Lenuxin®
- Escitalopram should not be prescribed concomitantly with MAO inhibitors due to the risk of developing serotonin syndrome. Escitalopram can be prescribed 14 days after stopping treatment with irreversible MAO inhibitors and at least 1 day after stopping treatment with a reversible MAO type A inhibitor (moclobemide). At least 7 days must pass after stopping escitalopram before treatment with non-selective MAO inhibitors can be started.
- In children, adolescents and young adults (under 24 years of age) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and behavior. Therefore, when prescribing Lenuxin® or any other antidepressants to children, adolescents and young adults (under 24 years of age), the risk of suicide should be weighed against the benefits of their use. If a decision is made to initiate antidepressant therapy, the patient should be closely monitored for early detection of disturbances or changes in behavior, as well as suicidality.
- When using drugs belonging to the therapeutic group of SSRIs, including escitalopram, the following should be considered: some patients with panic disorder may experience increased anxiety when starting treatment with SSRIs. This paradoxical reaction usually disappears within the first two weeks of treatment. To reduce the likelihood of an anxiogenic effect, it is recommended to use low initial doses. The drug should be discontinued if seizures develop. Use in patients with unstable epilepsy is not recommended; Controlled seizures require careful monitoring. If the frequency of seizures increases, SSRIs, including escitalopram, should be discontinued.
- SSRIs and SNRIs (selective norepinephrine reuptake inhibitors) have been associated with the development of akathisia, a condition characterized by unpleasant, debilitating restlessness and hyperactivity, often accompanied by an inability to sit or stand in one place. This condition most likely occurs during the first few weeks of therapy. Increasing the dose may be harmful to patients who experience these symptoms.
- 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, treatment with escitalopram may change blood glucose levels. Therefore, dose adjustments of insulin and/or oral hypoglycemic drugs may be required.
— The risk of committing suicide is inherent in depression and can persist until a significant improvement in the condition occurs spontaneously or as a result of therapy. Careful monitoring of patients being treated with antidepressants is necessary, especially at the beginning of treatment, due to the possibility of clinical deterioration and/or the emergence of suicidal manifestations (thoughts and behavior). This precaution should also be observed when treating other mental disorders due to the possibility of concurrent depressive episodes.
- Hyponatremia, possibly associated with impaired secretion of antidiuretic hormone (ADH), occurs rarely when taking escitalopram and usually disappears when therapy is discontinued. Caution should be exercised when prescribing escitalopram and other SSRIs to persons at risk of developing hyponatremia: the elderly, patients with cirrhosis, and those taking drugs that can cause hyponatremia.
- When taking escitalopram, skin hemorrhages (ecchymosis and purpura) may develop. Escitalopram should be used with caution in patients with a tendency to bleed, as well as those taking oral anticoagulants and medications that affect blood clotting.
- Since clinical experience with the simultaneous use of escitalopram and ECT (electroconvulsive therapy) is limited, caution should be exercised in such cases.
- In rare cases, patients taking escitalopram and other SSRIs concomitantly with serotonergic drugs may develop serotonin syndrome. Escitalopram should be used with caution concomitantly with drugs that have serotonergic effects.
— Due to limited clinical experience, caution is recommended when using the drug in patients with coronary heart disease (CHD).
- After long-term use, abrupt cessation of escitalopram therapy in some patients may lead to a “withdrawal” reaction; gradual withdrawal of the drug over 1-2 weeks is recommended.
— Interaction with alcohol:
escitalopram does not interact pharmacodynamically or pharmacokinetically with alcohol. However, as with other antidepressants, you should avoid drinking alcohol during the entire period of treatment with the drug.
Lenuxin tablet 10 mg No. 28
Compound
Active substance: escitalopram -10 mg. Excipients: microcrystalline cellulose, croscarmellose sodium, talc, microcrystalline siliconized cellulose 90 (Prosolv 90) (microcrystalline cellulose - 98%, colloidal silicon dioxide - 2%), microcrystalline siliconized cellulose HD90 (Prosolv HD90) (microcrystalline cellulose - 98%, silicon colloidal dioxide - 2%), magnesium stearate.
Pharmacokinetics
Suction
Absorption is almost complete and does not depend on food intake. The average time to reach Cmax in blood plasma is 4 hours after repeated use. The absolute bioavailability of escitalopram is about 80%.
