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Instructions

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Instruction for use: Zylaksera

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Dosage form: tablets

Active substance: Aripiprazole *

ATX

N05AX12 Aripiprazole

Pharmacological group:

Neuroleptics

The nosological classification (ICD-10)

F20 Schizophrenia: Schizophrenic conditions; Exacerbation of schizophrenia; Schizophrenia; Chronic schizophrenia; Dementia praecox; Bleuler's disease; Psychotic discordant; Dementia early; The febrile form of schizophrenia; Chronic schizophrenic disorder; Psychosis of the schizophrenic type; Acute form of schizophrenia; Acute schizophrenic disorder; Cerebral Organic Insufficiency in Schizophrenia; Acute attack of schizophrenia; Schizophrenic psychosis; Acute schizophrenia; Sluggish schizophrenia; Sluggish schizophrenia with apathoabulic disorders; Acute stage of schizophrenia with excitation

F30 Manic episode: Manic-depressive disorder; Manic agitation; Manic state; Manic conditions; A manic condition; Manic syndrome; Acute manic syndrome

F31.1 Bipolar affective disorder, current episode of mania without psychotic symptoms: Mania in bipolar disorders

F31.2 Bipolar affective disorder, current episode of mania with psychotic symptoms: Manic episode of bipolar disorder; Mania in bipolar disorders

F32 Depressive episode: Adynamic subdepression; Astheno-adynamic subdepressive states; Asthenodepressive disorder; Astheno-depressive disorder; Asthenodepressive state; Astheno-depressive state; Major Depressive Disorder; Vyaloapatichesky depression with retardation; Double depression; Depressive pseudodement; Depressive illness; Depressive mood disorder; Depressive disorder; Depressive mood disorder; Depressive state; Depressive disorders; Depressive syndrome; Depressive syndrome larviated; Depressive syndrome with psychoses; Depressed masks; Depression; Depression Depletion; Depression with the phenomena of inhibition within the framework of cyclothymia; Depression is smiling; Involutional depression; Involutionary melancholy; Involutional depression; Manic-depressive disorder; Masked Depression; Melancholic Attack; Neurotic depression; Neurotic depression; Shallow Depression; Organic depression; Organic depressive syndrome; Simple depression; Simple melancholic syndrome; Psychogenic depression; Reactive depression; Reactive depression with moderate psychopathological symptoms; Reactive depressive states; Reactive depression; Recurrent depression; Seasonal depressive syndrome; Severostatic depression; Senile Depression; Senile Depression; Symptomatic Depression; Somatogenic depression; Cyclotymic depression; Exogenous Depression; Endogenous depression; Endogenous Depressive Conditions; Endogenous Depression; Endogenous depressive syndrome

F33 Recurrent depressive disorder: Major depressive disorder; Secondary depression; Double depression; Depressive pseudodement; Depressive mood disorder; Depressive disorder; Depressive mood disorder; Depressive state; Depressive syndrome; Depressed masks; Depression; Depression is smiling; Involutional depression; Involutional depression; Masked Depression; Melancholic Attack; Reactive depression; Reactive depression with moderate psychopathological symptoms; Reactive depressive states; Exogenous Depression; Endogenous depression; Endogenous Depressive Conditions; Endogenous Depression; Endogenous depressive syndrome

Composition

Tablets 1 table.

active substance:

aripiprazole fumarate semi-finished granule 148.5 / 222.75 / 445.5 mg

active substance of semifinished products-granules:

aripiprazole fumarate 11.3 / 16.95 / 33.90 mg

corresponds to aripiprazole 10/15/30 mg

auxiliary substances of semi-finished products-granules: lactose monohydrate; starch

HT1a-serotonin receptors and antagonistic activity against 5-HT2a-serotonin receptors.

Aripiprazole has a high affinity for in vitro D2 and D3 dopamine receptors, 5-HT1a and 5-HT2a-serotonin receptors and moderate affinity for D4-dopamine, 5-HT2c and 5-HT7 serotonin, and alpha 1-adrenergic receptors and H1-histamine receptors. Aripiprazole is also characterized by moderate affinity for the sites of serotonin reuptake and lack of affinity for muscarinic cholinergic receptors. Aripiprazole in animal experiments showed antagonism with respect to dopaminergic hyperactivity and agonism with respect to dopaminergic hypoactivity. Some clinical effects of aripiprazole can be explained by interaction with other receptors, in addition to dopamine and serotonin.

