Instructions for Cyclox tablets 10 mg No. 56
Composition
active ingredient: escitalopram oxalate;
1 tablet contains escitalopram oxalate equivalent to escitalopram 10 mg or 20 mg;
excipients: microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, purified talc, magnesium stearate, coating "Opadry white 03F58750" (hypromellose, titanium dioxide (E 171), macrogol, talc).
Dosage form
Film-coated tablets.
Main physicochemical properties:
Oval, biconvex tablets, white or almost white, film-coated, with a breakline on one side and smooth on the other side.
Pharmacotherapeutic group
Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATX code N06A B10.
Pharmacological properties
Pharmacodynamics.
Escitalopram is a selective serotonin reuptake inhibitor (SSRI) with high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter, with a 1000-fold lower affinity for this site.
Escitalopram has no or very weak binding to 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 opiate receptors.
Inhibition of 5-HT reuptake is the only possible mechanism of action that could explain the pharmacological and clinical effects of escitalopram.
Pharmacodynamic effects
In one double-blind, placebo-controlled study of ECG parameters in healthy subjects, the prolongation of the QTc interval (corrected according to the Friederichia formula) from baseline was 4.3 ms (90% CI: 2.2, 6.4) at a dose of 10 mg/day and 10.7 ms (90% CI: 8.6, 12.8) at a supratherapeutic dose of 30 mg/day (see sections “Contraindications”, “Special instructions for use”, “Interaction with other medicinal products and other types of interactions”, “Adverse reactions”, “Overdose”).
Clinical efficacy
Major depressive episodes
The efficacy of escitalopram in the treatment of acute major depressive episodes has been demonstrated in 3 of 4 double-blind, placebo-controlled, short-term (8-week) studies. In a long-term relapse prevention study, 274 patients who responded to escitalopram 10 or 20 mg/day during the initial 8-week open-label phase of the study were randomized to continue escitalopram at the same dose or placebo for up to 36 weeks. In this study, patients who continued to receive escitalopram had a statistically significantly longer time to relapse within the next 36 weeks compared with those who received placebo.
Social anxiety disorder
Escitalopram has been 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 optimal dose study, escitalopram was shown to be effective 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.
In a pooled analysis of three studies with a similar design, involving a total of 421 patients treated with escitalopram and 419 patients treated with placebo, 47.5% and 28.9% of patients respectively responded to treatment, and 37.1% and 20.8% of patients respectively achieved remission. 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 maintenance study in 373 patients who responded to the drug during the initial 12 weeks of open-label treatment.
Obsessive-compulsive disorder
In a randomized, double-blind clinical trial, escitalopram 20 mg/day demonstrated a difference from placebo in the total score of the Y-BOCS (Yale-Brown Obsessive Compulsive Scale) after 12 weeks of treatment. After 24 weeks, benefits were observed for both escitalopram 10 mg/day and 20 mg/day compared to placebo.
The efficacy of the drug in preventing relapse was demonstrated for escitalopram at doses of 10 and 20 mg/day in patients who responded to escitalopram in a 16-week open-label period and were included in a 24-week randomized double-blind placebo-controlled period.
Pharmacokinetics.
Absorption is almost complete and independent of food intake. Maximum plasma concentration (Tmax) is reached 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%. The protein binding of escitalopram and its major metabolites is below 80%.
Metabolism occurs in the liver to demethylated and didemethylated metabolites. Both are pharmacologically active. Alternatively, nitrogen oxidation to form the N-oxide metabolite is possible. Both the parent compound and the metabolites are partly excreted as glucuronides. With repeated administration of the drug, the average concentrations of the demethylated and didemethylated metabolites are usually 28-31% and < 5% of the concentration of escitalopram, respectively. The biotransformation of escitalopram to the demethylated metabolite is mainly mediated by CYP2C19. Some involvement of the enzymes CYP3A4 and CYP2D6 is possible.
Elimination
The elimination half-life (t½β) of the drug is approximately 30 hours. The oral clearance (Cloral) 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 the kidneys. Most of the dose is excreted as metabolites in the urine.
