Cipralex has an antidepressant effect.
- depressive episodes of any severity;
- panic disorder with or without agoraphobia;
- social anxiety disorder (social phobia);
- generalized anxiety disorder;
- obsessive-compulsive disorder.
H. Lundbeck A / O, Denmark
1 film-coated tablet contains:
escitalopram oxalate 12.77 mg (equivalent to 10 mg escitalopram, respectively),
talc – 7 mg;
croscarmellose sodium – 4.5 mg;
MCC – 97.49 mg;
colloidal silicon dioxide – 1.99 mg;
magnesium stearate – 1.25 mg,
hypromellose 5cP – 2.19 mg;
macrogol 400 – 0.2 mg;
titanium dioxide (E171) – 0.73 mg.
Escitalopram is an antidepressant, SSRI, with a high affinity for the primary binding site. Escitalopram also binds to the allosteric binding site of the transporter protein, with a thousand-fold lower affinity. 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 little ability to bind to a number of receptors, including: serotonin 5-HT 1A -, 5-HT 2 -receptors, dopamine D 1 – and D 2 -receptors, α 1 -, α 2 -, β- adrenergic receptors, histamine H 1 receptors, m-cholinergic receptors, benzodiazepine and opioid receptors.
Absorption is almost complete and does not depend on food intake. The average T max in blood plasma is 4 hours after repeated use. The absolute bioavailability of escitalopram is about 80%.
The apparent V d after oral administration is from 12 to 26 l / kg. The binding of escitalopram and its main metabolites with blood 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 an N-oxide metabolite. The main substance and its metabolites are partially excreted 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 escitalopram concentration. Biotransformation of escitalopram into a demethylated metabolite occurs mainly with the help of the isoenzyme CYP2C19. Some involvement of the isoenzymes CYP3A4 and CYP2D6 is possible. In individuals with a weak activity of the isoenzyme CYP2C19, the concentration of escitalopram is two times higher than in cases with a high activity of this isoenzyme.
T 1/2 after repeated use is about 30 hours. Clearance for oral administration is about 0.6 l / min. The main metabolites of escitalopram have a longer half-life. Escitalopram and its main metabolites are excreted by the liver (metabolic pathway) and kidneys; most of it is excreted in the form of metabolites in the urine.
The kinetics of escitalopram is linear. Equilibrium concentration is reached after about 1 week. Average C ss , 50 nmol / L (20 to 125 nmol / L), is achieved with a daily dose of 10 mg.
Special patient groups
Patients over 65. In the elderly, escitalopram is excreted more slowly than in younger patients. The amount of a substance in the systemic circulation, calculated using the pharmacokinetic index AUC, is 50% higher in the elderly than in young healthy volunteers.
Application during pregnancy and lactation
There are limited data on the use of escitalopram during pregnancy.
If escitalopram is continued late in pregnancy, especially in the third trimester, 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 / SNRIs in late pregnancy, the newborn may develop the following side effects: respiratory depression, cyanosis, apnea, convulsive disorders, temperature fluctuations, feeding difficulties, vomiting, hypoglycemia, hypertension, muscle hypotension, hyperreflexia, tremor, increased neuro-reflex irritability, irritability, lethargic sleep, constant crying, drowsiness, poor sleep. These symptoms can occur due to the development of a withdrawal syndrome or serotonergic action.
In most cases, these complications occur within 24 hours after birth. During pregnancy, escitalopram should be taken only when absolutely necessary and after careful assessment of the benefit / risk ratio. Epidemiological data suggest that the use of SSRIs during pregnancy, especially in late pregnancy, may increase the risk of developing persistent pulmonary hypertension in the newborn.
It is expected that escitalopram will be excreted in breast milk, therefore, breastfeeding is not recommended during escitalopram treatment.
- hypersensitivity to escitalopram and other components of the drug Cipralex;
- concomitant use of non-selective irreversible MAO inhibitors;
- simultaneous administration of pimozide;
- children and adolescents (up to 18 years old).
