Instructions Escitalopram Asino film-coated tablets 20 mg blister No. 60
Composition
active ingredient: escitalopram;
1 tablet contains escitalopram oxalate (12.775 mg or 25.55 mg) equivalent to escitalopram 20 mg;
excipients: microcrystalline cellulose, croscarmellose sodium, hydroxypropylmethylcellulose (hypromellose), colloidal anhydrous silicon dioxide, talc, magnesium stearate;
Opadry II White shell: polyvinyl alcohol, titanium dioxide (E 171), polyethylene glycol (macrogol), talc.
Dosage form
Film-coated tablets.
Main physicochemical properties:
20 mg tablets: round tablets with a biconvex surface, film-coated in white, with a score.
Pharmacotherapeutic group
Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATC code N06A B10.
Pharmacological properties
Pharmacodynamics
Escitalopram is an antidepressant, a selective serotonin reuptake inhibitor, which determines the clinical and pharmacological effects of the drug. It has high affinity for the main binding element and the adjacent allosteric element of the serotonin transporter and 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-, M-cholinoreceptors, benzodiazepine and opiate receptors.
Escitalopram is the S-enantiomer of racemic citalopram with its own therapeutic activity. The R-enantiomer has been shown to be inert and to antagonize the serotonergic properties and corresponding pharmacological effects of the S-enantiomer.
Pharmacokinetics
Absorption is almost complete and independent of food intake. Maximum plasma concentrations are reached 4 hours after administration. The bioavailability of escitalopram is approximately 80%. The apparent volume of distribution (Vd, β/F) after oral administration is 12 to 26 l/kg.
The binding of escitalopram and its main metabolites to blood proteins is less than 80%.
In the liver, metabolites are formed that are demethylated and didemethylated and are pharmacologically active. Nitrogen can also be oxidized to the N-oxide metabolite.
Both metabolites and the parent compound are partially excreted in the form of glucuronides.
After multiple administration, the average concentration of demethyl and didemethyl metabolites is usually 28-31% and < 5% of the concentration of escitalopram, respectively. Biotransformation of escitalopram to the demethyl metabolite occurs mainly with the help of cytochrome CYP2C19. Minor participation in the process isoenzymes CYP3A4 and CYP2D6 isoenzymes is possible. The half-life (T1/2) of the drug is approximately 30 hours. Clearance (Cloral) when taken orally is approximately 0.6 l / min. The main metabolites have a longer half-life. Escitalopram and its main metabolites are excreted by the liver (metabolic pathway) and the kidneys. Most of the dose is excreted in the form of metabolites with urine. The kinetics of escitalopram are linear. Equilibrium concentration is reached after approximately 1 week. The average steady-state concentration of 50 nmol/l (range 20 to 125 nmol/l) is achieved with a daily dose of 10 mg.
In elderly patients (65 years and older), escitalopram is eliminated more slowly than in young patients. Systemic exposure (AUC) in elderly subjects is 50% higher than in young healthy volunteers.
In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the half-life was twice as long and exposure was 60% higher than in subjects with normal hepatic function.
In patients with reduced renal function (CLcr 10-53 ml/min) a longer half-life and slightly higher exposure were observed with racemic citalopram. Plasma concentrations of metabolites have not been studied but may be increased.
Patients with poor CYP2C19 metaboliser function had twice the plasma concentrations of escitalopram as patients with normal CYP2C19 function. No significant changes in exposure were observed with reduced CYP2D6 function.
Indication
Treatment of major depressive episodes, panic disorders with or without agoraphobia, social anxiety disorders (social phobia), generalized anxiety disorders, obsessive-compulsive disorders.
Contraindication
Hypersensitivity to escitalopram or to any of the other ingredients of the drug; concomitant treatment with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) or pimozide.
Interaction with other medicinal products and other types of interactions
Pharmacodynamic interactions
Contraindicated combinations
Pimozide: The combination of pimozide and racemic citalopram resulted in a mean prolongation of the QTc interval of approximately 10 msec. Due to the interaction of escitalopram with low doses of pimozide and increased side effects of the latter, concomitant use is contraindicated.
Combinations requiring caution
Reversible selective MAO inhibitor type A (moclobemide). Due to the risk of serotonin syndrome, the combination of escitalopram with a MAO inhibitor type A, such as moclobemide, is contraindicated. If the need for this combination is proven, the minimum recommended doses should be prescribed initially with careful clinical monitoring. Treatment with escitalopram can be started no earlier than 1 day after discontinuation of the reversible MAOI moclobemide.
