Zilaxera - instructions for use, dose, side effects, contraindications

Active substance: Aripiprazole fumarate semi-finished granule 74.25 mg [Active substance of semi-finished granules: Aripiprazole fumarate 5.65 mg, which corresponds to aripiprazole 5 mg

Auxiliary substances of semifinished products-granules: lactose monohydrate 49.47 mg, corn starch 8.67 mg, microcrystalline cellulose 8.67 mg, giprolose 1.73 mg, dye blue [dye blue patented (E131), dye diamond black (E151)] 0.06 mg]

Excipients: magnesium stearate 0.75 mg

1 tablet of 10 mg contains:

Active substance:

Aripiprazole fumarate semi-finished granule 148,50 mg [Active ingredient semi-finished granules: Aripiprazole fumarate 11.30 mg, which corresponds to aripiprazole 10 mg

Auxiliary substances of semifinished products-granules: lactose monohydrate 98.95 mg, corn starch 17.36 mg, microcrystalline cellulose 17.36 mg, giprolose 3.46 mg, iron dye oxide red, E172 0.07 mg]

Excipients: Magnesium stearate 1.50 mg

1 tablet of 15 mg contains:

Active substance: Aripiprazole fumarate semi-finished granule 222.75 mg [Active substance of semi-finished granules: Aripiprazole fumarate 16.95 mg, which corresponds to aripiprazole 15 mg

Auxiliary substances of semifinished products-granules: lactose monohydrate 148.42 mg, corn starch 26.04 mg, cellulose microcrystalline 26.04 mg, giprolose 5.19 mg, iron dye oxide yellow, E172 0.11 mg]

Excipients: magnesium stearate 2.25 mg

1 tablet of 30 mg contains:

Active substance: Aripiprazole fumarate semi-finished granule 445.50 mg [Active substance of semi-finished granules: Aripiprazole fumarate 33.90 mg, which corresponds to aripiprazole 30 mg

Auxiliaries of the semi-fabrics of iqat granules: lactose monohydrate 296.84 mg, corn starch 52.08 mg, microcrystalline cellulose 52.08 mg, giprolose 10.38 mg, iron oxide red oxide, E172 0.22 mg]

Excipients: magnesium stearate 4.50 mg

Description:Tablets 5 mg: capsular, slightly biconvex tablets, light blue with marbling and possible dark impregnations.

Tablets 10 mg: capsular, slightly biconvex tablets, light pink with marbling and dark impregnations.

Tablets 15 mg: Round, slightly biconvex tablets with a bevel, light yellow with marbling and possible dark impregnations.

Tablets of 30 mg: round, slightly biconcave tablets with a bevel, light pink color with marbling and dark impregnations.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.12 Aripiprazole

Pharmacodynamics:

It is suggested that the therapeutic effect of aripiprazole in schizophrenia and type I bipolar disorder is due to the combination of partial agonistic activity in relation to D2-dopamine and 5HT1a-serotonin receptors and antagonistic activity against 5HT2a-serotonin receptors.

Pharmacodynamics

Aripiprazole has a high affinity in in vitro conditions to D2- and D3-dopamine receptors, 5HT1a- and 5HT2a-serotonin receptors and moderate affinity for D4-dopamine, 5HT2-and 5HT7-serotonin, alpha1-adrenoreceptors 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, exhibited 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. Using aripiprazole orally at doses of 0.5 to 30 mg once a day in healthy volunteers for 2 weeks leads to a dose-dependent decrease in the binding of 11C-rakloprid, D2 / D3-dopamine receptor ligand, with a caudate nucleus and a fence positron emission tomography).

Pharmacokinetics:

The activity of Zylaxer® is mainly due to the presence of aripiprazole. The average half-life (T1 / 2) of aripiprazole is approximately 75 hours. The equilibrium concentration is achieved 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 was found that the main metabolite of the drug in human blood plasma, dehydroaripiprazole, has the same affinity for D2-dopamine receptors, as well as aripiprazole.

