Pharmacological properties

Pharmacodynamics. to estsitalopra is antidepressant, selective serotonin reuptake inhibitor (siozs) that 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 or β-adrenergic receptors, histamine the h1st has very weak ability to contact a number of receptors, including serotoninovy 5-ht1a-, 5-ht2-receptors, dopamine d1 — and d2-receptors, α1-, α2-, m-holinoretseptory, benzodiazepine and opiate receptors.

Oppression of the return capture 5-HT serotonin are only the probable mechanism of action which can explain pharmacological and clinical effects of an estsitalopram.

Pharmacokinetics. Absorption almost full also does not depend on meal. The C _max in blood plasma is reached in 4 h after reception. The bioavailability of an estsitalopram is about 80%. The visible volume of distribution (Vd, β/F) after oral administration is from 12 to 26 l/kg.

Linking of an estsitalopram and its main metabolites with blood proteins of 80%.

Metabolism happens in a liver before formation of metabolites which demetilirutsya and didemetilirutsya. Both that and others are pharmacological active. Both metabolites, and initial connection are partially removed in the form of glucuronides. After repeated use the average concentration demetil- and didemetilmetabolit usually makes according to 28–31% and 5% of concentration of an estsitalopram. Biotransformation of an estsitalopram to a demetilirovanny metabolite happens to the help of CYP cytochrome 2C19. Perhaps insignificant participation in process of isoenzymes of CYP 3A4 and CYP 2D6. T _½ medicament makes ≈30 h. The clearance at oral administration is ≈0.6 l/min. At the main metabolites of T _½ is longer. Estsitalopram and his main metabolites are allocated with a liver (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 in ≈1 week. Average equilibrium concentration the 50th nmol/l (from 20 to 125 nmol/l) is reached at a daily dose of 10 mg. At patients of advanced age (65 years are more senior) to estsitalopra it is removed more slowly, than at persons of young age. System exposure (AUC) at elderly people is 50% higher, than at young healthy volunteers.

easy or moderate severity (Chayld ― I Drink classes A and B on classification) T _½ was twice longer than

At patients with an abnormal liver function, and exposure 60% higher, than at persons with normal function of a liver.

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At patients with a renal failure (clearance of creatinine of 10-53 ml/min.) at use of a racemic tsitalopram observed long T _½ and a little big exposure. Concentration of metabolites in blood plasma is not investigated, but can be raised.

At patients with weak metabolic function of CYP 2C19 noted twice higher concentration of an estsitalopram in blood plasma, than at patients with normal CYP function 2C19. Significant changes in exposure at reduced CYP function 2D6 were not noted.

Indication

Treatment of big depressive episodes, panic disorders with or without agoraphobia, social anxiety disorders (social phobia), generalized anxiety disorders, obsessivno-compulsive disorders (okras).

Use Safety of use of doses over 20 mg/days is not established to

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. to estsitalopra apply at adults in 1 times a day irrespective of meal.

Big depressive episode. Usually appoint 10 mg of 1 times a day. Depending on individual reaction of the patient the daily dose can be raised to 20 mg.

Antidepressive effect usually develops in 2–4 weeks. After disappearance of symptoms the treatment needs to be continued within 6 months for the purpose of fixing of effect.

Panic disorders with an agoraphobia or without. For the 1st week the initial dose of 5 mg/days is recommended then the dose can be raised to 10 mg/days. The dose can be raised further to 20 mg/days depending on individual reaction of the patient.

Maximum effect at treatment of panic disorders is reached by

in 3 months. The term of treatment is several months and depends on disease severity.

Social anxiety disorders (social phobia). Usually appoint 10 mg of 1 times a day. Reduction of expressiveness of symptoms, as a rule, occurs in 2–4 weeks of treatment. Depending on individual sensitivity of the patient further the dose can be lowered to 5 mg/days or to increase to maximum ― 20 mg/days

As the social anxiety disorder is a disease with a chronic course, it is recommended to continue treatment during 12 weeks for fixing of the reached effect. Long-term treatment for 6 months is appointed for the purpose of prevention of a recurrence, considering individual manifestations of a disease; regularly estimate efficiency of therapy.