Distribution
Apparent Vd (Vd,β/F) after oral administration ranges from 12 to 26 l/kg. The binding of escitalopram and its main metabolites to plasma proteins is below 80%. The kinetics of escitalopram is linear. Css is achieved in approximately 1 week. An average Css of 50 nmol/l (range 20 to 125 nmol/l) is achieved with a daily dose of 10 mg.
Metabolism
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 unchanged 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 concentration of escitalopram. Biotransformation of escitalopram into a demethylated metabolite occurs mainly with the help of the CYP2C19 isoenzyme, with some participation of the CYP3A4 and CYP2D6 isoenzymes possible.
Removal
T1/2 after repeated use is about 30 hours. Oral clearance is about 0.6 l/min. The main metabolites of escitalopram have a longer T1/2. Escitalopram and its main metabolites are excreted by the liver (metabolic pathway) and kidneys; most of it is excreted as metabolites by the kidneys.
Special patient groups
Elderly patients (over 65 years old). In elderly patients (over 65 years of age), escitalopram is eliminated more slowly than in younger patients. AUC in elderly patients is 50% greater than in young healthy volunteers.
Patients with impaired liver function. In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the T1/2 of escitalopram is approximately 2 times greater and the AUC is 60% greater than in subjects with normal hepatic function.
Patients with impaired renal function. In the case of racemic citalopram, in patients with impaired renal function (creatinine clearance 10-53 ml/min), a longer T1/2 and a slight increase in AUC are observed. Concentrations of metabolites in blood plasma have not been studied, but they may be increased.
Polymorphism. In patients with low activity of the CYP2C19 isoenzyme, the concentration of escitalopram may be 2 times higher than in patients with high activity of this isoenzyme. No significant changes in the concentration of escitalopram in the blood plasma were detected with low activity of the CYP2D6 isoenzyme.
Indications for use
- depressive episodes of any severity;
- panic disorder with or without agoraphobia;
- obsessive-compulsive disorder.
Contraindications
- hypersensitivity to escitalopram and other components of the drug;
- children and adolescents (up to 18 years of age) (efficacy and safety have not been established);
- history of QT prolongation, including congenital long QT syndrome;
- simultaneous use with non-selective irreversible MAO inhibitors;
- simultaneous use with reversible MAO inhibitors, MAO-A (for example, moclobemide) or reversible non-selective MAO inhibitors (linezolid);
- simultaneous use of drugs that can prolong the QT interval (for example, class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides);
- simultaneous use of pimozide;
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
With caution: severe renal failure (creatinine clearance less than 30 ml/min), hypomania, mania, pharmacologically uncontrolled epilepsy, severe suicidal behavior, diabetes mellitus, old age (over 65 years), electroconvulsive therapy (ECT), liver cirrhosis, bleeding tendency ; simultaneous use with drugs that lower the seizure threshold, with an MAO-B inhibitor (selegiline), serotonergic drugs, lithium, tryptophan, drugs containing St. John's wort, oral anticoagulants and drugs that affect blood clotting, drugs that can cause hyponatremia , drugs metabolized by the CYP2C19 isoenzyme, ethanol; pregnancy, breastfeeding period.
Directions for use and doses
The drug is taken orally 1 time/day, regardless of meals.
Depressive episodes
Usually prescribed 10 mg 1 time/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 the start of treatment. After the symptoms of depression disappear, it is necessary to continue therapy to consolidate the effect for at least 6 months.
Panic disorders with or without agoraphobia
During the first 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. Therapy lasts several months.
Obsessive-compulsive disorder
Usually prescribed 10 mg 1 time/day. Depending on the patient's individual response, the dose may subsequently be increased to a maximum of 20 mg/day. Because obsessive-compulsive disorder is a chronic disorder, treatment should be long enough to provide complete relief of symptoms, lasting at least 6 months. To prevent relapses, treatment for at least 1 year is recommended.
Elderly patients (over 65 years of age) are recommended to take half the usual recommended dose of 5 mg/day. The maximum dose is 10 mg/day.
Lenuxin® 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 regarding growth, maturation, cognitive and behavioral development
Renal impairment: For mild to moderate renal failure, no dose adjustment is required. In patients with severe renal failure (creatinine clearance below 30 ml/min), the drug is prescribed with caution.
