Cipralex pills 10mg, 14pcs

Composition

1 film-coated tablet contains:

Active ingredient:

escitalopram oxalate 12.77 mg (equivalent to 10 mg of escitalopram, respectively),

excipients:

talcum powder — 7 mg;

croscarmellose sodium-4.5 mg;

MCC-97.49 mg;

colloidal silicon dioxide-1.99 mg;

magnesium stearate-1.25 mg,

 film shell:

Hypromellose 5 cP — 2.19 mg;

macrogol 400-0.2 mg;

titanium dioxide (E 171) – 0.73 mg

Pharmacological action

Cipralex has an antidepressant effect.

Pharmacodynamics

Escitalopram is an antidepressant, an SSRI, with a high affinity for the primary binding site. Escitalopram also binds to the allosteric binding site of the transporter protein, with an affinity less than a thousand times. Allosteric modulation of the transporter protein enhances the binding of escitalopram at the primary binding site, which leads to a more complete inhibition of serotonin reuptake.

Escitalopram 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}-receptors, m-holinoreceptors, benzodiazepine and opioid receptors.

Pharmacokinetics

Absorption is almost complete and does not depend on food intake. The mean T_max in blood plasma is 4 hours after repeated use. The absolute bioavailability of escitalopram is about 80%.

The apparent vd after oral use is between 12 and 26 l / kg. Binding of escitalopram and its major metabolites to plasma proteins is below 80%.

Escitalopram is metabolized in the liver to demethylated and didemethylated metabolites. They are both pharmacologically active. Nitrogen can be oxidized to the N-oxide metabolite. The main substance and its metabolites are partially released in the form of glucuronides. After repeated use, the average concentration of demethyl and didemethyl metabolites is usually 28-31% and less than 5%, respectively, of the concentration of escitalopram. Escitalopram is biotransformed to a demethylated metabolite mainly by the CYP2C19 isoenzyme. Some involvement of CYP3A4 and CYP2D6 isoenzymes is possible. In individuals with low activity of the CYP2C19 isoenzyme, the concentration of escitalopram is twice as high as in cases with high activity of this isoenzyme. Significant changes in the drug concentration in cases with weak activity of the CYP2D6 isoenzyme were not detected.

T_1/2 after repeated use is about 30 h. The clearance with oral use is about 0.6 l / min. The main metabolites of escitalopram have a longer half-life. Escitalopram and its major metabolites are excreted by the liver (metabolic pathway) and kidneys; most are excreted as metabolites in the urine.

The kinetics of escitalopram is linear. The equilibrium concentration is reached after about 1 week. The average C_ss,50 nmol / l (from 20 to 125 nmol/L), is achieved at a daily dose of 10 mg.

Special patient groups

Patients over 65 years of age. Escitalopram is excreted more slowly in the elderly than in younger patients. The amount of substance in the systemic circulation, calculated using the pharmacokinetic index AUC, is 50% higher in the elderly than in young healthy volunteers.

Indications

• depressive episodes of any severity;
• panic disorder with or without agoraphobia;
• social anxiety disorder (social phobia);
• generalized anxiety disorder;
• obsessive-compulsive disorder.

Use during pregnancy and lactation

There are limited data on the use of escitalopram during pregnancy.

If the use of escitalopram continued in the late stages of pregnancy, especially in the third trimester, then the newborn should be monitored. If escitalopram continued until delivery or was discontinued shortly before delivery, the newborn may develop withdrawal symptoms.

If the mother takes SSRIs/SSRIs in late pregnancy, the newborn may develop the following side effects: respiratory depression, cyanosis, apnea, convulsive disorders, temperature jumps, feeding difficulties, vomiting, hypoglycemia, hypertension, muscle hypotension, hyperreflexia, tremor, increased neuro-reflex excitability, irritability, lethargic sleep, constant crying, drowsiness, poor sleep. These symptoms may occur due to the development of withdrawal syndrome or serotonergic action.

In most cases, such complications occur within 24 hours after birth. Escitalopram should be taken during pregnancy only when absolutely necessary and after careful assessment of the benefit / risk ratio. Data from epidemiological studies suggest that the use of SSRIs during pregnancy, especially in the late stages, may increase the risk of developing persistent pulmonary hypertension in the newborn.

Escitalopram is expected to be excreted in breast milk, so breast-feeding is not recommended during treatment with escitalopram.

