Estsitalopram-Teva of the tab. of p/o of 20 mg No. 28

Pharmacological properties

Pharmacodynamics. the estsitalopram-teva is antidepressant, selective serotonin reuptake inhibitor (siozs) (5-nt) with high affinity to primary binding site. it also contacts the allosteric site of the carrier of serotonin with affinity, smaller by 1000 times.

Estsitalopram has no

or has very weak ability to contact a set of receptors, including 5-HT ₁ - 5-HT ₂ - dopamine D ₁ — and D ₂ - receptors, α ₁ - α ₂ - β-adrenergic receptors, histamine H ₁ - muskarinovy, cholinergic, benzodiazepine and opiate receptors.

Suppression of the return capture 5-HT serotonin are only the probable mechanism of action which is capable to explain pharmacological and clinical effects of an estsitalopram.

Pharmacokinetics. Absorption almost full also does not depend on meal. The average time of achievement of the C _max is about 4 h. Absolute bioavailability of an estsitalopram — about 80%.

Imaginary volume of distribution (Vd, β/F) after oral administration is 12–26 l/kg of body weight. Linking of an estsitalopram and its main metabolites with proteins of blood plasma — less than 80%.

Estsitalopram is metabolized by

in a liver to demetilirovanny and didemetilirovanny metabolites. Both of them are biologically active. Nitrogen can be also oxidized in the form of a N-oxidic metabolite. Both metabolites, and initial connection are partially removed in the form of glucuronides. After repeated use the average concentration demetil- and didemetilmetabolit usually makes respectively 28–31 and 5% of concentration of an estsitalopram. Biotransformation of an estsitalopram in a demetilirovanny metabolite happens mainly to the help of CYP 2C19. Perhaps certain participation and CYP enzymes 3A4 and CYP 2D6.

T _½ after repeated use is made by about 30 h. Plasma clearance at oral administration — 0.6 l/min. At the main metabolites of an estsitalopram of T _½ longer. It is considered that and its main metabolites are allocated to estsitalopra with a liver (metabolic way) and kidneys. The most part is removed in the form of metabolites with urine.

Kinetics of an estsitalopram linear. Equilibrium concentration is reached approximately for 1 week. Average equilibrium concentration the 50th nmol/l (from 20 to 125 nmol/l) is reached at a daily dose of 10 mg.

Patients of advanced age (65 years are more senior). At elderly people to estsitalopra it is removed more slowly, than at younger patients. The amount of the substance which is in system blood circulation, AUC calculated by means of a pharmacokinetic indicator at elderly people is 50% above, than at young healthy volunteers.

Insufficiency of function of a liver. At patients with a moderate or slight liver failure (by criteria And yes In Chayld — I Drink) T _½ an estsitaloprama almost doubled, and exposure — is 60% higher, than at persons with normal function of a liver.

Weakening of function of kidneys. At patients with reduced function of kidneys (clearance of creatinine — 10–53 ml/min.) noted increase in T _½ a ratsematny tsitalopram and insignificant increase in exposure. Concentration of metabolites in blood plasma was not investigated, but it is possible to assume its increase.

At insufficient activity of an isoenzyme of CYP 2C19 noted double concentration in blood plasma in comparison with normal metabolism of an estsitalopram.

by

At insufficiency of CYP enzyme 2D6 of significant changes of exposure it is not revealed.

Indication

Big depressive episodes; panic disorders with/without agoraphobia; social anxiety disorders (social phobia); generalized anxiety disorder; obsessivno-compulsive disorders (okras).

Use

Safe use of a dose more than 20 mg were not shown to

by

.

Estsitalopram-Tev's

is appointed in 1 times a day irrespective of meal.

Big depressive episodes. Usually appoint 10 mg/days. Depending on individual reaction of the patient the dose can be raised to maximum — 20 mg/days. The antidepressant effect, as a rule, develops in 2–4 weeks after an initiation of treatment. After disappearance of symptoms of a depression it is necessary to continue treatment at least 6 more months for fixing of the reached effect.

Panic disorders with/without agoraphobia. In the 1st week of treatment the dose of 5 mg/days is recommended, then it is raised to 10 mg/days. Depending on individual reaction of the patient the dose can be raised further to maximum — 20 mg/days

Maximum therapeutic effect are reached by

in 3 months. Therapy lasts several months.