Social anxiety disorder has accurately certain diagnostic terminology of a specific disease, it should not be confused with hypertrophied shyness. The pharmacotherapy is shown only for disorder which significantly affects professional and social activity of the person. The importance of such treatment in comparison with cognitive behavioural therapy was not investigated. The pharmacotherapy has to be a part of the general therapeutic strategy.

Generalized anxiety disorders. Usually appoint 10 mg of 1 times a day. Depending on individual sensitivity the dose can be raised a maximum to 20 mg/days

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

SURROUNDING. Usually appoint 10 mg of 1 times a day. Depending on individual sensitivity the dose can be raised to 20 mg/days. ROC — the chronic disease, treatment has to last the sufficient period for ensuring total disappearance of symptoms which can be several months or even more.

Patients of advanced age (65 years are more senior). The initial dose makes 5 mg/days. Depending on individual sensitivity and weight of a depression the daily dose can be raised to maximum — 10 mg/days

Renal failure. In a renal failure of easy and average degree there is no need for dose adjustment. With care it is necessary to use medicament at patients with a heavy renal failure (clearance of creatinine of 30 ml/min.).

Depression of function of a liver. At patients with a liver failure of easy or moderate degree the recommended initial dose for the first 2 weeks of treatment makes 5 mg/days. Depending on individual reaction of the patient the dose can be raised to 10 mg/days. In a heavy liver failure are necessary care in appointment and careful titration of a dose.

Reduced activity of cytochrome of an isoenzyme of CYP 2C19. For patients with reduced activity of an isoenzyme of CYP 2C19 the recommended initial dose for the first 2 weeks of treatment makes 5 mg/days. Depending on individual reaction of the patient the dose can be raised to 10 mg/days

treatment Termination. It is necessary to avoid the sharp termination of treatment. At the termination of treatment by Estsitam Asino the dose needs to be reduced gradually for 1–2 weeks in order to avoid emergence of reaction to cancellation of administration of drug. If after a dose decline or the termination of treatment there are undesirable reactions, it is possible to restore earlier appointed dose. Further the doctor can continue to reduce a dose, but more gradually.

Contraindication

Hypersensitivity to an estsitalopram or other components of drug, simultaneous use with Mao's inhibitors as there is a risk of development of the serotoninovy syndrome which is shown excitement, a tremor, a hyperthermia. prolongation of an interval q–t or congenital syndrome of long q–t. simultaneous use with medicines which extend q–t interval, and with Pimozidum.

Side effects

Side effects are noted by

for the 1st or 2nd week of treatment and usually their frequency and intensity gradually decrease at further treatment.

Side reactions characteristic of all medicaments of class SIOZS and estsitalopram which are noted in placebo - controlled researches and at medical use are listed to

on the systems of bodies and frequency: very often (≥1/10), it is frequent (≥1/100, 1/10), infrequently (≥1/1000, ≤1/100), is rare (≥1/10,000, ≤1/1000), frequency is unknown (it is impossible to establish).

from blood and lymphatic system: frequency is unknown ― thrombocytopenia.

from the immune system: seldom ― anaphylactic reactions.

from an endocrine system: frequency is unknown ― disturbance of secretion of antidiuretic hormone (ADG).

from metabolism and a metabolism: often ― decrease or strengthening of appetite, increase in body weight; infrequently ― degrowth of a body; frequency is unknown ― a hyponatremia, anorexia ² .

from mentality: often ― alarm, concern, unusual dreams, decrease in a libido at men and women, an anorgazmiya at women; infrequently ― bruxism, excitement, nervousness, panic attacks, confusion of consciousness; seldom ― aggression, depersonalization, hallucinations; frequency is unknown ― a mania, suicide thoughts, suicide behavior ¹ .

from nervous system: very often ― headache; often ― insomnia, drowsiness, dizziness, paresthesias, tremor; infrequently ― disturbance of taste, sleep disorder, loss of consciousness; seldom ― serotoninovy syndrome; frequency is unknown ― dyskinesia, motive disorders, spasms, psychomotor concern / akathisia ² .

from an organ of sight: infrequently ― mydriasis, turbidity of sight.

from an organ of hearing: infrequently ― a ring in ears.

from a cardiovascular system: infrequently ― tachycardia; seldom ― bradycardia; frequency is unknown ― prolongation of an interval of Q-T on the ECG, ventricular arrhythmia, including torsade de pointes; frequency is unknown ― orthostatic hypotension.