Contraindications

• hypersensitivity to escitalopram and other components
• of Cipralex; concomitant use of non-selective irreversible MAO inhibitors;
• concomitant use of pimozide;
• children and adolescents (up to 18 years).

With caution: severe renal insufficiency (creatinine clearance below 30 ml/min); mania and hypomania; pharmacologically uncontrolled epilepsy; severe suicidal behavior; diabetes mellitus; cirrhosis of the liver; tendency to bleeding; concomitant use with an MAO A inhibitor (moclobemide) and an MAO B inhibitor (selegiline), serotonergic drugs, drugs that reduce the threshold of convulsive readiness, lithium, tryptophan, drugs containing St. John’s wort, oral anticoagulants and other drugs that affect blood clotting, drugs that can cause hyponatremia, drugs that are metabolized with the participation of the CYP2C19 isoenzyme, ethanol; electroconvulsive therapy; the elderly; pregnancy; breastfeeding.

Side effects

Side effects most often develop at the 1st or 2nd week of treatment and then usually become less intense and occur less frequently with continued therapy.

The following are the side effects that occur when taking SSRI medications and are noted when taking escitalopram. The information is based on data from placebo-controlled clinical trials and spontaneous reports. The frequency is specified as: very often – ≥1/10; often-from ≥1/100 to

From the blood and lymphatic system: unknown-thrombocytopenia.

From the immune system: rarely — anaphylactic reactions.

Endocrine system disorders: unknown-insufficient ADH secretion.

Metabolic disorders and eating disorders: often-decreased appetite, increased appetite, weight gain; infrequently-weight loss; unknown-hyponatremia, anorexia.

From the side of the psyche: often-anxiety, restlessness, unusual dreams, decreased libido, anorgasmia (in women); infrequently — bruxism, agitation, nervousness, panic attacks, confusion; rarely — aggression, depersonalization, hallucinations; unknown — mania, suicidal thoughts, suicidal behavior. Cases of suicidal thoughts and behaviors have been reported with escitalopram and immediately after discontinuation of therapy.

From the nervous system: often-insomnia, drowsiness, dizziness, paresthesia, tremor; infrequently-taste disorders, sleep disorders, syncopal states; rarely-serotonin syndrome; unknown-dyskinesia, motor disorders, convulsive disorders, psychomotor agitation/akathisia.

From the side of the organ of vision: infrequently-mydriasis (dilated pupil), visual disturbances.

From the side of the organ of hearing and labyrinth disorders: infrequently-tinnitus (tinnitus).

From the cardiovascular system: infrequently-tachycardia; rarely-bradycardia; unknown-prolongation of the QT interval on the ECG, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders: often-sinusitis, yawning; infrequently-nosebleeds.

From the gastrointestinal tract: very often-nausea; often-diarrhea, constipation, vomiting, dry mouth; infrequently-gastrointestinal bleeding (including rectal).

From the liver and biliary tract: unknown-hepatitis, impaired liver function.

From the skin and subcutaneous tissues: often-increased sweating; infrequently-urticaria, alopecia, rash, pruritus; unknown-ecchymosis, angioedema.

Musculoskeletal and connective tissue disorders: often-arthralgia, myalgia.

Renal and urinary tract disorders: unknown-urinary retention.

From the reproductive system and breast: often-impotence, ejaculation disorders; infrequently-metrorrhagia (uterine bleeding), menorrhagia; unknown-galactorrhea, priapism.

On the part of the body as a whole and disorders at the injection site: often — weakness, hyperthermia; infrequently — edema.

In the post-marketing period, cases of prolongation of the QT interval were noted, mainly in patients with pre-existing heart diseases. In double-blind placebo-controlled ECG studies in healthy volunteers, the change from the baseline QTc value (correction according to the Friederichia formula) was 4.3 ms at a dose of 10 mg / day and 10.7 ms at 30 mg / day.

Epidemiological studies involving patients aged 50 years and older have shown an increased risk of bone fractures in patients taking SSRIs and tricyclic antidepressants. The mechanism of occurrence of this risk has not been established.

Withdrawal (especially abrupt) of SSRI/SSRI medications often leads to withdrawal symptoms. The most common symptoms are dizziness, sensory disturbances (including paresthesia and current flow sensations), sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances. As a rule, these effects are mild or moderate and pass quickly, however, in some patients they may appear in a more acute form and/or for a longer time. It is recommended to gradually cancel the drug by reducing its dose.

