Элицея®

General characteristics. Structure:

Active ingredient: 6,39 mg, 12,78 mg, 25,56 mg of an estsitalopram of oxalate (that there correspond 5,0 mg, 10,0 mg and 20,0 mg) an estsitaloprama.

Excipients: lactoses monohydrate; кросповидон; K30 povidone; MKTs; starch prezhelatinizirovanny; magnesium stearate.

Cover: опадрай white 33G28707 (Opadray white 33G28707 consists of gipromelloza mix 6 Wednesday, titanium of dioxide, lactose of monohydrate, a macrogoal 3000 and triacetin).

Antidepressive means.

Pharmacological properties:

Pharmacodynamics. Estsitalopram – antidepressant, the selective serotonin reuptake inhibitor (SSRI), increases concentration of a neurotransmitter in a synaptic gap at the expense of inhibition of the return neyronalny serotonin reuptake, strengthens and prolongs effect of serotonin on postsynaptic receptors. Estsitalopram practically does not possess or has very weak affinity to a number of receptors, including serotoninovy: 5-HT1A, 5-HT2, dopamine: D1 and D2; alfa1 and alfa2 and to beta adrenoceptors, H1-histamine, m-holinoretseptoram, benzodiazepine and opioid receptors that causes absence or weak expressiveness of various anticholinergic, sedative, cardiovascular side effects. Estsitalopram also does not communicate or has very low affinity in relation to various ion channels, including Na+, K+, Cl-, Ca2+-channels.

Pharmakodinamichesky properties. Absorption. Absorption does not depend on meal. Time of achievement of the maximum concentration (TCmax), makes about 4 h after repeated use. Bioavailability – 80%.

Distribution. The seeming distribution volume (Vd, β/F) after intake makes, about, 12-26 l/kg. Communication of an estsitalopram and its main metabolites with proteins of a blood plasma is lower than 80%. The kinetics of an estsitalopram is linear. Equilibrium concentration (Css) is reached in 1 week, average Css - the 50th nmol/l (from 20 to 125 nmol/l) is reached at a daily dose of 10 mg.

Metabolism. It is metabolized in a liver to pharmacological active metabolites (demetilirovanny and didemetilirovanny). The main substance and metabolites are partially removed in the form of glucuronides. After repeated use average concentration of demetilirovanny and didemetilirovanny metabolites make 28-31% and less than 5%, respectively, of concentration of an estsitalopram. Metabolism of an estsitalopram and demetilirovanny metabolite proceeds with the dominating participation of the following isoenzymes of P450 cytochrome: CYP2C19, CYP3A4 and CYP2D6.

Removal. The elimination half-life (T1/2) after repeated use makes about 30 h.

The clearance at intake makes 0,6 l/min from which 7% - renal. At the main metabolites of T1/2 is much higher. Estsitalopram and his main metabolites are removed by a liver and the most part - kidneys, is partially removed in the form of glucuronides.

T1/2 and AUC increases at elderly patients.

Special groups of patients. Advanced age (65 years are more senior). At elderly patients to estsitalopra it is removed more slowly, than at young patients. The quantity of the estsitalopram which is in a system blood-groove (AUC - the area under a curve "concentration time") at elderly patients is 50% more, than at young people.

Abnormal liver functions. At patients with a liver failure of a class A and B on classification of Chayld-Pyyu of T1/2 increases twice.

Polymorphism (at persons with low activity of an isoenzyme of CYP2C19 or CYP2D6):

at persons with low activity of an isoenzyme of CYP2C19 concentration of an estsitalopram can be twice higher, than at persons with high activity of this isoenzyme. Considerable changes of concentration of an estsitalopram at weak activity of an isoenzyme of CYP2D6 are not noted.

Renal failures. For a racemic tsitalopram bigger T1/2 at patients with reduced function of kidneys (KK of 10-53 ml/min.) is noted.

Indications to use:

Depression, panic frustration (including with an agoraphobia).

Route of administration and doses:

Inside, 1 time a day, irrespective of meal.