Respiratory disorders: often ― sinusitis, yawning; infrequently ― nasal bleeding.

from a GIT: very often ― nausea; often ― diarrhea, a constipation, vomiting, dryness in a mouth; infrequently ― gastrointestinal bleedings (including rectal).

from a liver and biliary tract: frequency is unknown ― hepatitis, changes of functional hepatic tests.

from skin and hypodermic cellulose: often ― the increased perspiration, infrequently ― rash, baldness, urticaria, an itching; frequency is unknown ― hematomas, hypostases.

Skeletal and muscular disturbances: often ― arthralgia, myalgia.

from kidneys and urinary tract: frequency is unknown ― an urination delay.

from a reproductive system and mammary glands: often ― at men of disorder of an ejaculation, impotence; infrequently ― at women a metrorrhagia, a menorrhagia; frequency is unknown ― a galactorrhoea, at men ― a priapism.

General disturbances: often ― fatigue, pyrexia; infrequently ― swelled.

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¹ About cases of suicide thoughts and behavior it was reported during treatment estsitalopramy or soon after its termination.

Such cases are known to

² for means of all class SIOZS.

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It was reported about cases of prolongation of an interval of Q-Ti of ventricular arrhythmia, including torsade de pointes which otmechalipreimushchestvenno at female patients with a hypopotassemia or previously existing lengthening of an interval of Q-T, or other heart diseases.

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It was reported that epidemiological researches, mainly at patients are aged more senior than 50 years, showed the increased risk of bone fractures at use of SIOZS, including estsitalopra, and tricyclic antidepressants. The mechanism of this phenomenon is unknown.

cancellation Symptoms. The termination of treatment of SIOZS (especially sudden) usually leads to cancellation symptoms. Dizziness, touch disorders (including paresthesias and feeling of electric shock), sleep disorders (including insomnia and bright dreams), excitement or alarm, nausea and/or vomiting, a tremor, confusion of consciousness, the increased sweating, a headache, diarrhea, tachycardia, emotional instability, irritability and disorders of vision are the most frequent reactions. Usually these symptoms are easy or average on weight and passing, however at some patients can be heavy and/or long. Thus, the gradual termination of treatment estsitalopramy is recommended at a dose decline.

Special instructions

features of use Given below concern therapeutic group siozs.

Paradoxical alarm. Some patients with panic disorders in an initiation of treatment of SIOZS can have an increase in expressiveness of alarm. Similar paradoxical reaction usually disappears for 2 weeks of treatment. To reduce the probability of emergence of anksiogenny effect, low initial doses are recommended.

Convulsive attacks. It is necessary to cancel medicament if at the patient the convulsive attack developed for the first time or if attacks become more frequent (patients with the established diagnosis have epilepsies). It is necessary to avoid use of SIOZS for patients with unstable epilepsy, and ― to provide to patients with controlled epilepsy careful observation.

Mania. SIOZS should 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. At patients with diabetes the treatment of SIOZS can change glycemic control (hypoglycemia or a hyperglycemia). Dosing of insulin and/or oral hypoglycemic medicament can demand correction.

Suicide, suicide thoughts or clinical deterioration. The depression is connected with risk of suicide thoughts, self-traumatizing and a suicide. This risk exists before achievement of steady remission. As improvement of a state can be not reached within the first weeks of treatment or more, it is necessary to watch carefully patients before improvement of their state. It is known that the risk of a suicide can increase at early stages of recovery.

Other states at which apply to estsitalopra can be also connected by

with risk of suicide behavior. Besides, such states can be comorbid with big depressive disorder. These cautions concern also treatment of patients with other mental disorders.