Liver dysfunction: in case of liver failure, 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.
Reduced activity of the CYP2C19 isoenzyme: for patients with low activity of the CYP2C19 isoenzyme, 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.
Discontinuation of treatment: When stopping treatment, the dose should be reduced gradually over 1-2 weeks to avoid withdrawal symptoms.
Storage conditions
The drug should be stored out of the reach of children, in its original packaging at a temperature not exceeding 25°C.
Best before date
2 years. Do not use the drug after the expiration date indicated on the package.
special instructions
Antidepressants should not be prescribed to children and adolescents under 18 years of age due to an 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 to initiate antidepressant therapy based on clinical assessment, the patient should be closely monitored for early detection of disturbances or changes in behavior, as well as suicidality.
When using drugs belonging to the SSRI therapeutic group, including escitalopram, the following should be considered:
- Some patients with panic disorder may experience increased anxiety when starting SSRI treatment. This paradoxical reaction usually disappears within the first two weeks of treatment. To reduce the likelihood of anxiogenic effects, low initial doses are recommended.
The drug should be discontinued in the event of the primary development of convulsive seizures or in the event of an increase in their frequency (in patients with previously diagnosed epilepsy). SSRIs should not be used in patients with unstable epilepsy; Controlled seizures require careful monitoring.
- 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 alter plasma glucose concentrations. Therefore, dose adjustment of insulin and/or oral hypoglycemic drugs may be required.
- Depression is associated with an increased risk of suicidal ideation, self-harm, and suicide (suicidal events). This risk persists until significant remission occurs. Since improvement may not be observed during the first few weeks of therapy or even longer, patients should be closely monitored until their condition improves, as there is a possibility of clinical worsening and/or the emergence of suicidal symptoms (thoughts and behavior) or self-harm . General clinical practice shows that in the early stages of recovery the risk of suicide may increase.
Other psychiatric conditions for which escitalopram is prescribed may also be associated with an increased risk of suicidal events and events. In addition, these conditions may be a comorbidity in relation to a depressive episode. When treating patients with other mental 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 before treatment are at greater risk for suicidal ideation or suicide attempts and should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders found that there is an increased risk of suicidal behavior in patients under 25 years of age when taking antidepressants compared with placebo. Drug treatment of these patients, and in particular those at high risk for suicide, should be accompanied by careful monitoring, especially early in treatment and during dose changes.
Patients (and caregivers) should be warned to monitor for any signs of clinical worsening, suicidal behavior or ideation, or unusual changes in behavior, and to seek immediate medical advice if these symptoms occur.
- SSRI/SNRI use is associated with the development of akathisia, characterized by the development of subjectively unpleasant or distressing restlessness and a need for constant movement, often combined with an inability to sit or stand quietly. This most often occurs during the first few weeks of treatment. In patients with such symptoms, increasing the dose may lead to worsening.
- 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 persons at risk of developing hyponatremia: the elderly, patients with cirrhosis, and those taking drugs that can cause hyponatremia.
- When taking SSRIs, skin hemorrhages (ecchymosis and purpura) may develop. Escitalopram should be used with caution in patients with a tendency to bleed, as well as those taking oral anticoagulants and drugs that affect blood clotting.
- Since clinical experience with the simultaneous use of escitalopram and ECT is limited, caution should be used in such cases.
- Combining escitalopram with MAO-A inhibitors is not recommended due to the risk of developing serotonin syndrome.
- Escitalopram should be used with caution concomitantly with drugs that have serotonergic effects (for example, sumatriptan or other triptans, tramadol and tryptophan). Patients taking escitalopram and other SSRIs concomitantly with serotonergic drugs 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, concomitant treatment with SSRIs and serotonergic drugs should be discontinued immediately and symptomatic treatment initiated.
- Due to limited experience with use in patients with coronary artery disease, caution is recommended when using the drug.
- Escitalopram has been found to cause a dose-dependent prolongation of the QT interval. Cases of QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP), have been reported post-marketing, predominantly in female patients with hypokalemia, or pre-existing QT prolongation, or other cardiac disease.
Caution is required when using the drug in patients with severe bradycardia or in patients with recent acute myocardial infarction or decompensated heart failure.
