Instructions for Esobel film-coated tablets 10 mg No. 28
Composition
active ingredient: escitalopram;
1 tablet contains escitalopram oxalate equivalent to escitalopram 10 mg;
excipients: copovidone, lactose monohydrate, corn starch, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, Sepifilm LP 770 coating: hydroxypropylmethylcellulose, microcrystalline cellulose, stearic acid, titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties:
10 mg tablets: oval, film-coated tablets, white in color, with a breakline on one side and engraved with "10" on the other.
Pharmacotherapeutic group
Antidepressants. Selective serotonin reuptake inhibitors.
ATX code N06A B10.
Pharmacological properties
Pharmacodynamics
Essobel® is an antidepressant, a selective serotonin reuptake inhibitor (SSRI), which determines the clinical and pharmacological effects of the drug. It has a high affinity for the main binding element and the adjacent allosteric element of the serotonin transporter and has no or very weak ability to bind 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.
Escitalopram is the S-enantiomer of racemic citalopram with its own therapeutic activity. The R-enantiomer has been shown to be inert and to antagonize the serotonergic properties and corresponding pharmacological effects of the S-enantiomer.
Pharmacokinetics
Absorption is almost complete and independent of food intake. Maximum plasma concentration is reached 4 hours after administration. Bioavailability of escitalopram is approximately 80%.
The binding of escitalopram and its main metabolites to blood proteins is below 80%.
Metabolism occurs in the liver to demethylated and didemethylated metabolites. Both of them are pharmacologically active. Biotransformation of escitalopram to the demethylated metabolite occurs with the help of cytochrome CYP2C19. Minor participation in the process of isoenzymes CYP3A4 and CYP2D6 isoenzymes is possible. The half-life of the drug is approximately 30 hours. Creatinine clearance after oral administration is approximately 0.6 l / min. The main metabolites have a longer half-life. Escitalopram and its main metabolites are excreted by the liver (metabolic pathway) and the kidneys. Most of the dose is excreted as metabolites in the urine. The kinetics of escitalopram are linear. Equilibrium concentration is reached after approximately 1 week. In elderly patients (from 65 years), escitalopram is excreted more slowly than in young patients.
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.
In patients with reduced renal function, a longer half-life and slightly higher exposure were observed when racemic citalopram was administered. Plasma concentrations of metabolites have not been studied but may be increased.
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.
Indication
Treatment of major depressive episodes, panic disorders with or without agoraphobia, social anxiety disorders (social phobia), generalized anxiety disorders, obsessive-compulsive disorders.
Contraindication
Hypersensitivity to escitalopram or to any of the other ingredients of the drug; concomitant treatment with non-selective, irreversible monoamine oxidase (MAO) inhibitors, as there is a risk of developing serotonin syndrome, manifested by agitation, tremor, hyperthermia; combination with reversible MAO-A inhibitors (e.g. moclobemide) or the reversible, non-selective MAO inhibitor linezolid, as there is a risk of developing serotonin syndrome; prolongation of the QT interval or congenital long QT syndrome; concomitant use with drugs that prolong the QT interval; concomitant treatment with pimozide.
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 selective serotonin reuptake inhibitors (SSRIs) in combination with a non-selective irreversible MAOI, and in patients who have recently stopped treatment with an SSRI and started taking an MAOI. In some cases, serotonin syndrome has developed. The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Treatment with escitalopram 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.
The combination of pimozide and racemic citalopram resulted in a mean prolongation of the QTc interval of approximately 10 msec. Due to the interaction of escitalopram with low doses of pimozide and increased side effects of the latter, the simultaneous use of these drugs is contraindicated.
Reversible selective MAOI type A (moclobemide)
Due to the risk of serotonin syndrome, the combination of escitalopram with the type A MAOI moclobemide is not recommended. If the need for this combination is proven, the minimum recommended doses should be prescribed initially with careful clinical monitoring.
Treatment with escitalopram can be started no earlier than 1 day after stopping the reversible MAOI moclobemide.
The antibiotic linezolid is not recommended for use in patients taking escitalopram. If the combination is absolutely necessary, treatment should be initiated at the lowest recommended dose with close clinical monitoring.
QT prolongation
Pharmacokinetic and pharmacodynamic studies of escitalopram in combination with other drugs that increase the QT interval have not been conducted. A cumulative effect of escitalopram and these drugs cannot be excluded. Therefore, concomitant administration of escitalopram with drugs that prolong the QT interval, such as class IA and III antiarrhythmics, neuroleptics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobials (e.g. sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials, including halofantrine), certain antihistamines (astemizole, mizolastine), is contraindicated.
Selegiline
The combination with selegiline (an irreversible type B MAOI) requires caution due to the risk of serotonin syndrome.
Combinations requiring caution
Serotonergic medications
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 advised when concomitantly using medicinal products 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.
Concomitant use of nonsteroidal anti-inflammatory drugs may increase the tendency to bleed.
