Eccitalopram Canon,10 mg 28 pcs

-Depressive disorders;

Panic disorder with/without agoraphobia;

Obsessive-compulsive disorders.

Active ingredient

Composition

1 film-coated tablet, 10.00 mg contains:

the active ingredient:

escitalopram oxalate 12.78 mg,

in terms of escitalopram 10.00 mg;

auxiliary substances:

croscarmellose sodium 4.50 mg,

magnesium stearate 1.50 mg,

Prosolete [microcrystalline cellulose 98%, colloidal silicon dioxide 2%] 159.72 mg,

stearic acid 1.50 mg;

film shell:

Opadray white 6,000 mg, including: hypromellose (hydroxypropyl methylcellulose) 2.025 mg, hyprolose (hydroxypropyl cellulose) 2.025 mg, talc 1.200 mg, titanium dioxide 0.750 mg.

How to take, the dosage

Overly, once daily, regardless of meals.

The maximum daily dose is 20 mg.

Depressive disorders

The usual dose is 10 mg/day. Depending on the clinical condition of the patient, the dose of the drug may be increased to a maximum of 20 mg/day.

The antidepressant effect usually develops 2-4 weeks after the start of treatment. After symptoms of depression have disappeared, it is necessary to continue therapy for at least another 6 months to consolidate the effect obtained.

Panic disorder with/without agoraphobia

The recommended initial dose for the first week of therapy is

5 mg with subsequent increase to 10 mg/day. Depending on the clinical condition of the patient, the dose can be increased up to a maximum of

20 mg/day. Maximum clinical effect is achieved 3 months after the start of therapy. Treatment continues for several months.

Obsessive-compulsive disorder

Preferably 10 mg once daily is prescribed. Depending on the patient’s individual response, the dose may subsequently be increased to a maximum of 20 mg per day. Since obsessive-compulsive disorder is a disease with a chronic course, the course of treatment should be long enough to provide complete relief from symptoms and should last for at least 6 months. A course of treatment of at least 1 year is recommended to prevent relapses.

Elderly patients (over 65 years)

The starting dose is half of the recommended dose (5 mg). Depending on the clinical condition of the patient, the dose of the drug may be increased to 10 mg/day.

Patients with renal failure

There is no need for dose adjustment in mild to moderate renal failure. If creatinine clearance is less than 30 ml/min, the drug should be used with caution under medical supervision.

Patients with hepatic impairment

For patients with mild to moderate hepatic impairment (Child-Pugh class A or B), the initial dose for the first two weeks is 5 mg/day. Depending on the clinical condition of the patient, the drug dose may be increased to 10 mg/day. In severe hepatic insufficiency (grade C on the Child-Pugh scale) the drug is prescribed under close medical supervision.

CYP2C19 isoenzyme deficiency

For patients with CYP2C19 isoenzyme deficiency, the initial dose for the first 2 weeks is 5 mg/day. Depending on the clinical condition of the patient, the drug dose may be increased to 10 mg/day.

Interaction

Pharmacodynamic interactions

Contraindicated combinations:

Unreversible non-selective MAO inhibitors

Serious adverse reactions have been reported in patients receiving combined therapy with SSRIs and non-reversible non-selective MAO inhibitors, as well as patients who recently discontinued SSRI therapy and started therapy with such MAO inhibitors. In some cases, patients have developed serotonin syndrome. Escitalopram may be prescribed 14 days after discontinuation of treatment with non-reversible non-selective MAO inhibitors. At least 7 days must pass after stopping escitalopram before treatment with irreversible non-selective MAOI inhibitors can be started.

The reversible selective MAO inhibitors type A (moclobemide)

Because of the risk of serotonin syndrome, co-administration of escitalopram with reversible selective MAO inhibitors such as moclobemide is contraindicated. If there is a reasonable need for such a combination, treatment should be started with the lowest recommended dose under increased clinical monitoring.

The reversible non-selective MAO inhibitors (linezolid)

The antibiotic linezolid is a reversible non-selective MAO inhibitor and should not be used in patients receiving treatment with escitalopram. If there is a reasonable need for this combination, treatment should be started with minimal doses under close clinical observation.