Electrolyte imbalances, such as hypokalemia and hypomagnesemia, increase the risk of developing malignant arrhythmias; these disturbances must be corrected before starting treatment with escitalopram. In patients with stable coronary artery disease, an ECG should be performed before starting treatment. If signs of cardiac arrhythmia occur during treatment with escitalopram, it is necessary to stop therapy and perform an ECG.
- SSRIs, including escitalopram, can change pupil size, producing a mydriatic effect. In this case, narrowing of the lateral angle of the eye is possible, which leads to increased intraocular pressure and angle-closure glaucoma, especially in patients with a predisposition to this disease. Therefore, escitalopram should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.
- Withdrawal symptoms are common when stopping treatment, especially if treatment is stopped abruptly. In clinical studies, adverse events at treatment discontinuation occurred in approximately 25% of patients treated with escitalopram and in 15% of patients treated with placebo.
The risk of withdrawal symptoms may depend on several factors, including the duration of therapy and drug dose, and the rate of dose reduction. The most commonly reported reactions were dizziness, sensory disturbances (including paresthesia and electric shock), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache pain, diarrhea, palpitations, emotional instability, irritability and visual disturbances. These symptoms are usually mild to moderate, but may be severe in some patients.
Symptoms usually occur within the first few days after stopping treatment, but such symptoms have been extremely rarely reported in patients who accidentally missed taking the drug. Typically, these symptoms resolve on their own, usually within two weeks, although in some patients they may be prolonged (2-3 months or more). Therefore, when stopping treatment, it is recommended to gradually reduce the dose over several weeks or months in accordance with the patient's condition.
- Patients with rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take Lenuxin®.
- Escitalopram does not interact pharmacodynamically or pharmacokinetically with alcohol. However, as with other antidepressants, you should avoid drinking alcohol during the entire period of treatment with the drug.
Description
Antidepressant.
Dosage form
White or almost white, film-coated tablets, round, biconvex, engraved “N54” on one side and scored on the other side; on a cross section, white or almost white.
Use in children
Contraindicated in children under 18 years of age.
Pharmacodynamics
Escitalopram is an antidepressant, selective serotonin reuptake inhibitor (SSRI) with high affinity for the primary binding site. Escitalopram also binds to the allosteric binding site of the transporter protein, with an affinity 1000 times lower. Allosteric modulation of the transporter protein enhances the binding of escitalopram at the primary binding site, resulting in 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-cholinergic receptors, benzodiazepine and opioid receptors.
Side effects
Side effects most often occur in the first or second week of treatment with the drug and then usually become less intense and occur less frequently as therapy is continued.
Undesirable adverse reactions are presented by system-organ classes in accordance with the MedDRA classification and with the frequency of development according to the WHO classification: very often - 1/10 prescriptions (≥10%), often - 1/100 prescriptions (≥1% and <10%) , uncommon - 1/1000 prescriptions (≥0.1% and <1%), rare - 1/10,000 prescriptions (≥0.01% and <0.1%), very rare - 1/10,000 prescriptions (<0.01%), unknown ( incidence cannot be estimated from existing data).
From the hematopoietic system: unknown - thrombocytopenia.
From the immune system: rarely - anaphylactic reactions.
From the endocrine system: unknown - insufficient secretion of ADH.
Metabolism: often - decreased appetite, increased appetite, weight gain; infrequently - weight loss; unknown - hyponatremia, anorexia.
Mental disorders: 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 behavior have been reported while taking escitalopram and immediately after discontinuation of therapy.
Discontinuation of SSRI/SNRI drugs (especially abrupt) often leads to withdrawal symptoms. The most common symptoms include dizziness, sensory disturbances (including paresthesia and current 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, visual disturbances. As a rule, these effects are mild or moderate and disappear quickly, but in some patients they may occur in a more acute form and/or for a longer period of time. It is recommended to gradually discontinue the drug by reducing its dose.
From the nervous system: very often - headache; often - dizziness, insomnia or drowsiness, tremor, paresthesia; infrequently - disturbance of taste, sleep disturbance, fainting; rarely - serotonin syndrome; unknown - dyskinesia, movement disorders, seizure disorders, psychomotor agitation/akathisia.