Linearity
Escitalopram has linear kinetics. 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
Escitalopram is eliminated more slowly in patients aged 65 years and older than in younger patients. Systemic exposure (AUC) in healthy elderly volunteers is approximately 50% higher than in young healthy volunteers (see section 4.2).
Liver failure
In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the half-life was twice as long and exposure was 60% higher than in subjects with normal hepatic function (see section 4.2).
Kidney failure
In patients with reduced renal function (CLcr 10-53 ml/min) a longer half-life and slightly higher exposure were observed with racemic citalopram. Plasma concentrations of metabolites have not been studied but may be increased (see section 4.2).
Polymorphism
Patients with poor CYP2C19 metaboliser function had twice the plasma concentrations of escitalopram as patients with normal CYP2C19 function. No significant changes in exposure were observed with reduced CYP2D6 function (see section 4.2).
Indication
Major depressive episodes.
Panic disorder with or without agoraphobia.
Social anxiety disorder (social phobias).
Obsessive-compulsive disorder.
Generalized anxiety disorders.
Contraindication
Hypersensitivity to escitalopram or to any of the other ingredients of the drug.
Concomitant treatment with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome with agitation, tremor, hyperthermia and other symptoms (see section "Interaction with other medicinal products and other types of interactions").
The combined use of escitalopram and reversible MAO inhibitors type A (e.g. moclobemide) or 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 types of interactions").
Escitalopram is contraindicated for use in patients with known QT prolongation or congenital long QT syndrome.
Escitalopram is contraindicated for use concomitantly with drugs that may prolong the QT interval (see section "Interaction with other medicinal products and other types of interactions").
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions
Contraindicated combinations.
Non-selective irreversible MAOIs
Serious reactions have been reported in patients receiving SSRIs in combination with non-selective irreversible MAOIs and in patients who have recently stopped SSRIs and started taking an MAOI (see section 4.3). Serotonin syndrome has been reported in some cases (see section 4.8). The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Escitalopram treatment should be initiated 14 days after discontinuation of the irreversible MAOI. Treatment with non-selective irreversible MAOIs should be initiated no earlier than 7 days after discontinuation of escitalopram.
Combinations that require caution.
Reversible selective MAOI type A (moclobemide)
Due to the risk of serotonin syndrome, the combination of escitalopram with the type A MAOI moclobemide is contraindicated (see section 4.3). If the need for this combination is proven, the minimum recommended doses should be used initially with increased clinical monitoring.
Non-selective reversible MAO inhibitor (linezolid)
The antibiotic linezolid is a non-selective, reversible MAOI and should not be given to patients receiving escitalopram. If such a combination is necessary, the lowest doses of both drugs should be used under close clinical supervision (see section 4.3).
Selective irreversible MAO inhibitor type B (selegiline)
Selegiline at doses up to and including 10 mg/day has been safely co-administered with racemic citalopram.
QT prolongation
Pharmacokinetic and pharmacodynamic studies of the combined use of escitalopram with other drugs that prolong the QT interval have not been conducted. When using escitalopram together with such drugs, an additive effect cannot be excluded. In this regard, the simultaneous use of escitalopram with drugs that prolong the QT interval, such as antiarrhythmic drugs of class IA and III, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobials (e.g. sparfloxacin, moxifloxacin, erythromycin for intravenous administration, pentamidine, antimalarials, including halofantrine), some antihistamines (astemizole, hydroxyzine, mizolastine), is contraindicated.
Serotonergic drugs
Concomitant use with serotonergic agents (e.g. tramadol, sumatriptan and other triptans) may lead to serotonin syndrome.
Medications that lower the seizure threshold
SSRIs may lower the seizure threshold. Caution is advised when concomitantly using drugs that may lower the seizure threshold (e.g. antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion and tramadol).
Lithium, tryptophan
Since cases of enhanced effects have been reported with the combined use of SSRIs and lithium or tryptophan, it is recommended to prescribe these drugs concomitantly with caution.
Hypericum
Concomitant use of SSRIs and herbal remedies containing St. John's wort may lead to an increased incidence of adverse reactions.
