Cipralex, 10 mg 14 pcs

Cipralex has antidepressant effects.

Pharmacodynamics

Escitalopram is an antidepressant, SSRI, with high affinity for the primary binding site. Excitalopram also binds to the allosteric binding site of the transporter protein, with an affinity that is a thousand times lower. Allosteric modulation of the transporter protein enhances the binding of escitalopram at the primary binding site, resulting in a more complete inhibition of serotonin reuptake.

Escitalopram has no or very weak ability to bind to a number of receptors, including: serotonin 5-HT_1A-, 5-HT₂-receptors, dopamine D₁– and D₂-receptors, α₁-, α₂-, β-adrenoreceptors, histamine H₁-receptors, m-cholinoreceptors, benzodiazepine and opioid receptors.

Pharmacokinetics

Intake is almost complete and independent of food intake. Mean T_max in plasma is 4 hours after repeated administration. Absolute bioavailability of escitalopram is about 80%.

The apparent V_d after oral administration is 12 to 26 L/kg. The binding of escitalopram and its major metabolites to plasma proteins is below 80%.

Escitalopram is metabolized in the liver to demethylated and didemethylated metabolites. They are both pharmacologically active. Nitrogen can be oxidized to the metabolite N-oxide. The main substance and its metabolites are partially excreted as 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 to a demethylated metabolite occurs primarily via the CYP2C19 isoenzyme. Some involvement of CYP3A4 and CYP2D6 isoenzymes is possible. In persons with weak activity of CYP2C19 isoenzyme, the concentration of escitalopram is twice as high as in cases with high activity of this isoenzyme. No significant changes in drug concentrations were found in cases with weak CYP2D6 isoenzyme activity.

The T_1/2 after multiple administration is about 30 h. Clearance with oral administration is about 0.6 l/min. The main metabolites of escitalopram have a longer elimination half-life. Excitalopram and its major metabolites are excreted by the liver (metabolic route) and the kidneys; most are excreted as metabolites in the urine.

The kinetics of escitalopram are linear. Equilibrium concentration is reached after approximately 1 week. An average C_ss, 50 nmol/L (20 to 125 nmol/L), is reached at a daily dose of 10 mg.

Particular patient groups

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

Indications

Active ingredient

Composition

1 film-coated tablet contains:

acting substance:

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

auxiliary substances:

talc, 7 mg;

croscarmellose sodium, 4.5 mg;

MCC, 97.49 mg;

Colloidal silicon dioxide – 1.99 mg;

Magnesium stearate – 1.25 mg,

coat film:

Hypromellose 5cP – 2.19 mg;

macrogol 400 – 0.2 mg;

titanium dioxide (E171) – 0.73 mg.

How to take, the dosage

Ingestion, regardless of meals, once daily.

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

Panic disorder with or without agoraphobia: A dose of 5 mg/day is recommended for the first week of treatment, which is then increased to 10 mg/day. Depending on the individual response of the patient, the dose may be increased to a maximum of 20 mg/day. Maximum therapeutic effect is achieved about 3 months after the start of treatment. Therapy lasts for several months.

Social anxiety disorder (social phobia): usually 10 mg once daily is prescribed. Depending on the individual response of the patient, the dose may be increased to a maximum of 20 mg/day. Relief of symptoms usually develops in 2-4 weeks after the beginning of treatment. Since social anxiety disorder is a disease with a chronic course, the minimum recommended duration of therapy is 3 months. In order to prevent relapses of the disease, the drug may be prescribed for 6 months or longer, depending on the individual patient’s response. It is recommended that the ongoing treatment be evaluated regularly.

Generalized anxiety disorder: 10 mg once daily is usually prescribed. Depending on the individual response of the patient, the dose may be increased to a maximum of 20 mg/day. Minimum recommended duration of therapy course is 3 months. To prevent recurrence of the disease, long-term use of the drug (6 months and longer) is allowed. It is recommended to evaluate the treatment on a regular basis.

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

Particular patient groups

Elderly patients (over 65 years of age). Half the normally recommended dose (i.e., only 5 mg/day) and a lower maximum dose (10 mg/day) are recommended.

Children and adolescents (under 18 years of age). Cipralex should not be used in children and adolescents under 18 years of age. In addition, there are insufficient long-term safety studies of the drug in children and adolescents regarding growth, maturation, cognitive and behavioral development.

Kidney dysfunction. No dose adjustment is required in mild to moderate renal impairment. Caution should be exercised when prescribing Cipralex in patients with significant renal impairment (creatinine Cl below 30 ml/min).