Alcohol
Escitalopram does not interact with alcohol in a pharmacodynamic or pharmacokinetic manner. However, the combination with alcohol is undesirable.
Drugs causing hypokalemia/hypomagnesemia
Caution should be exercised when concomitantly using medicinal products that cause hypokalaemia/hypomagnesaemia, as the risk of developing malignant arrhythmias may be increased.
Pharmacokinetic interactions
Effect of other agents on the pharmacokinetics of escitalopram
The metabolism of escitalopram is mainly mediated by CYP2C19.
Co-administration of escitalopram and omeprazole (a CYP2C19 inhibitor) leads to a moderate (approximately 50%) increase in escitalopram plasma concentrations.
Concomitant administration of escitalopram and cimetidine (a moderately potent major enzyme inhibitor) results in a moderate (approximately 70%) increase in escitalopram plasma concentrations.
Therefore, when escitalopram is co-administered with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) and with cimetidine, a lower dosage may be necessary depending on the results of monitoring of adverse reactions during co-administration (see section 4.4).
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 (CNS) 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 doubling of the plasma levels of these two agents.
Caution is recommended when used concomitantly with drugs metabolized by CYP2C19.
Application features
Paradoxical anxiety
Some patients with panic disorder may experience increased anxiety when starting antidepressant treatment. This paradoxical reaction usually resolves within two weeks of treatment. A low initial dose is recommended to reduce the likelihood of anxiogenic effects.
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 treatment are at greatest risk of suicidal thoughts or attempts and require close monitoring during treatment. A meta-analysis of studies has found an increased risk of suicidal behavior among patients under 25 years of age who took antidepressants compared with those who took 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
The use of SSRIs or serotonin-norepinephrine reuptake inhibitors (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 due 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, liver cirrhosis, or concomitant treatment with drugs that cause hyponatremia).
Hemorrhages
Skin bleeding, ecchymosis and purpura may occur with SSRIs. SSRIs should be used with caution in patients receiving concomitant anticoagulants, drugs that affect platelet function (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs (NSAIDs), dipyridamole and ticlopidine), and in patients with bleeding tendencies.
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.
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 and resolve within 2 weeks, but may be more prolonged (2-3 months or longer) in some patients. Therefore, gradual discontinuation of escitalopram treatment by reducing the dose over a period of several weeks or months, depending on the patient's condition, is recommended.
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, predominantly in female patients with hypokalaemia or pre-existing QT prolongation or other cardiac disease.
Caution is recommended in patients with marked bradycardia or in patients with 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 treatment with escitalopram.
In patients with stable cardiac disease, an ECG should be reviewed before treatment is initiated. If signs of cardiac arrhythmia occur during treatment with escitalopram, therapy should be discontinued and an ECG should be performed.
Angle-closure glaucoma
SSRIs, including escitalopram, can affect pupil size.
This mydriatic effect has the potential to narrow the anterior chamber angle, which in turn may lead to increased intraocular pressure and the development of 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.
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 persistent sexual dysfunction, with symptoms persisting despite discontinuation of SSRIs/SNRIs.
Essobel® contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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.
Use during pregnancy or breastfeeding
Clinical data on the use of escitalopram in pregnant women are limited.
Escitalopram is contraindicated in pregnant women, except in cases where the need for the drug has been clearly demonstrated after careful consideration of all the disadvantages and benefits. Careful examination of newborns whose mothers took escitalopram during pregnancy, especially in the third trimester, is recommended.
The following symptoms may occur in newborns whose mothers took SSRIs/SNRIs in the late stages of pregnancy: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, apathy, constant crying, drowsiness and difficulty sleeping. Such symptoms may develop either as a result of excessive serotonergic action or as withdrawal symptoms. In most cases, such complications occur immediately or shortly (up to 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, according to 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 data have shown that some SSRIs 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.
Method of administration and doses
Essobel® is prescribed to adults orally once a day, regardless of meals.
The safety of doses above 20 mg per day has not been established.
Major depressive episode
The antidepressant effect usually occurs after 2–4 weeks. After the symptoms disappear, treatment should be continued, usually for 6 months, in order to consolidate the effect.
Panic disorders with/without agoraphobia
An initial dose of 5 mg per day is recommended for the first week, after which the dose can be increased to 10 mg per day. The dose can be further increased to 20 mg per day, depending on the individual sensitivity of the patient.
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. Depending on the individual sensitivity of the patient, it is recommended to increase the dose to 20 mg per day.
Symptom relief usually occurs after 2–4 weeks of treatment. It is recommended to continue treatment for 3 months. Long-term treatment for 6 months is prescribed to prevent relapse, taking into account individual manifestations of the disease; the effectiveness of treatment should be regularly assessed.
Generalized anxiety disorders
Usually prescribed 10 mg once a day. Depending on individual sensitivity, the dose may be increased to a maximum of 20 mg per day.