Anticoagulants
The effects of anticoagulants may be altered by concomitant use with escitalopram. If patients are taking oral anticoagulants, careful monitoring of the blood coagulation system is necessary before and after the use of escitalopram (see section "Special instructions").
Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the tendency to bleed (see section "Special warnings and precautions for use").
Alcohol
Escitalopram does not interact with alcohol in a pharmacodynamic or pharmacokinetic manner. However, as with psychotropic drugs, the combination with alcohol is undesirable.
Drugs causing hypokalemia/hypomagnesemia
Caution should be exercised when using concomitant medications that can cause hypokalemia/hypomagnesemia, as this increases the risk of developing malignant arrhythmias (see section "Special warnings and precautions for use").
Pharmacokinetic interactions
Effect of other Icaric agents on the pharmacokinetics of escitalopram
The metabolism of escitalopram is mainly mediated by CYP2C19. The enzymes CYP3A4 and CYP2D6 may also play some role in its metabolism, although to a lesser extent. The metabolism of the main metabolite S-DCT (demethylated escitalopram) appears to be partly catalyzed by CYP2D6.
Co-administration of escitalopram and omeprazole 30 mg once daily (CYP2C19 inhibitor) leads to a moderate (approximately 50%) increase in escitalopram plasma concentrations.
Concomitant administration of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) resulted in a moderate (approximately 70%) increase in escitalopram plasma concentrations. Caution should be exercised when escitalopram is administered in combination with cimetidine. Dose adjustment may be required (see section 4.4).
Therefore, caution should be exercised when prescribing the upper limit doses of escitalopram when co-administered with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) and with cimetidine. A dose reduction of escitalopram may be necessary based on clinical judgment.
Effect of escitalopram on the pharmacokinetics of other drugs
Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is advised when escitalopram is co-administered with medicinal products that are primarily metabolised by this enzyme and have a narrow therapeutic index, such as flecainide, propafenone and metoprolol (in heart failure), or with certain central nervous system agents that are primarily metabolised by CYP2D6, such as antidepressants such as desipramine, clomipramine and nortriptyline, and antipsychotics such as risperidone, thioridazine and haloperidol. Dose adjustment may be necessary.
Combination with desipramine or metoprolol resulted in a twofold increase in plasma levels of these two CYP2D6 substrates.
In vitro studies have shown that escitalopram may also cause slight inhibition of CYP2C19.
Caution is recommended when used concomitantly with drugs metabolized by CYP2C19.
Application features
The following features of use apply to the therapeutic class of selective serotonin reuptake inhibitors (SSRIs).
Some patients with panic disorder may experience increased anxiety when starting treatment with antidepressants. This paradoxical reaction usually disappears within two weeks of treatment. A low initial dose is recommended to reduce the likelihood of anxiogenic effects (see section "Dosage and administration").
Convulsive seizures
Escitalopram should be discontinued if the patient develops a seizure for the first time or if the seizures become more frequent (in patients with established epilepsy). SSRIs should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be closely monitored.
Mania
SSRIs should be used with caution in patients with a history of mania/hypomania. If a manic state occurs, the SSRI should be discontinued.
Diabetes mellitus
In patients with diabetes mellitus, treatment with SSRIs may alter glycemic control. The dose of insulin and/or oral hypoglycemic agents may need to be adjusted.
Suicide, suicidal thoughts, or clinical worsening
Depression is associated with a risk of suicidal ideation, self-harm and suicide. This risk persists until sustained remission is achieved. As improvement may not occur within the first few weeks or more of treatment, patients should be closely monitored until improvement occurs. It is known that the risk of suicide may be increased in the early stages of recovery.
Other conditions for which escitalopram is used may also be associated with a risk of suicidal behaviour. In addition, such conditions may be comorbid with major depressive disorder. These warnings also apply to the treatment of patients with other psychiatric disorders.
Patients with a history of suicidal behavior prior to initiation of treatment are at greatest risk of suicidal thoughts or attempts and require close monitoring during treatment. A meta-analysis of studies has shown an increased risk of suicidal behavior in patients under 25 years of age who received antidepressants compared with those who received placebo. Close monitoring of high-risk patients is particularly necessary at the beginning of treatment and during dose changes.
