Asitalox
UkraineTable of Contents
INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASITALOX (ASITALOX)
Composition:
Active substance: escitalopram;
One tablet contains escitalopram oxalate equivalent to 10 mg or 20 mg of escitalopram;
Excipients: silicilated microcrystalline cellulose, sodium croscarmellose, butylhydroxytoluene (E 321), butylhydroxyanisole (E 320), microcrystalline cellulose, colloidal anhydrous silicon dioxide, talc, magnesium stearate, hypromellose, macrogol 400, titanium dioxide (E 171).
Pharmaceutical form. Film-coated tablets.
Main physicochemical properties:
10 mg tablets: white or almost white, oval-shaped, biconvex, film-coated tablets, with "F" engraved on one side and "54" on the other side, with a deep score line between "5" and "4";
20 mg tablets: white or almost white, oval-shaped, biconvex, film-coated tablets, with "F" engraved on one side and "56" on the other side, with a deep score line between "5" and "6".
Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). 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 times lower.
Escitalopram has no or very weak affinity for a number of receptors, including serotonin 5-HT1A and 5-HT2 receptors, dopamine D1 and D2 receptors, α1-, α2-, and 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 study of ECG parameters in healthy subjects, QTc interval prolongation (corrected using Fridericia's formula) from baseline was 4.3 ms (90% CI: 2.2, 6.4) with a daily dose of 10 mg and 10.7 ms (90% CI: 8.6, 12.8) with a supratherapeutic dose of 30 mg/day (see sections "Contraindications", "Special Warnings and Precautions for Use", "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 who continued receiving escitalopram had a statistically significantly longer time to relapse over the subsequent 36 weeks compared to those receiving placebo.
Social Anxiety Disorder
Escitalopram was shown to be effective in the treatment of social anxiety disorder in both three short-term (12-week) studies and a 6-month relapse prevention study. Efficacy of escitalopram at doses of 5, 10, and 20 mg was demonstrated in a 24-week optimal dose study.
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 design, involving a total of 421 patients receiving escitalopram and 419 patients receiving placebo, treatment response was achieved in 47.5% and 28.9% of patients, respectively, while 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 at a dose of 20 mg/day was demonstrated in a 24–76-week randomized maintenance efficacy study involving 373 patients who responded to the drug during an initial 12-week open-label treatment phase.
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. After 24 weeks, both 10 mg/day and 20 mg/day doses of escitalopram showed advantages over placebo.
The efficacy of the drug in preventing relapses was demonstrated for escitalopram at doses of 10 and 20 mg/day in patients who responded to escitalopram during a 16-week open-label period and were subsequently enrolled in a 24-week randomized, double-blind, placebo-controlled phase.
Pharmacokinetics
Absorption
Absorption is nearly complete and is not affected by 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 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
Metabolism occurs in the liver, producing demethylated and didemethylated metabolites. Both are pharmacologically active. Alternatively, nitrogen oxidation may occur, forming an N-oxide metabolite. Both the parent compound and metabolites are partially excreted as glucuronides. With repeated dosing, mean concentrations of the demethylated and didemethylated metabolites typically amount to 28–31% and < 5% of escitalopram concentration, respectively. The biotransformation of escitalopram to its demethylated metabolite is mediated by the cytochrome CYP2C19. Minor contributions from CYP3A4 and CYP2D6 isoenzymes are possible.
Elimination
The elimination half-life (t1/2) of the drug is approximately 30 hours. Oral clearance (Cloral) is approximately 0.6 L/min. The main metabolites have a longer t1/2. Escitalopram and its main metabolites are eliminated via the liver (metabolic pathway) and kidneys. The majority 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 dysfunction (Child-Pugh classes A and B), t1/2 was twice as long and exposure 60% higher compared to individuals with normal liver function (see section "Dosage and Administration").
Renal Impairment
In patients with reduced renal function (CLcr 10–53 mL/min), administration of racemic citalopram resulted in a longer t1/2 and slightly increased exposure. Plasma concentrations of metabolites have not been studied but may be elevated (see section "Dosage and Administration").
Polymorphism
Patients with poor metabolic function of CYP2C19 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.
Treatment of major depressive episodes, panic disorders with or without agoraphobia, social anxiety disorders (social phobia), generalized anxiety disorders, and obsessive-compulsive disorder (OCD).
Contraindications.
Hypersensitivity to escitalopram or to any of the excipients of the medicinal product.
Concomitant treatment with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome, which may manifest as agitation, tremor, hyperthermia, etc. (see section "Interaction with other medicinal products and other forms of interaction").