From the side of the organ of vision: infrequently - mydriasis (pupil dilation), visual impairment.
From the organ of hearing and labyrinthine disorders: infrequently - tinnitus (tinnitus).
From the cardiovascular system: infrequently - tachycardia; rarely - bradycardia; unknown - prolongation of the QT interval on the ECG, orthostatic hypotension. Cases of QT interval prolongation were observed mainly in patients with a history of cardiovascular disease.
From the respiratory system: often - sinusitis, yawning; infrequently - nosebleeds.
From the digestive system: very often - nausea; often - diarrhea, vomiting, dry mouth, constipation; uncommon - gastrointestinal bleeding (including rectal bleeding).
From the liver and biliary tract: unknown - hepatitis, abnormal liver function parameters.
From the skin and subcutaneous tissues: often - increased sweating; uncommon - urticaria, alopecia, rash, itching; unknown - ecchymosis, angioedema.
From the musculoskeletal system: often - arthralgia, myalgia. In patients aged 50 years and older, while taking SSRIs and tricyclic antidepressants, an increased risk of fractures was found, the mechanism of which has not been established.
From the reproductive system and mammary gland: often - ejaculation disorders, impotence; infrequently - metrorrhagia (uterine bleeding), menorrhagia; unknown - galactorrhea, priapism.
From the urinary system: unknown - urinary retention.
General reactions: often - weakness, hyperthermia; infrequently - swelling.
Use during pregnancy and breastfeeding
Pregnancy
There are limited data on the use of escitaloiram during pregnancy. Preclinical studies of escitalopram have demonstrated reproductive toxicity.
Escitalopram should only be taken during pregnancy when absolutely necessary and after a careful benefit/risk assessment.
If escitalopram was continued during late pregnancy, especially in the third trimester, the newborn should be monitored. If escitalopram was continued until delivery or was discontinued shortly before delivery, the newborn may develop withdrawal symptoms or serotonergic effects. In most cases, such complications occur within 24 hours after birth.
Evidence from epidemiological studies suggests that use of SSRIs during pregnancy, especially later in pregnancy, may increase the risk of developing persistent pulmonary hypertension of the newborn (PPHN). The observed risk was about 5 cases per 1000 pregnancies. In the general population, there are 1-2 cases of PPHN per 1000 pregnancies.
Breastfeeding period
Escitalopram is expected to pass into breast milk and breastfeeding is not recommended during treatment with escitalopram.
Fertility
Preclinical data have shown that some SSRIs may affect sperm quality; similar preclinical data are not available for escitalopram. Reports of the use of some SSRIs in humans have shown that the effects of these drugs on sperm quality are reversible. So far, no effect of escitalopram on human fertility has been observed.
Interaction
To avoid possible drug interactions with Lenuxin®, other drugs can be used only after consultation with your doctor.
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 when starting MAO inhibitors in patients who had recently stopped taking SSRIs. In some cases, patients developed serotonin syndrome. The use of escitalopram simultaneously with non-selective irreversible MAO inhibitors is prohibited. Escitalopram can be started 14 days after discontinuation of irreversible MAO inhibitors. Before starting to take non-selective irreversible MAO inhibitors, at least 7 days must pass after stopping taking escitalopram.
Reversible selective MAO-A inhibitor (moclobemide)
Due to the risk of developing serotonin syndrome, it is not recommended to use escitalopram concomitantly with the MAO-A inhibitor moclobemide. If taking 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 can be started at least one day after discontinuation of the reversible MAO-A inhibitor moclobemide.
Reversible non-selective MAO inhibitor (linezolid)
The antibiotic linezolid is a reversible, non-selective MAO inhibitor and is therefore not recommended for use in patients receiving escitalopram. If the need for such combination therapy is proven, it should be prescribed in a minimal dose and under close monitoring of the patient.
Irreversible MAO-B inhibitor (selegiline)
Due to the risk of developing serotonin syndrome, caution should be exercised when taking escitalopram concomitantly with the irreversible MAO-B inhibitor selegiline.