Social anxiety disorder. Usually appoint in a dose 10 mg of 1 times a day. Reduction of expressiveness of symptoms, as a rule, is reached during 2–4 weeks. Depending on individual reaction of the patient the dose can be lowered further to 5 mg/days or to raise to maximum — 20 mg/days. As the social anxiety disorder is a chronic disease, for fixing of the reached effect the minimum recommended duration of treatment is 12 weeks. For prevention of a recurrence of a disease it is possible to appoint medicament within 6 months depending on individual reaction of patients. It is necessary to check therapeutic advantage of treatment regularly.

Social anxiety disorder has accurately certain diagnostic terminology of a specific disease which should not be confused with hypertrophied shyness. The pharmacotherapy is shown only for disorder significantly affecting professional and social activity of the person. The efficiency 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 disorder. The recommended initial dose — 10 mg of 1 times a day. Depending on individual reaction of the patient the dose can be raised further to maximum — 20 mg/days. It is recommended to continue treatment within 3 months. Long prescribing of medicament (6 months) in a dose of 20 mg/days for the purpose of prevention of a recurrence is allowed. It is necessary to check therapeutic advantage of treatment regularly.

Obsessivno-kompulsivnoye Disorder (OKD). Usually appoint 10 mg of 1 times a day. Depending on individual sensitivity the dose can be raised to 20 mg/days. ROC — a chronic disease, treatment should continue 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). An initial dose — 5 mg/days. Depending on the answer of the specific patient the dose can be raised to 10 mg of 1 times a day. Appoint a minimal effective dose.

Estsitaloprama-Tev's Efficiency in a social anxiety disorder was not investigated among patients of advanced age.

Renal failure. With a moderate and weak renal failure of dose adjustment it is not required to patients. Patients with heavy deterioration in function of kidneys (clearance of creatinine of 30 ml/min.) should appoint medicament with care.

Abnormal liver function. To patients with a moderate and weak liver failure the recommended initial dose in the first 2 weeks makes 5 mg/days. Depending on individual reaction of the patient the dose can be raised further to 10 mg/days. In a serious liver failure are necessary care in appointment and careful titration of a dose.

Reduced activity of an isoenzyme of CYP 2C19. For patients with the known weak activity of an isoenzyme of CYP 2C19 the recommended initial dose of Estsitaloprama-Tev in the first 2 weeks makes 5 mg/days. Depending on individual reaction of the patient the dose can be raised further to 10 mg/days

cancellation Symptoms after the treatment termination. It is necessary to avoid the sharp termination of intake of this drug. The dose of an estsitalopram is gradually reduced with intervals of 1–2 weeks for prevention of reactions of cancellation. If during a gradual dose decline there are intolerance symptoms, it is possible to restore the previous dose. Further the doctor can continue a dose decline, but more gradually.

Contraindication

Hypersensitivity to active ingredient or any other component of drug.

Combined treatment by the MAO non-selective irreversible inhibitors in connection with risk of development of the serotoninovy syndrome which is shown excitement, a tremor, a hyperthermia.

Combined treatment using an estsitalopram and the MAO reversible inhibitors of A type (for example a moklobemida) or the MAO reversible non-selective inhibitors (linezolid) is also contraindicated to

in connection with risk of development of a serotoninovy syndrome. If it is known of existence at the patient of lengthening of an interval of Q-T or a congenital syndrome of lengthening of Q-T, it is contraindicated to use medicament together with medicines which extend Q–T interval. Simultaneous treatment by Pimozidum.