Patients and caregivers should be warned to monitor for any worsening of condition, suicidal behavior or thoughts, and unusual changes in behavior and to seek immediate medical advice if these symptoms develop.
Akathisia/psychomotor agitation
The use of SSRIs/SNRIs has been associated with the development of akathisia, a condition characterized by an unpleasant, debilitating feeling of restlessness and a need to move, often accompanied by an inability to sit or stand still. This condition is most likely to occur during the first few weeks of treatment. Increasing the dose may be harmful in patients who develop these symptoms.
Hyponatremia
Hyponatremia, possibly related to impaired antidiuretic hormone secretion, occurs rarely with SSRIs and usually resolves after discontinuation of therapy. SSRIs should be prescribed with caution in patients at risk (elderly age, presence of liver cirrhosis, or concomitant treatment with drugs that cause hyponatremia).
Hemorrhages
Skin bleeding, ecchymosis and purpura may occur with SSRIs. SSRIs/NSAIDs may increase the risk of postpartum haemorrhage (see sections “Use during pregnancy or lactation” and “Adverse reactions”). SSRIs should be used with caution in patients receiving concomitant anticoagulants, medicinal products that affect 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 tendency to bleed.
Electroconvulsive therapy (ECT)
Clinical experience with the concomitant use of SSRIs and ECT is limited, therefore caution is advised.
Reversible, selective type A MAOIs
Combining escitalopram and type A MAOIs is not recommended due to the risk of serotonin syndrome.
Serotonin syndrome
Caution is recommended when escitalopram is used concomitantly with serotonergic agents such as sumatriptan or other triptans, tramadol and tryptophan.
Serotonin syndrome has been reported in isolated cases in patients taking SSRIs concomitantly with serotonergic drugs. Caution should be exercised when escitalopram is used concomitantly with drugs that have serotonergic effects. The 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 drug should be discontinued immediately and symptomatic treatment initiated.
Hypericum
Concomitant use of SSRIs and herbal remedies containing St. John's wort may lead to an increased incidence of adverse reactions (see section "Interaction with other medicinal products and other types of interactions").
Withdrawal symptoms
The risk of withdrawal symptoms may depend on several factors, including duration and dose, 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 lability, irritability and visual disturbances are the most common reactions. These symptoms are usually mild to moderate in severity, but may be more severe in some patients. They usually occur within the first few days after discontinuation of treatment, but there have been very rare reports of such symptoms in patients who accidentally missed a dose. These withdrawal symptoms usually resolve within 2 weeks, but may be more prolonged (2–3 months or longer) in some patients. Therefore, it is recommended to gradually discontinue escitalopram treatment by reducing the dose over a period of several weeks or months, depending on the patient's condition (see section 4.2).
Sexual dysfunction
Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-term sexual dysfunction where symptoms persist despite discontinuation of SSRIs/SNRIs.
Coronary heart disease
Due to limited clinical experience, caution is recommended when using the drug in patients with ischemic heart disease.
QT prolongation
Escitalopram has been shown to cause dose-dependent prolongation of the QT interval. Cases of QT prolongation and ventricular arrhythmias, including torsade de pointes, have been reported in the post-marketing setting, predominantly in women, in patients with hypokalaemia and in patients with pre-existing QT prolongation or other cardiac disease (see sections 4.3, 4.5, 4.8, 4.1, 4.2, and 4.8).
The drug should be used with caution in patients with severe bradycardia and in patients with a recent acute myocardial infarction or decompensated heart failure.
Electrolyte imbalances, such as hypokalemia and hypomagnesemia, increase the risk of malignant arrhythmias and should be corrected before starting treatment with escitalopram.
In patients with stable heart disease, a careful ECG evaluation should be performed before initiating treatment with escitalopram.
If signs of cardiac arrhythmia occur during treatment with escitalopram, the drug should be discontinued and an ECG should be performed.