Combination of escitalopram with reversible MAO-A inhibitors (e.g., moclobemide) or with the reversible non-selective MAOI 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 known prolongation of the QT interval or congenital long QT syndrome.
Concomitant use of escitalopram with medicinal products that prolong the QT interval is contraindicated (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 have 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. Escitalopram treatment 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.
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 be initiated with the lowest recommended doses and under intensified clinical monitoring.
Reversible non-selective MAOI (linezolid)
The antibiotic linezolid is a reversible non-selective MAO inhibitor and should not be administered to patients receiving escitalopram. If combination therapy is necessary, it should be administered with minimal doses and under close clinical supervision (see section "Contraindications").
Irreversible selective MAOI type B (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 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, particularly halofantrine), and certain antihistamines (e.g., astemizole, hydroxyzine, mizolastine) is contraindicated.
Combinations requiring caution
Serotonergic medicinal products
Concomitant use with serotonergic agents, such as opioids (including tramadol) and triptans (including sumatriptan), may lead to serotonin syndrome.
Medicinal products that lower the seizure threshold
SSRIs may lower the seizure threshold. Caution is recommended when using concomitantly with medicinal products that may lower the seizure threshold (e.g., antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol).
Lithium, tryptophan
Since enhanced effects have been reported with concomitant use of SSRIs and lithium or tryptophan, caution is recommended when co-administering these agents.
St. John’s wort (Hypericum perforatum)
Concomitant use of SSRIs and herbal medicinal products containing St. John’s wort may increase the frequency of adverse reactions.
Anticoagulants
Changes in the effects of anticoagulants may occur with concomitant use of escitalopram. If patients are taking oral anticoagulants, careful monitoring of the coagulation system is required before and during treatment with escitalopram (see section "Special precautions for use").
Concomitant use of nonsteroidal 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 hypokalaemia/hypomagnesaemia
Caution is required when using medicinal products that cause hypokalaemia/hypomagnesaemia concomitantly, as these conditions increase the risk of life-threatening arrhythmias (see section "Special precautions for use").
Pharmacokinetic interactions
Effect of other medicinal products on the pharmacokinetics of escitalopram
Escitalopram metabolism 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 (demethylated 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) leads 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").
Therefore, caution is advised when combining escitalopram 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 necessary depending on clinical assessment.
Effect of escitalopram on the pharmacokinetics of other medicinal products
Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution is recommended when escitalopram is used concomitantly with medicinal products that are primarily metabolized by this enzyme and have a narrow therapeutic index, such as flecainide, propafenone, and metoprolol (in heart failure), or with certain central nervous system-acting agents primarily metabolized by CYP2D6, such as antidepressants (e.g., desipramine, clomipramine, nortriptyline) and antipsychotics (e.g., risperidone, thioridazine, haloperidol). Dose adjustment may be required.
Combination with desipramine or metoprolol has been shown to double plasma levels of these two CYP2D6 substrates.
In vitro studies have demonstrated that escitalopram may also cause weak inhibition of CYP2C19. Caution is recommended when using concomitantly with medicinal products metabolized by CYP2C19.
Special precautions for use.
The following special precautions apply to the 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 2 weeks of treatment. To reduce the likelihood of an anxiogenic effect, a low initial dose is recommended (see section "Dosage and administration").
Seizures
Escitalopram 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 close monitoring is required in patients with controlled epilepsy.
Mania
SSRIs should be used with caution in patients with a history of mania/hypomania. SSRIs should be discontinued if a manic state develops.
Diabetes
In patients with diabetes, treatment with SSRIs may alter glycemic control. The dose of insulin and/or oral hypoglycemic 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 a 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 a risk of suicidal behavior. In addition, such disorders 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 behavior prior to the start of treatment 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 behavior among patients under 25 years of age taking 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 warned to monitor for any worsening of symptoms, suicidal behavior or thoughts, or unusual changes in behavior, and to seek immediate medical advice if such symptoms occur.
Akathisia/Psychomotor agitation
The use of SSRIs/SNRIs (selective serotonin and norepinephrine reuptake inhibitors) has been associated with the development of akathisia—a condition characterized by a distressing, exhausting 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.
Hyponatremia
Hyponatremia, possibly related to impaired secretion of antidiuretic hormone, occurs rarely with SSRIs and usually resolves after discontinuation of therapy. SSRIs should be used with caution in patients at risk (elderly patients, patients with liver cirrhosis, or those taking concomitant medications that may cause hyponatremia).
Bleeding
Skin hemorrhages, ecchymoses, and purpura have been reported during SSRI treatment. SSRIs should be used with caution in patients receiving concomitant oral anticoagulants, drugs affecting platelet function (e.g., atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs, dipyridamole, and ticlopidine), and in patients with a predisposition to bleeding.