Drugs that prolong the QT interval
Pharmacokinetic and pharmacodynamic studies of the use of escitalopram in combination with other drugs that prolong the QT interval have not been conducted. The possibility of an additive effect from the use of escitalopram in combination with these drugs cannot be excluded. Therefore, the combined use of escitalopram with drugs that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (for example, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial drugs (for example, sparfloxacin, moxifloxacin, erythromycin for /in administration, pentamidine, antimalarials, especially halofantrine), some antihistamines (astemizole, mizolastine).
Serotonergic drugs
Concomitant use with serotonergic drugs (for example, tramadol, sumatriptan and other triptans) may lead to the development of serotonin syndrome.
Medicines that lower the seizure threshold
SSRIs may lower the seizure threshold. Caution is required when using escitalopram concomitantly with other drugs that lower the seizure threshold (tricyclic antidepressants; SSRIs; antipsychotics - derivatives of phenothiazine, thioxanthene and butyrophenone; mefloquine; bupropion; tramadol).
Lithium and tryptophan
With simultaneous use of escitalopram and lithium or tryptophan, cases of increased effect of escitalopram have been reported.
St. John's wort (Hypericum perforatum)
The simultaneous use of escitalopram and St. John's wort preparations may lead to an increase in the number of side effects.
Anticoagulants and other drugs that affect blood clotting
With 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 NSAIDs, ticlopidine and dipyridamole), a blood clotting disorder may occur. In such cases, regular monitoring of blood clotting is necessary at the beginning or end of therapy with escitalopram. Concomitant use with non-steroidal anti-inflammatory drugs may lead to an increase in the number of bleedings.
Medicines that cause hypokalemia/hypomagnesemia
Caution should be exercised when co-administering escitalopram with drugs that cause hypokalemia/hypomagnesemia, as these disorders increase the risk of malignant arrhythmias.
Ethanol
Escitalopram does not interact pharmacodynamically or pharmacokinetically with ethanol. However, as with other psychotropic drugs, the simultaneous use of escitalopram and alcohol is not recommended.
Pharmacokinetic interaction
Effect of other drugs on the pharmacokinetics of escitalopram
The metabolism of escitalopram is mainly carried out with the participation of the CYP2C19 isoenzyme. To a lesser extent, isoenzymes CYP3A4 and CYP2D6 may participate in metabolism. Metabolism of the main metabolite, demethylated escitalopram, appears to be partially catalyzed by the CYP2D6 isoenzyme.
The simultaneous use of escitalopram and esomeprazole (inhibitor of the CYP2C19 isoenzyme) leads to a moderate (approximately 50%) increase in the concentration of escitalopram in the blood plasma.
The simultaneous use of escitalopram and cimetidine at a dose of 400 mg 2 times / day (an inhibitor of the isoenzymes CYP2D6, CYP3A4 and CYP1A2) leads to an increase (approximately 70%) in the concentration of escitalopram in the blood plasma.
Therefore, maximum possible doses of escitalopram should be used with caution concomitantly with inhibitors of the CYP2C19 isoenzyme (for example, omeprazole, esomeprozole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and cimetidine. If escitalopram is used concomitantly with the above drugs, it may be necessary to reduce the dose of escitalopram based on clinical assessment.
Effect of escitalopram on the pharmacokinetics of other drugs
Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Caution should be exercised when using escitalopram simultaneously with drugs metabolized by this isoenzyme and having a low therapeutic index, for example, flecainide, propafenone and metoprolol (when used for heart failure), or drugs primarily metabolized by the CYP2D6 isoenzyme and acting on CNS, for example, antidepressants: desipramine, clomipramine, nortriptyline, or antipsychotics: 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 latter two drugs. Escitalopram may slightly inhibit the CYP2C19 isoenzyme. Therefore, caution is recommended during concomitant use of escitalopram and drugs metabolized by CYP2C19.
Overdose
Data on overdose of escitalopram are limited, and many such cases have involved overdose of other drugs. In most cases, symptoms of overdose do not appear or are mild. Cases of overdose of escitalopram (without taking other drugs) with a fatal outcome are rare; in most cases, overdose of other drugs also occurs. When taking escitalopram at a dose of 400-800 mg as monotherapy, no clinically significant symptoms of overdose occurred.
Symptoms: mainly symptoms arise 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), from the cardiovascular system (arterial hypotension, tachycardia, prolongation of the interval QT and arrhythmia) and electrolyte imbalance (hypokalemia, hyponatremia).