Angle-closure glaucoma
SSRIs, including escitalopram, may affect pupil size, resulting in mydriasis. This mydriatic effect may potentially narrow the angle of the eye, leading to increased intraocular pressure and angle-closure glaucoma, especially in predisposed patients. Escitalopram should therefore be used with caution in patients with angle-closure glaucoma or a history of glaucoma.
Excipients
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
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 in pregnant women, unless the need for the drug has been clearly demonstrated after a careful assessment of the risk-benefit ratio. Careful examination of newborns whose mothers took escitalopram during pregnancy, especially in the third trimester, is recommended. Abrupt withdrawal of the drug during pregnancy should be avoided.
The following symptoms may occur in newborns whose mothers took SSRIs/SNRIs in late pregnancy: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, agitation, irritability, apathy, constant crying, drowsiness, and difficulty sleeping. These symptoms may be due to either serotonergic effects or withdrawal symptoms. In most cases, these complications occur immediately or shortly (up to 24 hours) after delivery.
Epidemiological data have shown that the use of SSRIs in pregnant women may increase the risk of persistent pulmonary hypertension in the newborn (up to 5 cases per 1000 pregnant women, according to observational data). In the general population, 1 to 2 cases per 1000 pregnant women occur.
Breastfeeding
Since escitalopram passes into breast milk, breastfeeding is not recommended during treatment.
Observational results indicate an increased risk (< 2-fold) of postpartum hemorrhage after use of SSRIs or SSRIs within the month before delivery (see sections “Adverse reactions” and “Special precautions for use”).
Animal data have shown that escitalopram may affect sperm quality. Reports from some SSRIs in humans have shown that the effects on sperm quality are reversible. Effects on human fertility have not been observed to date.
Ability to influence reaction speed when driving vehicles or other mechanisms
Although escitalopram does not affect intellectual or psychomotor functioning, any psychoactive drug may impair skills or the ability to think rationally. Patients should be warned of the potential risk of impairment in driving or operating machinery.
Method of administration and doses
The safety of doses above 20 mg per day has not been established.
The drug Cyclox® is administered orally to adults once a day, regardless of meals.
Major depressive episode
Usually, 10 mg is prescribed once a day. Depending on the individual sensitivity of the patient, the daily dose may be increased to a maximum of 20 mg.
The antidepressant effect usually occurs after 2–4 weeks. After the symptoms disappear, treatment should be continued for at least 6 months to consolidate the effect.
Panic disorder with or without agoraphobia
An initial dose of 5 mg per day is recommended for the first week before increasing to 10 mg per day. The dose may be further increased to a maximum of 20 mg per day, depending on the individual patient's sensitivity.
The maximum effect in the treatment of panic disorders is achieved after 3 months. The duration of treatment is several months and depends on the severity of the disease.
Social anxiety disorder (social phobia)
Usually prescribed 10 mg 1 time per day. Usually, 2-4 weeks of therapy are required to relieve symptoms. Later, depending on the individual patient's response, the dose may be reduced to 5 mg or increased to a maximum of 20 mg per day. Social anxiety disorder is a chronic disease, and to consolidate the effect, it is recommended to continue treatment for 12 weeks.
Long-term treatment for 6 months has been shown to prevent relapse and can be individualized; the benefits of treatment should be regularly assessed.
Social anxiety disorder is a well-defined diagnostic term for a specific disorder, not to be confused with excessive shyness. Drug therapy is indicated only if the disorder significantly interferes with occupational and social functioning.
The value of this treatment compared to cognitive behavioral therapy has not been evaluated. Drug therapy is one component of the patient's overall treatment strategy.
Generalized anxiety disorders
The usual dose is 10 mg once daily. Depending on individual sensitivity, the dose may be increased to a maximum of 20 mg per day.
Long-term treatment has been studied for at least 6 months in patients receiving a dose of 20 mg per day; the benefit of treatment should be assessed regularly (see section 5.1).
Obsessive-compulsive disorder (OCD)
Usually, the initial dose is 10 mg once daily. Depending on individual sensitivity, the dose can be increased to 20 mg daily. OCD is a chronic disease, treatment should last for a sufficient period to ensure complete resolution of symptoms, which may be several months or even longer. The benefit of treatment and the dose of the drug should be assessed at regular intervals (see section "Pharmacodynamics").
