate that SSRI use during pregnancy increases the risk of persistent pulmonary hypertension in the newborn (up to 5 cases per 1000 pregnancies). In the general population, the incidence is 1 to 2 cases per 1000 pregnancies.
Breastfeeding. Since escitalopram passes into breast milk, breastfeeding is not recommended during treatment.
Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI or SNRI use within one month prior to delivery (see sections "Adverse reactions" and "Special precautions for use").
Fertility. Animal studies have shown that escitalopram may affect sperm quality. Reports on the use of certain SSRIs in humans suggest that the effect on sperm quality is reversible. No effect on human fertility has been observed to date.
Ability to affect reaction speed when driving or operating machinery.
Although escitalopram does not affect cognitive function or psychomotor performance, any psychoactive drug may impair skills and the ability to think rationally. Patients should be warned about the potential risk of impaired ability to drive or operate machinery.
Dosage and Administration.
The safety of doses exceeding 20 mg per day has not been established.
The medicinal product should be administered orally once daily to adults, independent of food intake.
Major Depressive Episode.
The usual dose is 10 mg once daily. Depending on individual patient sensitivity, the daily dose may be increased up to the maximum of 20 mg.
The antidepressant effect usually occurs within 2–4 weeks. After symptom remission, treatment should be continued for at least 6 months to consolidate the therapeutic effect.
Panic Disorders with or without Agoraphobia.
An initial dose of 5 mg daily is recommended during the first week before increasing to 10 mg daily. The dose may be further increased up to the maximum of 20 mg daily, depending on individual patient sensitivity.
Maximum therapeutic effect in the treatment of panic disorders is achieved within 3 months. The duration of treatment lasts several months and depends on the severity of the condition.
Social Anxiety Disorders (Social Phobia).
The usual dose is 10 mg once daily. Symptom relief usually requires 2–4 weeks of therapy. Subsequently, depending on individual patient response, the dose may be reduced to 5 mg or increased up to the maximum of 20 mg daily. Social anxiety disorder is a chronic condition, and treatment should be continued for at least 12 weeks to consolidate the effect.
Long-term treatment for 6 months has been shown to prevent relapse and may be prescribed individually; the benefits of treatment should be regularly evaluated.
Social anxiety disorder is a clearly defined diagnostic term for a specific disorder and should not be confused with excessive shyness. Pharmacotherapy is indicated only when this disorder significantly impairs professional functioning and social activity.
The role of pharmacotherapy relative to cognitive-behavioral therapy has not been evaluated. Medication is one component of an overall treatment strategy.
Generalized Anxiety Disorders.
The usual dose is 10 mg once daily. Depending on individual sensitivity, the dose may be increased up to a maximum of 20 mg daily.
Long-term treatment has been studied for at least 6 months in patients receiving a 20 mg daily dose; the benefits of treatment should be regularly evaluated (see section "Pharmacodynamics").
Obsessive-Compulsive Disorders (OCD).
The usual initial dose is 10 mg once 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 duration to ensure complete symptom remission, which may take several months or longer. The benefit of treatment and the dose of escitalopram should be regularly evaluated (see section "Pharmacodynamics").
Elderly Patients (aged 65 years and older).
The initial dose is 5 mg daily. Depending on individual sensitivity and severity of depression, the daily dose may be increased up to a maximum of 10 mg daily (see section "Pharmacokinetics").
The efficacy of escitalopram in elderly patients with social anxiety disorder has not been evaluated.
Paediatric Population.
The medicinal product should not be used for the treatment of children and adolescents (under 18 years of age) (see section "Special Warnings and Precautions for Use").
Renal Impairment.
No dosage adjustments are required in patients with mild to moderate renal impairment. Escitalopram should be used with caution in patients with severe renal impairment (creatinine clearance < 30 mL/min) (see section "Pharmacokinetics").
Hepatic Impairment.
The recommended initial dose during the first two weeks of treatment is 5 mg daily in patients with mild or moderate hepatic impairment. Depending on individual patient response, the dose may be increased to 10 mg daily. Escitalopram should be used with caution and dose titration should be carefully considered in patients with severe hepatic impairment (see section "Pharmacokinetics").
Reduced CYP2C19 Enzyme Activity.
For patients with poor CYP2C19 enzyme activity, the recommended initial dose during the first two weeks of treatment is 5 mg daily. Depending on individual patient response, the dose may be increased to 10 mg daily (see section "Pharmacokinetics").
Withdrawal Symptoms upon Discontinuation.
Abrupt discontinuation of the medicinal product should be avoided. When stopping treatment with escitalopram, the dose should be gradually reduced over at least 1–2 weeks to minimize the risk of withdrawal symptoms (see sections "Special Warnings and Precautions for Use" and "Undesirable Effects"). If intolerable symptoms occur after dose reduction or discontinuation, consideration should be given to resuming the previously prescribed dose. Thereafter, the physician may continue tapering the dose, but more gradually.
Children.
Antidepressants should not be used for the treatment of children and adolescents (under 18 years of age). Suicidal behaviour (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour, and anger) have been observed more frequently in clinical trials among children and adolescents treated with antidepressants compared to those receiving placebo. If a clinical decision to prescribe is made, careful monitoring for the emergence of suicidal symptoms is essential.
Overdose.
Toxicity. Clinical data on escitalopram overdose are limited. Many cases involve concomitant overdose with other medicinal products. Most reported cases have been associated with mild symptoms or no symptoms. Reports of fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other medications. Doses of escitalopram ranging from 400–800 mg have not resulted in severe symptoms.
Symptoms. Signs of escitalopram overdose are primarily related to the central nervous system (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, arrhythmias), and fluid/electrolyte imbalance (hypokalaemia, hyponatraemia).
