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CITOLESE Composition and Dosage Form Coated tablets: 28 tablets per pack. 1 tablet - Escitalopram . . . . . . . 10 mg Oral drops: 15 ml per bottle. 1 ml - Escitalopram . . . . . . . 10 mg (20 drops) Clinical-Pharmacological Group Antidepressant, SSRI See blog: Citolese — Tablets and Drops for Depression and Anxiety Disorders Pharmacological Properties Escitalopram, the S-enantiomer of citalopram, is a selective serotonin (5-HT) reuptake inhibitor. Inhibition of 5-HT reuptake accounts for the pharmacological and clinical effects of escitalopram. Escitalopram has practically no interaction with serotonin 5-HT1A, 5-HT2A, and dopamine D1 and D2, adrenergic α1, α2, and β, histaminergic H1, muscarinic, benzodiazepine, and opioid receptors. The antidepressant mechanism of escitalopram is likely related to the potentiation of serotonergic activity in the central nervous system. According to studies, escitalopram is a potent selective inhibitor of serotonin reuptake, with minimal effect on norepinephrine and dopamine neuronal reuptake. Escitalopram is 100 times more effective than the R-enantiomer in inhibiting 5-HT reuptake and 5-HT neuronal excitability. Escitalopram also does not bind or binds minimally to Na+, K+, Cl+, and Ca++ channels. Pharmacokinetics The oral bioavailability of escitalopram is approximately 100%, and food does not affect its absorption. Peak plasma concentration is reached in 4 hours. As with racemic citalopram, the protein binding of the main metabolites of escitalopram is less than 80%. Escitalopram is metabolized in the liver to demethylcitalopram and didemethylcitalopram. Both metabolites are pharmacologically active. Unchanged escitalopram is the dominant structure in plasma. It exhibits linear kinetics. Steady-state plasma concentration is reached in about one week. The elimination half-life of the drug is 30 hours, and the clearance is approximately 0.6 L/min. Excretion is mainly through urine and feces. Most of the absorbed dose is excreted in the urine as its metabolites. Elderly patients (65 years or older): In elderly patients, escitalopram is eliminated more slowly compared to younger patients. Systemic exposure (area under the AUC curve) is approximately 50% higher in elderly patients compared to younger patients. Hepatic impairment: In patients with mild to moderate hepatic impairment (Child-Pugh criteria A and B), the half-life of escitalopram is approximately twice as long, and exposure is approximately 60% higher than in patients with normal liver function. Renal impairment: In mild and moderate renal failure with racemic citalopram, clearance is reduced compared to healthy individuals, and the half-life doubles. (CLcr 10-53 ml/min). Plasma concentrations of metabolites have not been studied, but their concentrations may increase. Polymorphism: It has been found that minor metabolites of escitalopram related to CYP2C19 have 2 times higher plasma concentrations than most metabolites. No changes were observed in minor metabolites related to CYP2D6. Indications Used in the treatment of the following conditions: - Major depressive disorder; - Panic disorder with or without agoraphobia; - Social anxiety disorder. Dosage Regimen Tablets The drug is taken once a day and can be taken at any time of the day, regardless of food intake. Its safety has not been established at daily doses above 20 mg. Major depressive disorder: Usually taken 10 mg once a day. The daily dose can be increased to 20 mg according to the patient's individual needs and the severity of depression. The antidepressant effect is usually achieved in 2-4 weeks. Antidepressant treatment is symptomatic, so the drug should be used for 6 months or more for relapse prophylaxis. Anxiety disorder with and without agoraphobia: Treatment with escitalopram starts with 5 mg per day for the first week and is usually increased to 10 mg per day. Later, the daily dose can be increased to 20 mg per day according to the patient's individual needs. Maximum effect is achieved in 3 months. Treatment lasts for several months. Social anxiety disorder (social phobia): Usually prescribed 10 mg per day. A treatment period of 2-4 weeks is required to relieve symptoms. Depending on the patient's individual needs, the dose can be reduced to 5 mg or increased to the maximum recommended dose of 20 mg. Social anxiety disorder is a chronic condition, and it is recommended to assess the patient's response after 12 weeks of treatment. It should be used for 6 months or more for relapse prophylaxis. The effectiveness of treatment should be reviewed at regular intervals. Social anxiety disorder is a well-defined diagnostic terminology for a specific disorder and should not be confused with hyperthymia. Treatment with the drug is prescribed only if the disease significantly affects professional and social activities. Treatment with this drug during general cognitive behavioral therapy has not been studied. Treatment with the drug is part of a comprehensive therapeutic strategy. Generalized anxiety disorder: Usually prescribed 10 mg per day. Depending on the patient's individual needs, the dose can be increased to a maximum of 20 mg. Generalized anxiety disorder is a chronic condition, and long-term treatment is recommended to prevent relapse. Elderly patients (>65 