Selegiline: Combination with selegiline (an irreversible MAOI type B inhibitor) requires caution due to the risk of serotonin syndrome.
Serotonergic drugs: Concomitant use with serotonergic drugs (e.g. tramadol, sumatriptan and other triptans) may lead to the development of serotonin syndrome.
Agents that lower the seizure threshold. SSRIs may lower the seizure threshold. Caution is advised with concomitant use of agents that lower the seizure threshold, such as antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol.
Lithium, tryptophan. Since cases of enhanced effects have been reported with the combined use of SSRIs and lithium or tryptophan, caution is recommended when these drugs are prescribed simultaneously.
St. John's wort. Concomitant use of SSRIs and herbal remedies containing St. John's wort may lead to an increased incidence of adverse reactions.
Anticoagulants: The effects of oral anticoagulants may be altered by concomitant use with escitalopram. Patients taking oral anticoagulants should have their blood coagulation status monitored closely before and after use of escitalopram.
Concomitant use of nonsteroidal anti-inflammatory drugs may increase the tendency to bleed.
Alcohol: Escitalopram does not interact pharmacodynamically or pharmacokinetically with alcohol. However, as with other psychotropic drugs, the combination with alcohol is undesirable.
Pharmacokinetic interactions
Effect of other agents on the pharmacokinetics of escitalopram
The metabolism of escitalopram is mainly mediated by CYP2C19.
Co-administration of escitalopram and omeprazole (CYP2C19 inhibitor) leads to a moderate (approximately 50%) increase in escitalopram plasma concentrations.
Concomitant administration of escitalopram and cimetidine (a moderate general enzyme inhibitor) increases the plasma concentration of escitalopram by approximately 70%.
Therefore, caution should be exercised when escitalopram is co-administered with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. A dose reduction of escitalopram may be required when co-administered with the above-mentioned drugs.
Effect of escitalopram on the pharmacokinetics of other drugs. Escitalopram is an inhibitor of the CYP2D6 enzyme.
Caution is advised when escitalopram is co-administered with drugs that are primarily metabolised by this enzyme and have a narrow therapeutic index, such as flecainide, propafenone and metoprolol (in heart failure), or with some drugs that affect the central nervous system and are primarily metabolised by CYP2D6, such as antidepressants such as desipramine, clomipramine and nortriptyline, and antipsychotics such as risperidone, thioridazine and haloperidol. Dose adjustment may be necessary.
Combination with desipramine or metoprolol resulted in a twofold increase in plasma levels of these two agents.
Caution is recommended when used concomitantly with drugs metabolized by CYP2C19.
Application features
The following application features apply to the therapeutic group of selective serotonin reuptake inhibitors (SSRIs).
Paradoxical anxiety. Some patients with panic disorder may experience increased anxiety when starting treatment with SSRIs. This paradoxical reaction usually resolves within two weeks of treatment. To reduce the likelihood of anxiogenic effects, low initial doses are recommended.
Seizures. The drug should be discontinued if the patient develops a seizure for the first time or if seizures become more frequent (in patients with established epilepsy). SSRIs should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be closely monitored.
Mania: SSRIs should be used with caution in patients with a history of mania/hypomania. If a manic state occurs, SSRIs should be discontinued.
Suicide, suicidal ideation or clinical worsening. Depression is associated with a risk of suicidal ideation, self-harm and suicide. This risk persists until sustained remission is achieved. As improvement may not be achieved within the first few weeks of treatment or longer, patients should be closely monitored until their condition improves. It is known that the risk of suicide may be increased in the early stages of recovery.
Other conditions for which escitalopram is used may also be associated with a risk of suicidal behaviour. In addition, such conditions may be comorbid with major depressive disorder. These warnings also apply to the treatment of patients with other psychiatric disorders.
Patients with a history of suicidal behaviour prior to initiation of treatment are at greatest risk of suicidal thoughts or suicide attempts and require close monitoring during treatment. A meta-analysis of studies with escitalopram found an increased risk of suicidal behaviour in patients aged <25 years who received antidepressants compared with those who received placebo. Close monitoring of patients at high risk is particularly necessary at the start of treatment and when changing the dose.
