Epracad
UkraineTable of Contents
INSTRUCTION for medical use of the medicinal product EPRACAD (EPRACAD)
Composition:
Active substance: escitalopram;
1 tablet contains escitalopram oxalate equivalent to escitalopram 5 mg or 10 mg or 15 mg or 20 mg;
Excipients: microcrystalline cellulose, colloidal anhydrous silicon dioxide, talc, sodium croscarmellose, magnesium stearate (E 470b); coating: Opadry White Y-1-7000 (hypromellose, polyethylene glycol 400, titanium dioxide (E 171)).
Pharmaceutical form. Film-coated tablets.
Main physicochemical properties:
5 mg tablets: white, round, biconvex film-coated tablets, embossed with "B2" on one side and smooth on the other side;
10 mg tablets: white, biconvex, film-coated, oval-shaped tablets with a score line on one side, embossed with "B" to the left of the score line and "3" to the right of the score line, and smooth on the other side;
15 mg tablets: white, modified capsule-shaped, biconvex film-coated tablets with a score line on both sides, embossed with "15" on one side of the score line on one side of the tablet;
20 mg tablets: white, biconvex, oval-shaped film-coated tablets with a score line on one side, embossed with "B4" on the side with the score line and smooth on the other side.
Pharmacotherapeutic group.
Antidepressants. Selective serotonin reuptake inhibitors.
ATC code N06AB10.
Pharmacological Properties
Pharmacodynamics
Mechanism of Action
Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class with high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter with 1000-fold lower affinity.
Escitalopram has no or very weak 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 probable mechanism of action that may explain the pharmacological and clinical effects of escitalopram.
Clinical Efficacy
Major Depressive Episodes
In three out of four double-blind, placebo-controlled, short-term (8-week) studies, escitalopram was shown to be effective in the acute treatment of major depressive episodes. In a long-term relapse prevention study, 274 patients who responded to an initial 8-week treatment with escitalopram at doses of 10 or 20 mg/day were randomized to either continue escitalopram treatment at the same dose for up to 36 weeks or switch to placebo. In this study, patients who continued receiving escitalopram had a significantly longer time to relapse after 36 weeks of treatment compared to those receiving placebo.
Social Anxiety Disorders
Escitalopram was effective in three short-term (12-week) studies and in a six-month relapse prevention study of social anxiety disorder. In a 24-week dose study, efficacy of escitalopram at doses of 5, 10, and 20 mg was demonstrated.
Generalized Anxiety Disorders
Escitalopram at doses of 10 and 20 mg/day was effective in all four placebo-controlled studies.
Pooled data from three studies involving 421 patients treated with escitalopram and 419 patients treated with placebo showed response rates of 47.5% and 28.9%, respectively. A sustained effect was observed from the first week.
The sustained efficacy of escitalopram at a dose of 20 mg/day was demonstrated in a randomized study lasting 24 to 76 weeks involving 373 patients who responded to treatment in an initial 12-week open-label study.
Obsessive-Compulsive Disorders
In a randomized, double-blind, clinical trial, escitalopram at a dose of 20 mg/day differed from placebo in the total Y-BOCS score after 12 weeks. After 24 weeks, escitalopram doses of 10 and 20 mg/day produced significantly better outcomes compared to placebo.
Prevention of relapse with escitalopram doses of 10 and 20 mg/day was demonstrated in a 16-week open-label study followed by a 24-week randomized, double-blind, placebo-controlled study involving patients who responded to initial treatment.
Pharmacokinetics
Absorption
Absorption is nearly complete and is not affected by food intake. The median time to reach maximum plasma concentration (Tmax) after multiple dosing is 4 hours. Similar to racemic citalopram, the absolute bioavailability of escitalopram is expected to be approximately 80%.
Distribution
The apparent volume of distribution (Vα,β/F) after oral administration is approximately 12–26 L/kg. Protein binding of escitalopram and its major metabolites is less than 80%.
Biotransformation
Escitalopram is metabolized in the liver to dimethyl- and didemethyl metabolites. These metabolites are pharmacologically active. In addition, nitrogen may be oxidized to form an N-oxide metabolite. These parent compounds and metabolites are partially excreted as glucuronides. After repeated administration, the average concentrations of the dimethyl- and didemethyl metabolites are typically 28–31% and < 5% of the escitalopram concentration, respectively. The biotransformation of escitalopram to its demethyl metabolite is primarily mediated by CYP2C19. A minor contribution from CYP3A4 and CYP2D6 enzymes is also possible.