Unreversible selective MAO type B inhibitors (selegiline)

Caution is necessary when using escitalopram and an irreversible selective MAO type B inhibitor (selegiline) together because of the risk of serotonin syndrome. Selegiline in doses up to 10 mg per day has been used successfully with racemic citalopram.

Drugs that prolong the QT interval

Pharmacokinetic and pharmacodynamic studies of escitalopram in combination with other drugs that prolong the QT interval have not been conducted. Additive effect of escitalopram and these drugs cannot be excluded. Thus, concomitant administration of escitalopram with drugs that prolong the QT interval, such as antiarrhythmic drugs of Class IA and III, neuroleptics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (e.g., sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarials, especially halofantrine), some antihistamines (astemizole, misolastine), contraindicated.

The concomitant administration of drugs that require caution in use:

Drugs that lower the seizure threshold

Escitalopram may lower the seizure threshold. Caution should be exercised when concomitant use of escitalopram and other drugs which decrease the seizure threshold (tricyclic antidepressants, SSRIs, neuroleptics – phenothiazine derivatives, tioxanthone and butyrophenone, mefloquine and tramadol) is required.

In concomitant use of lithium and tryptophan drugs there have been recorded cases of increased effect of escitalopram.

Simultaneous use with preparations of Hypericum perforatum may increase the number of side effects.

Anticoagulants and agents that affect blood clotting

Simultaneous use of anticoagulants and agents that affect blood clotting When anticoagulants and other drugs that affect blood clotting (e.g., atypical neuroleptics and phenothiazine derivatives, tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, ticlopidine, dipyridamole) are used concomitantly, clotting disorders may occur.

Escitalopram has no pharmacodynamic or pharmacokinetic interaction with ethanol. However, as with other psychotropic drugs, concomitant use of escitalopram and alcohol is not recommended.

Drugs causing hypokalemia/hypomagnesemia

Caution is required with concomitant use of drugs causing hypokalemia/hypomagnesemia because these conditions increase the risk of malignant arrhythmias.

Pharmacokinetic interactions

The effect of other drugs on the pharmacokinetics of escitalopram

The metabolism of escitalopram is primarily through the CYP2C19 enzyme. CYP3A4 and CYP2D6 enzymes may also participate in metabolism, although to a lesser extent. The metabolism of the main metabolite, S-DCT (demethylated escitalopram), is partially catalyzed by CYP2D6.

Concomitant administration of escitalopram and omeprazole 30 mg once daily (CYP2C19 inhibitor) resulted in a moderate (approximately 50%) increase in plasma concentration of escitalopram.

The concomitant administration of escitalopram and cimetidine 400 mg 2 times daily (a general moderate enzyme inhibitor) resulted in a moderate (approximately 70%) increase in plasma concentrations of escitalopram. Escitalopram should be combined with cimetidine with caution. Dose adjustment is recommended.

Thus, the drug should be combined with caution with CYP2C19 inhibitors (such as omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. After monitoring for side effects caused by concomitant use of other drugs, it may be necessary to reduce the dose of escitalopram.

The effect of escitalopram on the pharmacokinetics of other drugs

Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution should be exercised when concomitant use of escitalopram and drugs with a narrow therapeutic range, which are mainly metabolized by this enzyme, such as flecainide, propafenone and metoprolol (for use in heart failure), or certain CNS-acting drugs that are primarily metabolized by CYP2D6, such as antidepressants such as desipramine, clomipramine and nortriptyline or neuroleptics such as risperidone, thioridazine and haloperidol. Dose adjustments may be recommended.

The concomitant administration of the drugs with desipramine or metoprolol resulted in a twofold increase in plasma concentrations of these CYP2D6 substrates.

In vitro studies have shown that escitalopram may also be a weak inhibitor of CYP2C19. It is recommended with caution to use the drug concomitantly with drugs metabolized by CYP2C19.

Special Instructions

Use with MAO inhibitors

Escitalopram should not be prescribed concomitantly with MAO inhibitors because of the risk of serotonin syndrome. Escitalopram may be prescribed 14 days after stopping treatment with non-reversible MAO inhibitors and at least 1 day after stopping treatment with reversible type A MAO inhibitors (moclobemide).At least 7 days must pass after stopping escitalopram before treatment with non-selective MAO inhibitors may be started.