The use of aripiprazole orally at doses of 0.5 to 30 mg once a day in healthy volunteers for 2 weeks results in a dose-dependent decrease in the binding of 11C-raclopride, D2 / D3 ligand - dopamine receptors, with a caudate nucleus and a fence (according to the positron- emission tomography).

Pharmacokinetics

The activity of Zylaksera ® is due to the presence of aripiprazole. The average T1 / 2 aripiprazole is about 75 h. Css is reached after 14 days. Cumulation of aripiprazole with multiple admission is predictable. The pharmacokinetics of aripiprazole in the equilibrium state are proportional to the dose. There were no daily fluctuations in the distribution of aripiprazole and its metabolite, dehydroaripiprazole. It has been established that the main metabolite of the drug in human blood plasma, dehydroaripiprazole, has the same affinity for D2-dopamine receptors as aripiprazole.

Suction. Aripiprazole is rapidly absorbed after oral administration of Zylaksera ® tablets, while Cmax of aripiprazole in blood plasma is reached after 3-5 hours.

The bioavailability of the tablets of the preparation Zylaksera ® when taken orally is 87%. Eating food does not affect the bioavailability of aripiprazole.

Distribution. Aripiprazole is well distributed in tissues, with an apparent Vd of 4.9 l / kg, indicating an intensive extravascular distribution. At a therapeutic concentration of more than 99%, aripiprazole binds to blood serum proteins, mainly with albumin.

Metabolism. Aripiprazole undergoes pre-systemic metabolism only to a minimal extent. Aripiprazole is metabolized in the liver in three ways: by dehydrogenation, hydroxylation and N-dealkylation. According to the in vitro study, the dehydrogenation and hydroxylation of aripiprazole occurs under the action of the isoenzymes CYP3A4 and CYP2D6, and the N-dealkylation is catalyzed by the CYP3A4 isoenzyme.

Aripiprazole is the main component of the drug in the blood plasma. At equilibrium, the AUC of dehydroaripiprazole, the active metabolite, is approximately 40% of aripiprazole AUC in the blood plasma.

Excretion. The mean T1 / 2 aripiprazole is about 75 hours in patients with high isozyme activity CYP2D6 and 146 hours in patients with low activity. After a single oral administration of labeled [14C] aripiprazole, approximately 27% and 60% of radioactivity is determined in urine and feces, respectively. Less than 1% of unchanged aripiprazole is determined in urine and approximately 18% of the dose taken is unchanged through the intestines with bile. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to excretion by the liver.

Special patient groups

Patients of the older age group. Age differences in the parameters of aripiprazole pharmacokinetics in adult patients with schizophrenia, as well as in healthy volunteers, have not been revealed.

Gender features. The sex differences in the parameters of aripiprazole pharmacokinetics in adult patients with schizophrenia, as well as in healthy volunteers, were not detected.

Race affiliation. Clinically significant differences in the pharmacokinetics of aripiprazole, depending on race, were not observed.

Smoking. Smoking does not affect the pharmacokinetics of aripiprazole.

Impaired renal function. Parameters of pharmacokinetics of aripiprazole and dehydroaripiprazole in patients with severe kidney diseases do not differ from those of healthy volunteers.

Violation of the function of the liver. After a single administration of aripiprazole by patients with varying degrees of severity of liver cirrhosis, there was no significant effect of liver dysfunction on the pharmacokinetics of aripiprazole and dehydroaripiprazole. However, only 3 patients with decompensated liver cirrhosis (class C according to the Child-Pugh classification) participated in the study, and it is therefore impossible to draw definitive conclusions about liver metabolic activity in patients with decompensated liver cirrhosis.

Indication for the Zylaksera

schizophrenia: acute attacks and maintenance therapy;

bipolar disorder type I: manic episodes and maintenance therapy to prevent relapse in patients with type I bipolar disorder who have recently undergone a manic or mixed episode;

addition to antidepressant therapy for major depressive disorder.