Elimination
The elimination half-life (t1/2β) after multiple dosing is approximately 30 hours, and the oral plasma clearance (Cloral) is about 0.6 L/min. The major metabolites have significantly longer elimination half-lives. Escitalopram and its major metabolites are primarily eliminated via both hepatic (metabolic) and renal routes, with the majority of the dose excreted as metabolites in the urine.
Escitalopram pharmacokinetics are linear.
Steady-state plasma concentrations are reached within 1 week. The average steady-state concentration of 50 mmol/L (20–125 mmol/L) is achieved at a daily dose of 10 mg.
Elderly Patients (> 65 years)
In elderly patients, escitalopram is likely eliminated more slowly than in younger patients. Systemic exposure (AUC) in elderly patients is approximately 50% higher than in younger healthy volunteers.
Hepatic Impairment
In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the elimination half-life of escitalopram was approximately twice as long, and plasma concentrations were 60% higher compared to individuals with normal liver function.
Renal Impairment
With racemic citalopram, a longer elimination half-life and slight increase in concentration have been observed in patients with renal impairment (CLcr 10–53 mL/min). Plasma concentrations of metabolites have not been studied but may be elevated.
Polymorphism
Poor metabolizers of CYP2C19 had approximately twice the plasma concentration of escitalopram compared to extensive metabolizers. No significant changes in escitalopram concentration were observed in poor metabolizers of CYP2D6.
Clinical characteristics.
Indications.
Treatment of major depressive episodes.
Treatment of panic disorders with or without agoraphobia.
Treatment of social anxiety disorders (social phobia).
Treatment of generalized anxiety disorders.
Treatment of obsessive-compulsive disorders.
Contraindications.
Hypersensitivity to escitalopram or to any of the excipients of the medicinal product.
Concomitant use with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome with 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, and in patients who have recently discontinued SSRIs and started treatment with such MAOIs. In some cases, serotonin syndrome occurred. The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Treatment with escitalopram may be initiated no earlier than 14 days after discontinuation of irreversible MAOIs. Conversely, treatment with MAOIs may be initiated only 7 days after discontinuation of escitalopram.
Reversible selective MAO-A inhibitor (moclobemide)
Due to the risk of developing serotonin syndrome, the combination of escitalopram with the MAO-A inhibitor moclobemide is contraindicated. If combination is necessary, treatment should be initiated with the lowest recommended doses and clinical monitoring should be intensified.
Reversible non-selective MAOI (linezolid)
The antibiotic linezolid is a reversible non-selective MAO inhibitor and should not be used in patients receiving escitalopram. If combination is necessary, it should be administered with minimal doses and under close clinical monitoring.
Irreversible selective MAO-B inhibitor (selegiline)
Combination with selegiline (an irreversible MAO-B inhibitor) requires caution due to the risk of serotonin syndrome. Doses of selegiline up to 10 mg/day have 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, 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 (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 concomitantly with medicinal products that may reduce the seizure threshold (e.g., antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol).
Lithium, tryptophan
Since increased serotonergic effects have been reported when SSRIs are used in combination with lithium or tryptophan, caution is recommended when escitalopram is used concomitantly with these medicinal products, and regular monitoring of lithium and tryptophan levels is mandatory.
St. John’s wort
Concomitant use of escitalopram and herbal preparations containing St. John’s wort (Hypericum perforatum) may increase the frequency of adverse reactions; therefore, their concomitant use should be avoided.
Anticoagulants
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.
Alcohol
Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interaction with alcohol. However, combination with alcohol is undesirable.
Medicinal products causing hypokalemia/hypomagnesemia
Caution is required when co-administering medicinal products that cause hypokalemia/hypomagnesemia, as this may increase the risk of developing life-threatening arrhythmias.
Pharmacokinetic interactions.