Elderly patients (aged 65 years and over)
The initial dose is 5 mg per day. Depending on individual sensitivity and severity of depression, the daily dose may be increased to a maximum of 10 mg per day (see Pharmacokinetics).
The efficacy of escitalopram in social anxiety disorder in elderly patients has not been evaluated.
Pediatric population
The drug Cyclox® should not be used to treat children and adolescents (under 18 years of age) (see the section “Children”).
Kidney failure
There are no restrictions in the presence of mild to moderate renal impairment. The drug should be used with caution in patients with severe renal impairment (CLCR <30 mL/min) (see Pharmacokinetics).
Liver failure
The recommended starting dose during the first two weeks of treatment is 5 mg per day for patients with mild to moderate hepatic impairment. Depending on the individual patient response, the dose may be increased to 10 mg per day. In patients with severe hepatic impairment, caution and careful dose titration are recommended (see section 5.2).
Reduced activity of the CYP2C19 isoenzyme
For patients with poor CYP2C19 activity, the recommended starting dose is 5 mg/day for the first two weeks of treatment. Depending on the individual patient response, the dose may be increased to 10 mg/day (see Pharmacokinetics).
Abrupt discontinuation of the drug should be avoided. When stopping treatment with escitalopram, the dose should be reduced gradually over at least 1-2 weeks to reduce the risk of withdrawal symptoms (see sections "Special instructions" and "Adverse reactions"). If unacceptable symptoms occur after dose reduction or discontinuation, a return to the previously prescribed dose may be considered. In the future, the doctor may continue to reduce the dose, but more gradually.
Children.
Antidepressants should not be used in children and adolescents (under 18 years of age). Suicidal behaviour (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials in children and adolescents treated with antidepressants compared to those treated with placebo. If a decision to prescribe is made for clinical reasons, the patient should be closely monitored for suicidal symptoms.
Overdose
Toxicity. Clinical data on escitalopram overdose are limited. Many cases have been caused by concomitant overdose with other drugs. In most cases, mild or asymptomatic symptoms of overdose have been reported. Reports of fatal outcomes from escitalopram overdose are exceptional, most of them involving concomitant overdose with other drugs. Escitalopram doses of 400–800 mg have not caused any severe symptoms.
Symptoms.
Signs of escitalopram overdose are mainly central nervous system symptoms (ranging from dizziness, tremor and agitation to rare cases of serotonin syndrome, convulsions and coma), gastrointestinal system (nausea, vomiting), cardiovascular system (hypotension, tachycardia, QT prolongation, arrhythmia) and electrolyte/fluid imbalance (hypokalaemia, hyponatraemia).
Treatment.
There is no specific antidote. Maintain proper respiratory function and ensure adequate oxygenation. Gastric lavage and activated charcoal may be considered. Monitoring of cardiac and vital signs is recommended along with symptomatic supportive treatment.
In case of overdose, ECG monitoring is recommended in patients with congestive heart failure/bradyarrhythmias, patients concomitantly taking drugs that prolong the QT interval, and patients with impaired drug metabolism, such as patients with hepatic insufficiency.
Side effects
Adverse reactions are most often observed during the first or second week of treatment and usually their frequency and intensity gradually decrease with continued treatment.
Adverse reactions known for SSRIs and escitalopram, which have been observed in placebo-controlled studies and during clinical use, are listed below by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) or not known (frequency cannot be estimated from the available data).
Blood and lymphatic system disorders: frequency unknown - thrombocytopenia.
On the part of the immune system: rare - anaphylactic reactions.
On the part of the endocrine system: frequency unknown - impaired secretion of antidiuretic hormone.
Metabolism and nutrition: frequent - decreased or increased appetite, weight gain; uncommon - decreased body weight; frequency unknown - hyponatremia, anorexia1.
On the part of the psyche: frequent - anxiety, restlessness, abnormal dreams, decreased libido, anorgasmia in women; infrequent - bruxism (teeth grinding), agitation (excitement), nervousness, panic attacks,
