Estsitam

General characteristics. Structure:

Active ingredient: estsitaloprama oxalate hydrogen respectively 10 mg and 20 mg;

Excipients: cellulose microcrystallic (type 101), cellulose microcrystallic (type 102), sodium of a kroskarmelloz, talc, magnesium stearate, silicon dioxide colloid anhydrous;

Mix for a film covering of Opadry white: gipromelloza, titanium dioxide (Е 171), polyethyleneglycol 4000.

Pharmacological properties:

Pharmacodynamics. Estsitam is antidepressant, selective serotonin reuptake inhibitor which causes clinical and pharmacological effects of drug. It has high affinity to the basic connecting element and an allosteric element of the conveyor of serotonin, adjacent with it, and does not possess absolutely or has very weak ability to contact a number of receptors, including serotoninovy 5-HT1A-, 5-HT2-receptors, dopamine D1-and D2 receptors, α1-, α2-, β-adrenergic receptors, histamine H1-, M-holinoretseptory, benzodiazepine and opiate receptors.

Pharmacokinetics. Absorption almost full also does not depend on meal. The maximum concentration in a blood plasma is reached in 4 h after reception. Bioavailability of an estsitalopram makes about 80%.
Linkng of an estsitalopram and its main metabolites with blood proteins is not lower than 80%.
Metabolism happens in a liver before formation of metabolites which demetilirutsya and didemetilirutsya. Both that and others are pharmacological active. Biotransformation of an estsitalopram to a demetilirovanny metabolite happens to the help of CYP 2C19 cytochrome. Perhaps insignificant participation in process of isoenzymes of CYP3A4 and CYP2D6. The elimination half-life (T1/2) of drug makes about 30 h. Cloral at oral administration makes about 0,6 l/min. At the main metabolites the elimination half-life is longer. Estsitalopram and his main metabolites are removed through a liver (a metabolic way) and kidneys. The most part of a dose is removed in the form of metabolites with urine. Kinetics of an estsitalopram linear. Equilibrium concentration is reached approximately in 1 week. At patients of advanced age (65 years are more senior) to estsitalopra it is removed more slowly, than at patients of young age.

Indications to use:

Treatment of big depressive episodes, panic frustration with or without agoraphobia, social alarming frustration (a social phobia), generalized alarming frustration, obsessivno-compulsive frustration.

Route of administration and doses:

Estsitalopram apply at adults in 1 times a day irrespective of meal.
Big depressive episode
Usually appoint 10 mg once a day. Depending on individual reaction of the patient the daily dose can be raised to 20 mg.
The antidepressive effect usually develops in 2-4 weeks. After disappearance of symptoms treatment needs to be continued within 6 months for the purpose of fixing of effect.
Panic frustration with an agoraphobia or without it
For the first week the initial dose of 5 mg a day then the dose can be raised to 10 mg a day is recommended. The dose can be raised further to 20 mg a day depending on individual reaction of the patient.

The maximum effect at treatment of panic frustration is reached in 3 months. The term of treatment makes several months and depends on disease severity.

Social alarming frustration (social phobia)

Usually appoint 10 mg once a day. Depending on individual sensitivity of the patient it is recommended to raise a dose to 20 mg a day.

Weakening of symptoms, as a rule, happens in 2-4 weeks of treatment. It is recommended to continue treatment for 3 months. Prolonged treatment for 6 months is appointed for the purpose of prevention of a recurrence, considering individual displays of a disease; regularly estimate efficiency of treatment.

Generalized alarming frustration
Usually appoint 10 mg once a day. Depending on individual sensitivity the dose can be raised a maximum to 20 mg a day.

It is recommended to continue treatment for 3 months. Long treatment for 6 months is appointed for the purpose of prevention of a recurrence, considering individual displays of a disease; efficiency of treatment is regularly estimated.

Obsessivno-kompulsivnye Frustration (OKF)
Usually appoint 10 mg of 1 times a day. Depending on individual sensitivity the dose can be increased to 20 mg a day. ROC - the chronic disease, treatment has to last the sufficient period for ensuring total disappearance of symptoms which can make several months or even more.

Patients of advanced age (65 years are more senior)
The initial dose has to make a half of the usual recommended dose. The recommended daily dose for elderly people makes 5 mg. Depending on individual sensitivity and weight of a depression the daily dose can be raised to maximum - 10 mg a day.