Contraindications

hypersensitivity to aripiprazole or other components of the drug;

deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome (because the composition contains lactose);

the period of breastfeeding;

age to 18 years (efficacy and safety not established).

With caution: cardiovascular disease (coronary heart disease or a previous myocardial infarction, chronic heart failure or conduction disorders); cerebrovascular diseases; conditions predisposing to the development of arterial hypotension (dehydration, hypovolemia, use of antihypertensive drugs) in connection with the possibility of development of orthostatic hypotension; convulsive seizures or diseases in which convulsions are possible, an increased risk of hyperthermia (for example, intense physical exertion, overheating, use of m-holinoblockers, dehydration, since antipsychotics are able to disrupt thermoregulation); patients with an increased risk of aspiration pneumonia because of the risk of developing a violation of the motor function of the esophagus and aspiration; obesity or diabetes in a family history; patients with a high risk of suicide (psychotic diseases, bipolar disorders, major depressive disorder); persons aged 18-24 years due to the risk of developing suicidal behavior.

Application in pregnancy and lactation

Adequate and well-controlled studies in pregnant women have not been conducted. It is not known whether the use of aripiprazole in a pregnant woman can have a harmful effect on the fetus or cause reproductive harm. It is known that in newborns, whose mothers took neuroleptics during the III trimester of pregnancy, in the postpartum period there is a risk of developing extrapyramidal disorders and / or withdrawal syndrome. They showed excitement, muscle hypertension or hypotension, tremor, drowsiness, respiratory distress syndrome, eating disorders. These symptoms were of varying severity, sometimes they were treated without treatment, while in other cases the newborns needed intensive therapy and continued hospitalization. When using aripiprazole, development in newborns of such a symptomatology was very rare.

It is necessary to warn patients that they should immediately inform the doctor about the onset of pregnancy against the background of treatment, and also inform the doctor about the planned pregnancy.

Zylaksera ® can be used during pregnancy.

The drug Zylaksera ® penetrates into the human breast milk. Breastfeeding with the use of the drug is contraindicated.

Side effects

The most common adverse reactions (HP) recorded in placebo-controlled studies include akathisia and nausea, which were noted by more than 3% of patients taking aripirazole inwards.

Classification of the incidence of side effects recommended by WHO: very often ≥1 / 10; often from ≥1 / 100 to <1/10; infrequently from ≥1 / 1000 to <1/100; rarely from ≥1 / 10000 to <1/1000; very rarely <1/10000; frequency is unknown - can not be estimated based on available data.

Within each group, the frequencies of HP are listed in order of decreasing severity. The frequency of HP during the post-registration period of observation can not be determined, since the information was obtained from spontaneous reports. Therefore, the frequency of occurrence of HP data is classified as frequency is unknown.

On the part of the blood and lymphatic system: the frequency is unknown - leukopenia, neutropenia, thrombocytopenia.

On the part of the immune system: the frequency is unknown - allergic reactions (anaphylaxis, angioedema, including swelling of the tongue, face swelling, itching, urticaria).

From the endocrine system: infrequently - giperprolaktinemiya; frequency unknown - diabetic hyperosmolar coma, diabetic ketoacidosis, hyperglycemia.

From the side of metabolism and nutrition: often - diabetes mellitus; infrequently hyperglycemia; frequency is unknown - hyponatremia, anorexia, weight loss, weight gain.

Mental disorders: often - insomnia, anxiety, anxiety; infrequently - depression, hypersexuality; frequency is unknown - suicide attempts, suicidal thoughts and completed suicide (see "Special instructions"), pathological attraction to gambling, aggression, agitation, nervousness.

From the side of the nervous system: often - acacia, extrapyramidal disorders, tremor, headache, sedation, drowsiness, dizziness; infrequently - tardive dyskinesia, dystonia; frequency unknown - malignant neuroleptic syndrome (CNS), major epileptic seizure, serotonin syndrome, speech impairment.

From the side of the organ of vision: often - blurred vision; infrequently it is diplopia.