The use of the drug in children and adolescents under the age of 18

Antidepressants are contraindicated in children and adolescents under the age of 18 because of increased risk of suicidal behavior (suicide attempts and suicidal thoughts), hostility (with a predominance of aggressive behavior, tendency toward confrontation and irritation).

In young adults under 25 years of age with depression and other psychiatric disorders, antidepressants, compared with placebo, increase the risk of suicidal ideation and suicidal behavior.

So when prescribing the drug and any other antidepressants to young people under 25 years of age, the risk of suicide should be weighed against the benefits of their use. If the decision is made to start antidepressant therapy, the patient should be closely monitored for the early detection of impairment or behavioral changes, as well as suicidal tendencies.

Paradoxical Anxiety

When using drugs belonging to the therapeutic group of SSRIs, including escitalopram, it should be considered that some patients with panic disorder may experience increased anxiety at the beginning of SSRI treatment. This paradoxical reaction usually disappears within the first two weeks of treatment. Low initial doses are recommended to reduce the likelihood of anxiogenic effects.

Epileptic seizures

The use of escitalopram should be discontinued if the patient first has an epileptic seizure or if seizures become more frequent (in patients with a history of epilepsy).

Patients with unstable epilepsy should avoid taking SSRIs, and patients with controlled epilepsy should be closely monitored.

Mania

Escitalopram is recommended with caution in patients with a history of mania, hypomania. If a manic state develops, escitalopram should be discontinued.

Diabetes

In patients with diabetes mellitus, treatment with escitalopram may alter plasma glucose levels. Therefore, it may be necessary to adjust the doses of insulin and/or oral hypoglycemic drugs.

Suicidal/suicidal thoughts or clinical worsening of depressive states

Careful monitoring of patients taking antidepressants is necessary, especially at the beginning of therapy because of the possibility of clinical worsening and/or the appearance of suicidal thoughts and behavior. Clinical experience shows that an increased risk of suicide tends to be seen in the early stages of recovery.

Other psychiatric disorders for which escitalopram is prescribed may also be associated with an increased risk of suicidal behaviors and manifestations. In addition, these disorders may accompany severe depressive disorder. The precautions taken when treating patients with major depressive disorder should also be followed when treating patients with other psychiatric disorders.

Patients with a history of suicidal behaviors and manifestations, or those who exhibited suicidal ideation prior to treatment, are known to be at greater risk for suicidal intentions or attempts, so they should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behavior with antidepressants compared to placebo in patients less than 25 years of age. Close monitoring of patients, particularly those at high risk, should accompany medication therapy, particularly at the beginning of treatment and after dose changes.

Patients and caregivers should be warned to monitor for any clinical deterioration, suicidal behavior or intent, and unusual behavioral changes, and to contact a physician immediately if they notice the manifestation of such symptoms.

Akathisia/psychomotor agitation

The use of SSRIs is associated with the development of akathisia, a condition characterized by an unpleasant debilitating feeling of restlessness and hyperactivity and often accompanied by an inability to sit or stand in one place. This condition is most likely to occur during the first few weeks of therapy. Increasing the dose may be detrimental to patients who experience these symptoms.

Hyponatremia

Hyponatremia occurs with drug administration, possibly associated with impaired secretion of antidiuretic hormone (ADH). It usually disappears with discontinuation of therapy.

We should use caution when prescribing the drug in patients with a history of or at risk for hyponatremia: elderly people, patients with cirrhosis of the liver.

Bleeding

The development of skin bleeding (ecchymosis and purpura) is possible during administration of escitalopram. Caution is necessary when using the drug in patients at risk of bleeding, as well as patients taking oral anticoagulants and agents affecting blood clotting.

Electroconvulsive therapy

Cautions should be taken with concomitant use of the drug and electroconvulsive therapy (ECT) due to limited experience of use.

Serotonin syndrome

Patients taking escitalopram and other SSRIs concomitantly with serotonergic drugs may rarely develop serotonin syndrome. A combination of symptoms such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition. In this situation, the SSRI and serotoninergic medication should be stopped immediately and symptomatic treatment should be initiated.

The withdrawal symptoms after discontinuation of treatment

The withdrawal symptoms when discontinuing treatment are common, especially if treatment is stopped abruptly. In clinical trials, adverse events upon treatment discontinuation have been observed in approximately 25% of patients who received escitalopram and 15% of patients who received placebo.