Interaction

Pharmacodynamic interaction

Non-selective irreversible MAO inhibitors. Serious adverse reactions have been reported with concomitant use of SSRIs and non-selective irreversible MAO inhibitors, as well as with the initiation of MAO inhibitors in patients who have recently stopped taking SSRIs. In some cases, patients developed serotonin syndrome. Escitalopram should not be used concomitantly with non-selective irreversible MAO inhibitors. Escitalopram may be started 14 days after discontinuation of irreversible MAO inhibitors. At least 7 days after the end of escitalopram should elapse before starting non-selective irreversible MAO inhibitors.

Reversible selective MAO A inhibitor (moclobemide). Due to the risk of serotonin syndrome, escitalopram should not be used concomitantly with the MAO A inhibitor moclobemide. If the use of such a combination of drugs is considered clinically necessary, it is recommended to start with the lowest possible doses, as well as to conduct constant clinical monitoring of the patient’s condition. Escitalopram should be started at least one day after discontinuation of the reversible MAO A inhibitor moclobemide.

An irreversible MAO B inhibitor (selegiline). Due to the risk of serotonin syndrome, caution should be exercised when taking escitalopram concomitantly with the irreversible MAO B inhibitor selegiline.

Serotonergic drugs. Concomitant use with serotonergic medications (such as tramadol, sumatriptan, and other triptans) may lead to the development of serotonin syndrome.

Medications that reduce the threshold of convulsive readiness. SSRIs can lower the seizure alert threshold. Caution should be exercised when using other medications that reduce the seizure threshold (tricyclic antidepressants, SSRIs, mefloquine, bupropion, tramadol, and antipsychotic drugs (neuroleptics)at the same time as escitalopram – derivatives of phenothiazine, thioxanthene and butyrophenone).

Lithium, tryptophan. Since there have been reported cases of increased activity with concomitant use of SSRIs and lithium or tryptophan, caution is recommended when escitalopram is co-administered with lithium and tryptophan.

St. John’s wort holed. Concomitant use of SSRIs and medications containing St. John’s wort (Hypericum perforatum) may lead to an increase in the number of side effects.

Anticoagulants and other drugs that affect blood clotting. Blood clotting disorders may occur when escitalopram is co-administered with oral anticoagulants and other medications that affect blood clotting (for example, atypical antipsychotics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and other NSAIDs, ticlopidine and dipyridamole). In such cases, when starting or ending escitalopram therapy, careful monitoring of blood clotting is necessary. Concomitant use with NSAIDs may lead to an increase in the number of bleeding events.

Pharmacokinetic interaction

Effect of other drugs on the pharmacokinetics of escitalopram. Escitalopram is mainly metabolized by the CYP2C19 isoenzyme. To a lesser extent, the isoenzymes CYP3A4 and CYP2D6 can participate in the metabolism. Metabolism of the main metabolite, demethylated escitalopram, appears to be partially catalyzed by the CYP2D6 isoenzyme.

Concomitant use of escitalopram and omeprazole (an inhibitor of the CYP2C19 isoenzyme) leads to a moderate (approximately 50%) increase in the concentration of escitalopram in blood plasma.

Concomitant use of escitalopram and cimetidine (an inhibitor of the isoenzymes CYP2D6, CYP3A4 and CYP1A2) leads to an increase (approximately 70%) in the concentration of escitalopram in blood plasma.

Therefore, caution should be exercised when using the maximum possible dose of escitalopram concomitantly with inhibitors of the CYP2C19 isoenzyme (for example, omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and cimetidine. When escitalopram and the above medications are co-administered, a reduction in the dose of escitalopram may be necessary based on clinical evaluation.

Effect of escitalopram on the pharmacokinetics of other drugs. Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Caution should be exercised when using escitalopram concomitantly with drugs that are metabolized by this isoenzyme and have a low therapeutic index, for example, flecainide, propafenone and metoprolol (in cases of use in heart failure) or drugs that are mainly metabolized by CYP2D6 and act on the central nervous system, for example, antidepressants: desipramine, clomipramine, nortriptyline or antipsychotic drugs: risperidone, thioridazine, haloperidol. In these cases, a dose adjustment may be necessary.