From the heart: infrequently - tachycardia; frequency unknown - sudden unexplained death, ventricular pirouette tachycardia, QT interval prolongation, ventricular arrhythmias, sudden cardiac arrest, bradycardia.

From the side of the vessels: infrequently - orthostatic hypotension; frequency unknown - venous thromboembolism (including pulmonary embolism and deep vein thrombosis), hypertension, syncope.

From the respiratory system, chest and mediastinum: infrequently - hiccough; frequency unknown - aspiration pneumonia, laryngospasm, spasm of the oropharynx.

From the digestive tract: often - constipation, dyspepsia, nausea, hypersecretion of the salivary glands, vomiting; frequency unknown - pancreatitis, dysphagia, diarrhea, discomfort in the abdomen and stomach.

From the liver and bile ducts: the frequency is unknown - liver failure, hepatitis, jaundice, increased activity of ALT, ACT, GGT and phosphatase in the blood plasma.

From the skin and subcutaneous tissues: the frequency is unknown - skin rash, photosensitivity reactions, alopecia, increased sweating.

From the musculoskeletal system and connective tissue: the frequency is unknown - rhabdomyolysis, myalgia, muscle stiffness.

From the side of the kidneys and urinary tract: the frequency is unknown - urinary incontinence, urinary retention.

Pregnancy, postpartum and perinatal conditions: the frequency is unknown - an abstinent narcotic syndrome of newborns (see "Application in pregnancy and lactation").

On the part of the genitals and mammary glands: the frequency is unknown - priapism.

General disorders and disorders at the injection site: often - increased fatigue; frequency unknown - impaired thermoregulation (eg hypothermia, pyretic reaction), chest pain, peripheral edema.

Laboratory and instrumental data: the frequency is unknown - increased blood glucose, increased glycated Hb, fluctuations in blood glucose concentration, increased activity of CK.

Description of individual adverse reactions

Extrapyramidal symptoms (EPS)

Schizophrenia: In a long, 52-week, controlled study, patients who received aripiprazole had a generally low incidence of EPS (25.8%), including parkinsonism, akathisia, dystonia, and dyskinesia, compared with patients treated with haloperidol (57.3% ). In a long 26-week placebo-controlled study, the incidence of EPS was 19% in the aripiprazole group and 13.1% in the placebo group. In another long 26-week controlled study, the incidence of EPS was 14.8% in the aripiprazole group and 15.1% in the olanzapine group.

Manic episodes and type I bipolar disorder: in a 12-week controlled study, the incidence of EPS was 23.5% in the aripiprazole group and 53.3% in the haloperidol group. In another 12-week study, the incidence of EPS was 26.6% in the aripiprazole group and 17.6% in the lithium group. In the 26-week maintenance phase of a prolonged placebo-controlled study, the incidence of EPS was 18.2% in the aripiprazole group and 15.7% in the placebo group.

Akathisia

In placebo-controlled studies, incidence of akathisia in patients with bipolar disorder was 12.1% in the aripiprazole group and 3.2% in the placebo group. In patients with schizophrenia, the incidence of akathisia was 6.2% in the aripiprazole group and 3% in the placebo group.

Dystonia

Class effect: in the first days of treatment sensitive patients may have symptoms of dystonia, prolonged pathological contractions of muscle groups. Symptoms of dystonia include: spasm of the neck muscles, sometimes progressing to a feeling of tightness in the throat, difficulty swallowing, difficulty breathing and / or protrusion of the tongue. Although these symptoms can occur at low doses, they are more common and more pronounced when higher doses of highly active neuroleptics of the first generation are used. There is an increased risk of developing acute dystonia in men and young patients.

Prolactin

In clinical studies of the use of aripiprazole for registered indications and during post-registration observation, there was an increase and decrease in serum prolactin concentration in comparison with baseline values.

Laboratory indicators

Comparisons of aripiprazole and placebo in terms of the proportion of patients with potentially clinically significant changes in standard laboratory and lipid indices did not reveal clinically significant differences. Increased activity of CK in blood plasma, as a rule, short-term and asymptomatic, was noted in 3.5% of patients receiving aripiprazole, and in 2% of patients receiving placebo.