Depressive episodes. The recommended dose - 10 mg a day.

Depending on individual reaction of the patient the dose can be increased to maximum - 20 mg a day.

The antidepressive effect develops in 2-4 weeks after an initiation of treatment. After disappearance of symptoms of a depression it is necessary to continue therapy not less than 6 months for fixing of the gained effect.

For the therapy termination estsitalopramy it is necessary to reduce gradually a dose within 1-2 weeks for decrease in risk of development of a syndrome of "cancellation".

Panic frustration (including with an agoraphobia). On 5 mg/days within the first week, then on 10-20 mg/days.

The maximum daily dose - 20 mg.

The maximum therapeutic effect is reached approximately in 3 months after an initiation of treatment.

Elderly patients (65 years are more senior). The dose - 5 mg a day, the maximum daily dose of-10 mg a day is recommended.

Renal failures. At easy or moderate degree of a renal failure (the clearance of creatinine (CC) more than 30 ml/min.) dose adjustment is not required;

At heavy degree of a renal failure (KK less than 30 ml/min.) – drug should appoint with care.

Abnormal liver function. At an abnormal liver function an initial dose - 5 mg a day within 2 weeks. Depending on individual reaction of the patient the dose can be increased to 10 mg a day;

At heavy abnormal liver functions slower titration of doses is recommended.

Reduced activity of an isoenzyme of CYP2C19. The recommended initial dose within the first 2 weeks - 5 mg a day, depending on individual reaction of the patient a dose can be increased to 10 mg a day.

Features of use:

It is necessary to stop use of the drug Elitseya® in case of development of convulsive frustration, epileptic seizures or their increase at pharmacological uncontrollable epilepsy.

At development of a maniacal state the drug Elitseya® has to be cancelled.

Estsitalopram can increase concentration of glucose in blood at a diabetes mellitus that can demand correction of doses of peroral hypoglycemic drugs and/or insulin.

The hyponatremia connected with decrease in secretion of adrenocorticotropic hormone (ADG) against the background of use of the drug Elitseya® arises seldom (more often at the elderly people, patients with cirrhosis or who are constantly accepting the drugs capable to cause a hyponatremia) and usually disappears at drug withdrawal.

At development of a serotoninovy syndrome drug has to be the symptomatic treatment is immediately cancelled and is appointed.

With care estsitalopra should apply at patients with instructions in the anamnesis on a mania/hypomania. At development of a maniacal state estsitalopra need to cancel.

The Malignant Antipsychotic Syndrome (MAS) – the rare, potentially dangerous state connected using antidepressants including an estsitaloprama. ZNS symptoms: fervescence (hyper pyrexia), muscular rigidity, change of the mental status and instability of the autonomic nervous system (arrhythmia, fluctuations of the ABP, tachycardia, profuse sweating, disturbance of a heart rhythm). At identification of ZNS it is necessary to stop drug Elitseya® use immediately.

Within the first two weeks development of an akathisia / psychomotor excitement is possible (subjectively unpleasant or irritating concern and need of the movement, is frequent in combination with impossibility quietly to sit or stand).

At use of the drug Elitseya® development of skin hemorrhages (ecchymomas and purpuras) is possible. It is necessary to apply with care to estsitalopra at the patients with tendency to bleedings and also accepting the indirect anticoagulants and other drugs influencing coagulability of blood.

Simultaneous use of an estsiatalopram and ethanol is not recommended.

Clinical experience of use of electroconvulsive therapy (EST) and estsitalopram is limited therefore it is recommended to be careful.

Experience of use of an estsitalopram for patients with an ischemic heart disease therefore the drug Elitseya® is recommended to be used with care at this group of patients is limited.

At bystry cancellation of therapy estsitalopramy often there is a syndrome of "cancellation": dizziness, touch disturbances (including paresthesias), sleep disorders (sleeplessness, unusual dreams), psychomotor arousing, alarm, nausea and/or vomiting, tremor, confusion of consciousness, perspiration, headache, diarrhea, heart consciousness, emotional lability and vision disorders. Expressiveness of these reactions usually easy or moderate and duration is limited. In this regard, the drug Elitseya® is recommended to be cancelled gradually, reducing doses within several weeks or months.