With care: severe renal failure (Cl creatinine below 30 ml / min); mania and hypomania; pharmacologically uncontrolled epilepsy; pronounced suicidal behavior; diabetes; cirrhosis of the liver; bleeding tendency; simultaneous administration with an MAO A inhibitor (moclobemide) and an MAO B inhibitor (selegiline), serotonergic drugs, drugs that reduce the seizure threshold, lithium, tryptophan, drugs containing St. John’s wort, oral anticoagulants and other drugs that affect blood , drugs that can cause hyponatremia, drugs metabolized with the participation of the CYP2C19 isoenzyme, ethanol; electroconvulsive therapy; elderly age; pregnancy; period of breastfeeding.
Side effects most often develop in the 1st or 2nd week of treatment and then usually become less intense and occur less often with continued therapy.
The following are the side effects that occur when taking drugs belonging to the SSRI class and noted when taking escitalopram. The information is presented based on data from placebo-controlled clinical trials and spontaneous reports. The frequency is indicated as: very often – ≥1 / 10; often – from ≥1 / 100 to
On the part of the blood and lymphatic system: unknown – thrombocytopenia.
From the immune system: rarely – anaphylactic reactions.
From the endocrine system: unknown – insufficient secretion of ADH.
Metabolic and eating disorders: often – decreased appetite, increased appetite, weight gain; infrequently – weight loss; unknown – hyponatremia, anorexia.
From the side of the psyche: often – anxiety, anxiety, 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 behavior have been reported with escitalopram and immediately after discontinuation of therapy.
From the nervous system: often – insomnia, drowsiness, dizziness, paresthesia, tremor; infrequently – disturbances in taste, sleep disturbances, syncope; rarely – serotonin syndrome; unknown – dyskinesia, movement disorders, convulsive disorders, psychomotor agitation / akathisia.
From the side of the organ of vision: infrequently – mydriasis (dilated pupil), visual impairment.
On the part of the organ of hearing and labyrinth disorders: infrequently – tinnitus (tinnitus).
From the CCC: infrequently – tachycardia; rarely – bradycardia; unknown – prolongation of the QT interval on the ECG, orthostatic hypotension.
From the respiratory system, chest and mediastinal organs: often – sinusitis, yawning; infrequently – nosebleeds.
From the gastrointestinal tract: very often – nausea; often – diarrhea, constipation, vomiting, dry mouth; infrequently – gastrointestinal bleeding (including rectal).
Liver and biliary tract disorders: unknown – hepatitis, impaired liver function.
On the part of the skin and subcutaneous tissues: often – increased sweating; infrequently – urticaria, alopecia, rash, itching; unknown – ecchymosis, angioedema.
Musculoskeletal and connective tissue disorders: often – arthralgia, myalgia.
From the kidneys and urinary tract: unknown – urinary retention.
Reproductive system and breast disorders: often – impotence, impaired ejaculation; infrequently – metrorrhagia (uterine bleeding), menorrhagia; unknown – galactorrhea, priapism.
From the side of the body as a whole and disorders at the injection site: often – weakness, hyperthermia; infrequently – edema.
In the post-registration period, there were cases of prolongation of the QT interval, mainly in patients with pre-existing heart disease. In double-blind, placebo-controlled ECG studies in healthy volunteers, the change from the baseline QTc value (correction according to the Fridericia formula) was 4.3 ms at a dose of 10 mg / day and 10.7 ms at a dose of 30 mg / day.
Epidemiological studies in patients aged 50 and over have shown an increased risk of bone fractures in patients taking SSRIs and tricyclic antidepressants. The mechanism behind this risk has not been established.
Cancellation (especially abrupt) of SSRI / SNRI drugs often leads to withdrawal symptoms. The most common occurrences are dizziness, sensitivity disorders (including paresthesias and sensations of current flow), sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremors, confusion, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability, visual disturbances. As a rule, these effects are mild or moderate and quickly disappear, however, in some patients, they may appear in a more acute form and / or for a longer period. It is recommended to gradually withdraw the drug by reducing its dose.