Side effects

Side reactions arise in the 1st and 2nd week of treatment more often and further become less intensive, and their frequency decreases at treatment continuation.

from blood and lymphatic system: thrombocytopenia.

from the immune system: anaphylactic reactions.

from an endocrine system: disturbance of secretion of antidiuretic hormone.

from food and a metabolism: decrease or strengthening of appetite, increase in body weight, degrowth of a body, hyponatremia, anorexia ¹ .

from mentality: alarm, fear, concern, a dysphoria, abnormal dreams, decrease in a libido at men and women, an anorgazmiya at women, gnashing by teeth during sleep, excitement, nervousness, panic attacks, confusion of consciousness, aggression, depersonalization, hallucinations, a mania, suicide thoughts, suicide behavior ² .

from nervous system: headache, insomnia, drowsiness, dizziness, paresthesias, tremor, disturbance of taste, sleep disorder, faints, serotoninovy syndrome, dyskinesia, motive disorders, spasms, psychomotor concern / akathisia ¹ .

from an organ of sight: mydriasis, misting of sight.

from an organ of hearing: a ring in ears.

from a cardiovascular system: tachycardia, bradycardia, ventricular arrhythmia, including arrhythmia of torsade de pointes, lengthening of an interval of Q-T on the ECG, orthostatic hypotension.

Respiratory disturbances: sinusitis, yawning, nasal bleeding.

from digestive system: nausea, diarrhea, a constipation, vomiting, dryness in a mouth, gastrointestinal bleedings (including rectal).

from a liver and biliary tract: hepatitis, changes of functional hepatic tests.

from skin and hypodermic cellulose: the strengthened sweating, skin rash, baldness, a small tortoiseshell, an itching, bruises, hypostases.

Disturbance from the musculoskeletal system: arthralgia, myalgia.

from kidneys and urinary tract: urination delay.

from a reproductive system and mammary glands: galactorrhoea; at men: ejaculation disorders, priapism, impotence; at women: metrorrhagia, menorrhagia.

General disturbances: fatigue, pyrexia, hypostasis.

to

¹ About these side reactions it was reported for a therapeutic class of medicaments of the selective serotonin reuptake inhibitors (SSRI) in general.

Cases of suicide thinking or behavior noted

² both at therapy estsitalopramy, and right after the treatment termination.

During the post-marketing period were noted by cases of lengthening of an interval of Q-T, in particular spindle-shaped arrhythmia, mainly at patients is a female with a hypopotassemia or previously existing lengthening of an interval Q–T or other heart diseases.

Klassspetsifichesky effects of SIOZS: in the epidemiological researches conducted generally with participation of patients at the age of ≥50 years the increased risk of bone fractures at the patients receiving SIOZS and tricyclic antidepressants is established. The mechanism of this phenomenon is unknown.

cancellation Symptoms at the sudden termination of reception. The termination of treatment of SIOZS (especially sudden) usually leads to development of symptoms of cancellation. Dizziness, touch disturbances (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 lability, irritability and disorders of vision which according to messages were the most frequent reactions. Usually these symptoms easy or moderate severity also are passing, however at some patients can be heavy and/or long. Therefore the gradual termination of reception of an estsitalopram by a dose decline for several weeks or several months depending on a condition of the patient is recommended.

Special instructions

Following special preventions and cautions extend to all therapeutic class siozs.

Paradoxical alarm. At some patients with panic disorder in an initiation of treatment antidepressants can note increase in expressiveness of symptoms of alarm. This paradoxical reaction usually disappears during the first 2 weeks of treatment. To reduce the probability of emergence of anksiogenny effect, it is recommended to appoint low initial doses of drug.

Convulsive attacks. Use of an estsitalopram needs to be stopped if at the patient the convulsive attack for the first time developed or 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 patients with controlled epilepsy need careful observation.

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

Diabetes. At patients with diabetes the treatment of SIOZS can influence glycemic control. The dose of insulin and/or oral hypoglycemic means can demand correction.

Suicide / suicide thoughts or clinical deterioration. The depression is connected with the increased risk of a suicide, suicide thoughts and drawings to itself harm (suicide actions). This risk remains before achievement of steady remission. As improvement of a state can not be reached within the first weeks of treatment or more, it is necessary to observe carefully the patients who are on therapy by antidepressants. It is known that the risk of a suicide can increase at early stages of recovery.

Other mental disorders in which apply Estsitalopram-Tev can be also connected by

with increase in risk of suicide actions. Besides, these states can be followed by big depressive disorder. The similar precaution needs to adhere also at treatment of other mental disorders because of a possibility of simultaneous development of big depressive disorder.

to

Because of high risk of suicide thoughts and actions during treatment needs careful observation of patients with suicide thoughts or behavior in the anamnesis or with the considerable level of suicide thinking prior to treatment. Medicamentous therapy has to be followed by careful observation of patients, especially with the increased risk, in particular, in an initiation of treatment and after change of a dose. Patients (and persons who look after them) need to be warned about need of control of manifestation of similar actions and the request for emergency aid at emergence of the corresponding symptoms.