The risk of treatment withdrawal may depend on several factors, including duration, dose during treatment, and rate of dose reduction. The most commonly observed reactions include dizziness, sensory disturbances (including paresthesias and shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or restlessness, nausea and/or vomiting, tremors, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances. Typically, these symptoms are mild to moderate, but in some patients they may be severe.

These usually occur within the first few days of treatment withdrawal, with similar symptoms less commonly reported in patients who have accidentally missed a dose.

In general, these symptoms are self-limiting and usually go away within 2 weeks, although some people may experience them for longer periods (2-3 months or more). Therefore, it is recommended that the dose of escitalopram be gradually reduced after withdrawal of treatment over a period of weeks or months, depending on the patient’s needs.

Ischemic heart disease

Because of limited experience with its use, caution should be exercised when using the drug in patients with coronary heart disease (CHD).

Evidence of QT interval prolongation

Escitalopram has been found to cause dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular arrhythmias, including bidirectional tachycardia, have been reported during the post-registration period, predominantly in female patients, with hypokalemia, or with pre-existing QT interval prolongation or other cardiovascular disease.

We recommend caution when recommending the drug for patients with severe bradycardia, patients after recent acute myocardial infarction, or patients with uncompensated heart failure.

Electrolyte disturbances, such as hypokalemia and hypomagnesemia, increase the risk of dangerous arrhythmias, and these conditions should be corrected before prescribing escitalopram.

If the drug is prescribed in patients with ongoing heart disease, an ECG should be done before starting treatment.

If signs of cardiac arrhythmia occur during treatment with escitalopram, treatment should be stopped and an EKG should be done.

Escitalopram has no pharmacodynamic or pharmacokinetic interaction with alcohol. However, as with other psychotropic medications, concomitant use of escitalopram and alcohol is not recommended.

Impact on driving, operating machinery

When using escitalopram, you should refrain from engaging in potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

. -concomitant use with monoamine oxidase inhibitors (MAOIs), monoamine oxidase-A (MAOA) (e.g., moclobemide) or reversible non-selective MAOI inhibitors;

Patients with prolonged QT interval (congenital long QT interval syndrome); concomitant use of drugs that may prolong the QT interval (e.g., antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, macrolides);

-pregnancy;

-period of breastfeeding;

-children under 18 years of age;

-concurrent use of pimozide.

With caution

Renal insufficiency (KC less than 30 ml/min), manic disorders (including history), pharmacologically uncontrolled epilepsy, depression with suicide attempts, diabetes mellitus, electroconvulsive therapy; elderly age (over 65), cirrhosis of the liver, susceptibility to bleeding, concurrent use with ethanol, drugs that lower the threshold of seizure readiness, lithium, tryptophans, drugs containing St. John’s wort; with drugs that cause hyponatremia, anticoagulants for oral administration and drugs that affect blood clotting; with drugs metabolized with participation of CYP2C19 system.

Side effects

Adverse reactions with escitalopram are observed during the first one to two weeks of treatment and usually subside significantly as therapy continues and patients improve.

The incidence of adverse reactions (according to WHO classification): very common – ≥10%; common – ≥1%, but <10%; infrequent – ≥0.1%, but <1%; rare – ≥0.01%, but <0.1%; very rare – <0.01%, unknown – no data on the incidence of adverse reactions are available at this time.

The following adverse reactions may occur:

Blood and lymphatic system: unknown – thrombocytopenia.

Allergic reactions: infrequent – hypersensitivity; very rare – anaphylactic reactions.

The central nervous system: very frequently – somnolence, headache, tremor, dizziness; frequently – migraine, paresthesia, sleep disorder; infrequently – extrapyramidal disorders, syncopal states, taste disorders; rarely – serotonin syndrome (combination of agitation, tremor, myoclonus and hyperthermia); unknown – dyskinesia, motor disorders, convulsive disorders.

Psychiatric disorders: very often – agitation, nervousness; often – decreased libido, impaired orgasm (in women), anxiety, confusion, drowsiness, impaired concentration, strange dreams, amnesia; infrequently – aggression, depersonalization, hallucinations, euphoria, increased libido, bruxism, panic attacks; unknown – mania, suicidal thoughts1, psychomotor agitation, akathisia2.