Renal failure
In case of existence of a renal failure of easy and average degree there are no restrictions. With care it is necessary to use drug at patients with a heavy renal failure (clearance of creatinine <30 ml/min.).

Liver depression of function 
The recommended initial dose for the first two weeks of treatment makes 5 mg a day. Depending on individual reaction of the patient the dose can be raised to 10 mg a day.

Reduced activity of cytochrome of an isoenzyme of CYP2C19
For patients with reduced activity of an isoenzyme of CYP2C19 the recommended initial dose for the first two weeks of treatment makes 5 mg a day. Depending on individual reaction of the patient the dose can be raised to 10 mg a day.

Treatment termination
At the termination of treatment by Estsitam the dose needs to be reduced gradually for 1-2 weeks in order to avoid emergence of reaction to cancellation of administration of drug.

Features of use:

Use during pregnancy or feeding by a breast.
Clinical data on use of an estsitalopram at treatment of pregnant women are limited. Estsitam it is not necessary to appoint pregnant. An exception are cases when after thorough examination of all shortcomings and advantages need of purpose of drug was accurately proved. Careful inspection of newborns whose mothers accepted Estsitam throughout the pregnancy period, especially in the third trimester is recommended. It is necessary to avoid sudden phase-out of drug during pregnancy.
At newborns whose mothers accepted SIOZS/SIOZSN in late stages of pregnancy emergence of the following symptoms is possible: respiratory distress, cyanosis, apnoea, spasms, fluctuations of body temperature, difficulty of suction, vomiting, hypoglycemia, arterial hypertension or hypotension, hyperreflexia, tremor, nervous excitement, irritability, apathy, constant crying, drowsiness and sleep disorders. Such symptoms can develop owing to as serotonergic effects, well withdrawal signs. In most cases manifestations of complications arise during 24 h after the delivery.

As to estsitalopra gets into breast milk, the women nursing are not recommended to appoint drug or it is necessary to cancel feeding of грудью.Дети.
Antidepressants should not be applied to treatment of children. The suicide behavior (suicide attempts and suicide thoughts) and hostility (preferential aggression, oppositional behavior and anger) were more often observed in clinical tests among the children and teenagers accepting antidepressants compared with those which accepted placebo. If for clinical reasons the decision on prescription of antidepressants after all is made, it is necessary to provide attentive observation of emergence of suicide moods in the patient.

Paradoxical alarm
At some patients with panic frustration in an initiation of treatment the selective serotonin reuptake inhibitors (SSRI) strengthening of alarm can be observed. Similar paradoxical reaction usually disappears for two weeks of treatment. To reduce probability of emergence of anksiogenny effect, low initial doses are recommended.

Convulsive attacks
It is necessary to cancel drug in case of development of convulsive attacks.

Mania
SIOZS has to be applied with care to treatment of patients with a mania/hypomania in the anamnesis. At emergence of a maniacal condition of SIOZS it is necessary to cancel.

Diabetes mellitus
At patients with a diabetes mellitus treatment of SIOZS can change glycemic control (a hypoglycemia or a hyperglycemia). Dosing of insulin and/or peroral hypoglycemic drug can demand correction.

Suicide
Suicide attempts are characteristic of persons in a condition of a depression, their threat can exist up to achievement of permanent remission as it is spontaneous, and owing to therapy. It is necessary to watch a condition of the patients accepting antidepressants, especially at the beginning of therapy, rather clinical deterioration and/or emergence of suicide thoughts and behavior carefully.
It concerns also treatment of patients with other mental disorders because of possible existence of the accompanying big depressive frustration.

Akathisia
Use of SIOZS/SIOZSN is connected with development of an akathisia - a state which is characterized by unpleasant wearisome feeling of concern and requirement to move and often is followed by inability to sit or stand on one place. Such state most possibly arises for the first several weeks of therapy. Increase in a dose can do much harm to patients who had such symptoms.

Hyponatremia
The hyponatremia which is possibly connected with disturbance of secretion of antidiuretic hormone (ADG) against the background of reception of SIOZS arises seldom and usually disappears at therapy cancellation. SIOZS needs to appoint with care to patients of risk group (advanced age, existence of cirrhosis or simultaneous treatment by the drugs causing a hyponatremia).