Patients with the anamnesis of suicide behavior even prior to treatment have the highest risk of suicide thoughts or suicide attempts and demand fixed observation during treatment. During the metaanalysis of researches with use of an estsitalopram the increased risk of suicide behavior among patients aged up to 25 years accepting antidepressants in comparison with those who accepted placebo was revealed. Fixed observation of patients with high risk is especially necessary in an initiation of treatment and at change of a dose.

Patients and persons who look after them should warn about need of observation concerning any aggravation of symptoms, suicide behavior or thoughts and unusual changes in behavior and also about need of the immediate address to the doctor in case of development of these symptoms.

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 probably ADG connected with disturbance of secretion, 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, presence of cirrhosis or simultaneous treatment by the medicaments causing a hyponatremia).

Hemorrhage. At reception of SIOZS the development of skin hemorrhages (ecchymoma and a purpura) is possible. It is necessary to apply with care SIOZS at the patients accepting at the same time the anticoagulants and medicines influencing function of thrombocytes (for example atypical antipsychotic means, fenotiazina, tricyclic antidepressants, acetylsalicylic acid and NPVP, Dipiridamolum and tiklopidin) and also at patients with tendency to bleedings.

EST (electroconvulsive therapy). Clinical experience of simultaneous use of SIOZS and EST is limited, therefore the care is recommended.

MAO Reversible 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. The care at simultaneous use of an estsitalopram with the medicaments having serotonergic effect is recommended such as sumatriptan or other triptanes, tramadol and tryptophane.

At the patients accepting SIOZS along with serotonergic medicaments the development of a serotoninovy syndrome is possible

in isolated cases. 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, SIOZS and serotonergic medicaments it is necessary to cancel and appoint symptomatic therapy urgently.

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

cancellation Symptoms. Cancellation symptoms at the end of treatment, especially sharp, are common. It is known that in researches at the treatment termination the side effects arose approximately at 25% of patients who were accepted to estsitalopra, and at 15% of the patients accepting placebo. The risk of a withdrawal can depend on several factors, including on duration and a dose, dose decline speed. Dizziness, touch disturbances (including paresthesias, feeling of electric shock), sleep disorders (including insomnia, bright dreams), excitement or alarm, nausea and/or vomiting, a tremor, confusion of consciousness, the increased sweating, a headache, diarrhea, tachycardia, emotional instability, irritability and disorders of vision are the most frequent reactions. Usually these symptoms are easy or average on weight, but at some patients can be heavy. They usually arise during the first several days after the treatment termination, but the patients who accidentally passed a dose had very rare messages about similar symptoms. As a rule, symptoms of cancellation pass during 2 weeks, however at some patients can last more (≥2–3 months). Thus, the gradual termination of treatment estsitalopramy by a dose decline within several weeks or months, depending on a condition of the patient is recommended.

Coronary artery disease. Because of restrictions of clinical experience the care at use of medicament for patients with a coronary artery disease is recommended.

Lengthening of an interval of Q-T. It is revealed that to estsitalopra causes dose-dependent lengthening of an interval of Q-T. It was reported about cases of lengthening of an interval of Q-T and ventricular arrhythmia, including torsade de pointes, mainly at patients is a female with a hypopotassemia or earlier existing lengthening of an interval of Q-T, or other heart diseases.

Is recommended to be applied with care at patients with the profound bradycardia and patients with recently postponed acute myocardial infarction or dekompensirovanny heart failure. Electrolytic disorders, such as hypopotassemia and hypomagnesiemia, increase risk of developing of malignant arrhythmias, and they should be adjusted prior to treatment estsitalopramy.

At patients with a stable course of a heart disease prior to treatment should revise the ECG. At emergence of symptoms of cardiac arrhythmia at treatment estsitalopramy it is necessary to stop therapy and to execute the ECG.

Glaucoma. To SIOZS, including estsitalopra, can influence the pupil size. This mydriatic effect can potentially narrow a corner of an anterior chamber of an eye that, in turn, can cause increase in intraocular pressure and development of closed-angle glaucoma, especially in the patients predisposed to it. Therefore estsitalopra should apply with care at patients with closed-angle glaucoma or glaucoma in the anamnesis.