Hepatic impairment. The recommended initial dose during the first 2 weeks of treatment is 5 mg/day. Depending on the individual reaction of the patient, the dose may be increased to 10 mg/day.

Decreased activity of CYP2C19 isoenzyme. For patients with weak CYP2C19 isoenzyme activity, the recommended initial dose for the first 2 weeks of treatment is 5 mg/day. The dose may be increased to 10 mg/day depending on the individual response of the patient.

Stopping treatment

When therapy with Cipralex is discontinued, the dose should be reduced gradually over 1-2 weeks to avoid withdrawal symptoms.

Interaction

Pharmacodynamic interactions

Nonselective non-reversible MAOI inhibitors. Serious adverse reactions have been reported when concomitant use of SSRIs and nonselective irreversible MAO inhibitors is reported, as well as when patients who have recently stopped taking SSRIs start taking MAO inhibitors. In some cases, patients developed serotonin syndrome. It is prohibited to use escitalopram concomitantly with non-selective non-reversible MAO inhibitors. The use of escitalopram may be started 14 days after discontinuation of non-selective MAO inhibitors. Before starting non-selective irreversible MAO inhibitors, it should be at least 7 days after discontinuation of escitalopram.

The reversible selective MAOA inhibitor A (moclobemide). Because of the risk of serotonin syndrome, it is not recommended to use escitalopram simultaneously with the MAO A inhibitor moclobemide. If such a combination of drugs is clinically necessary, it is recommended to start with the lowest possible doses, and to monitor the patient’s condition on an ongoing clinical basis. The administration of escitalopram may be started at least one day after withdrawal of the reversible MAOA inhibitor moclobemide.

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

Serotoninergic drugs. Co-administration with serotonergic drugs (e.g., tramadol, sumatriptan and other triptans) may lead to the development of serotonin syndrome.

Drugs that lower seizure threshold. SSRIs may decrease the seizure threshold. Caution is required when using other drugs which lower the seizure threshold (tricyclic antidepressants, SSRIs, mefloquine, bupropion, tramadol and antipsychotics (neuroleptics) – phenothiazine, thioxanthene and butyrophenone derivatives) simultaneously with escitalopram.

Lithium, tryptophan. Because cases of enhanced effects have been reported with concomitant use of SSRIs and lithium or tryptophan, caution is recommended when concomitantly using escitalopram with lithium and tryptophan.

Wortwood. Simultaneous use of SSRIs and drugs containing St. John’s Wort (Hypericum perforatum) may result in increased side effects.

Anticoagulants and other agents that affect blood clotting. Impairment of blood clotting may occur during concomitant use of escitalopram with oral anticoagulants and other drugs affecting blood clotting (e.g. atypical neuroleptics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and other NSAIDs, ticlopidine and dipyridamole). In such cases, careful monitoring of blood clotting is necessary at the beginning or end of therapy with escitalopram. Simultaneous use with NSAIDs may lead to increased bleeding.

Pharmacokinetic interaction

The effect of other drugs on the pharmacokinetics of escitalopram. Metabolism of escitalopram mainly occurs with the participation of CYP2C19 isoenzyme. CYP3A4 and CYP2D6 isoenzymes may participate in metabolism to a lesser extent. The metabolism of the main metabolite, demethylated escitalopram, is apparently partially catalyzed by CYP2D6 isoenzyme.

The concomitant use of escitalopram and omeprazole (CYP2C19 isoenzyme inhibitor) leads to a moderate (about 50%) increase in plasma concentrations of escitalopram.

The simultaneous use of escitalopram and cimetidine (inhibitor of CYP2D6, CYP3A4 and CYP1A2 isoenzymes) leads to increased (approximately 70%) plasma concentrations of escitalopram.

Thus, maximum possible doses of escitalopram concomitantly with CYP2C19 isoenzyme inhibitors (e.g., omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and cimetidine should be used with caution. Concomitant administration of escitalopram and the above drugs may require reduction of the dose of escitalopram based on clinical evaluation.

The effect of escitalopram on the pharmacokinetics of other drugs. Excitalopram is an inhibitor of CYP2D6 isoenzyme. Caution should be exercised when concomitant use of escitalopram and drugs that are metabolized with this isoenzyme and have a low therapeutic index, such as flecainide, propafenone and metoprolol (in cases of use in heart failure) or medical drugs mainly metabolized by CYP2D6 and acting on the CNS, such as antidepressants: Desipramine, clomipramine, nortriptyline or antipsychotic drugs: risperidone, thioridazine, haloperidol. Dose adjustment may be necessary in these cases.