Suction

Aripiprazole is rapidly absorbed after oral administration of Zilaxera® tablets, with the maximum concentration of aripiprazole in blood plasma to be achieved in 3-5 hours. The bioavailability of the tablets of the preparation Zilaxer ® when taken orally is 87%. Eating food does not affect the bioavailability of aripiprazole.

Distribution

Aripiprazole is well distributed in tissues, and the apparent volume of distribution is 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. Biotransformation (metabolism) Aripiprazole is subjected to presystemic metabolism only to a minimal extent. Aripiprazole metabolized in the liver in three ways: 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. In the equilibrium state, the area under the concentration-time curve (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 activity of the isoenzyme 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.

Pharmacokinetics of special groups of patients

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 feature

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

Race

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.

Impaired liver function

After a single administration of aripiprazole by patients with varying 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 the metabolic activity of the liver in patients with decompensated liver cirrhosis.

Indications:

Treatment of schizophrenia.

Treatment of manic episodes with type I bipolar disorder of moderate and severe severity and prevention of a new manic episode in adults who develop predominantly manic episodes that are treatable with aripiprazole.

As an adjunct 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 (since the composition contains lactose).

- Age to 18 years (effectiveness and safety not established).

- Breastfeeding period.

Carefully:

With caution: cardiovascular disease (coronary heart disease (CHD) or previous myocardial infarction, chronic heart failure (CHF) 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 developing orthostatic hypotension, convulsive seizures or diseases,which may cause seizures, an increased risk of hyperthermia (for example, intense physical exertion, overheating, m-cholinergic blocking, dehydration, because neuroleptics 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 aspirations, obesity or diabetes in a family history, patients with a high risk of suicide (psychotic illness, bipolar disorder, major depressive disorder), in persons aged 18-24 years in connection with the risk of developing suicidal behavior.

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, whereas in other cases, newborns needed intensive care 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, should also inform the doctor about the planned pregnancy. Zilaxera® may be taken during pregnancy only if the potential benefit to the mother is greater than the potential risk to the fetus. The drug Zilaxer ® penetrates into the human breast milk. Breastfeeding when using the drug is not recommended.

Dosing and Administration:

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

Schizophrenia

The initial dose of 10-15 mg once a day. The maintenance dose is 15 mg / day.

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

The maximum daily dose is 30 mg / day.

Manic episodes with type I bipolar disorder

The initial dose is 15-30 mg / day.

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

In clinical trials, the efficacy of the drug at 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 type I bipolar disorder who have had a manic or mixed episode who have had symptoms stabilized against aripiprazole (15 mg / day or 30 mg / day) for 6 weeks, then 6 months and beyond, for 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 Zylaxer® in an initial dose of 5 mg / day. If necessary and good tolerability of therapy, the daily dose of Zilaxera® can be increased weekly by 5 mg to a maximum of 15 mg / day.The duration of therapy with Zilaxera® for all of the above indications is not established, it is necessary to regularly check the patient for the possibility of canceling therapy.

Special patient groups

Patients with renal insufficiency

Dose adjustments in patients with renal insufficiency are not required.

Patients with hepatic insufficiency

In patients with mild and moderate hepatic insufficiency, dose adjustment is not required. Patients with severe hepatic impairment should be dosed with caution. In patients with severe hepatic insufficiency, the maximum daily dose of 30 mg should be used with caution.

Elderly patients

Dose correction is not required

Gender features

Dosage regimen for patients of both sexes is the same.

Smoking

Dosage regimen for smoking and non-smoking patients is the same.

Dosing regimen with concomitant therapy

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

With the simultaneous use of potent inhibitors of the isoenzyme CYP2D6 (quinidine, fluoxetine, paroxetine) the dose of Zylaxer® should be reduced, at least, by half. Accordingly, with the cancellation of inhibitors of the isoenzyme CYP2D6, the dose of Zylaxer® should be increased.