Hemorrhages
At reception of SIOZS development of hemorrhages (an ecchymoma and a purpura) is possible. It is necessary to appoint with care SIOZS sick with tendency to bleedings, and also the patients accepting the anticoagulants and drugs influencing a blood coagulation. EST (electroconvulsive therapy)
Clinical experience of simultaneous use of SIOZS and EST is limited, therefore care is recommended.

MAO reverse selection inhibitors of A type
It is not recommended to combine to estsitalopra and MAO inhibitors of A type because of risk of emergence of a serotoninovy syndrome.

Serotoninovy syndrome
At the patients accepting SIOZS along with serotonergic drugs development of a serotoninovy syndrome is possible in isolated cases. It is necessary to apply with care to estsitalopra along with the medicines possessing serotonergic action. The combination of such symptoms as agitation, a tremor, a myoclonus, a hyperthermia, can indicate development of a serotoninovy syndrome. If there was such situation that, SIOZS and serotonergic drugs it is necessary to cancel and appoint symptomatic therapy urgently.

St. John's Wort
Simultaneous use of SIOZS and the vegetable drugs containing a St. John's Wort can lead to increase in frequency of side reactions.

Ability to influence speed of response at control of motor transport or work with other mechanisms.
In general to estsitalopra does not influence intellectual functions or psychomotor reactions, but it is necessary to consider possible development of such side reactions from a nervous system as dizziness, drowsiness.

Side effects:

Side effects of Estsitam, as a rule, are passing and insignificant. They are observed for the first or second week of treatment and gradually disappear in process of recovery of the patient.
The side effects characteristic of all drugs of class SIOZS and estsitalopram which were observed in placebo - controlled researches and at a medical use are listed on systems of bodies and frequency:

very often (≥1/10), it is frequent (≥1/100, <1/10), infrequently (≥1/1000, ≤1/100), is rare (≥1/10000, ≤1/1000), frequency is unknown (it is impossible to establish).

Very often: nausea.
Often:
from the alimentary system - decrease or strengthening of appetite, diarrhea, a lock, vomiting, dryness in a mouth
from TsNS - alarm, concern, abnormal dreams, decrease in a libido, an anorgazmiya at women, sleeplessness, drowsiness, dizziness, paresthesia, a tremor
from respiratory system - sinusitis, yawning
from skin and hypodermic cellulose - sweating strengthening
from a musculoskeletal system - an arthralgia, a mialgiya
from reproductive system - frustration of an ejaculation at men, impotence
the general frustration - fatigue, a pyrexia
are found in researches - increase in body weight

Infrequently:
from cardiovascular system - tachycardia
from TsNS - a bruxism, excitement, irritability, the panic attacks, confusion of consciousness, disturbance of taste, a sleep disorder, a faint
from respiratory system - nasal bleeding
from the alimentary system - gastrointestinal bleedings (including rectal)
from skin and hypodermic cellulose - rash, baldness, an itch
from reproductive system - a metrorrhagia, a menorrhagia at women
from organs of sight - a mydriasis, sight opacification
from acoustic organs - a ring in ears
the general frustration - hypostasis
are found in researches - a body degrowth

Seldom:
from cardiovascular system - bradycardia
from TsNS - aggression, depersonalization, hallucinations, suicide attempts, a serotoninovy syndrome
from immune system - anaphylactic reactions

Frequency is unknown:
from cardiovascular system - orthostatic hypotension
from TsNS - a mania, dyskinesia, motive frustration, spasms
from the alimentary system - hepatitis
from kidneys and an urinary system - an urination delay
from blood and lymphatic system - thrombocytopenia
from endocrine system - disturbance of secretion of antidiuretic hormone
from reproductive system - a priapism, a galactorrhoea at men
from a metabolism - a hyponatremia
from skin and hypodermic cellulose - bruises, hypostases
are found in researches - abnormal indicators of function of a liver

There are messages on such side effects at use of drugs of class SIOZS as anorexia and an akathisia. Cases of prolongation of an interval of QT were observed preferential at patients with the existing heart disease, at the same time the causal relationship is not established.

Cancellation symptoms usually arise for the several first days after the sudden termination of treatment and pass in most cases for 2 weeks. In clinical trials symptoms of cancellation were observed approximately at 25% of the patients accepting to estsitalopra and at 15% of the patients accepting placebo. Dizziness, a headache, touch disturbances, sleep disorders, alarm, nausea and/or vomiting, a tremor, confusion of consciousness, the increased sweating, diarrhea, tachycardia, emotional lability, irritability and vision disorders were observed most often. The majority of these symptoms are insignificant and passing, however can have a heavy and/or long current at some patients. For the purpose of avoidance of symptoms of cancellation gradual phase-out of drug for 1-2 weeks is recommended.