Akathisia and psychomotor excitement. Use of SIOZS/SIOZS and noradrenaline is connected with development of an akathisia — the state which is characterized by unpleasant wearisome feeling of concern and need to move, often followed by inability to sit or stand on one place. Such situation can most possibly arise within the first several weeks of treatment. Increase in a dose can damage to patients at whom such symptoms developed.

Hyponatremia. During use of SIOZS it was reported about separate cases of a hyponatremia probably to the secretion of antidiuretic hormone (SIADH) caused by disturbances which usually disappeared after therapy cancellation. The extra care is necessary at treatment of patients from risk groups (advanced age, presence of cirrhosis or simultaneous use of medicines with giponatriyemichesky properties).

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

Electroconvulsive therapy (EST). Clinical experience of simultaneous use of SIOZS and carrying out EST is limited therefore it is recommended to be careful.

Reverse, MAO selection inhibitors of A type. To combine to estsitalopra and MAO inhibitors of A type contraindicated because of risk of emergence of a serotoninovy syndrome.

Serotoninovy syndrome. The care at simultaneous use of an estsitalopram with means of serotonergic action is necessary, such as sumatriptan or other triptanes, tramadol and tryptophane.

to

It was reported about development of a serotoninovy syndrome in isolated cases at the patients accepting SIOZS along with serotonergic medicines. Such symptoms as agitation, a tremor, a myoclonus and a hyperthermia can be signs of the beginning of development of this state. In this case it is necessary to stop immediately reception of an estsitalopram and to begin symptomatic treatment.

St. John's wort. Simultaneous use of SIOZS and the vegetable medicaments containing a St. John's wort (Hypericum perforatum) can increase the frequency of development of side effects.

Coronary artery disease. Because of limitation of clinical experience the care at treatment of patients with a coronary artery disease is necessary.

cancellation Symptoms. At the treatment termination (especially sudden) usually there are cancellation symptoms. During clinical trials the side effects connected with the treatment termination noted approximately at 25% of patients of group of an estsitalopram and at 15% of patients of group of placebo.

Risk of emergence of symptoms of cancellation depends on several factors, in particular on duration of therapy, a dose and gradualness of a dose decline. Dizziness, touch disturbances (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 noted as the most frequent reactions. Usually these symptoms are easy or moderate on weight and passing, however at some patients can be heavy and/or long. Thus, it is recommended to stop gradually use of an estsitalopram by a dose decline within several weeks or several months depending on a condition of the patient.

Lengthening of an interval of Q-T. It is established what to estsitalopra causes dose-dependent lengthening of an interval of Q-T. During the post-marketing period it was reported about cases of lengthening of an interval of Q-T, in particular to spindle-shaped arrhythmia, mainly at patients is a female with a hypopotassemia or earlier existing lengthening of an interval Q–T or other heart diseases.

Is recommended to be applied with care at patients with considerable bradycardia or recently postponed acute myocardial infarction or noncompensated heart failure.

Electrolytic disturbances, such as hypopotassemia and hypomagnesiemia, increase risk of developing of malignant arrhythmias, and they should be adjusted prior to treatment estsitalopramy.

At treatment of patients with a stable heart disease prior to treatment should revise the ECG.

If during treatment estsitalopramy symptoms of cardiac arrhythmia arise, it is necessary to stop treatment and to make the ECG.

during treatment estsitalopramy should not take alcoholic beverages.

Closed-angle glaucoma. To SIOZS, including estsitalopra, can influence the pupil size, causing a mydriasis. In turn, mydriasis can cause narrowing of a corner of an eye and, as a result, increase intraocular pressure and provoke development of closed-angle glaucoma, especially at 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 or feeding by a breast

Pregnancy. Data on use of an estsitalopram at pregnancy are limited. Estsitalopram is contraindicated to pregnant women, except for cases when after thorough examination of all shortcomings and advantages the need of prescribing of medicament is accurately proved. Careful inspection of newborns whose mothers accepted to estsitalopra during pregnancy, especially in the III trimester is recommended.