The simultaneous use of escitalopram and desipramine or metoprolol leads to a twofold increase in concentrations of the latter two drugs.

Escitalopram may slightly inhibit the CYP2C19 isoenzyme. Therefore, caution is recommended when concomitant use of escitalopram and drugs metabolized by CYP2C19 isoenzyme.

Special Instructions

Antidepressants should not be prescribed to children and adolescents under 18 years of age because of the increased risk of suicidal behavior (suicide attempts and suicidal ideation), hostility (with a predominance of aggressive behavior, confrontational tendencies and irritability). If the decision is made to initiate antidepressant therapy on the basis of a clinical assessment, the patient should be closely monitored.

Some patients with panic disorder may have increased anxiety at the start of antidepressant treatment. This paradoxical reaction usually disappears within the first 2 weeks of treatment. To reduce the likelihood of an anxiogenic effect, low starting doses are recommended.

Escitalopram should be discontinued in cases of primary seizure development or increased seizure frequency (in patients with previously diagnosed epilepsy). SSRIs should not be used in patients with unstable epilepsy; if seizures are controlled, close monitoring is necessary.

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

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

Depression is associated with an increased risk of suicidal ideation, self-inflicted injuries, and suicide (suicidal ideation). This risk persists until the onset of significant remission. Because improvement may not be seen for the first few weeks of therapy or even longer, patients should be monitored closely until improvement occurs.

Common clinical practice shows that in the early stages of recovery, there may be an increased risk of suicide.

Other psychiatric conditions for which escitalopram is prescribed may also be associated with an increased risk of suicidal events and phenomena. In addition, these conditions may be co-occurring pathology in relation to the depressive episode. Patients with other psychiatric disorders should be treated with the same precautions as patients with a depressive episode. Patients with a history of suicidal behavior or patients with significant levels of suicidal ideation prior to treatment are at greater risk for suicidal thoughts or suicide attempts, so they should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants involving adult patients with psychiatric disorders found that there is an increased risk of suicidal behavior when taking antidepressants in patients younger than 25 years old compared to taking placebo. Medication treatment of these patients, and in particular those at high risk for suicide, should be accompanied by close monitoring, especially in the early phase of treatment and during dose changes. Patients (and caregivers) should be warned to monitor for any signs of clinical deterioration, suicidal behavior or thoughts, and unusual behavioral changes, and to seek medical advice immediately if these symptoms occur.

The administration of SSRIs/ SSRIs is associated with the development of akathisia, characterized by the development of subjectively unpleasant or depressing restlessness and a need for constant movement, often combined with an inability to sit or stand still. This most often manifests itself during the first few weeks of treatment. In patients with these symptoms, increasing the dose may lead to worsening.

Hyponatremia, possibly associated with impaired ADH secretion, is rare with SSRIs and usually resolves with treatment withdrawal. Caution should be used when prescribing escitalopram and other SSRIs for those at risk for hyponatremia: the elderly, those with cirrhosis of the liver, and those taking medications that may cause hyponatremia.

When taking SSRIs, there have been cases of skin bleeding (ecchymosis and purpura). Caution is necessary when using escitalopram in patients taking oral anticoagulants and drugs that affect blood clotting, as well as in patients who are prone to bleeding.

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

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

Escitalopram should be used with caution concomitantly with drugs with serotonergic effects, such as 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 serotoninergic drugs should be stopped immediately and symptomatic treatment should be initiated.

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

The effect on the ability to drive or operate machinery. Although Cipralex has no effect on intellectual functions and psychomotor activity, patients are not recommended to drive or operate machinery during treatment.

Contraindications

With caution: Severe renal insufficiency (creatinine Cl below 30 ml/min); mania and hypomania; pharmacologically uncontrolled epilepsy; marked suicidal behavior; diabetes mellitus; liver cirrhosis; susceptibility to bleeding; concomitant use with MAO A inhibitor (moclobemide) and MAO B inhibitor (selegiline), serotonergic drugs, drugs that reduce seizure threshold, lithium, tryptophan, drugs St. John’s wort, oral anticoagulants and other drugs that affect blood clotting, drugs that may cause hyponatremia, drugs metabolized with the participation of CYP2C19 isoenzyme, ethanol; electroconvulsive therapy; advanced age; pregnancy; breast-feeding.