Treatment: There is no specific antidote. It is recommended to carry out symptomatic and supportive therapy. Normal airway patency, oxygenation and ventilation of the lungs should be ensured. 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.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, you should refrain from performing potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions (driving vehicles, working with moving mechanisms, working as a dispatcher, operator).
Lenuxin®
Escitalopram should not be co-administered with MAO inhibitors due to the risk of developing serotonin syndrome. Escitalopram can be prescribed 14 days after stopping treatment with irreversible MAO inhibitors and at least 1 day after stopping treatment with a reversible MAO type A inhibitor (moclobemide). At least 7 days must pass after stopping escitalopram before treatment with non-selective MAO inhibitors can be started.
In children, adolescents and young adults (<24 years of age) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and behavior. Therefore, when prescribing Lenuxin® or any other antidepressants to children, adolescents and young adults (under 24 years of age), the risk of suicide should be weighed against the benefits of their use. If a decision is made to initiate antidepressant therapy, the patient should be closely monitored for early detection of disturbances or changes in behavior, as well as suicidality.
When using drugs belonging to the SSRI therapeutic group, including escitalopram, the following should be considered:
Some patients with panic disorder may experience increased anxiety when starting SSRI treatment. This paradoxical reaction usually disappears within the first two weeks of treatment. To reduce the likelihood of an anxiogenic effect, it is recommended to use low initial doses.
The drug should be discontinued if seizures develop. Use in patients with unstable epilepsy is not recommended; Controlled seizures require careful monitoring. If the frequency of seizures increases, SSRIs, including escitalopram, should be discontinued.
SSRIs and SNRIs (selective norepinephrine reuptake inhibitors) have been associated with the development of akathisia, a condition characterized by unpleasant, debilitating restlessness and hyperactivity, often accompanied by an inability to sit or stand in one place. This condition most likely occurs during the first few weeks of therapy. Increasing the dose may be harmful to patients who experience these symptoms.
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 blood glucose levels. Therefore, dose adjustments of insulin and/or oral hypoglycemic drugs may be required.
The risk of committing suicide is inherent in depression and may persist until the condition significantly improves, either spontaneously or as a result of therapy. Careful monitoring of patients being treated with antidepressants is necessary, especially at the beginning of treatment, due to the possibility of clinical deterioration and/or the emergence of suicidal manifestations (thoughts and behavior). This precaution should also be observed when treating other mental disorders due to the possibility of concurrent depressive episodes.
Hyponatremia, possibly associated with impaired ADH secretion, occurs rarely with escitalopram and usually disappears when therapy is discontinued. Caution should be exercised when prescribing escitalopram and other SSRIs to persons at risk of developing hyponatremia: the elderly, patients with cirrhosis, and those taking drugs that can cause hyponatremia.
When taking escitalopram, skin hemorrhages (ecchymosis and purpura) may develop. Escitalopram should be used with caution in patients with a tendency to bleeding, as well as those taking oral anticoagulants and medications that affect blood clotting.
Since clinical experience with the simultaneous use of escitalopram and ECT (electroconvulsive therapy) is limited, caution should be exercised in such cases.
In rare cases, patients taking escitalopram and other SSRIs concomitantly with serotonergic drugs may develop serotonin syndrome. Escitalopram should be used with caution concomitantly with drugs that have serotonergic effects.
Due to limited clinical experience, caution is recommended when using the drug in patients with coronary artery disease.
After long-term use, abrupt cessation of escitalopram therapy may lead to a withdrawal reaction in some patients. Undesirable reactions such as dizziness, headaches and nausea may occur. The severity of these reactions is usually mild and their duration is limited. To avoid withdrawal reactions, gradual withdrawal of the drug over 1-2 weeks is recommended.