At children, teenagers and young people (24 years are younger) with a depression, other mental disturbances antidepressants, in comparison with placebo, increase risk of emergence of suicide thoughts and suicide behavior. Therefore, at use of an estsitalopram or any other antidepressants for children, teenagers and young people (24 years are younger) it is necessary to correlate risk of a suicide and advantage of their use. In short-term researches at people 24 years are more senior the risk of a suicide did not increase, and at people 65 years are more senior decreased a little. Any depressive frustration in itself increases risk of a suicide. Therefore, during treatment by antidepressants for all patients observation for the purpose of early identification of disturbances or changes of behavior, and also suicide bents has to be established.

The drug Elitseya® is not used at pregnancy (safety is not established).

Because to estsitalopra cosecretes in breast milk, use of drug during breastfeeding is not recommended. In case of need uses of the drug Elitseya® in the period of a lactation, breastfeeding it is necessary to stop.

 During treatment it is necessary to abstain from control of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions in connection with a possibility of development of dizziness, hallucinations, confusion of consciousness, depersonalization, etc. side effects.

Side effects:

Classification of frequency of development of side effects (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from> 1/1000 to <1/100

seldom from> 1/10000 to <1/1000

very seldom from <1/10000, including separate messages.

From cardiovascular system: infrequently – tachycardia; seldom – bradycardia; very seldom – orthostatic hypotension;

From system of a hemopoiesis: very seldom – thrombocytopenia;

From a nervous system: often – sleeplessness, drowsiness, dizziness, paresthesias, a tremor, alarm, concern, dreadful dreams; infrequently – disturbances of taste, a sleep disorder, a syncope, a gnash teeth, psychomotor excitement, an akathisia, an acrimony, panic frustration, confusion of consciousness; seldom – a serotoninovy syndrome (agitation, a tremor, a myoclonus, a hyperthermia), aggression, depersonalization, hallucinations, suicide thoughts and behavior; very seldom – dyskinesia, convulsive and maniacal frustration;

From a respiratory organs: often – sinusitis, yawning; infrequently – nasal bleedings;

From the alimentary system: very often – nausea; often – increase or a loss of appetite, diarrhea, a lock, vomiting, dryness of a mucous membrane of an oral cavity; infrequently – gastrointestinal bleedings (including rectal); very seldom – hepatitis;

From urinogenital system: often – disturbances of an ejaculation, impotence, decrease in a libido, an anorgazmiya (at women); seldom – a metrorrhagia, a menorrhagia; very seldom – an ischuria, a priapism, a galactorrhoea;

From sense bodys: infrequently – a mydriasis, visual disturbances, a sonitus;

From integuments: often – the increased perspiration, an alopecia; very seldom – ecchymomas;

From a musculoskeletal system: often – an arthralgia, a mialgiya;

From endocrine system: very seldom – inadequate secretion of antidiuretic hormone (ADG), a galactorrhoea;

Allergic reactions: often – urticaria, skin rash, a skin itch; seldom – anaphylactic reactions, it is very rare – a Quincke's disease (Quincke's edema);

Others: often – weakness, fervescence; infrequently – hypostases;

Laboratory indicators: often – increase in body weight; infrequently – decrease in body weight; very seldom – a hyponatremia, change of laboratory indicators of function of a liver.

At sharp drug withdrawal development of a syndrome of "cancellation" is possible.

Interaction with other medicines:

Simultaneous use with MAO-A inhibitors is contraindicated (risk of development of a serotoninovy syndrome).

At simultaneous use (трамадол, суматриптан, etc. triptanes) it is necessary to be careful with serotonergic medicines (risk of development of a serotoninovy syndrome). Doses of a selegilin to 10 mg a day were safely applied with a racemic tsitalopram.

Contraindicated simultaneous use of an estsitalopram and Pimozidum.