Effect of other medicinal products on escitalopram pharmacokinetics
Metabolism of escitalopram is primarily mediated by CYP2C19. CYP3A4 and CYP2D6 may also contribute to metabolism, although to a lesser extent. 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 administration of escitalopram and cimetidine 400 mg twice daily (a moderately potent non-specific enzyme inhibitor) results in a moderate (approximately 70%) increase in plasma escitalopram concentrations. Escitalopram should be prescribed with caution in combination with cimetidine. Dose adjustment may be required.
Therefore, caution is advised when escitalopram is used concomitantly with CYP2C19 inhibitors (e.g., omeprazole, fluoxetine, fluconazole, fluvoxamine, lansoprazole, ticlopidine) and with cimetidine. Based on monitoring of adverse effects during concomitant therapy, a reduction in escitalopram dose may be necessary.
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 certain central nervous system (CNS) agents primarily metabolized by CYP2D6, such as the antidepressants desipramine, clomipramine, and nortriptyline, and antipsychotics such as risperidone, thioridazine, and haloperidol. Dose adjustment may be necessary.
Combination with desipramine or metoprolol has resulted in a doubling of plasma levels of these two medicinal products.
In vitro studies have demonstrated that escitalopram may also cause weak 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 SSRIs (Selective Serotonin Reuptake Inhibitors).
Children
Epikad should not be used for the treatment of children. Suicidal behaviour (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behaviour and anger) were observed more frequently in clinical trials among children receiving antidepressants compared to children receiving placebo. If, based on clinical necessity, a decision to treat is made, patients should be closely monitored for the emergence of suicidal symptoms. Furthermore, there is a lack of data on the long-term safety in children regarding effects on growth, maturation, cognitive and behavioural development.
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 starting dose is recommended.
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 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 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 conditions for which escitalopram is used may also be associated with a risk of suicidal behaviour. Additionally, these 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 the start of treatment are at the highest risk of suicidal thoughts or attempts and require close monitoring during treatment. A meta-analysis of studies has shown an increased risk of suicidal behaviour among patients under 25 years of age who were taking antidepressants compared to those taking placebo. Close monitoring of high-risk patients is particularly necessary at the beginning of treatment and when the dose is changed.
Patients and their caregivers should be warned to monitor for any worsening of symptoms, suicidal behaviour or thoughts, and unusual changes in behaviour, and to seek immediate medical advice if such symptoms develop.
Akathisia/Psychomotor restlessness
The use of SSRIs/SNRIs (Selective Serotonin and Norepinephrine Reuptake Inhibitors) has been associated with the development of akathisia—a condition characterised by a distressing, exhausting sense of inner restlessness and a compelling need to move, often accompanied by an inability to sit or stand still. This condition is most likely to occur during the first few weeks of treatment. Increasing the dose may worsen symptoms in patients who develop such symptoms.
Hyponatraemia
Hyponatraemia, possibly related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), 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 hepatic cirrhosis, or those taking concomitant medications that may cause hyponatraemia).
Bleeding
Skin haemorrhages, ecchymoses, and purpura have been reported during SSRI use. SSRIs should be used with caution in patients receiving concomitant oral anticoagulants, medications 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.
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 the concomitant use of SSRIs and ECT is limited; therefore, caution is recommended.
Serotonin syndrome
Caution is advised when escitalopram is used concomitantly with serotonergic agents such as sumatriptan or other triptans, tramadol, and tryptophan.
Serotonin syndrome has been reported rarely in patients taking SSRIs concomitantly with serotonergic drugs. The combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. In such cases, SSRIs and the serotonergic agent should be discontinued immediately, and symptomatic treatment initiated.
St. John’s wort
Concomitant use of SSRIs and herbal preparations containing St. John’s wort may lead to an increased frequency of adverse reactions.
Withdrawal symptoms
Withdrawal symptoms upon discontinuation of treatment, particularly abrupt discontinuation, are common. In clinical trials, adverse reactions during treatment 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 use, dose, and rate 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 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 typically occur within the first few days after discontinuation of treatment, but very rarely have been reported in patients who accidentally missed a dose.
Usually, these symptoms 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.
Sexual dysfunction
SSRIs/SNRIs may cause symptoms of sexual dysfunction (see section "Adverse reactions"). Reports have described persistent sexual dysfunction, with symptoms continuing despite discontinuation of SSRIs/SNRIs.