Zilaxera® should be used without changing the dosage regimen if it is prescribed as adjunctive therapy in patients with major depressive disorder.

At simultaneous application of powerful inhibitors of isoenzymes CYP2D6 (quinidine, fluoxetine, paroxetine) and CYP3A4 (ketoconazole, clarithromycin), the dose of Zylaxer® should be reduced by 3/4 (that is, up to 25 % of the usual dose).

Accordingly, with the cancellation of inhibitors of isoenzymes CYP2D6 and / or CYP3A4, the dose of Zylaxer® should be increased.

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

For patients with a low activity of the isoenzyme CYP2D6, the dose of Zilaxera® should initially be reduced by half, and then increased to achieve the optimal clinical outcome. When a powerful inhibitor of the CYP3A4 isoenzyme is used simultaneously, in patients with a low activity of the CYP2D6 isoenzyme, the dose of Zylaxer® should be reduced by 3/4 (i.e., up to 25% of the usual dose).

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

Side effects:

Classification of the incidence of side effects recommended by the World Health Organization (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

the frequency of the unknown can not be estimated from the available data.

Disturbances from the blood and lymphatic system: infrequently: iron-deficiency anemia; very rarely: leukopenia, neutropenia, thrombocytopenia.

Impaired immune system: very rare: allergic reactions (anaphylaxis, angioedema, skin itching, urticaria), laryngospasm.Disorders from the endocrine system: infrequently: hypoglycemia, diabetes mellitus; rarely: hyperglycemia, diabetic ketoacidosis, diabetic hyperosmolar coma.

Disorders from the metabolism and nutrition: often: weight loss; infrequently: dehydration, edema, hypercholesterolemia, hypokalemia, hyperlipidemia, thirst, increased urea in the blood plasma, increased activity of alkaline phosphatase, increased lactate dehydrogenase activity, obesity; rarely: gout, hypernatremia, cyanosis, urine acidification; very rarely: hyponatremia, anorexia.

Disorders of the psyche: very often: insomnia; often: psychomotor agitation, depression, nervousness, hostility, suicidal thoughts, manic thoughts; infrequently: panic reactions, hyperactivity, depersonalization; rarely: obsessive thoughts.

Disturbances from the nervous system: very often: drowsiness, headache, akathisia; often: dizziness, tremor, extrapyramidal syndrome, confusion, resistance to the implementation of passive movements ("cogwheel" syndrome), lethargy, decreased concentration, sedation; infrequently: dystonia,muscular twitching, paresthesia, tremor of the extremities, impotence, bradykinesia, decreased / increased libido, apathy, memory loss, stupor, amnesia, stroke, dyskinesia, restless legs syndrome, myoclonus, depressed mood, increased reflexes, slowing of mental function, hypersensitivity to irritants, violation of the oculomotor reaction; rarely: delirium, euphoria, bucco-glossal syndrome, akinesia, depression of consciousness down to loss of consciousness, decreased reflexes, malignant neuroleptic syndrome; very rarely: speech disorder, convulsions.

Disorders from the side of the eye: often: blurred vision, photophobia; infrequently: dry eyes, pain in the eyes, blepharitis; rarely: increased lacrimation, frequent blinking, amblyopia, diplopia, intraocular hemorrhage.

Hearing disorders and labyrinthine disturbances: often: pain in the ears; infrequent: ringing in the ears, inflammation of the middle ear; rarely: external otitis media, deafness.

Disturbances from the heart: often: tachycardia; infrequent: bradycardia, palpitations, myocardial infarction, QT interval prolongation, sudden cardiac arrest,atrial fibrillation, heart failure, atrioventricular blockade, myocardial ischemia, extrasystole; rarely: enlargement of the heart, atrial flutter; very rarely: faint.