Interaction

The mechanism of action of aripiprazole is related to the effect on the central nervous system, which must be taken into account when used simultaneously with other drugs that have a central effect. Having antagonistic action against alpha 1-adrenergic receptors, aripiprazole can enhance the effect of antihypertensive drugs.

Caution should be exercised with the simultaneous use of aripiprazole and medications that cause prolongation of the QT interval or disturb the electrolyte balance.

Aripiprazole does not affect the pharmacokinetics and pharmacodynamics of warfarin, it does not displace warfarin from its association with plasma proteins.

The H1,2-histamine receptor blocker, famotidine, which causes severe suppression of hydrochloric acid secretion in the stomach, decreases the rate of absorption of aripiprazole, but this does not affect the clinical effect of aripiprazole.

Various routes of metabolism of aripiprazole are known, including with the participation of CYP2D6 and CYP3A4 isoenzymes. In studies in healthy volunteers, potent inhibitors of the isoenzymes CYP2D6 (quinidine) and CYP3A4 (ketoconazole) had an effect on the pharmacokinetics of aripiprazole, therefore, doses of aripiprazole should be reduced when used in various combinations with inhibitors of the CYP3A4 and CYP2D6 isoenzymes (see Dosage and Administration) . With the simultaneous use of aripiprazole and weak inhibitors of CYP3A4 isoenzymes (diltiazem, escitalopram) or CYP2D6, a small increase in the aripiprazole concentration in the blood plasma can be expected. Due to the fact that the CYP1A isoenzyme is not involved in the metabolism of aripiprazole, smoking does not affect the pharmacokinetics and clinical effect of aripiprazole. When used simultaneously with carbamazepine, a powerful inducer of the isoenzyme CYP3A4, the metabolism of aripiprazole is enhanced, so the dose of aripiprazole should be adjusted (see "Method of administration and dose"). You can expect a similar action and with simultaneous application with other powerful inductors of CYP3A4 and CYP2D6 isoenzymes.

The isozymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2E1 do not participate in the metabolism of aripiprazole in in vitro conditions, and it is unlikely that it interacts with drugs and other factors (eg smoking) that are able to inhibit or induce these enzymes.

Simultaneous administration of lithium or valproic acid with 30 mg of aripiprazole did not have a clinically significant effect on the pharmacokinetics of aripiprazole.

In clinical studies, aripiprazole at doses of 10-30 mg / day had no significant effect on substrate metabolism of isoenzymes CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin), and CYP3A4 (dextromethorphan). In addition, aripiprazole and its main metabolite dehydroaripiprazole did not change metabolism involving the isoenzyme CYP1A2 under in vitro conditions. The clinically significant effect of aripiprazole on drugs metabolized with the participation of these isoenzymes is unlikely.

With simultaneous use of aripiprazole (10-30 mg / day) and lamotrigine (100-400 mg / day) in patients with bipolar disorder there was no change in the pharmacokinetics of lamotrigine, so correction of its dose is not required.

Aripiprazole had no effect on the pharmacokinetics of escitalopram and venlafaxine in healthy volunteers, so dose adjustments for these drugs are not required when used concomitantly with aripiprazole.

When used in patients with major depressive disorder aripiprazole simultaneously with fluoxetine (20-40 mg / day), paroxetine (37.5-50 mg / day) or sertraline (2-20 mg / day), significant changes in the concentration of antidepressants in blood plasma revealed.

The use of ethanol during treatment with aripiprazole may increase the sedative effect of the drug, so it should be avoided.

Dosing and Administration

Inside, 1 time per day, regardless of food intake.

Schizophrenia

The recommended initial dose is 10-15 mg / day. The maintenance dose is usually 15 mg / day.

In clinical trials, the effectiveness of the drug in doses of 10 to 30 mg / day is shown.

Manic episodes with type I bipolar disorder, monotherapy

The recommended initial dose is 15 mg / day.

If necessary, dose adjustment is carried out with an interval of at least 24 hours.

In clinical trials, the effectiveness of the drug in doses of 15-30 mg / day for manic episodes during admission for 3-12 weeks was demonstrated. Safety of a dose above 30 mg / day in clinical studies was not evaluated.