Interaction with alcohol
Escitalopram does not interact pharmacodynamically or pharmacokinetically with alcohol. However, as with other antidepressants, you should avoid drinking alcohol during the entire period of treatment with the drug.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Reduxin
Reduxin (Sibutramine + Microcrystalline cellulose) is a drug for getting rid of excess fat deposits, realizing its therapeutic potential thanks to the combined action of its constituent components. Sibutramine becomes a true drug only after metabolic transformations in the biological environment of the body. The active metabolites of the drug - primary and secondary amines - inhibit the reverse neuronal uptake of the neurotransmitters serotonin and norepinephrine. An increase in the concentration of the latter in the synapses of nerve endings activates serotonin 5-hydroxytryptamine receptors and adrenoreceptors, which, in turn, contributes to the development of a feeling of satiety, a decrease in the psychological need for food, and an increase in heat production. By stimulating beta-3 adrenergic receptors, sibutramine acts on adipose tissue (the so-called “brown fat”). A decrease in the proportion of adipose tissue in the body composition is accompanied by an increase in the level of high-density lipoproteins (the so-called “good cholesterol”) in the blood with a simultaneous decrease in the concentration of triglycerides, low-density lipoproteins (“bad cholesterol”), total cholesterol and uric acid.
Being a pronounced enterosorbent, microcrystalline cellulose has good absorption capacity and detoxification properties. Absorbs and ensures elimination from the body of various pathogens, exogenous and endogenous toxins, allergens, as well as potentially toxic metabolites.
After oral administration, Reduxin is quickly and significantly (about 80%) absorbed in the digestive tract.
It is subject to the effect of the first passage through the liver (it is at this stage that active metabolites of the drug are formed). The half-life of sibutramine is about 1 hour, its active metabolites are 14-16 hours. The drug is excreted mainly by the kidneys. The frequency of taking Reduxin is 1 time per day. The dose in each specific case is determined by the doctor, observing the individual reaction of the patient’s body in the initial phase of the therapeutic course. 10 mg is used as such a test dose; if adverse reactions to the drug are noted, the dose is halved; if individual intolerance is confirmed, it is canceled. The optimal time of administration is in the morning, after waking up, but if necessary, Reduxin can be taken with food at a later time. If in the first month of drug therapy body weight has decreased by less than 5%, then the dose is increased by 1.5 times (up to 15 mg). The duration of the therapeutic course in the absence of positive results should not exceed 90 days. If, based on its results, a reduction in body weight of more than 5% was not achieved, the treatment is considered unsuccessful. The same conclusion follows if the patient, after an initial decrease in body weight, begins to gain weight again (3 kg or more). The total duration of taking Reduxin should not exceed two years, since this drug is relatively new, and to date there has not yet been enough information about its effectiveness and safety. When taking Reduxin, you must adhere to a balanced diet and devote enough time to physical exercise.
Lenuxin, 28 pcs., 10 mg, film-coated tablets
Inside,
1 time per day, regardless of meals.
Moderate to severe depression
Usually prescribed 10 mg once daily. 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 the start of treatment. After the symptoms of depression disappear, it is necessary to continue therapy to consolidate the effect for at least 6 months.
Panic disorders 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. Therapy lasts several months.
Social anxiety disorder (social phobia)
Usually prescribed 10 mg 1 time per day. Relief of symptoms usually develops 2–4 weeks after the start of treatment. Depending on the patient's individual response, the dose may subsequently be reduced to 5 mg/day or increased to a maximum of 20 mg/day. Since social anxiety disorder is a chronic disease, the minimum recommended duration of treatment is 12 weeks. To prevent relapse of the disease, repeated therapy may be prescribed for 6 months or longer, depending on the individual patient's response.
Before prescribing the drug, it is necessary to differentiate social phobia from ordinary shyness or timidity.
Generalized anxiety disorder
The recommended starting dose is 10 mg 1 time per day. Depending on the patient’s individual response, the dose can be increased to a maximum of 20 mg/day. Long-term administration of the drug (6 months or longer) at a dose of 20 mg/day is allowed.
Special patient groups
Elderly (over 65 years old).
It is recommended to use half the usual recommended dose of 5 mg/day. The maximum dose is 10 mg/day.
Reduced kidney function.
For moderate renal failure, no dose adjustment is required. In patients with severe renal failure (creatinine Cl below 30 ml/min), the drug is prescribed with caution.
Decreased liver function.
For mild to moderate liver failure, the recommended initial 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. In cases of severe liver failure, care must be taken during titration.
Reduced activity of the CYP2C19 isoenzyme.
For patients with low activity of the CYP2C19 isoenzyme, 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.
Stopping treatment.
When stopping treatment, the dose should be gradually reduced over 1–2 weeks to avoid withdrawal syndrome.