Use of medicament during pregnancy should not stop suddenly.

by

recorded such disturbances at newborns whose mothers accepted SIOZS/SIOZS and noradrenaline on pregnancy deadlines: respiratory distress syndrome, cyanosis, apnoea, spasms, instability of body temperature, difficulty of suction, vomiting, hypoglycemia, AG, arterial hypotension, hyper reflexes, tremor, nervous initiation, irritability, drowsiness, constant crying, slackness and difficulties of backfilling. These disturbances can be manifestation of serotonergic effects or a withdrawal. In most cases complications began at once or through short time (24 h) after the delivery.

to

It was reported that use of SIOZS for pregnant women can increase risk of steady pulmonary hypertensia at newborns.

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

Fertility. Data of researches on animals showed that some SIOZS can affect quality of sperm. Messages about use of some of SIOZS for people demonstrate that influence on quality of sperm is reversible. Influence on fertility of the person is still noted.

Children. Antidepressants are contraindicated for treatment of children. The suicide behavior (suicide attempts and thoughts) and hostility (mainly aggression, tendency to confrontation and anger) noted at the children and teenagers accepting antidepressants than at the accepting placebos more often. If the clinical situation nevertheless demands purpose of such treatment, the patient needs to be observed carefully for early detection of suicide symptoms.

Besides, do not have data on further safety for children and teenagers on growth, puberty and cognitive and behavioral development.

Ability to influence speed of response at control of vehicles or other mechanisms. Though Estsitalopram-Teva has insignificant or moderate impact on ability to run vehicles, but, as well as in case of use of other psychotropic drugs, patients should be warned about potential risk of negative impact on ability to run vehicles and to work with other mechanisms.

Interaction

Pharmakodinamichesky interactions.

Combination which purpose is contraindicated.

Lengthening of an interval of Q-T. Pharmacokinetic and pharmakodinamichesky researches of an estsitalopram with other medicines which extend Q–T interval were not conducted to combinations. 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 for in/in introductions, pentamidine, antimalarial means, in particular galofantrin), certain antihistaminic medicaments (astemizol, mizolastin), contraindicated.

MAO Non-selective inhibitors. It was reported about cases of serious reactions at the patients accepting SIOZS in combination with the MAO non-selective irreversible inhibitors and at patients who stopped accepting SIOZS recently and passed to therapy with the MAO similar inhibitors. Sometimes at patients the serotoninovy syndrome developed. The combined use of an estsitalopram with the MAO non-selective irreversible inhibitors is contraindicated. Treatment estsitalopramy can be begun not earlier than in 14 days after the last use of the MAO irreversible inhibitor. In turn, treatment by MAO inhibitors can be begun only in 7 days after the end of treatment estsitalopramy.

Antibiotic linezolid the patients receiving therapy estsitalopramy are not recommended to appoint

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

Simultaneous use of an estsitalopram with reversible selection MAO-A (moklobemidy) is not recommended to

because of risk of development of a serotoninovy syndrome. If such combination is extremely necessary, treatment is begun in the minimum recommended dose with obligatory careful clinical monitoring. Treatment estsitalopramy can be begun not earlier than in 1 days after the termination of intake of the MAO reversible inhibitor of a moklobemid.

care at the combined use of an estsitalopram is necessary for

Because of risk of development of a serotoninovy syndrome with selegiliny (the MAO irreversible inhibitor of V type). For simultaneous use with a racemic tsitalopram the doses of a seleginin up to 10 mg/days

Combination demanding care

Serotoninergichesky medicines are safe. Simultaneous use with serotonergic medicaments (for example sumatriptany, other triptanes, tramadoly, oxytriptane and tryptophane) can cause a serotoninovy syndrome.

Medicines reducing a threshold of convulsive readiness. SIOZS are capable to reduce a threshold of convulsive readiness. The care at co-administration of an estsitalopram with other medicaments which can reduce this threshold (for example antidepressants is necessary (tricyclic, SIOZS), neuroleptics (fenotiazina, thioxanthenes and phenyl propyl ketones), meflokhin, buproprion and tramadol).