Ischaemic heart disease
Due to limited clinical experience, SSRIs should be used with caution in patients with ischaemic heart disease.
QT interval prolongation
Escitalopram has been shown to cause dose-dependent QT interval prolongation. Cases of QT interval prolongation and ventricular arrhythmias, including torsade de pointes, have been reported during the post-marketing period, primarily in female patients, those with hypokalaemia, or those with pre-existing QT interval prolongation or other cardiac conditions.
Caution is recommended in patients with significant bradycardia, 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.
When prescribing the drug to patients with stable cardiac conditions, an ECG should be performed before initiating treatment.
If signs of cardiac arrhythmia occur during treatment with escitalopram, treatment should be discontinued and an ECG 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 prior history of the condition. Therefore, escitalopram should be used with caution in patients with closed-angle glaucoma or a history of glaucoma.
This medicinal product contains less than 1 mmol sodium (23 mg)/dose, i.e. essentially "sodium-free".
Use during pregnancy or breastfeeding.
Clinical data on the use of escitalopram during pregnancy 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.
Close monitoring of newborns whose mothers have taken escitalopram during pregnancy, particularly in the third trimester, is recommended. Abrupt discontinuation of treatment during pregnancy should be avoided.
Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following escitalopram use within one month of delivery (see sections "Special precautions for use" and "Adverse reactions").
Newborns whose mothers have taken SSRIs/SNRIs during 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 arise either due to excessive serotonergic activity or as withdrawal symptoms. In most cases, such complications occur immediately or shortly (within 24 hours) after delivery.
Epidemiological data have shown that the use of SSRIs during pregnancy may increase the risk of persistent pulmonary hypertension in the newborn (up to 5 cases per 1000 pregnancies, based on observational data). In the general population, the incidence is 1 to 2 cases per 1000 pregnancies.
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 drive and use machines.
Although escitalopram does not affect cognitive or psychomotor functions, any psychoactive agent may impair skills or the ability to make sound judgments. Patients should be warned of the potential risk of impaired ability to drive or operate machinery.
Dosage and Administration
The safety of doses above 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 be continued for at least 6 months to consolidate the therapeutic effect.
Panic Disorder with or without Agoraphobia
A starting dose of 5 mg once daily (administered at the corresponding dosage strength) is recommended for the first week before increasing to 10 mg once daily. The dose may subsequently be increased up to a maximum of 20 mg daily, depending on individual patient sensitivity.
Maximum therapeutic effect in panic disorder is achieved after 3 months. The duration of treatment is several months and depends on the severity of the condition.
Social Anxiety Disorder (Social Phobia)
The usual dose is 10 mg once daily. Symptom improvement usually occurs within 2–4 weeks of treatment. Thereafter, depending on individual patient response, the dose may be reduced to 5 mg or increased up to a maximum of 20 mg daily.
Social anxiety disorder is a chronic condition, and treatment for at least 12 weeks is recommended to consolidate the effect. Long-term treatment for 6 months has been shown to prevent relapse and may be prescribed individually; the benefits of continued treatment should be regularly evaluated.
Social anxiety disorder is a clearly defined diagnostic entity and should not be confused with excessive shyness. Pharmacotherapy is indicated only when the disorder significantly impairs professional or social functioning.
The role of this treatment compared to cognitive-behavioral therapy has not been established. 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 for at least 6 months has been studied. 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 disorder, and treatment should continue for a sufficient duration 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 used 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. Caution is advised 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 careful dose titration are recommended in patients with significantly impaired liver function.
Reduced CYP2C19 Isoenzyme Activity
For patients with poor 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 treatment with escitalopram, 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 reinstating the previously prescribed dose. The physician may then continue tapering the dose more gradually.
Administration
The drug should be administered orally to adults once daily, independent of food intake.
Children
Antidepressants are contraindicated for use in children. Suicidal behavior (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) have been observed more frequently in children and adolescents receiving antidepressants compared to those receiving placebo in clinical trials. If a decision to prescribe is made based on clinical judgment, careful monitoring for the emergence of suicidal symptoms is essential.