SSRIs/SNRIs may increase the risk of postpartum hemorrhage (see sections "Use during pregnancy or breastfeeding" and "Adverse reactions").
Electroconvulsive therapy (ECT)
Clinical experience with the 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 recommended when escitalopram is used concomitantly with serotonergic agents such as triptans (including sumatriptan), opioids (including tramadol), and tryptophan.
Serotonin syndrome has been reported in rare cases in patients taking SSRIs concomitantly with serotonergic drugs. Escitalopram should be used with caution when combined with serotonergic medications. A combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. In such cases, the SSRI 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").
Withdrawal symptoms
Withdrawal symptoms upon discontinuation of treatment, especially abrupt discontinuation, are common. In clinical trials, adverse reactions during discontinuation occurred in approximately 25% of patients treated with escitalopram and in 15% of patients receiving placebo.
The risk of withdrawal symptoms may depend on several factors, including duration of treatment, dose, and rate of dose reduction. Dizziness, sensory disturbances (including paresthesia, electric shock sensations), sleep disturbances (including insomnia, 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, although in some patients they may be more pronounced.
These symptoms usually occur within the first few days after discontinuation of treatment, but very rarely have been reported in patients who accidentally missed a dose.
These symptoms usually resolve without treatment within 2 weeks, although in some patients they may persist longer (2–3 months or more). 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
SSRIs/SNRIs may cause symptoms of sexual dysfunction (see section "Adverse reactions"). Reports of persistent sexual dysfunction have been received, where symptoms continued despite discontinuation of SSRIs/SNRIs.
Ischemic heart disease
Due to limited clinical experience, caution is recommended when prescribing the drug to patients with ischemic heart disease.
QT interval prolongation
Escitalopram has been shown to cause dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular arrhythmias, including torsade de pointes, have been reported during the post-marketing period, primarily in female patients, patients with hypokalemia, or those with pre-existing QT interval prolongation or other cardiac diseases (see sections "Contraindications", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", "Overdose", and "Pharmacodynamics").
Caution is recommended in patients with significant bradycardia, recent acute myocardial infarction, or uncompensated heart failure.
Electrolyte disturbances such as hypokalemia and hypomagnesemia increase the risk of malignant arrhythmias and should be corrected before initiating escitalopram treatment.
In patients with stable cardiac disease, an ECG should be performed prior to starting treatment.
If signs of cardiac arrhythmia occur during treatment with escitalopram, treatment 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 narrow the angle of the eye, resulting in increased intraocular pressure and closed-angle glaucoma, particularly in patients with a history of such condition. Therefore, escitalopram should be used with caution in patients with closed-angle glaucoma or a history of glaucoma.
Excipients
This medicinal product contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially "sodium-free".
Use during pregnancy or breastfeeding.
Clinical data on the use of escitalopram in pregnant women are limited.
Animal studies have shown reproductive toxicity.
Escitalopram should not be used during pregnancy unless absolutely necessary and only after careful benefit-risk assessment.
Newborns whose mothers received escitalopram during pregnancy, especially in the third trimester, should be carefully monitored. Abrupt discontinuation of treatment during pregnancy should be avoided.
Newborns whose mothers received SSRIs/SNRIs in late pregnancy may develop symptoms such as respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, apathy, persistent crying, somnolence, and sleep disturbances. These symptoms may result from excessive serotonergic activity or may represent withdrawal symptoms. In most cases, such complications occur immediately or shortly (within 24 hours) after delivery.
Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage following SSRI/SNRI use within one month before delivery (see sections "Special precautions for use" and "Adverse reactions").
Epidemiological data suggest that SSRI use during pregnancy may increase the risk of persistent pulmonary hypertension in newborns (up to 5 cases per 1000 pregnancies, according to observational data). In the general population, the incidence is 1 to 2 cases per 1000 pregnancies.
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 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 intellectual or psychomotor performance, any psychoactive drug may impair skills or the ability to think rationally. 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 per day has not been established.
Major Depressive Episode
The usual dose is 10 mg once daily. Depending on individual patient sensitivity, the daily dose may be increased to a maximum of 20 mg.
Antidepressant effect usually occurs within 2–4 weeks. After symptom remission, treatment should continue for at least 6 months to consolidate the therapeutic effect.
Panic Disorders with or without Agoraphobia
A starting dose of 5 mg once daily (using the appropriate dosage form) is recommended for the first week before increasing to 10 mg daily. The dose may subsequently be increased up to a maximum of 20 mg daily, depending on individual patient sensitivity.