Patients and caregivers should be warned about the need to monitor for any worsening of condition, suicidal behavior or thoughts, and unusual changes in behavior, and to seek medical advice immediately if these symptoms develop.
Akathisia. The use of SSRIs/SNRIs has been associated with the development of akathisia, a condition characterised by an unpleasant, debilitating feeling of restlessness and a need to move, often accompanied by an inability to sit or stand still. This condition is most likely to occur during the first few weeks of treatment. Increasing the dose may worsen the condition of patients who develop these symptoms.
Hyponatremia. Hyponatremia, possibly related to impaired antidiuretic hormone (ADH) secretion, occurs rarely with SSRIs and usually resolves after discontinuation of therapy. SSRIs should be used with caution in patients at risk (elderly, with cirrhosis of the liver, or concomitant treatment with drugs known to cause hyponatremia).
Bleeding. When taking SSRIs, skin bleeding (ecchymosis and purpura) may develop. SSRIs should be used with caution in patients taking anticoagulants and drugs that affect platelet function (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, dipyridamole and ticlopidine), as well as in patients with a tendency to bleeding.
ECT (electroconvulsive therapy): Clinical experience with the concomitant use of SSRIs and ECT is limited, so caution is recommended.
Reversible selective MAO type A inhibitors. Combining escitalopram and MAO type A inhibitors is contraindicated due to the risk of serotonin syndrome.
Serotonin syndrome: Caution is recommended when escitalopram is used concomitantly with drugs that have serotonergic effects, such as sumatriptan or other triptans, tramadol and tryptophan.
In patients taking SSRIs concomitantly with serotonergic drugs, serotonin syndrome may develop in isolated cases. Its development may be indicated by a combination of symptoms such as agitation, tremor, myoclonus, hyperthermia. If this situation occurs, SSRIs and serotonergic drugs should be urgently discontinued and symptomatic treatment should be prescribed.
St. John's wort. Concomitant use of SSRIs and herbal remedies containing St. John's wort may lead to an increased incidence of adverse reactions.
Withdrawal symptoms. Withdrawal symptoms are common when treatment is discontinued, especially if it is abrupt. In studies, it is known that adverse reactions occurred in approximately 25% of patients taking escitalopram and in 15% of patients taking placebo. The risk of withdrawal symptoms may depend on several factors, including duration and dose, and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia, electric shock sensations), sleep disturbances (including insomnia, vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhoea, palpitations, emotional lability, irritability and visual disturbances are the most common reactions. These symptoms are usually mild to moderate in severity, but may be more severe in some patients. They usually occur within the first few days after stopping treatment, but there have been very rare reports of similar symptoms in patients who have accidentally missed a dose. Withdrawal symptoms usually resolve within 2 weeks, but may last longer in some patients (2-3 months or more). Therefore, it is recommended to gradually discontinue escitalopram treatment by reducing the dose over a period of several weeks or months, depending on the patient's condition.
Sexual dysfunction: SSRIs may cause symptoms of sexual dysfunction (see section 4.8). In some cases, these symptoms have persisted after discontinuation of treatment.
Ability to influence reaction speed when driving vehicles or other mechanisms
Escitalopram does not generally affect intellectual function or psychomotor reactions, but it should be borne in mind that any psychoactive drug may impair the skills or ability to think rationally. Patients should be warned of the potential risk of impairment in driving or operating machinery.
Use during pregnancy or breastfeeding
Clinical data on the use of escitalopram in pregnant women are limited.
Escitalopram® Asino is contraindicated in pregnant women, except in cases where the need for the drug has been clearly demonstrated after careful consideration of all the disadvantages and benefits. Careful examination of newborns whose mothers took Escitalopram® Asino during pregnancy, especially in the third trimester, is recommended. Abrupt discontinuation of the drug during pregnancy should be avoided.
Neonates whose mothers took SSRIs/SNRIs in late pregnancy may experience the following symptoms: respiratory distress, cyanosis, apnea, seizures, temperature fluctuations, feeding difficulties, vomiting, hypoglycemia, hypertension or hypotension, hyperreflexia, tremor, agitation, irritability, apathy, constant crying, drowsiness, and difficulty sleeping. These symptoms may be due to serotonergic effects or may be signs of withdrawal. In most cases, the symptoms of complications occur immediately or shortly (< 24 hours) after delivery.