Concomitant use of escitalopram and desipramine or metoprolol leads to a twofold increase in the concentration of the latter two drugs.

Escitalopram may slightly inhibit the CYP2C19 isoenzyme. Therefore, caution is recommended when using escitalopram concomitantly with drugs that are metabolized by the CYP2C19 isoenzyme.

How to take, course of use and dosage

Inside, regardless of food intake,1 time a day.

Depressive episodes: usually prescribed 10 mg once a day. Depending on the individual response of the patient, the dose can be increased to a maximum of 20 mg/day. The antidepressant effect usually develops 2-4 weeks after the start of treatment. After the symptoms of depression disappear, at least for another 6 months, it is necessary to continue therapy to consolidate the effect obtained.

Panic disorder with or without agoraphobia: during the 1st week of treatment, a dose of 5 mg/day is recommended, which is then increased to 10 mg / day. Depending on the individual response of the patient, the dose can be increased to a maximum of 20 mg/day. The maximum therapeutic effect is achieved approximately 3 months after the start of treatment. The therapy lasts for several months.

Social anxiety disorder (social phobia): usually prescribed 10 mg once a day. Depending on the individual response of the patient, the dose can be increased to a maximum of 20 mg/day. Relief of symptoms usually develops 2-4 weeks after the start of treatment. Since social anxiety disorder is a chronic disease, the minimum recommended duration of the therapeutic course is 3 months. To prevent relapses of the disease, the drug can be prescribed for 6 months or longer, depending on the individual response of the patient. It is recommended to regularly evaluate the treatment performed.

Generalized anxiety disorder: usually prescribed 10 mg once a day. Depending on the individual response of the patient, the dose can be increased to a maximum of 20 mg/day. The minimum recommended duration of the therapeutic course is 3 months. To prevent relapses of the disease, long-term use of the drug is allowed (6 months or longer). It is recommended to regularly evaluate the treatment performed.

Obsessive-compulsive disorder: usually prescribed 10 mg once a day. Depending on the individual response of the patient, the dose can then be increased to a maximum of 20 mg/day. Since obsessive-compulsive disorder is a chronic disease, the course of treatment should be long enough to ensure complete relief from symptoms and last at least 6 months. To prevent relapses, treatment is recommended for at least 1 year.

Special patient groups

Elderly patients (over 65 years of age). It is recommended to use half of the usually recommended dose (i. e. only 5 mg/day) and a lower maximum dose (10 mg / day).

Children and teenagers (under 18 years of age). Cipralex should not be used in children and adolescents under 18 years of age. In addition, there is insufficient data from long-term studies on the safety of the drug in children and adolescents, related to growth, maturation, cognitive and behavioral development.

Impaired renal function. No dose adjustment is required for mild to moderate renal failure.Patients with severe renal insufficiency (creatinine clearance below 30 ml/min) should be prescribed Cipralex with caution.

Impaired liver function. The recommended starting dose for the first 2 weeks of treatment is 5 mg / day. Depending on the individual response of the patient, the dose can be increased to 10 mg/day.

Reduced activity of the CYP2C19 isoenzyme. For patients with low activity of the CYP2C19 isoenzyme, the recommended initial dose for the first 2 weeks of treatment is 5 mg / day. Depending on the individual response of the patient, the dose can be increased to 10 mg/day.

Discontinuation of treatment

When stopping treatment with Cipralex, the dose should be reduced gradually, over 1-2 weeks, in order to avoid the occurrence of withdrawal syndrome.

Overdose

Data on escitalopram overdose are limited, and in many such cases, there was also an overdose of other drugs. In most cases, overdose symptoms do not appear or are mild. Cases of overdose of escitalopram (without taking other drugs) with a fatal outcome are rare, in most cases there is also an overdose of other drugs.

Symptoms: mainly from the central nervous system (from dizziness, tremor and agitation to rare cases of serotonin syndrome, convulsive disorders and coma), from the gastrointestinal tract (nausea/vomiting), CVD (hypotension, tachycardia, QT prolongation and arrhythmia) and electrolyte balance disorders (hypokalemia, hyponatremia).

Treatment: There is no specific antidote to the drug. It is necessary to ensure normal airway patency, oxygenation and ventilation of the lungs. Gastric lavage should be performed and activated charcoal should be prescribed. Gastric lavage should be performed as soon as possible after taking the drug. It is recommended to monitor the performance of the heart and other vital organs and conduct symptomatic and supportive therapy.