Maximum efficacy in treating panic disorders is achieved within 3 months. The duration of treatment is several months and depends on disease severity.
Social Anxiety Disorder (Social Phobia)
The usual dose is 10 mg once daily. Symptom improvement usually occurs within 2–4 weeks of treatment. Subsequently, depending on the individual patient response, the dose may be reduced to 5 mg or increased up to a maximum of 20 mg per day.
Social anxiety disorder is a well-defined diagnostic entity and should not be confused with excessive shyness. Pharmacotherapy is indicated only when the disorder significantly impairs professional and social functioning.
The role of this treatment has not been evaluated in comparison with cognitive-behavioral therapy. Pharmacotherapy is part of an overall therapeutic strategy.
Generalized Anxiety Disorder
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 at a dose of 20 mg/day has been studied for at least 6 months. The benefits of treatment and dosage should be regularly evaluated.
Obsessive-Compulsive Disorder (OCD)
The usual dose is 10 mg once daily. Depending on individual sensitivity, the dose may be increased up to 20 mg daily. OCD is a chronic condition; treatment should continue for a sufficient period to ensure complete symptom remission, which may take several months or longer.
The benefits of treatment and dosage should be regularly evaluated.
Elderly Patients (aged 65 years and older)
The initial dose is 5 mg daily. Depending on individual sensitivity, the daily dose may be increased to 10 mg daily.
The efficacy of escitalopram in social anxiety disorder has not been studied in elderly patients.
Children
Escitalopram should not be prescribed for the treatment of children and adolescents under 18 years of age.
Renal Impairment
No dose adjustment is required in patients with mild to moderate renal impairment. The drug should be used with caution in patients with severe renal impairment (creatinine clearance <30 mL/min).
Hepatic Impairment
The recommended initial dose during the first 2 weeks of treatment is 5 mg daily. Depending on individual patient response, the dose may be increased to 10 mg daily. Caution and particularly careful dose titration are recommended in patients with significantly impaired liver function.
Reduced CYP2C19 Isoenzyme Activity
For patients with low CYP2C19 isoenzyme activity, the recommended initial dose during the first 2 weeks of treatment is 5 mg daily. Depending on individual patient response, the dose may be increased to 10 mg daily.
Discontinuation of Treatment
Abrupt discontinuation of the drug should be avoided. When stopping escitalopram treatment, the dose should be gradually reduced over at least 1–2 weeks to minimize the risk of withdrawal symptoms. If intolerable symptoms occur after dose reduction or upon discontinuation, consideration should be given to resuming the previously prescribed dose. The physician may then continue tapering the dose more gradually.
Method of Administration
The drug is administered orally to adults once daily, independent of food intake.
Children
Antidepressants are contraindicated for the treatment of children and adolescents (under 18 years of age). Suicidal behavior (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behavior, and anger) have been observed more frequently in clinical trials among children and adolescents treated with antidepressants compared to those receiving placebo. If a decision to prescribe is made based on clinical judgment, careful monitoring for the emergence of suicidal symptoms should be ensured.
Overdose.
Toxicity. Clinical data on escitalopram overdose are limited. Many cases involve concomitant overdose with other medicinal products. In most cases, mild or no symptoms were reported. Reports of fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other drugs. Doses of escitalopram ranging from 400–800 mg have not caused any 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 (arterial hypotension, tachycardia, QT interval prolongation, arrhythmia), and fluid/electrolyte imbalance (hypokalemia, hyponatremia).
Treatment. There is no specific antidote. Adequate respiratory function should be maintained and adequate oxygenation ensured. Gastric lavage and activated charcoal may be used. Continuous monitoring of cardiac and vital functions, along with symptomatic and supportive treatment, is recommended.
In cases of overdose, ECG monitoring is recommended for patients with congestive heart failure/bradyarrhythmias, patients concurrently taking drugs that prolong the QT interval, and patients with impaired drug metabolism, such as those with 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 known for SSRIs and escitalopram, observed during placebo-controlled studies and post-marketing use, are listed below by system organ class and frequency in the following table. Frequency is defined as: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), or frequency not known (cannot be estimated from available data).