Lities, tryptophane. As cases of strengthening of serotonergic effects at use of SIOZS in a combination with lithium or tryptophane are recorded, it is recommended to be careful at co-administration of an estsitalopram with these drugs. At the same time surely it is necessary to carry out regular monitoring of level of lithium and tryptophane.

St. John's wort. Simultaneous use of an estsitalopram and vegetable medicaments with the maintenance of a St. John's wort (Hypericum perforatum) can increase the frequency of development of side reactions. Therefore estsitalopra should not appoint at the same time and the medicaments containing a St. John's wort.

Anticoagulants and medicaments affecting blood clotting. The care at treatment of the patients in parallel accepting the anticoagulants, medicaments influencing function of thrombocytes, in particular NPVP, acetylsalicylic acid, Dipiridamolum, tiklopidin or other means is necessary (for example atypical anti-psychotics, fenotiazina, tricyclic depressants) which can increase risk of bleeding.

Ethanol. Estsitalopram-TEVa has no pharmakodinamichesky or pharmacokinetic interaction with ethanol, but, as well as in case of use of other psychotropic medicines, the concomitant use of an estsitalopram with the medicaments containing ethanol is not recommended.

Medicines causing a hypopotassemia/hypomagnesiemia. The care at simultaneous use of the medicines causing a hypopotassemia/hypomagnesiemia as it increases risk of malignant arrhythmias is necessary.

Influence of other medicines on pharmacokinetics of an estsitalopram. Metabolism of an estsitalopram happens, mainly, with the participation of CYP 2C19, but CYP 3A4 and CYP 2D6, though to a lesser extent are also 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 in day (CYP inhibitor 2C19) caused moderate increase (approximately for 50%) concentration of an estsitalopram in blood plasma.

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

Thus, it is necessary to appoint with care to estsitalopra along with inhibitors of CYP cytochrome 2C19 (for example omeprazolum, esomeprazole, fluvoksaminy, lansoprazoly, tiklopidiny) or Cimetidinum. At simultaneous use with the above-stated medicaments the monitoring of side effects can cause the necessity of a dose decline of an estsitalopram.

Influence of an estsitalopram on pharmacokinetics of other medicines. Estsitalopram is inhibitor of CYP enzyme 2D6. The care when assigning an estsitalopram along with medicaments which metabolism happens with the participation of this enzyme is necessary and also with the medicaments having the low therapeutic index, for example flekainidy, propafenony, metoprololy (which is applied in heart failure), or with the medicines operating on central nervous system and which are generally metabolized with the participation of CYP 2D6, for example antidepressants — desipramine, klomipraminy and nortriptiliny; antipsychotic medicaments — risperidony, thioridazine or a haloperidol. In these cases the dose adjustment can be required.

Simultaneous use with desipramine (main metabolite of Imipraminum) or metoprololy leads

to double increase in plasma levels of two CYP substrates 2D6. Estsitalopram causes weak oppression of CYP 2C19. Therefore the care at the combined use of medicines which metabolism happens with the participation of CYP 2C19 is recommended.

Overdose

Data on overdose of an estsitalopram are limited to

. in most cases symptoms were absent or were mild. at overdose of an estsitalopram about lethal cases it was reported seldom. in the majority of such cases noted the accompanying overdose of other drugs. doses of an estsitalopram of 400-800 mg did not cause development of heavy symptoms.

Symptoms about which it was reported at overdose of an estsitalopram in general touched central nervous system (from dizziness, a tremor, agitation prior to exceptional cases of a serotoninovy syndrome, spasms and a coma), a GIT (vomiting, nausea), a cardiovascular system (arterial hypotension, tachycardia, lengthening of an interval Q–T and arrhythmia) and also balance of electrolytes and liquid (hypopotassemia, a hyponatremia).

Treatment. There is no specific antidote. Support and ensuring passability of airways, adequate oxygenation and respiratory function. Gastric lavage which should be carried out as soon as possible after oral administration of drug, and use of activated carbon. Continuous monitoring of functions of a cardiovascular system and key indicators of a condition of an organism in combination with the general symptomatic supporting measures is recommended.

In a case an overdose