years): At the initial stage of treatment, half of the recommended dose is prescribed, and for maintenance therapy, the lowest maximum dose. Children and adolescents (Renal impairment: Dose adjustment is not necessary in mild to moderate renal impairment. There is no information on severe renal impairment (creatinine clearance < 30 ml/min). Hepatic impairment: A starting dose of 5 mg is recommended for the first two weeks of treatment. Then the daily dose can be increased to 10 mg according to the patient's individual needs. Patients with insufficient CYP2C19 metabolism: In patients with reduced CYP2C19 metabolism, a starting dose of 5 mg is recommended for the first two weeks of treatment. Then the daily dose can be increased to 10 mg according to the patient's individual needs. Discontinuation of treatment: To prevent possible withdrawal reactions, the dose of the drug should be gradually reduced over 1-2 weeks when discontinuing treatment. Oral drops The drug is taken once a day and can be taken at any time of the day, regardless of food intake. Its safety has not been established at daily doses above 20 mg (40 drops). Major depressive disorder: Usually taken 10 mg (20 drops) once a day. The daily dose can be increased to 20 mg (40 drops) according to the patient's individual needs and the severity of depression. The antidepressant effect is usually achieved in 2-4 weeks. Antidepressant treatment is symptomatic, so the drug should be used for 6 months or more for relapse prophylaxis. Anxiety disorder with and without agoraphobia: Treatment with escitalopram starts with 5 mg (10 drops) per day for the first week and is usually increased to 10 mg (20 drops) per day. Later, the daily dose can be increased to 20 mg (40 drops) per day according to the patient's individual needs. Maximum effect is achieved in 3 months. Treatment lasts for several months. Social anxiety disorder (social phobia): Usually prescribed 10 mg (20 drops) per day. A treatment period of 2-4 weeks is required to relieve symptoms. Depending on the patient's individual needs, the dose can be reduced to 5 mg (10 drops) or increased to the maximum recommended dose of 20 mg (40 drops). Social anxiety disorder is a chronic condition, and it is recommended to assess the patient's response after 12 weeks of treatment. It should be used for 6 months or more for relapse prophylaxis. The effectiveness of treatment should be reviewed at regular intervals. Social anxiety disorder is a well-defined diagnostic terminology for a specific disorder and should not be confused with hyperthymia. Treatment with the drug is prescribed only if the disease significantly affects professional and social activities. Treatment with this drug during general cognitive behavioral therapy has not been studied. Treatment with the drug is part of a comprehensive therapeutic strategy. Generalized anxiety disorder: Usually prescribed 10 mg (20 drops) per day. Depending on the patient's individual needs, the dose can be increased to a maximum of 20 mg (40 drops). Generalized anxiety disorder is a chronic condition, and long-term treatment is recommended to prevent relapse. Elderly patients (>65 years): At the initial stage of treatment, half of the recommended dose is prescribed, and for maintenance therapy, the lowest maximum dose. Children and adolescents (Renal impairment: Dose adjustment is not necessary in mild to moderate renal impairment. There is no information on severe renal impairment (creatinine clearance < 30 ml/min). Hepatic impairment: A starting dose of 5 mg (10 drops) is recommended for the first two weeks of treatment. Then the daily dose can be increased to 10 mg (20 drops) according to the patient's individual needs. Patients with insufficient CYP2C19 metabolism: In patients with reduced CYP2C19 metabolism, a starting dose of 5 mg (10 drops) is recommended for the first two weeks of treatment. Then the daily dose can be increased to 10 mg (20 drops) according to the patient's individual needs. Discontinuation of treatment: To prevent possible withdrawal reactions, the dose of the drug should be gradually reduced over 1-2 weeks when discontinuing treatment. Side Effects Adverse side effects during the use of Citolese are mild and temporary. They occur within the first 1-2 weeks of starting treatment and usually decrease as the depressive state improves. In some patients, withdrawal reactions may occur after sudden discontinuation of the drug after long-term treatment with antidepressants of the selective serotonin reuptake inhibitor group. However, withdrawal syndrome does not indicate the development of physical dependence. The most common side effects associated with escitalopram observed in double-blind, placebo-controlled studies. Metabolism and nutrition disorders: Frequent - decreased appetite. Psychiatric disorders: Frequent - decreased libido in women. Anorgasmia. Nervous system disorders: Frequent - insomnia, somnolence, and vertigo; Rare - altered taste and sleep disturbance. Respiratory, thoracic, and mediastinal disorders: Frequent - sinusitis, yawning. Gastrointestinal disorders: Very frequent - nausea; Frequent - diarrhea, constipation. Skin and subcutaneous tissue diseases: Frequent - increased sweating. Reproductive system and breast diseases: Frequent - ejaculation disorder and impotence. General disorders