When observing patients with bipolar disorder type I who have had a manic or mixed episode, who had symptom stabilization against the background of taking Zylaksera ® (15 or 30 mg / day at an initial dose of 30 mg / day) for 6 weeks, then 6 months and further, within 17 months - the favorable effect of such maintenance therapy has been established.

Periodically, patients should be examined to determine whether to continue supporting therapy.

Additional therapy for major depressive disorder

As an additional therapy for the treatment of antidepressants, it is recommended to use Zylaksera ® in an initial dose of 5 mg / day. If necessary and good tolerability of therapy, the daily dose of Zylaksera ® can be increased weekly by 5 mg to a maximum of 15 mg / day.

The duration of therapy with Zylaksera ® for all of the above indications is not established, it is necessary to regularly check the patient for the possibility of canceling therapy.

For patients with hepatic insufficiency, a dose of 30 mg is given with caution.

Special patient groups

Renal failure. Correction of dose when prescribing Zylaksera ® is not required for patients with renal insufficiency.

Liver failure. Correction of dose when prescribing Zylaksera ® is not required for patients with hepatic impairment ..

Elderly age. Correction of the dose is not required.

Gender features. The dosage regimen of Zylaksera ® for both sexes is the same.

Smoking. The dosage regimen of Zylaksera ® for smokers and non-smoking patients is the same.

Dosing regimen with concomitant therapy

With the simultaneous use of Zylaksera ® and powerful inhibitors of the isoenzyme CYP3A4 (ketoconazole, clarithromycin), the dose of Zylaksera ® should be reduced by half. Accordingly, with the cancellation of inhibitors of the isoenzyme CYP3A4, the dose of Zylaksera ® should be increased.

With the simultaneous use of Zylaksera ® and powerful inhibitors of the isoenzyme CYP2D6 (quinidine, fluoxetine, paroxetine), the dose of Zylaksera ® should be at least halved. Accordingly, with the cancellation of inhibitors of the isoenzyme CYP2D6, the dose of Zylaksera ® should be increased.

Zylaksera ® should be used without changing the dosage regimen if it is prescribed as an adjunct therapy for patients with major depressive disorder.

With the simultaneous use of Zylaksera ® and powerful inhibitors of CYP2D6 isoenzymes (quinidine, fluoxetine, paroxetine) and CYP3A4 (ketoconazole, clarithromycin), the dose of Zylaksera ® should be reduced by 3/4 (ie up to 25% of the usual dose). Accordingly, with the cancellation of CYP2D6 and / or CYP3A4 isoenzyme inhibitors, the dose of Zylaksera ® should be increased.

With simultaneous application of Zylaksera ® and powerful, moderate and weak inhibitors of CYP2D6 and / or CYP3A4 isoenzymes, the dose of Zylaksera ® can initially be reduced by 3/4 (ie, up to 25% of the usual dose) and then increased to achieve optimal clinical result.

For patients with a low activity of the isoenzyme CYP2D6, the dose of Zylaksera ® should initially be reduced by half, and then increased to achieve the optimal clinical outcome. With the simultaneous use of Zylaksera ® and a potent CYP3A4 isoenzyme inhibitor in patients with a low CYP2D6 isozyme activity, the dose of Zylaksera ® should be reduced by 3/4 (ie, up to 25% of the usual dose).

With the simultaneous use of the Zylaksera ® preparation and potential inducers of the CYP3A4 isozyme (carbamazepine), the dose of Zylaksera ® should be doubled. Accordingly, with the cancellation of CYP3A4 isoenzyme inducers, the dose of Zylaksera ® should be reduced to 10-15 mg.

Overdose

In clinical trials, random or deliberate overdoses of aripiprazole with a single dose of up to 1260 mg, not accompanied by a fatal outcome, are described.

Symptoms: lethargy, increased blood pressure, drowsiness, tachycardia, loss of consciousness. Clinically significant changes in basic physiological parameters, laboratory parameters and ECG were not detected in hospitalized patients. Cases of overdose of aripiprazole in children (intake up to 195 mg) are described. Potentially dangerous symptoms of overdose include extrapyramidal disorders and transient loss of consciousness.