It is recommended to continue treatment for 3 months. Long-term treatment for 6 months is prescribed to prevent relapse, taking into account individual manifestations of the disease; the effectiveness of treatment is regularly assessed.
Obsessive-compulsive disorder (OCD)
Usually prescribed 10 mg 1 time per day. Depending on individual sensitivity, the dose can be increased to 20 mg per day. OCD is a chronic disease, treatment should last a sufficient period to ensure complete disappearance of symptoms, which may be several months or even more.
Elderly patients (65 years and older)
The initial dose should be half the usual recommended dose. The recommended daily dose for elderly patients is 5 mg. Depending on individual sensitivity and severity of depression, the daily dose may be increased to a maximum of 10 mg per day.
Kidney failure
There are no restrictions in the presence of mild to moderate renal insufficiency. The drug should be used with caution in patients with severe renal insufficiency (creatinine clearance < 30 ml/min).
Decreased liver function
The recommended starting dose for the first two weeks of treatment is 5 mg per day. Depending on the individual patient's response, the dose may be increased to 10 mg per day.
Reduced activity of the cytochrome isoenzyme CYP2C19
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.
Treatment discontinuation
When discontinuing treatment with Essobel®, the dose should be gradually reduced over 1–2 weeks to avoid a withdrawal reaction.
Children
Antidepressants are contraindicated in children. Suicidal behavior (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) were observed more frequently in clinical trials among children and adolescents treated with antidepressants than in 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 overdose with escitalopram are limited. Many cases have been caused by concomitant overdose with other medicinal products. In most cases, mild or asymptomatic symptoms of overdose have been reported. Reports of fatal outcomes from overdose with escitalopram are exceptional, most of them involving concomitant overdose with other medicinal products. Escitalopram doses of 400–800 mg have not caused any severe symptoms.
Symptoms: Signs of escitalopram overdose are mainly symptoms from the CNS (ranging from dizziness, tremor and agitation to rare cases of serotonin syndrome, convulsions and coma), the digestive tract (nausea, vomiting), the 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 used. Monitoring of cardiac and vital signs is recommended along with symptomatic supportive treatment.
Adverse reactions
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.
From the blood system: thrombocytopenia.
Immune system disorders: anaphylactic reactions.
On the part of the endocrine system: impaired secretion of antidiuretic hormone.
Psychiatric: anxiety, restlessness, abnormal dreams, decreased libido in men and women, anorgasmia in women, teeth grinding, agitation, nervousness, panic attacks, confusion, aggression, depersonalization, hallucinations, mania, suicidal behavior1, suicidal thoughts.
Nervous system: insomnia, drowsiness, dizziness, paresthesia, tremor, taste disturbance, sleep disturbance, syncope, serotonin syndrome, dyskinesia, movement disorders, convulsions, psychomotor restlessness/akathisia2, headache.
On the part of the organs of vision: pupil dilation, blurred vision.
On the part of the organs of hearing: ringing in the ears.
Cardiovascular system: tachycardia, bradycardia, prolongation of the QT interval of the electrocardiogram, orthostatic hypotension, ventricular arrhythmia (including torsade de pointes).
Respiratory system: sinusitis, yawning, nosebleeds.
On the part of the digestive tract: nausea, diarrhea, constipation, vomiting, dry mouth, gastrointestinal bleeding (including rectal).
From the hepatobiliary system: hepatitis, changes in liver function tests.
Skin: increased sweating, rash, alopecia, urticaria, itching, bruising, angioedema.
Musculoskeletal system: arthralgia, myalgia.
On the part of the urinary system: urinary retention.
From the reproductive system: men: ejaculation disorders, impotence, priapism; women: metrorrhagia, menorrhagia, galactorrhea.
General disorders: fatigue, pyrexia, edema.
1 - Cases of suicidal thoughts and behavior have been reported during escitalopram treatment or shortly after its discontinuation.
2 - Such cases are known for the entire class of SSRIs.
Cases of QT prolongation and ventricular arrhythmias, including torsade de pointes, have been reported during clinical use, predominantly in female patients with hypokalemia or pre-existing QT prolongation or underlying cardiac disease. In one study in healthy volunteers, the mean change from baseline in QTc (Friedrich's formula) was 4.3 ms at 10 mg/day and 10.7 ms at 30 mg/day.
Epidemiological studies, mainly in patients over 50 years of age, have shown an increased risk of bone fractures with the use of SSRIs and tricyclic antidepressants. The mechanism of this phenomenon is unknown.
Withdrawal symptoms
Discontinuation of SSRI treatment (especially abrupt) usually leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, 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 and transient, but may be severe and/or prolonged in some patients. Therefore, gradual discontinuation of escitalopram treatment by dose reduction is recommended.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
14 tablets in a blister, 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
NOBEL ILACH SANAI VE TJARET A.Sh.
Location of the manufacturer and its business address
Sankaklar Quarter, Eski Akcakoca Ave., No. 299, 81100 Duzce, Turkey.