and administration site conditions: Frequent - fatigue, fever. Frequent: (>1/100, <1/10); Very frequent: (>1/10); Rare: (>1/100, <1/100). Specifically for the SSRI therapeutic class, side effects of escitalopram on the cardiovascular system manifest as postural hypotension. In case of any unexpected effect, consult a doctor. Contraindications Hypersensitivity to escitalopram or any other ingredient. The drug is contraindicated for use with monoamine oxidase (MAO) inhibitors. Pregnancy and Lactation The safety of escitalopram during pregnancy and lactation is unknown. The drug is excreted in breast milk in very low concentrations. For this reason, the use of the drug during pregnancy and lactation is not recommended unless the clinical benefit outweighs the potential risk. Special Instructions The use of antidepressants, especially in children and adolescents, may increase suicidal thoughts or behaviors. Therefore, at the start of treatment or during the first months, as well as when changing the dose, both increasing and decreasing, or when discontinuing treatment, the patient should be regularly monitored by family members or other caregivers for suicidal attempts or unusual changes in behavior, such as agitation and irritability. Paradoxical anxiety (fear): In panic disorders, some patients may experience an increase in anxiety symptoms at the start of antidepressant treatment. This paradoxical reaction generally subsides after the first two weeks of treatment. Starting treatment with a low dose is recommended to reduce such paradoxical anxiogenic effects. Seizures: The drug should be discontinued in all patients who develop seizures. SSRIs are not used in patients with unstable epilepsy, and in patients with controlled epilepsy, SSRIs can only be taken under careful monitoring. If the frequency of seizures increases, SSRIs should be discontinued immediately. Mania: Selective serotonin reuptake inhibitors should be used with caution in patients with mania or hypomania. The use of selective serotonin reuptake inhibitors should be discontinued if the patient enters a manic phase. Diabetes: Treatment with selective serotonin reuptuptake inhibitors can alter glycemic control in diabetic patients and may require dose adjustment of insulin and/or oral hypoglycemic agents. Hyponatremia: Rare cases of hyponatremia and syndrome of inappropriate secretion of antidiuretic hormone have been reported during treatment with selective serotonin reuptake inhibitors. Therefore, these drugs should be used with caution in patients at high risk of developing hyponatremia: the elderly, patients with cirrhosis, or patients taking drugs that cause hyponatremia. Hemorrhage: Bruising, purpura, and ecchymosis have been reported during treatment with selective serotonin reuptake inhibitors. SSRIs are prescribed with caution with oral anticoagulants and certain drugs that impair platelet function (e.g., atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, and non-steroidal anti-inflammatory drugs) or in patients with a tendency to bleed. ECT (Electroconvulsive Therapy): Caution is recommended as there are only a few clinical studies on the simultaneous use of SSRIs and electroconvulsive treatment. Reversible, selective MAO-A inhibitors: Concomitant use of escitalopram and MAO-A inhibitors is not possible due to the risk of serotonin syndrome. See "Drug Interactions and Other Forms of Interaction" for its concomitant use with non-selective, irreversible MAO inhibitors. Serotonin Syndrome: Escitalopram should be used with caution with other serotonergic drugs, such as sumatriptan and other triptans, tramadol, and tryptophan. However, serotonin syndrome has been rarely observed in patients taking serotonergic drugs with SSRIs. Agitation, tremor, myoclonus, and hyperthermia are a complex of symptoms indicating the development of this syndrome. In such cases, SSRIs and serotonergic drugs should be discontinued immediately, and symptomatic treatment should be initiated. Hypericum Perforatum: Concomitant use of selective serotonin reuptake inhibitors and herbal preparations containing Hypericum Perforatum (St. John's Wort) may increase the frequency of side effects. Withdrawal reactions: To prevent possible withdrawal reactions, discontinuation of treatment with Citolese oral drops should be carried out by gradually reducing the dose over 1-2 weeks. (See "Dosage and Administration"). Use in pediatrics: The safety and efficacy of the drug in children have not yet been established. Effect of the drug on driving or operating machinery: Escitalopram does not affect intellectual functions or psychomotor characteristics. It is known that any psychotropic drug can cause a general reduction in attention or concentration, due to the disease itself, the drug, or both factors combined. Such patients are advised to be cautious when driving or operating machinery. Overdose Toxicity: The amount of clinical data related to escitalopram overdose is very limited. However, it is known that a dose of 190 mg of escitalopram does not cause any serious complications. Symptoms: The following symptoms develop with overdose of racemic citalopram: dizziness, agitation, somnolence, decreased consciousness, seizures, tachycardia, electrocardiogram changes with ST-T variations, QRS complex widening, QT interval prolongation, arrhythmia, respiratory