Overdose
Toxicity. Clinical data on escitalopram overdose are limited. Most cases involve concomitant overdose with other medicinal products. Generally, mild symptoms or asymptomatic overdose have been observed. Fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other drugs. Ingestion of doses within the range of 400–800 mg of escitalopram has not caused any severe symptoms.
Symptoms. Overdose with escitalopram is primarily manifested by symptoms affecting 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, arrhythmia), and electrolyte imbalances (hypokalemia, hyponatremia).
Treatment. There is no specific antidote. Airway patency, adequate oxygenation, and respiratory support should be ensured. Gastric lavage and activated charcoal should be administered. Gastric lavage should be performed as soon as possible after oral ingestion. Continuous monitoring of cardiac and vital functions is required, along with symptomatic and supportive treatment.
ECG monitoring is recommended in cases of overdose in patients with congestive heart failure/bradyarrhythmia, in patients concurrently taking drugs that prolong the QT interval, or in patients with impaired metabolism, such as those with hepatic impairment.
Adverse reactions.
Adverse reactions most commonly occur during the first or second week of treatment and usually decrease in intensity and frequency with continued treatment.
The adverse reactions reported are listed below by system organ classes and frequency.
Frequency is known from clinical trial data; these data have not been adjusted for placebo. Frequency is defined as: very common (> 1/10), common (> 1/100 − <1/10), uncommon (> 1/1000 − <1/100), rare (> 1/10000 − <1/1000), very rare (< 1/10000), or not known (frequency cannot be estimated from available data).
| System organ class |
Frequency |
Adverse effect |
| Blood and lymphatic system disorders |
Unknown |
Thrombocytopenia |
| Immune system disorders |
Rare |
Anaphylactic reactions |
| Endocrine disorders |
Unknown |
Inadequate antidiuretic hormone secretion |
| Metabolism and nutrition disorders |
Common |
Decreased appetite, increased appetite, weight gain |
| Uncommon |
Weight loss |
|
| Unknown |
Hyponatremia, anorexia2 |
|
| Psychiatric disorders |
Common |
Anxiety, restlessness, abnormal dreams Men and women: decreased libido Women: anorgasmia |
| Uncommon |
Bruxism, agitation, nervousness, panic attacks, confusion |
|
| Rare |
Aggression, depersonalization, hallucinations |
|
| Unknown |
Mania, suicidal ideation, suicidal behaviour1 |
|
| Nervous system disorders |
Very common |
Headache |
| Common |
Insomnia, somnolence, dizziness, paraesthesia, tremor |
|
| Uncommon |
Taste disturbances, sleep disorders, syncope |
|
| 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). |
|
| Vascular disorders |
Unknown |
Orthostatic hypotension |
| Respiratory 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, angioneurotic 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 Postpartum haemorrhage* |
|
| General disorders |
Common |
Increased fatigue, pyrexia |
| Uncommon |
Oedema |
1Suicidal thoughts or behaviors were observed both during escitalopram therapy and immediately after discontinuation of treatment.
2These adverse reactions have been reported for the therapeutic class of SSRIs in general.
*This reaction has been reported for the SSRI/SSNRI therapeutic class as a whole (see sections "Special precautions", "Use during pregnancy or breastfeeding").
QT interval prolongation
During the post-marketing period, cases of QT interval prolongation, including torsade de pointes, have been reported, primarily in female patients with hypokalemia or pre-existing QT interval prolongation or other cardiac diseases.
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 abrupt discontinuation
Discontinuation of SSRIs/SSNRIs (especially abrupt) commonly leads to withdrawal symptoms. The most commonly reported reactions include 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. These symptoms are usually mild to moderate in severity and transient; however, in some patients they may be severe and/or prolonged. Therefore, it is recommended to gradually discontinue escitalopram by dose reduction over several weeks or months, depending on the patient's condition.
Shelf life. 2 years.
Storage conditions.
Store at temperatures not exceeding 25 °C, protected from light and kept out of the reach of children.
Packaging.
10 tablets per blister pack. 3 blisters per cardboard box.
Prescription status.
Prescription only.
Manufacturer.
Jubilant Generics Limited.
Manufacturer's address and site of operations.
Village Sikandarpur, Bhainswal, Roorkee-Dehradun Highway, Bhagwanpur, District Roorkee Haridwar, Uttarakhand, IN-247661, India.