Epidemiological data have shown that the use of SSRIs during pregnancy may increase the risk of persistent pulmonary hypertension in the newborn (up to 5 cases per 1000 pregnancies). In the general population, the incidence is 1 to 2 cases per 1000 pregnancies.
Since escitalopram passes into breast milk, breastfeeding is not recommended during treatment.
Fertility. Some SSRIs may affect sperm quality. Reports of some SSRIs have shown that the effects on sperm quality in humans are reversible. Effects on human fertility have not been observed to date.
Method of administration and doses
The safety of doses above 20 mg per day has not been established.
Escitalopram is administered orally to adults once a day, regardless of meals.
Major depressive episode
Usually, 10 mg is prescribed once a day. Depending on the individual sensitivity of the patient, the daily dose can be increased to a maximum of 20 mg.
The antidepressant effect usually occurs after 2-4 weeks. After the symptoms disappear, treatment should be continued for 6 months to consolidate the effect.
Panic disorder with or without agoraphobia
An initial dose of 5 mg per day is recommended during the first week, after which the dose can be increased to 10 mg per day. The dose can be further increased to a maximum of 20 mg per day, depending on the individual sensitivity of the patient.
The maximum effect in the treatment of panic disorders is achieved after 3 months. The duration of treatment is several months and depends on the severity of the disease.
Social anxiety disorder (social phobia)
Usually, 10 mg is prescribed once a day. Relief of symptoms usually occurs after 2-4 weeks of treatment. Depending on the individual patient's response, the dose can be further reduced to 5 mg/day or increased to a maximum of 20 mg/day.
Since social anxiety disorder is a chronic disease, it is recommended to continue treatment for 12 weeks to consolidate the achieved effect.
Long-term treatment for 6 months is prescribed to prevent relapse, taking into account individual manifestations of the disease; the effectiveness of treatment is regularly assessed.
Generalized anxiety disorders
The usual dose is 10 mg once daily. Depending on individual sensitivity, the dose may be increased to a maximum of 20 mg per day.
It is recommended to continue treatment for 3 months to consolidate the effect. Long-term treatment for 6 months is prescribed to prevent relapse, taking into account individual manifestations of the disease; the effectiveness of treatment is regularly assessed.
Obsessive-compulsive disorder (OCD)
Usually, 10 mg is prescribed once a day. Depending on individual sensitivity, the dose can be increased to 20 mg per day. OCD is a chronic disease, treatment should last for a sufficient period to ensure complete disappearance of symptoms, which may be several months or even more.
Elderly patients (aged 65 years and over)
The initial dose is 5 mg per day. Depending on the individual patient's response, the daily dose may be increased to 10 mg per day.
Kidney failure
In the presence of mild to moderate renal insufficiency, there is no need for dose adjustment. The drug should be used with caution in patients with severe renal insufficiency (creatinine clearance < 30 ml/min).
Decreased liver function
In patients with moderate and mild hepatic impairment, the recommended starting dose during the first two weeks of treatment is 5 mg per day. Depending on the individual patient response, the dose may be increased to 10 mg per day. In severe hepatic impairment, caution and careful dose titration are required.
For patients with poor CYP2C19 activity, the recommended starting dose is 5 mg/day for the first two weeks of treatment. Depending on the individual patient response, the dose may be increased to 10 mg/day.
Discontinuation of treatment
Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with Escitalopram, the dose should be reduced gradually over 1–2 weeks to avoid possible withdrawal symptoms.
Children
Antidepressants should not be prescribed for children. Suicidal behavior (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) are more common in children and adolescents taking antidepressants than in those taking placebo. If a decision to prescribe antidepressants is made for clinical reasons, the patient should be closely monitored for the development of suicidal thoughts.
Overdose
Toxicity. Data on overdose with escitalopram are limited. Most cases have been caused by concomitant overdose with other drugs. In most cases, mild or asymptomatic symptoms of overdose have been observed. Reports of fatal outcomes of escitalopram overdose are exceptional, most of them involving concomitant overdose with other drugs. Doses in the range of 400-800 mg of escitalopram have not caused any severe symptoms.
Symptoms: Escitalopram overdose is manifested mainly by symptoms from the central nervous system (ranging from dizziness, tremor and agitation to rare cases of serotonin syndrome, convulsions and coma), the gastrointestinal system (nausea/vomiting), the cardiovascular system (arterial hypotension, tachycardia, QT prolongation, arrhythmia) and electrolyte imbalance (hypokalemia, hyponatremia).