Use during pregnancy and feeding by a breast. Clinical data on use of an estsitalopram at treatment of pregnant women are limited. Estsitam Asino it is not necessary to appoint pregnant. An exception are cases when after thorough examination of all shortcomings and advantages the need of prescribing of medicament was accurately proved. Careful inspection of newborns whose mothers accepted Estsitam Asino during pregnancy, especially in the III trimester is recommended. It is necessary to avoid sudden phase-out of medicament during pregnancy.

At newborns whose mothers accepted SIOZS/SIOZSN in late stages of pregnancy the emergence of the following symptoms is possible

: respiratory distress, cyanosis, apnoea, spasms, fluctuations of body temperature, suction difficulty, vomiting, hypoglycemia, AG or hypotension, hyperreflexia, tremor, nervous excitement, irritability, apathy, constant crying, drowsiness and sleep disorders. Such symptoms can develop owing to as serotonergic effects, well symptoms of a withdrawal. In most cases manifestations of complications arise at once or during 24 h after the delivery.

Epidemiological data showed that use of SIOZS for pregnant women can increase risk of steady pulmonary hypertensia at newborns (up to 5 cases on 1000 pregnant women). In the general population there are from 1 to 2 cases on 1000 pregnant women.

As to estsitalopra gets into breast milk, during treatment the feeding is not recommended by a breast.

Fertility. Some SIOZS can affect quality of sperm. Messages about use of some of SIOZS showed that influence on quality of sperm at the person is reversible. Influence on fertility at the person still was not observed.

Children. Antidepressants should not be applied to treatment of children. The suicide behavior (suicide attempts and suicide thoughts) and hostility (mainly aggression, oppositional behavior and anger) were more often observed in clinical trials at the children and teenagers accepting antidepressants in comparison 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 mood in the patient. Besides, there are no data on further safety for children and teenagers concerning growth, puberty, cognitive and behavioral development.

Ability to influence speed of response at control of vehicles and work with other mechanisms. In general to estsitalopra does not influence intellectual functions or psychomotor reactions, but it is necessary to consider that any psychoactive means can break skills or ability to objective thinking. It is necessary to warn patients about potential risk of impact on control of vehicles or work with other mechanisms.

Interaction

Pharmakodinamichesky interactions

Contraindicated combinations

MAO Non-selective irreversible inhibitors. It was reported about cases of serious reactions at the patients accepting SIOZS in a combination with the MAO non-selective irreversible inhibitor and at patients who only finished treatment of SIOZS and began intake of MAO inhibitors. In certain cases the serotoninovy syndrome developed. The combination of an estsitalopram with the MAO non-selective irreversible inhibitors is contraindicated. Treatment estsitalopramy should be begun in 14 days after cancellation of the MAO irreversible inhibitor. Treatment by the MAO non-selective irreversible inhibitors should be begun not earlier than in 7 days after the termination of reception of an estsitalopram.

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

Prolongition's

an interval of Q-T. Pharmacokinetic and pharmakodinamichesky researches of an estsitalopram in combination with other medicines which extend Q–T interval were not conducted. It is impossible to exclude cumulative effect of an estsitalopram and these medicines. Therefore simultaneous use of an estsitalopram with medicines which extend Q–T interval, such as antiarrhytmic medicaments of the class IA and III, anti-psychotics (derivative a fenotiazina, Pimozidum, a haloperidol), tricyclic antidepressants, some antimicrobial medicaments (for example sparfloksatsin, moxifloxacin, erythromycin IV, pentamidine, antimalarial means, in particular galofantrin), certain antihistaminic medicaments (astemizol, mizolastin), contraindicated.

Combination which apply with care

MAO Reversible selection inhibitor of A type (moklobemid). Because of risk of development of a serotoninovy syndrome a combination of an estsitalopram with MAO inhibitor of A type, such as moklobemid, it is contraindicated. If purpose of this combination is necessary, then in the beginning appoint the minimum recommended doses with careful clinical monitoring.