| System, organ, class |
Frequency |
Adverse reactions |
| Blood and lymphatic system disorders |
frequency unknown |
thrombocytopenia |
| Immune system disorders |
rare |
anaphylactic reactions |
| Endocrine disorders |
frequency unknown |
disturbance of antidiuretic hormone secretion |
| Metabolism and nutrition disorders |
common |
decreased or increased appetite, weight gain |
| uncommon |
weight loss |
|
| frequency unknown |
hyponatremia, anorexia2 |
|
| Psychiatric disorders |
common |
anxiety, restlessness, abnormal dreams, decreased libido in males and females, anorgasmia in females |
| uncommon |
bruxism, excitement, nervousness, panic attacks, confusion |
|
| rare |
aggression, depersonalization, hallucinations |
|
| frequency unknown |
mania, suicidal thoughts, suicidal behavior1 |
|
| Nervous system disorders |
very common |
headache |
| common |
insomnia, somnolence, dizziness, paresthesia, tremor |
|
| uncommon |
taste disturbance, sleep disorder, loss of consciousness |
|
| rare |
serotonin syndrome |
|
| frequency unknown |
dyskinesia, movement disorders, seizures, psychomotor agitation/akathisia2 |
|
| Eye disorders |
uncommon |
pupil dilation, blurred vision |
| Ear and labyrinth disorders |
uncommon |
tinnitus |
| Cardiac disorders |
uncommon |
tachycardia |
| rare |
bradycardia |
|
| frequency unknown |
QT interval prolongation on electrocardiogram, ventricular arrhythmia, including torsade de pointes |
|
| Vascular disorders |
frequency unknown |
orthostatic hypotension |
| Respiratory system disorders |
common |
sinusitis, yawning |
| uncommon |
nosebleeds |
|
| Gastrointestinal disorders |
very common |
nausea |
| common |
diarrhea, constipation, vomiting, dry mouth |
|
| uncommon |
gastrointestinal hemorrhage (including rectal) |
|
| Hepatobiliary disorders |
frequency unknown |
hepatitis, changes in liver function tests |
| Skin and subcutaneous tissue disorders |
common |
increased sweating |
| uncommon |
rash, alopecia, urticaria, pruritus |
|
| frequency unknown |
bruising, swelling |
|
| Musculoskeletal and connective tissue disorders |
common |
arthralgia, myalgia |
| Renal and urinary disorders |
frequency unknown |
urinary retention |
| Reproductive system and breast disorders |
common |
males: ejaculation disorders, impotence |
| uncommon |
females: metrorrhagia, menorrhagia |
|
| frequency unknown |
galactorrhea females: postpartum hemorrhage⃰ males: priapism |
|
| General disorders |
common |
fatigue, pyrexia |
| uncommon |
edema |
-
Cases of suicidal thoughts and behavior have been reported during treatment with escitalopram or shortly after discontinuation.
-
Such cases are known for medications within the entire SSRI class.
⃠ This effect has been reported for the therapeutic class of SSRIs/SNRIs (see sections "Special precautions for use" and "Use during pregnancy or breastfeeding").
QT interval prolongation
Cases of QT interval prolongation and ventricular arrhythmias, including torsade de pointes, have been reported in the post-marketing period, primarily in female patients with hypokalemia or pre-existing QT interval prolongation or other cardiac conditions (see sections "Contraindications", "Special precautions for use", "Interaction with other medicinal products and other forms of interaction", "Overdose", and "Pharmacodynamics").
Class effects
Epidemiological studies, primarily in patients aged 50 years and older, have demonstrated an increased risk of bone fractures associated with the use of SSRIs and tricyclic antidepressants. The mechanism of this phenomenon is unknown.
Withdrawal symptoms
Discontinuation of SSRIs (especially abrupt discontinuation) is usually associated with 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, increased 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 to gradually discontinue escitalopram treatment by dose tapering (see sections "Dosage and administration" and "Special precautions for use").
Reporting suspected adverse reactions.
Reporting of suspected adverse reactions after drug registration 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.
2 years.
Storage conditions.
Store out of reach of children at a temperature not exceeding 25 °C.
Packaging.
10 mg tablets: 7 tablets per blister, 4 blisters per cardboard box.
20 mg tablets: 7 tablets per blister, 2 blisters per cardboard box.
Prescription status. Prescription only.
Manufacturer.
Aurobindo Pharma Limited – Unit III / Aurobindo Pharma Limited – Unit III.
Manufacturer's address and location of operations.
Survey No. 313, 314 – Blocks I, II, III, IV, Bachupally, Bachupally Mandal, Medchal-Malkajgiri District, Telangana State, 500090, India / Survey no.: 313, 314 – Block I, II, III, IV, Bachupally, Bachupally Mandal, Medchal-Malkajgiri District, Telangana State, 500090, India.
Marketing Authorization Holder.
Aurobindo Pharma Ltd, India / Aurobindo Pharma Ltd, India.
Address of Marketing Authorization Holder.
Plot №2, Maitrivihar, Ameerpet, Hyderabad – 500038, Telangana State, India / Plot №2, Maitrivihar, Ameerpet, Hyderabad – 500038, Telangana, India.