Non-selective, irreversible MAO inhibitors. Serious adverse reactions have been reported with the concomitant use of SSRIs and non-selective irreversible MAO inhibitors, as well as with the initiation of MAO inhibitors in patients who had recently stopped taking SSRIs. In some cases, patients have developed serotonin syndrome. It is prohibited to use escitalopram simultaneously with non-selective irreversible MAO inhibitors. Acitalopram can be started 14 days after the withdrawal of irreversible MAO inhibitors. Before you start taking non-selective irreversible MAO inhibitors, at least 7 days should pass after you stop taking escitalopram.
Reversible selective MAO A inhibitor (moclobemide). Due to the risk of developing serotonin syndrome, it is not recommended to use escitalopram simultaneously with the MAO A inhibitor moclobemide. If the use of such a combination of drugs is recognized clinically necessary, it is recommended to start with the lowest possible doses, as well as to conduct continuous clinical monitoring of the patient’s condition. You can start taking escitalopram at least one day after discontinuing the reversible MAO A inhibitor moclobemide.
Irreversible MAO B inhibitor (selegiline). Due to the risk of developing serotonin syndrome, care must be taken when taking escitalopram simultaneously with the irreversible MAO B inhibitor selegiline.
Serotonergic drugs. Concomitant use with serotonergic drugs (for example, tramadol, sumatriptan and other triptans) can lead to the development of serotonin syndrome.
Medicines that lower the seizure threshold. SSRIs can lower the seizure threshold. It is required to exercise caution with the simultaneous use of other drugs with escitalopram that reduce the seizure threshold (tricyclic antidepressants, SSRIs, mefloquine, bupropion, tramadol and antipsychotic drugs (neuroleptics) – derivatives of phenothiazine, thioxanthene and butyrophenone).
Lithium, tryptophan. Since there have been cases of increased action with the simultaneous use of SSRIs and lithium or tryptophan, it is recommended to exercise caution when using escitalopram with lithium and tryptophan.
St. John’s wort. The simultaneous use of SSRIs and preparations 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 can occur with the simultaneous use of escitalopram with oral anticoagulants and other drugs that affect blood clotting (for example, atypical antipsychotics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and other NSAIDs, ticlopidamoline) and dipyridamoline. In such cases, when starting or ending therapy with escitalopram, careful monitoring of blood clotting is necessary. Concomitant use with NSAIDs can lead to an increase in the number of bleeding.
The effect of other drugs on the pharmacokinetics of escitalopram. The metabolism of escitalopram is mainly carried out with the participation of the isoenzyme CYP2C19. To a lesser extent, CYP3A4 and CYP2D6 isoenzymes can participate in metabolism. The metabolism of the main metabolite, demethylated escitalopram, appears to be partially catalyzed by the CYP2D6 isoenzyme.
The simultaneous use of escitalopram and omeprazole (an inhibitor of the isoenzyme CYP2C19) leads to a moderate (approximately 50%) increase in the concentration of escitalopram in the blood plasma.
The simultaneous administration of escitalopram and cimetidine (an inhibitor of isoenzymes CYP2D6, CYP3A4 and CYP1A2) leads to an increase (approximately 70%) in the concentration of escitalopram in blood plasma.
Thus, the maximum possible dose of escitalopram should be used concomitantly with inhibitors of the isoenzyme CYP2C19 (eg omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and cimetidine with caution. With the simultaneous administration of escitalopram and the above drugs, based on clinical assessment, a dose reduction of escitalopram may be required.
The effect of escitalopram on the pharmacokinetics of other drugs. Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Care should be taken with the simultaneous use of escitalopram and drugs that are metabolized by this isoenzyme and have a low therapeutic index, such as flecainide, propafenone and metoprolol (in cases of use in heart failure) or drugs that are mainly metabolized by CYP2D6 and acting on the central nervous system, for example antidepressants: desipramine, clomipramine, nortriptyline, or antipsychotic drugs: risperidone, thioridazine, haloperidol. In these cases, dose adjustment may be required.
The simultaneous use of escitalopram and desipramine or metoprolol leads to a twofold increase in the concentration of the last two drugs.