Side effects

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

The following are the side effects of the drugs belonging to the class of SSRIs noted when taking escitalopram. The information is based on data from placebo-controlled clinical trials and spontaneous reports. Frequency is indicated as: very common – ≥1/10; common – ≥1/100 to

Blood and lymphatic system disorders: unknown – thrombocytopenia.

Immune system disorders: rare – anaphylactic reactions.

Endocrine system disorders: unknown – insufficient ADH secretion.

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

Psychiatric disorders: frequently – anxiety, restlessness, unusual dreams, decreased libido, anorgasmia (in women); infrequent – bruxism, agitation, nervousness, panic attacks, confusion of consciousness; rarely – aggression, depersonalization, hallucinations; unknown – mania, suicidal thoughts, suicidal behavior. Cases of suicidal thoughts and behavior have been noted while taking escitalopram and immediately after discontinuation of therapy.

Nervous system disorders: frequently – insomnia, somnolence, dizziness, dizziness, paresthesia, tremor; infrequently – taste disorders, sleep disorders, syncopal conditions; rarely – serotonin syndrome; unknown – dyskinesia, motor disorders, seizure disorders, psychomotor agitation/akathisia.

VIight: infrequent – mydriasis (dilation of the pupil), visual disturbances.

Hearing organ and labyrinth disorders: infrequent – tinnitus (tinnitus).

System effects: infrequent – tachycardia; rare – bradycardia; unknown – prolongation of QT interval on ECG, orthostatic hypotension.

Respiratory system, thorax and mediastinum: frequently – sinusitis, yawning; infrequently – nasal bleeding.

Gastrointestinal disorders: very frequently – nausea; frequently – diarrhea, constipation, vomiting, dry mouth; infrequently – gastrointestinal bleeding (including rectal bleeding).

Hepatic and biliary tract disorders: unknown – hepatitis, impairment of liver function parameters.

Skin and subcutaneous tissue: frequently – increased sweating; infrequent – urticaria, alopecia, rash, itching; unknown – ecchymosis, angioedema.

Skeletal, muscular and connective tissue disorders: often – arthralgia, myalgia.

Renal and urinary tract: unknown – urinary retention.

Reproductive system and breast: often – impotence, impaired ejaculation; infrequent – metrorrhagia (uterine bleeding), menorrhagia; unknown – galactorrhea, priapism.

The body in general and disorders at the site of administration: often – weakness, hyperthermia; infrequently – edema.

In the post-registration period, there have been 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 (Friedericia formula correction) was 4.3 ms at the 10 mg/day dose and 10.7 ms at 30 mg/day.

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

The withdrawal (especially abrupt) of SSRIs/ SSRIs often results in withdrawal symptoms. The most common are dizziness, sensory disturbances (including paresthesias and current sensations), sleep disturbances (including insomnia and intense dreaming), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability, visual disturbances. These effects are usually mild to moderate and pass quickly, but in some patients they may be more acute and/or last longer. Gradual withdrawal of the drug by reducing the dose is recommended.

Overdose

The data on overdose of escitalopram are limited, in many such cases there was also an overdose of other drugs. In most cases, the symptoms of overdose are mild or non-existent. Cases of fatal overdose of escitalopram (without taking other drugs) are rare, in most cases there is also an overdose of other drugs.

Symptoms: mainly CNS (from dizziness, tremor and agitation to rare cases of serotonin syndrome, seizure disorders and coma), GI (nausea/vomiting), CSS (hypotension, tachycardia, QT interval prolongation and arrhythmia) and electrolyte balance disorders (hypokalemia, hyponatremia).

Treatment: there is no specific antidote to the drug. Normal airway patency, oxygenation and ventilation of the lungs should be ensured. Gastric lavage should be performed and activated charcoal prescribed. Gastric lavage should be performed as soon as possible after ingestion. It is recommended to monitor the performance of the heart and other vital organs and to carry out symptomatic and supportive therapy.

Pregnancy use

There are limited data on administration of escitalopram during pregnancy.

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

If the mother takes SSRIs/ SSRIs in late pregnancy, the following side effects may develop in the newborn: Respiratory depression, cyanosis, apnea, seizure disorders, temperature spikes, feeding difficulties, vomiting, hypoglycemia, hypertension, muscle hypotonia, hyperreflexia, tremor, increased neuroreflex excitability, irritability, lethargic sleep, constant crying, drowsiness, poor sleep. These symptoms may occur due to the development of withdrawal syndrome or serotoninergic effects.

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

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

Similarities