Treatment: monitoring of vital functions, ECG (to detect possible arrhythmia), maintenance therapy, airway patency, oxygenation, effective ventilation, activated charcoal, symptomatic treatment, careful medical observation until symptoms disappear. Data on the use of hemodialysis in case of an overdose of aripiprazole is not available, a favorable effect of this method is unlikely, because aripiprazole is not excreted by the kidneys in unchanged form and largely binds to blood plasma proteins.

Special instructions

With the use of antipsychotics (neuroleptics) therapeutic effect develops within a few days - weeks. During this period it is necessary to observe the patient's condition.

Suicide attempts. The tendency to suicidal thoughts and attempts is characteristic of patients with psychosis, bipolar disorder and major depressive disorder, so drug therapy must be combined with careful medical supervision. The preparation of Zylaksera ® should be prescribed in a minimum amount sufficient to treat the patient, this will reduce the risk of overdose.

Admission of antidepressants, according to clinical studies, increases the risk of suicidal thoughts and attempts in young patients with depression and other mental disorders. In this regard, special care should be taken when using combination therapy with antidepressants and Zylaksera ® for the treatment of young patients. Patients over the age of 24 did not show an increase in the incidence of suicidal ideation and behavior under the influence of antidepressants, and in patients older than 65 years there was a decrease in the incidence of this side effect.

Late dyskinesia. The risk of developing tardive dyskinesia increases with the duration of therapy with antipsychotics, so when you see symptoms of tardive dyskinesia, you should reduce the dose of this drug or cancel it. After the withdrawal of therapy, these symptoms may temporarily increase or even appear for the first time.

ZNS. In the treatment of neuroleptics, incl. aripiprazole, describes a life-threatening symptom complex, known as the NSA. This syndrome is manifested by hyperpyrexia, muscle rigidity, mental disorders and instability of the autonomic nervous system (irregular pulse and BP, tachycardia, sweating and arrhythmia). In addition, sometimes there is an increase in activity of CK, myoglobinuria (rhabdomyolysis) and acute renal failure. In case of symptoms of NSA or unexplained fever, all antipsychotics, incl. preparation of Zylaksera ®, should be discontinued.

Convulsions. Like other antipsychotics, aripiprazole should be used with caution in patients with a history of seizures and the risk of their development.

Psychoses associated with senile dementia and Alzheimer's disease. Based on the results of placebo-controlled studies in elderly patients (56-99 years old, mean age 82.4 years) with psychoses due to Alzheimer's disease, compared with the placebo group, there was an increased risk of death with aripiprazole therapy.

The mortality in the group of patients treated with aripiprazole, compared with the placebo group, was 3.5 and 1.7%, respectively. Although the causes of death were different, most of them were cardiovascular (eg, heart failure, sudden cardiac death) or infectious (eg, pneumonia).

Cerebrovascular side effects: the same studies reported cerebrovascular adverse reactions (eg, stroke, transient ischemic attack), including. with a fatal outcome, in patients (78-88 years, mean age 84 years). In general, patients treated with aripiprazole had cerebrovascular adverse reactions in 1.3% of cases compared with 0.6% of patients receiving placebo. This difference was not statistically significant. However, in one of these fixed-dose studies, there was a marked dose-dependent effect on the increased incidence of cerebrovascular adverse reactions in patients treated with aripiprazole.

Zylaksera ® is not indicated for the treatment of psychosis with dementia.

Hyperglycemia and diabetes mellitus. Hyperglycemia, in some cases expressed and accompanied by ketoacidosis or hyperosmolar coma with a fatal outcome, was noted in patients taking atypical antipsychotics. Although the association between the administration of atypical antipsychotics and hyperglycemic disorders remains unclear, patients who have diabetes mellitus should regularly perform a blood glucose test when taking atypical antipsychotics. Patients who have risk factors for diabetes (obesity, history of diabetes in the family history) with the atypical antipsychotics should determine the blood glucose concentration at the beginning of the course and periodically during the process of taking Zylaksera ®.

Patients taking atypical antipsychotics need constant monitoring of symptoms of hyperglycemia, including increased thirst, frequent urination, polyphagia, and weakness. Particular attention should be paid to patients with diabetes mellitus and risk factors for its development.