Special instructions

Antidepressants should not be prescribed to children and adolescents under 18 years of age because of the increased risk of suicidal behavior (suicide attempts and suicidal thoughts), hostility (with a predominance of aggressive behavior, a tendency to confrontation and irritation). If a decision is made based on a clinical assessment to start antidepressant therapy, the patient should be closely monitored.

Some patients with panic disorder may experience increased anxiety at the beginning of treatment with antidepressants. This paradoxical reaction usually disappears within the first 2 weeks of treatment. To reduce the likelihood of an anxiogenic effect, it is recommended to use low initial doses.

Escitalopram should be discontinued if seizures develop initially or increase in frequency (in patients with previously diagnosed epilepsy). SSRIs should not be used in patients with unstable epilepsy; for controlled seizures, close monitoring is necessary.

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

In patients with diabetes mellitus, treatment with escitalopram may change the concentration of glucose in the blood. Therefore, it may be necessary to adjust the dose of insulin and / or oral hypoglycemic drugs.

Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicidal phenomena). This risk persists until a pronounced remission occurs. Since improvement may not be observed during the first few weeks of therapy or even longer, patients should be constantly monitored until their condition improves.

General clinical practice shows that in the early stages of recovery, the risk of suicide may increase.

Other psychiatric conditions that escitalopram is prescribed to treat may also be associated with an increased risk of suicidal events and phenomena. In addition, these conditions may be comorbidities in relation to a depressive episode. When treating patients with other psychiatric disorders, the same precautions should be taken as when treating patients with a depressive episode. Patients with a history of suicidal behavior or patients with a significant level of suicidal thoughts prior to treatment are more at risk of suicidal thoughts or suicide 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 that when taking antidepressants, patients younger than 25 years of age have an increased risk of suicidal behavior compared to placebo. Drug treatment of these patients, and in particular those at high risk of suicide, should be accompanied by close monitoring, especially at an early stage of treatment and when dose changes occur. Patients (and caregivers) should be warned to monitor any signs of clinical deterioration, suicidal behavior or thoughts, or unusual behavioral changes, and seek immediate medical advice if these symptoms occur.

Taking SSRIs / SSRIs is associated with the development of akathisia, characterized by the development of subjectively unpleasant or depressing anxiety and the need for constant movement, often combined with the inability to sit or stand still. This is most often seen during the first few weeks of treatment. In patients with such symptoms, increasing the dose may lead to deterioration.

Hyponatremia, possibly associated with impaired ADH secretion, occurs rarely with SSRIs and usually disappears when therapy is discontinued. Caution should be exercised when prescribing escitalopram and other SSRIs to people at risk of developing hyponatremia: the elderly, patients with cirrhosis of the liver, and taking medications that can cause hyponatremia.

When taking SSRIs, cases of skin hemorrhage (ecchymosis and purpura) have been reported. Escitalopram should be used with caution in patients taking oral anticoagulants and medications that affect blood clotting, as well as in patients with a tendency to bleeding.

Since clinical experience with concomitant use of SSRIs and electroconvulsive therapy (ECT) is limited, caution should be exercised when using escitalopram and ECT simultaneously.

The combination of escitalopram and MAO A inhibitors is not recommended due to the risk of serotonin syndrome.

Escitalopram should be used with caution concomitantly with medications that have serotonergic effects, such as sumatriptan or other triptans, tramadol and tryptophan. Patients taking escitalopram and other SSRIs concomitantly with serotonergic medications have rarely developed serotonin syndrome. Its development may be indicated by a combination of symptoms such as agitation, tremor, myoclonus and hyperthermia. If this occurs, you should immediately stop concomitant treatment with SSRIs and serotonergic drugs and start symptomatic treatment.

Alcohol. Escitalopram does not interact pharmacodynamically or pharmacokinetically with alcohol. However, as with other psychotropic medications, concomitant use of escitalopram and alcohol is not recommended.

Influence on the ability to drive vehicles or work with mechanisms. Despite the fact that Cipralex does not affect intellectual functions and psychomotor activity, patients are not recommended to drive a car or mechanisms during treatment.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Escitalopram

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as prescribed by a doctor, Children over 15 years of age, Children as prescribed by a doctor

Indications

Depression, Obsessive-compulsive disorder, Phobias and panic attacks