The digestive system: very often – nausea, vomiting; often – diarrhea, dry mouth, decreased appetite or increased appetite, constipation.

Liver and biliary tract: unknown – hepatitis.

The skin: very often – increased sweating, often – skin rash, itching; infrequently – photosensitization, urticaria, alopecia, purpura; unknown – angioedema, bruising (ecchymosis).

Cardiovascular system: very often – palpitations, very often – tachycardia, arterial hypertension, orthostatic hypotension; rarely – bradycardia, decreased arterial pressure, arrhythmia; unknown – QT interval prolongation on ECG.

Hemorrhagic organs: rarely – hemorrhages (e.g., gynecological bleeding, gastrointestinal bleeding).

Senses: very often – accommodation disorder; often – taste disorders, visual disturbances, infrequent – mydriasis, tinnitus (tinnitus).

Respiratory system: common – rhinitis, sinusitis, yawning; infrequent – cough, nasal bleeding; rare – dyspnea, tracheitis.

With the reproductive system: often – disorders of sexual function, namely, impaired ejaculation, decreased libido, impotence, menstrual disorders; infrequent – metrorrhagia, menorrhagia; unknown – galactorrhea, priapism.

Perior urinary system disorders: often – painful urination, urinary retention.

Metabolic disorders: often – decreased or increased appetite, weight gain; infrequent – weight loss; rarely – insufficient secretion of antidiuretic hormone (ADH), hyponatremia, hypokalemia; unknown – anorexia2.

Motor system disorders: infrequent – myalgia, arthralgia, increased risk of injuries and fractures.

Laboratory measures: frequently – changes in laboratory indexes of liver function; infrequent – increased activity of “liver” enzymes, electrocardiogram (prolongation of QT interval), hyponatremia.

Others: common – weakness; infrequent – edema; rarely – hyperthermia.

1- There have been reports of suicidal moods and suicidal behavior while taking escitalopram or immediately after stopping treatment.

2- There have been reports of these phenomena in relation to the SSRI treatment class.

In the post-registration period, cases of QT interval prolongation and ventricular arrhythmias, including pirouette-type ventricular tachycardia, were reported primarily in female patients with hypokalemia or pre-existing QT interval prolongation or other cardiovascular disease. In double-blind, placebo-controlled ECG studies in healthy volunteers, the change from baseline QTc (corrected by the Friedericia formula) was 4.3 msec at 10 mg/day and 10.7 msec at 30 mg/day.

Class effect

Epidemiological studies involving patients aged 50 years and older have reported an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism leading to this risk is unknown.

Discontinuation symptoms after treatment ends

Cessation of SSRIs/SRIs (selective norepinephrine and serotonin reuptake inhibitors) (especially abrupt) usually results in “withdrawal” symptoms. The most common symptoms are dizziness, sensory disturbances (including paresthesias and current sensations), sleep disturbances (including insomnia and vivid dreams), agitation or restlessness, nausea and/or vomiting, tremors, confusion, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances. These are usually mild to moderate in severity and pass on their own, but in some patients they may be severe and prolonged. Gradual withdrawal of the drug by reducing the dose is recommended.

Overdose

Toxicity

The clinical data on overdose with escitalopram are limited, and many cases include concomitant overdose with other drugs. In most cases, symptoms are mild or absent. Fatal cases resulting from overdose of escitalopram alone have rarely been reported; most overdose of concomitant drugs also occurs. Doses of 400 and 800 mg of escitalopram without taking other drugs are tolerated without any serious symptoms.

Symptoms: in overdose of the drug dizziness, tremor, agitation, nausea, vomiting, hypotension, tachycardia, prolongation of the QT interval, hypokalemia, hyponatremia, and in rare cases serotonin syndrome, cardiac arrhythmias, seizures and coma develop.

Treatment: specific antidote is unknown. Treatment is symptomatic: ensuring a constant supply of fresh air, support of external respiration function, adequate oxygenation, control of cardiac activity, gastric lavage, prescription of enterosorbents. Forced diuresis, hemodialysis, hemoperfusion are not effective.

Similarities