Antibiotic linezolid patients are not recommended to appoint

, to the accepting estsitalopra. If such combination is extremely necessary, treatment is begun with the minimum recommended dose with obligatory careful clinical monitoring.

Selegilin. The combination with selegiliny (the MAO irreversible inhibitor of B type) demands care in connection with risk of development of a serotoninovy syndrome. There is an experience of a safe combination of a selegilin in a dose up to 10 mg/days with a racemic tsitalopram.

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

Drugs reducing a convulsive threshold. SIOZS can reduce a convulsive threshold. The care at simultaneous use of the medicaments 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.

Lities, 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.

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

Anticoagulants. Change of effects of anticoagulants owing to simultaneous use with estsitalopramy is possible. At the patients accepting oral anticoagulants it is necessary to carry out monitoring of a system of fibrillation before use of an estsitalopram.

Simultaneous use of NPVP can enhance tendency to bleeding.

Alcohol. Estsitalopram does not enter with alcohol pharmakodinamichesky and pharmacokinetic interaction. However, as well as with other psychotropic medicines, the combination with alcohol is undesirable.

Pharmacokinetic interactions

Influence of other funds for pharmacokinetics of an estsitalopram

Metabolism of an estsitalopram is mainly mediated by CYP 2C19. Also CYP enzymes 3A4 and CYP 2D6, though to a lesser extent can be involved in metabolism. The partial catalyst of metabolism of the main metabolite S-DCT (demetilirovanny estsitalopram) the isoenzyme of CYP 2D6 is considered.

Combined use of an estsitalopram and omeprazolum of 30 mg of 1 times a day (CYP 2C19 of inhibitor) on average increases concentration of an estsitalopram in blood plasma by 50%.

Combined use of an estsitalopram and Cimetidinum (moderate general inhibitor of enzymes) of 400 mg 2 times a day approximately increase concentration of an estsitalopram in blood plasma by 70%.

Thus, at simultaneous use of an estsitalopram (for example omeprazolum, esomeprazole, fluvoksaminy, lansoprazoly, tiklopidiny) or with Cimetidinum it is necessary to be careful with CYP inhibitors 2C19. At simultaneous use with above-mentioned medicaments there can be a need for reduction of a dose of an estsitalopram.

Influence of an estsitalopram on pharmacokinetics of other means

Estsitalopram is inhibitor of CYP enzyme 2D6.

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recommends care at simultaneous use of an estsitalopram with medicines which are metabolized mainly by this enzyme and have the narrow therapeutic index, for example with flekainidy, propafenony and metoprololy (in heart failure), or with some means influencing central nervous system and which are metabolized mainly CYP 2D6, for example such antidepressants as desipramine, klomipramin and nortriptilin, such anti-psychotics as risperidon, thioridazine and a haloperidol. Dose adjustment is possible.

Combination with desipramine or metoprololy led

to double increase in level in blood plasma of these two means.

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recommends care at simultaneous use with medicines which are metabolized by CYP 2C19.

Overdose

Toxicity. data on overdose of an estsitalopram are limited. the majority of cases is caused by simultaneous overdose of other medicines. generally there were easy symptoms or the overdose proceeded asymptomatically. messages about lethal consequences of overdose of an estsitalopram are exclusive, most of them include simultaneous overdose of other medicines. reception of an estsitalopram within 400–800 mg did not cause any heavy symptoms.

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

Treatment. There is no specific antidote. It is necessary to provide passability of airways, adequate oxygenation and to support respiratory function. To carry out gastric lavage and to accept activated carbon. Gastric lavage should be carried out as soon as possible after administration of drug. Continuous monitoring of the vital functions together with the symptomatic supporting treatment is necessary.

monitoring of the ECG is recommended by

in case of overdose to patients with stagnant heart failure / bradyarrhythmia, to patients who combined take the medicaments extending Q–T interval or to patients with the changed metabolism, for example with a liver failure.

Storage conditions

In original packing at a temperature not above 25 °C.

ACIN-PIM-122016-005