Escitalopram may slightly inhibit the CYP2C19 isoenzyme. Therefore, it is recommended to exercise caution with the simultaneous use of escitalopram and drugs metabolized by the CYP2C19 isoenzyme.
How to take, course of administration and dosage
Inside, regardless of food intake, 1 time per day.
Depressive episodes: Usually 10 mg is given once a day. Depending on the patient’s individual response, the dose can be increased to a maximum of 20 mg / day. The antidepressant effect usually develops 2–4 weeks after starting treatment. After the disappearance of the symptoms of depression, at least 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 patient’s individual response, 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 10 mg is given once a day. Depending on the patient’s individual response, the dose can be increased to a maximum of 20 mg / day. Relief of symptoms usually develops 2–4 weeks after starting treatment. Since social anxiety disorder is a chronic disease, the minimum recommended course of treatment is 3 months. To prevent recurrence of the disease, the drug may be prescribed for 6 months or longer, depending on the individual patient’s response. Regular evaluation of the treatment is recommended.
Generalized Anxiety Disorder: Usually 10 mg is given once daily. Depending on the patient’s individual response, the dose can be increased to a maximum of 20 mg / day. The minimum recommended duration of a therapeutic course is 3 months. To prevent relapses of the disease, prolonged use of the drug is allowed (6 months or longer). Regular evaluation of the treatment is recommended.
Obsessive-compulsive disorder: Usually 10 mg is given once daily. Depending on the patient’s individual response, the dose can subsequently be increased to a maximum of 20 mg / day. Because obsessive-compulsive disorder is a chronic disease, treatment should be long enough to ensure complete relief of symptoms and last at least 6 months. Treatment for at least 1 year is recommended to prevent relapse.
Special patient groups
Elderly patients (over 65 years old). It is recommended to use half of the usual recommended dose (i.e. only 5 mg / day) and a lower maximum dose (10 mg / day).
Children and adolescents (up to 18 years old). Cipralex should not be used in children and adolescents under 18 years of age. In addition, there is not enough data from long-term studies on the safety of the drug in children and adolescents regarding growth, maturation, cognitive and behavioral development.
Impaired renal function. No dose adjustment is required for mild to moderate renal impairment. Patients with severe renal insufficiency (Cl creatinine below 30 ml / min) should be prescribed Cipralex with caution.
Liver dysfunction. The recommended starting dose for the first 2 weeks of treatment is 5 mg / day. Depending on the patient’s individual response, the dose may be increased to 10 mg / day.
Reduced activity of the isoenzyme CYP2C19. For patients with weak activity of the isoenzyme CYP2C19, the recommended initial dose during the first 2 weeks of treatment is 5 mg / day. Depending on the patient’s individual response, the dose may be increased to 10 mg / day.
Termination of treatment
When discontinuing treatment with Cipralex, the dose should be reduced gradually over 1–2 weeks in order to avoid withdrawal symptoms.
Data on escitalopram overdose are limited, 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 escitalopram overdose (without taking other drugs) with a lethal 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, seizure disorders and coma), from the gastrointestinal tract (nausea / vomiting), CVS (hypotension, tachycardia, prolongation of the QT interval and arrhythmia) and disorders electrolyte balance (hypokalemia, hyponatremia).
Treatment: there is no specific antidote to the drug. Ensure normal airway patency, oxygenation and ventilation of the lungs. Gastric lavage and activated charcoal should be administered. Gastric lavage should be carried out as soon as possible after taking the drug. It is recommended to monitor the performance of the heart and other vital organs and carry out symptomatic and supportive therapy.
Antidepressants should not be prescribed to children and adolescents under 18 years of age because of the increased risk of suicidal behavior (attempts at suicide and suicidal thoughts), hostility (with a predominance of aggressive behavior, tendency to confrontation and irritation). If a decision is made based on clinical judgment to initiate antidepressant therapy, the patient should be closely monitored.
Some patients with panic disorder may experience increased anxiety when starting antidepressant treatment. This paradoxical reaction usually disappears within the first 2 weeks of treatment. Low starting doses are recommended to reduce the likelihood of an anxiogenic effect.