depression, vomiting, rhabdomyolysis, metabolic acidosis, and hypokalemia. Similar symptoms are expected with escitalopram overdose. Treatment: There is no specific antidote. The airways must be kept clear to ensure adequate lung ventilation and oxygenation. Gastric lavage should be performed as soon as possible after drug administration. Monitoring of cardiac and vital signs is recommended, along with general symptomatic and supportive therapy. Drug Interactions Central Nervous System (CNS) drugs: Escitalopram should be used with caution with other CNS-acting drugs. Non-selective MAO inhibitors: The use of selective serotonin reuptake inhibitors with MAO inhibitors, as well as switching to MAO inhibitor treatment immediately after treatment with selective serotonin reuptake inhibitors, can cause serious and sometimes fatal reactions. Serotonin syndrome develops in some patients. Escitalopram cannot be used concomitantly with other non-selective MAO inhibitors. Treatment with escitalopram should be initiated at least 14 days after discontinuation of an irreversible MAO inhibitor or at least 1 day after discontinuation of treatment with a reversible MAO inhibitor, e.g., moclobemide. Treatment with escitalopram should be discontinued at least 7 days before starting treatment with a non-selective MAO inhibitor. Reversible, selective MAO-A inhibitors (moclobemide): Concomitant use of escitalopram with MAO-A inhibitors is not recommended due to the risk of developing serotonin syndrome. If necessary, treatment should be initiated at the minimum recommended dose and intensified with clinical monitoring. Combinations requiring special caution: Selegiline: The drug is used with caution with selegiline (an irreversible MAO-B inhibitor) due to the risk of developing serotonin syndrome. Racemic citalopram 10 mg/day is used with caution with selegiline. Serotonergic drugs: The use of the drug with serotonergic drugs (e.g., tramadol, sumatriptan or other triptans) can cause serotonin syndrome. Drugs that lower the seizure threshold: Selective serotonin reuptuptake inhibitors lower the seizure threshold. Therefore, caution is recommended when used concomitantly with antidepressants (tricyclic antidepressants, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol. Lithium, tryptophan: Caution should be exercised with the concomitant use of SSRIs and lithium and tryptophan, as lithium and tryptophan can enhance the serotonergic effect of SSRIs. Hypericum Perforatum: Concomitant use of SSRIs and herbal preparations containing Hypericum Perforatum (St. John's Wort) may increase the frequency of side effects. Hemorrhage: The anticoagulant effect is altered when used with oral anticoagulants. Therefore, coagulation monitoring is required at the start of concomitant use and upon discontinuation of the drug. Alcohol: Pharmacodynamic and pharmacokinetic interactions between alcohol and escitalopram are not expected. However, like other psychotropic drugs, alcohol consumption by patients taking escitalopram is not recommended. Although there are no pharmacodynamic and pharmacokinetic interactions between alcohol and escitalopram, alcohol consumption is not recommended during escitalopram treatment in patients with depression. The main enzyme involved in the metabolism of escitalopram is CYP2C19. CYP3A4 and CYP2D6 enzymes also contribute to the metabolism of the drug. It is considered that the metabolism of its primary metabolite, demethylcitalopram (S-DCT), is partially catalyzed by CYP2D6. Concomitant administration of escitalopram with a single 30 mg dose of omeprazole (a CYP2C19 inhibitor) led to an increase in the average plasma concentration of escitalopram (approximately 50%). Cimetidine 400 mg twice daily causes an increase in the average plasma level of escitalopram (approximately 70%). For this reason, caution is recommended when escitalopram is used concomitantly with CYP2C19 inhibitors (omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. It may be necessary to reduce the dose of escitalopram depending on the occurrence of side effects during complex therapy. Effect of Escitalopram on the Pharmacokinetics of Other Drugs Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution is advised when escitalopram is used concomitantly with drugs that are primarily metabolized by this enzyme and have a narrow therapeutic index (flecainide, propafenone, and metoprolol in heart failure) or with central nervous system drugs that are primarily metabolized by the CYP2D6 enzyme (antidepressants such as desipramine, clomipramine, and nortriptyline, or antipsychotics such as risperidone, thioridazine, and haloperidol). Dose adjustment may be necessary. Concomitant use with desipramine or metoprolol doubled the plasma concentrations of both CYP2D6 substrates. In vitro studies have shown that escitalopram weakly inhibits CYP2C19. Caution is recommended when used concomitantly with drugs that are metabolized by the CYP2C19 enzyme. Incompatibility The oral drops solution can only be taken with water, orange, or apple juice. As there are no other compatibility studies, mixing the drug with other solutions is not recommended. Storage Conditions and Expiry Date The drug should be stored at a temperature not exceeding 25°C, in a dry place, inaccessible to children. Shelf life - 2 years.