Simultaneous use with the medicines reducing a threshold of convulsive readiness (tricyclic antidepressants, antipsychotic means – derivatives of a fenotiazin, thioxanthene, phenyl propyl ketone; мефлохин, бупропион and трамадол) increases risk of development of spasms.

Estsitalopram strengthens effect of drugs of lithium, tryptophane.

Increases toxicity of drugs of a St. John's Wort of made a hole (Hypericum perforatum).

At simultaneous use of an estsitalopram with the indirect anticoagulants and drugs influencing aggregation of thrombocytes (atypical neuroleptics and typical antipsychotic means - derivatives of a fenotiazin, the majority of tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs (NPVP), тиклопидин and дипиридамиол) it is necessary to control indicators of coagulability of blood at the beginning of therapy and at its termination (risk of development of bleeding).

Simultaneous use of an estsitalopram and ethanol is not recommended.

Pharmacokinetic interaction. With care estsitalopra should apply along with CYP2C19 isoenzyme inhibitors (for example, омепразол, esomeprazole, флувоксамин, лансопразол, тиклопидин) or Cimetidinum since concentration of an estsitalopram in a blood plasma in this connection, perhaps, the dose decline of an estsitalopram will be required increases.

It is necessary to be careful at the simultaneous use of an estsitalopram and medicines which are metabolized an isoenzyme of CYP2C19 and having a small therapeutic index, for example, флекаинид, пропафенон, метопролол (at heart failure) or the drugs which are generally metabolized an isoenzyme of CYP2C19 and operating on the central nervous system (CNS), for example antidepressants (desipramine, a klomiprami, нортриптилин) or neuroleptics (рисперидон, thioridazine, a haloperidol). In these cases dose adjustment of these drugs can be required.

Simultaneous use with metoprololy or desipramine can lead to double increase in concentration of two last drugs.

Contraindications:

hypersensitivity to an estsitalopram and other components of drug;

simultaneous use with monoamine oxidase inhibitors (MAO);

age up to 18 years (efficiency and safety are not studied);

pregnancy and period of breastfeeding;

simultaneous use with Pimozidum;

galactosemia, deficit of lactase, syndrome of glyukozo-galaktozny malabsorption.

With care appoint. Pharmacological uncontrollable epilepsy, a mania/hypomania in the anamnesis, a diabetes mellitus, a depression with suicide attempts, advanced age, cirrhosis, a chronic renal failure (the clearance of creatinine (CC) less than 30 ml/min.), the coronary heart disease (CHD), tendency to bleedings; simultaneous use of the drugs capable to cause a hyponatremia, reducing a threshold of convulsive readiness, with the anticoagulants or drugs influencing aggregation of thrombocytes with the alcohol, with lithium, a St. John's Wort which is made a hole with tryptophane, medicines which are metabolized with participation of system of an isoenzyme of CYP2C19; at simultaneous use of electroconvulsive therapy (EST), age of 18-24 years (in connection with risk of development of suicide behavior).

Overdose:

Symptoms: dizziness, a tremor, agitation, drowsiness, a serotoninovy syndrome, spasms, oppression of awareness of varying severity (especially in a combination with the alcohol and/or other means oppressing the TsNS function), nausea, vomiting, a lowering of arterial pressure, tachycardia, changes on an ECG (change of a segment of ST, T tooth, expansion of the QRS complex, increase in an interval of QT), arrhythmias, respiratory depression, a metabolic acidosis, рабдомиолиз, a hypopotassemia, a hyponatremia.

Treatment: symptomatic and supporting: gastric lavage, reception of absorbent carbon, ensuring passability of respiratory tracts, adequate oxygenation, control of functions of cardiovascular and respiratory systems. The specific antidote does not exist.

Storage conditions:

At a temperature not higher than 30 degrees With, in original packaging. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 7 tablets in a blister strip packaging from the combined material OPA/Al/PVC (polyamide / an aluminum foil / polyvinylchloride) and aluminum foil. 4 blister strip packagings together with the application instruction place in a pack from a cardboard.