Treatment. There is no specific antidote. Maintain a patent airway, adequate oxygenation, and support respiratory function. Gastric lavage and administer activated charcoal. Gastric lavage should be performed as soon as possible after oral administration. Continuous monitoring of cardiac and vital signs is required, along with symptomatic supportive treatment.
Adverse reactions
Adverse reactions are most often observed during the first or second week of treatment, and usually their frequency and intensity gradually decrease with continued treatment.
Adverse reactions common to all SSRIs and escitalopram, observed in placebo-controlled studies and in clinical practice, are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) or frequency unknown (cannot be estimated from the available data).
From the side of the blood and lymphatic system: frequency unknown - thrombocytopenia.
On the part of the immune system: rare - anaphylactic reactions.
On the part of the endocrine system: unknown - impaired secretion of antidiuretic hormone.
Metabolism and metabolism: frequent - decreased or increased appetite, weight gain; infrequent - decreased body weight; frequency unknown - hyponatremia, anorexia2.
Psychiatric: common: anxiety, restlessness, abnormal dreams, decreased libido in men and women, anorgasmia in women; uncommon: teeth grinding, agitation, nervousness, panic attacks, confusion; rare: aggression, depersonalization, hallucinations; frequency unknown: mania, suicidal thoughts, suicidal behavior1.
Nervous system disorders: very common - headache; common - insomnia, drowsiness, dizziness, paresthesia, tremor; uncommon - taste disturbance, sleep disturbance, syncope; rare - serotonin syndrome; frequency unknown - dyskinesia, movement disorders, convulsions, psychomotor restlessness/akathisia2.
On the part of the organs of vision: infrequent - pupil dilation, blurred vision.
On the part of the organs of hearing: infrequent - ringing in the ears.
Cardiovascular system: infrequently - tachycardia; rare - bradycardia; frequency unknown - prolongation of the QT interval on the electrocardiogram, ventricular arrhythmia, including torsade de pointes; frequency unknown - orthostatic hypotension.
Respiratory disorders: common - sinusitis, yawning; uncommon - epistaxis.
Gastrointestinal: very common - nausea; common - diarrhea, constipation, vomiting, dry mouth; uncommon - gastrointestinal bleeding (including rectal).
Hepatobiliary disorders: frequency unknown - hepatitis, changes in liver function tests.
Skin and subcutaneous tissue disorders: frequent - increased sweating; infrequent - rash, alopecia, urticaria, itching; frequency unknown - bruising, swelling.
Musculoskeletal disorders: common – arthralgia, myalgia.
Renal and urinary disorders: frequency unknown - urinary retention.
From the reproductive system and mammary glands: frequent - in men: ejaculation disorders, impotence; infrequent - in women: metrorrhagia, menorrhagia; frequency unknown - galactorrhea, in men - priapism.
General disorders: common - fatigue, pyrexia; uncommon - edema.
1 Cases of suicidal ideation and behavior have been reported during escitalopram treatment or shortly after its discontinuation.
Cases of QT prolongation have been reported during medical use, mainly in patients with pre-existing cardiac disease. In one study in healthy volunteers, the mean deviation from baseline in the QTc interval (Friederitz formula) was 4.3 ms at 10 mg/day and 10.7 ms at 30 mg/day.
Epidemiological studies, mainly in patients aged 50 years and over, have been reported to show an increased risk of bone fractures with the use of SSRIs, including escitalopram, and tricyclic antidepressants. The mechanism of this effect is unknown.
Withdrawal symptoms. Discontinuation of SSRI treatment (especially abrupt) usually leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhoea, palpitations, emotional lability, irritability and visual disturbances are the most common reactions. These symptoms are usually mild to moderate in severity and transient, but may be severe and/or prolonged in some patients. Therefore, gradual discontinuation of escitalopram treatment by dose reduction is recommended.
Expiration date
3 years.
Storage conditions
Store out of the reach of children, in the original packaging, at a temperature not exceeding 25 °C.
Packaging
10 tablets in a blister; 3 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
Pharma Start LLC, Ukraine.
Location of the manufacturer and its business address
Ukraine, 03124, Kyiv, Vaclav Havel Boulevard, 8.