Treatment. There is no specific antidote. Supportive measures should maintain adequate respiratory function and ensure proper oxygenation. Gastric lavage and activated charcoal may be used. Monitoring of cardiac and vital functions together with symptomatic and supportive treatment is recommended. ECG monitoring is recommended in cases of overdose in patients with congestive heart failure/bradyarrhythmias, patients taking concomitant medications that prolong the QT interval, and patients with altered metabolism, e.g., due to hepatic impairment.
Adverse reactions.
Adverse reactions most commonly occur during the first or second week of treatment, and their frequency and intensity usually gradually decrease with continued treatment.
Adverse reactions characteristic of SSRIs and escitalopram, observed during placebo-controlled studies and in clinical use, are listed below by system organ class and frequency in the table. Frequency is defined as: 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 not known (cannot be estimated from available data).
| System Organ Class |
Frequency |
Reaction |
| Blood and lymphatic system disorders |
Unknown |
Thrombocytopenia |
| Immune system disorders |
Rare |
Anaphylactic reactions |
| Endocrine disorders |
Unknown |
Disturbance of antidiuretic hormone secretion |
| Metabolism and nutrition disorders |
Common |
Decreased or increased appetite, weight gain |
| Uncommon |
Weight loss |
|
| Unknown |
Hyponatremia, anorexia2 |
|
| Psychiatric disorders |
Common |
Anxiety, restlessness, abnormal dreams, decreased libido Women: anorgasmia |
| Uncommon |
Bruxism, excitement, nervousness, panic attacks, confusion |
|
| Rare |
Aggression, depersonalization, hallucinations |
|
| Unknown |
Mania, suicidal thoughts, suicidal behaviour1 |
|
| Nervous system disorders |
Very common |
Headache |
| Common |
Insomnia, somnolence, dizziness, paraesthesia, tremor |
|
| Uncommon |
Taste disturbance, sleep disorder, loss of consciousness |
|
| Rare |
Serotonin syndrome |
|
| Unknown |
Dyskinesia, movement disorders, seizures, psychomotor agitation/akathisia2 |
|
| Eye disorders |
Uncommon |
Mydriasis, blurred vision |
| Ear and labyrinth disorders |
Uncommon |
Tinnitus |
| Cardiac disorders |
Uncommon |
Tachycardia |
| Rare |
Bradycardia |
|
| Unknown |
QT interval prolongation on electrocardiogram, ventricular arrhythmia including torsade de pointes, orthostatic hypotension |
|
| Respiratory, thoracic and mediastinal disorders |
Common |
Sinusitis, yawning |
| Uncommon |
Nosebleeds |
|
| Gastrointestinal disorders |
Very common |
Nausea |
| Common |
Diarrhoea, constipation, vomiting, dry mouth |
|
| Uncommon |
Gastrointestinal haemorrhage (including rectal) |
|
| Hepatobiliary disorders |
Unknown |
Hepatitis, changes in liver function tests |
| Skin and subcutaneous tissue disorders |
Common |
Increased sweating |
| Uncommon |
Rash, alopecia, urticaria, pruritus |
|
| Unknown |
Ecchymosis, oedema |
|
| Musculoskeletal and connective tissue disorders |
Common |
Arthralgia, myalgia |
| Renal and urinary disorders |
Unknown |
Urinary retention |
| Reproductive system and breast disorders |
Common |
Men: ejaculation disorders, impotence |
| Uncommon |
Women: metrorrhagia, menorrhagia |
|
| Unknown |
Galactorrhea Men: priapism Women: postpartum haemorrhage3 |
|
| General disorders and administration site conditions |
Common |
Fatigue, pyrexia |
| Uncommon |
Oedema |
1 Suicidal thoughts and behavior have been reported during treatment with escitalopram or shortly after discontinuation.
2 Such adverse reactions are characteristic of SSRIs as a class.
3 Such cases have been reported with the use of SSRIs or SNRIs in general (see sections "Use during pregnancy or breastfeeding", "Special precautions for use").
QT interval prolongation.
During the post-marketing period, cases of QT interval prolongation and ventricular arrhythmias, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in women, patients with hypokalemia, and patients with pre-existing QT interval prolongation or other heart diseases (see sections "Contraindications", "Special precautions for use", "Interaction with other medicinal products and other forms of interaction", "Overdose", and "Pharmacodynamics").
Class effects.
Epidemiological studies, conducted mainly in patients aged 50 years and older, have demonstrated an increased risk of bone fractures in patients treated with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. The mechanism leading to this increased risk is currently unknown.
Withdrawal symptoms.
Discontinuation of SSRIs (especially abrupt discontinuation) usually leads to withdrawal symptoms. Dizziness, sensory disturbances (including paresthesia and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, excessive sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. These symptoms are usually mild to moderate in severity and transient; however, they may be severe and/or prolonged in some patients. Therefore, it is recommended that treatment with escitalopram be gradually discontinued by dose reduction (see sections "Dosage and administration" and "Special precautions for use"). Reporting suspected adverse reactions.
Reporting of adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua
Shelf life.
3 years.
Storage conditions.
Store in the original packaging to protect from light and moisture. No special storage conditions are required for this medicinal product. Keep out of reach and sight of children.
Packaging.
Tablets of 5 mg or 20 mg — 14 tablets in a blister, 2 blisters in a cardboard box; tablets of 10 mg — 14 tablets in a blister, 2 blisters in a cardboard box or 15 tablets in a blister, 4 blisters in a cardboard box.
Prescription status.
Prescription only.
Manufacturer.
Jenopharm S.A.
or
Farmapas S.A.
Manufacturer's location and address of place of business.
18th km Marathon Avenue, Pallini Attiki, 15351, Greece
or
28th October 1, Agia Varvara, 123 51, Greece.