Interaction with other medicines:

Contraindicated combinations.

MAO non-selective inhibitors. Estsitam it is not necessary to apply when patients accept non-selective irreversible inhibitors of a monoaminooxidase (MAO) and for two weeks after the termination of their reception. Treatment by MAO inhibitors needs to be begun not earlier than in 7 days after the termination of reception of Estsitam.

Pimozidum. Because of interaction of an estsitalopram with low doses of Pimozidum and strengthening of side effect of the last simultaneous use is contraindicated. Undesirable combinations.

Because of risk of development of a serotoninovy syndrome the combination of an estsitalopram with MAO inhibitor of A type moklobemidy is not recommended. If purpose of this combination is necessary, then in the beginning appoint the minimum recommended doses under careful medical observation.

Combinations which apply with care.

Selegilin. The combination with selegiliny (the MAO irreversible inhibitor of B type) demands care. There is an experience of a safe combination of a selegilin in a dose to 10 mg a day with a racemic tsitalopram.

Serotonergic drugs. Simultaneous use with serotonergic medicines (for example, with tramadoly, sumatriptany and other triptanes) can cause development of a serotoninovy syndrome.

The drugs reducing a convulsive threshold. SIOZS can reduce a convulsive threshold. Care at simultaneous use of the drugs causing decrease in a convulsive threshold, for example antidepressants is recommended (tricyclic, SIOZS), neuroleptics (fenotiazina, thioxanthenes, phenyl propyl ketones), a meflokhin, a bupropion and a tramadol.

Lithium, tryptophane. As cases of strengthening of action at combined use of SIOZS and lithium or tryptophane are registered, it is recommended to appoint at the same time with care these drugs.

Anticoagulants. Change of effects of anticoagulants owing to simultaneous use with estsitalopramy is possible. The patients accepting peroral anticoagulants need to carry out monitoring of system of a blood coagulation before use of an estsitalopram.

Alcohol. Estsitalopram does not enter with alcohol pharmakodinamichesky and pharmacokinetic interaction.

Joint purpose of an estsitalopram and omeprazol (inhibitor CYP2C19) as result on average for 50% increases concentration of an estsitalopram in a blood plasma.

Joint purpose of an estsitalopram and Cimetidinum as result, on average for 70% increases concentration of an estsitalopram in a blood plasma.

Thus, at simultaneous use of an estsitalopram inhibitors (for example omeprazoly, fluoxetine, fluvoksaminy, lansoprazoly, tiklopidiny) and with Cimetidinum it is necessary to be careful with CYP2C19, appointing upper limit doses of an estsitalopram. The dose decline of an estsitalopram can be necessary depending on clinical assessment.

Contraindications:

Hypersensitivity to an estsitalopram or to other components of drug, simultaneous use with MAO inhibitors or Pimozidum, the period of pregnancy and feeding by a breast, children's age.

Overdose:

Toxicity. Clinical data on overdose of an estsitalopram are limited. The majority of cases is caused by simultaneous overdose by other medicines. Easy symptoms or a bessimptomnost of overdose were generally observed. Messages on lethal effects of overdose of an estsitalopram are exclusive, most of them include simultaneous overdose by other medicines. Reception of a dose within 400-800 mg of an estsitalopram did not cause any heavy symptoms.

Symptoms. Signs of overdose of an estsitalopram are generally shown by symptoms from the central nervous system (from dizziness, a tremor and agitation prior to exceptional cases of a serotoninovy syndrome, spasms and a coma), a gastric path (nausea/vomiting), cardiovascular system (arterial hypotension, tachycardia, prolongation of an interval of QT, arrhythmia) and disturbances of electrolytic balance (a hypopotassemia, a hyponatremia).

Treatment. The specific antidote does not exist. It is necessary to support appropriate functioning of respiratory system, to provide adequate oxygenation, as soon as possible to impose gastric lavage. Use of absorbent carbon is possible. Continuous monitoring of the vital functions together with the symptomatic supporting treatment is necessary.

Storage conditions:

To store in the place, unavailable to children, in original packaging at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister; on 3 or 6 blisters in a cardboard box.