Escitalopram should be canceled in case of primary development of seizures or an increase in their frequency (in patients with previously diagnosed epilepsy). SSRIs should not be used in patients with unstable epilepsy; controlled seizures require close monitoring.
Escitalopram should be used with caution in patients with a history of mania / hypomania. With the development of a manic state, escitalopram should be canceled.
In patients with diabetes mellitus, treatment with escitalopram may alter the blood glucose concentration. Therefore, dose adjustment of insulin and / or oral hypoglycemic drugs may be required.
Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicidal events). This risk persists until severe remission occurs. Since improvement may not be observed during the first few weeks of therapy, or even longer, patients should be monitored continuously until their condition improves.
General clinical practice shows that the risk of suicide may increase in the early stages of recovery.
Other mental conditions for which escitalopram is prescribed may also be associated with an increased risk of suicidal events and events. In addition, these conditions can be a comorbidity in relation to a depressive episode. The same precautions should be followed when treating patients with other mental disorders as when treating patients with a depressive episode. Patients with a history of suicidal behavior or patients with significant levels of suicidal thinking before treatment are more at risk of suicidal ideation or attempted suicide and should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders showed that there is an increased risk of suicidal behavior when taking antidepressants in patients younger than 25 years compared with taking placebo. The medical treatment of these patients, and in particular those at high risk of suicide, must be closely monitored, especially during the early stages of treatment and when dose changes. Patients (and caregivers) should be warned to monitor any manifestations of clinical deterioration, suicidal behavior or thoughts, and unusual changes in behavior, and seek immediate medical advice if these symptoms appear. patients at high risk of suicide should be closely monitored, especially during the early stages of treatment and when dose changes. Patients (and caregivers) should be warned to monitor any manifestations of clinical deterioration, suicidal behavior or thoughts, and unusual changes in behavior, and seek immediate medical advice if these symptoms appear. patients at high risk of suicide should be closely monitored, especially during the early stages of treatment and when dose changes. Patients (and caregivers) should be advised to monitor any manifestations of clinical deterioration, suicidal behavior or thoughts, or unusual changes in behavior, and seek immediate medical advice if these symptoms appear.
The use of SSRIs / SNRIs has been 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 an inability to sit or stand still. This is most often seen during the first few weeks of treatment. In patients with these symptoms, increasing the dose may worsen.
Hyponatremia, possibly associated with impaired ADH secretion, occurs rarely while taking SSRIs and usually disappears with discontinuation of therapy. Caution should be exercised when prescribing escitalopram and other SSRIs to persons at risk of developing hyponatremia: the elderly, patients with cirrhosis of the liver and taking drugs that can cause hyponatremia.
When taking SSRIs, cases of skin hemorrhage (ecchymosis and purpura) have been reported. It is necessary to use escitalopram with caution in patients taking oral anticoagulants and drugs that affect blood clotting, as well as in patients with a tendency to bleeding.
Since clinical experience with the simultaneous use of SSRIs and electroconvulsive therapy (ECT) is limited, caution should be exercised when using escitalopram and ECT simultaneously.
Combining escitalopram and MAO A inhibitors is not recommended due to the risk of developing serotonin syndrome.
It is necessary to use escitalopram with caution simultaneously with medications with serotonergic effects, such as sumatriptan or other triptans, tramadol and tryptophan. In patients taking escitalopram and other SSRIs concurrently with serotonergic drugs, serotonin syndrome has developed in rare cases. Its development may be indicated by a combination of symptoms such as agitation, tremor, myoclonus and hyperthermia. If this happens, you should immediately stop the simultaneous treatment with SSRIs and serotonergic drugs and begin symptomatic treatment.
Alcohol. Escitalopram does not enter into pharmacodynamic or pharmacokinetic interactions with alcohol. However, as with other psychotropic drugs, the simultaneous use of escitalopram and alcohol is not recommended.
Influence on the ability to drive vehicles or operate machinery. Despite the fact that Cipralex does not affect intellectual functions and psychomotor activity, during the period of treatment, patients are not recommended to drive a car or machinery.