Increase in body weight. The increase in body weight is usually observed with schizophrenia and manic episodes in the background of bipolar disorder and the presence of concomitant diseases; the use of neuroleptics leads to an increase in body weight, unhealthy lifestyles and can lead to serious complications.

According to the post-marketing application of aripiprazole, there have been reports of an increase in body weight, usually in patients with severe risk factors, such as history of diabetes, thyroid disease or pituitary adenoma. According to clinical studies, the use of aripiprazole does not result in clinically significant weight gain in adults.

Leukopenia, neutropenia, agranulocytosis. It is known that neuroleptics, incl. drug Zylaksera ®, can cause temporary changes in the picture of blood - leukopenia, neutropenia, as well as agranulocytosis. Risk factors for development are a low concentration of white blood cells in a patient before the start of treatment, and also caused by other drugs leukopenia and neutropenia.

Regular monitoring of the blood picture should be carried out in these patients, especially during the first months of treatment with Zylaksera ®. With a clinically significant decrease in the concentration of white blood cells of unclear etiology, consideration should be given to the abolition of Zylaksera ®. Patients with clinically significant neutropenia should be closely monitored for evidence of elevated body temperature or other signs of infection with a view to initiating appropriate treatment immediately. In severe neutropenia (the number of neutrophils is less than 1000 / mm3), treatment with Zylaksera ® is interrupted until the blood picture is normalized.

Cardiovascular diseases. Due to the risk of orthostatic hypotension, aripiprazole should be used with caution in patients with cardiovascular disease (myocardial infarction, coronary heart disease, heart failure, cardiac conduction abnormalities), cerebral circulation disorders or conditions predisposing to arterial hypotension (dehydration, hypovolemia, therapy with antihypertensive drugs).

Violation of the exercise (prolongation of the QT interval). In clinical studies, the incidence of QT prolongation in patients treated with aripiprazole was comparable to the placebo group. In patients with congenital syndrome of the extended QT interval, aripiprazole, like other antipsychotics, should be used with caution.

Cognitive and motor disorders. Like other antipsychotics, Zylaksera ® can cause cognitive and motor disorders. In particular, in the clinical studies of the drug Zylaksera ® cases of drowsiness and inhibition were noted.

Violation of thermoregulation. It is known that neuroleptics can cause a violation of thermoregulation. This should be taken into account when prescribing Zylaksera ® to patients who have an increased risk of overheating due to intense physical exertion, high ambient temperature, medications with m-cholinoblocking activity, and dehydration.

Dysphagia. When using neuroleptics, cases of peristalsis of the esophagus and, as a consequence, aspiration pneumonia were noted. Care should be taken when using in patients with risk factors for the development of aspiration pneumonia.

Risk of development of VTE. The use of neuroleptics, incl. preparation of Zilaxera®, may be associated with a risk of developing VTE. In this regard, the risk factors for the development of this complication should be identified before the appointment of Zylaxer®, as well as during treatment with this drug. If necessary, measures should be taken to prevent the development of VTE.

Pathological attraction to gambling. According to the post-marketing application of aripiprazole, cases of the development of pathological attraction to gambling have been noted, regardless of whether the patients previously played gambling. Patients with a history of gambling are at increased risk and should be carefully monitored.

Patients with Attention Deficit Hyperactivity Disorder (ADHD). Despite the high incidence of concomitant pathology of type I bipolar disorder and ADHD, data on the safety of simultaneous use of aripiprazole and psychostimulating agents are limited. Therefore, special care must be taken when using them simultaneously.

Impact on the ability to drive and work with moving machinery. During treatment, patients should refrain from driving and dangerous mechanisms.

Release form

Tablets, 10 mg, 15 mg and 30 mg. According to Table 14. in a contour acheive box made of a combined material (PVC film / polyvinylidene chloride film) and aluminum foil. 2 contour mesh packages are placed in a pack of cardboard.

Conditions of leave from pharmacies

On prescription.

Storage conditions of the drug Zylaksera

At temperatures not higher than 30 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life of the drug Zylaksera

2 years.

Do not use after the expiry date printed on the package.

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