Vascular disorders: often: orthostatic hypotension; infrequently: deep vein thrombosis, phlebitis, hemorrhages, decreased blood pressure; rarely: vasovagal syndrome, thrombophlebitis, intracranial hemorrhage, cerebral ischemia; very rarely: increased blood pressure; frequency unknown: thromboembolism (including pulmonary embolism and deep vein thrombosis).

Disturbances from the respiratory system, chest and mediastinal organs: often: dyspnea, pneumonia; infrequently: epistaxis, hiccough, laryngitis; rarely, hemoptysis, increased sputum production, dryness of nasal mucosa, pulmonary edema, hypoxemia, respiratory distress, apnea; very rarely: aspiration pneumonia.

Disorders from the gastrointestinal tract: very often: nausea, loss of appetite; often: gain of appetite, dyspepsia, vomiting, constipation, hypersecretion of saliva, dryness of the oral mucosa, the severity of abdominal pain, diarrhea;

* in the treatment of depression in combination with antidepressants

infrequently: gastroenteritis, difficulty swallowing, flatulence, gastritis, dental caries, gingivitis, hemorrhoids, gastroesophageal reflux, gastrointestinal hemorrhage, periodontal abscess, swelling of the tongue, fecal incontinence, colitis, rectal hemorrhage, stomatitis, ulceration of the oral mucosa, fecaloma, candidiasis of the oral mucosa, belching, stomach ulcer, loss of taste; rarely: esophagitis, gum bleeding, tongue inflammation, bloody vomiting, intestinal bleeding, duodenal ulcer, cheilitis, perforation of the intestine; very rarely: pancreatitis, dysphagia.

Disorders from the liver and bile ducts: infrequently: cholecystitis; rarely: augmentation of the liver; very rarely: hepatitis, jaundice, increased activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT).

Disturbances from the skin and subcutaneous tissues: often: dry skin, itching, skin ulceration; infrequently: acne, vesiculobullae (bladder) rash, eczema, alopecia, psoriasis, seborrhea, photosensitivity; rarely: maculopapular rash, exfoliative dermatitis, urticaria, hyperhidrosis.

Disorders from the musculoskeletal and connective tissue: often: arthralgia, rigidity of muscles; infrequently: myasthenia gravis, arthritis, arthrosis, muscle weakness, muscle spasms, bursitis; very rarely: rhabdomyolysis, tendonitis, tenobursitis, myalgia.

Disorders from the kidneys and urinary tract: infrequent: cystitis, frequent urination, leukorrhea, hematuria, dysuria, renal insufficiency, albuminuria, kidney stones, nocturia, polyuria, false urge to urinate; rarely: burning in the area of the urethra and external genitalia, glucosuria; Very rarely: urinary incontinence, urinary retention.

Violations from the genitals and breast: infrequently: amenorrhea, premature ejaculation, vaginal bleeding, vaginal candidiasis, uterine bleeding, menorrhagia; rarely: pain in the mammary gland, cervicitis, galactorrhea, anorgasmia, gynecomastia, painful erection; very rarely: priapism.

General disorders and disorders at the site of administration: often: asthenia, fatigue, flu-like syndrome, sensation of trembling in the body; infrequently: peripheral edema, edema of the face, malaise, jaw pain, chills, stiffness of the jaws,chest pain; rare: sore throat, tightness, back pain, heaviness in the head, candidiasis, a feeling of constriction in the throat, Mendelson's syndrome, heat stroke; very rarely: a violation of temperature regulation, pyrexia, pain in the chest, in the neck.

Laboratory and instrumental data: very rarely: increased activity of creatine phosphokinase.

Additional information on the side effects of the drug

Adverse events occurring in the treatment of antipsychotic drugs, were noted also during therapy with aripiprazole, including rare cases of neuroleptic malignant syndrome as well as infrequent cases of tardive dyskinesia and seizures.

Sensitive patients in the first days of treatment may have symptoms of dystonia - prolonged pathological muscle spasms. The symptoms of dystonia are trachelism, sometimes with a feeling of constriction in the throat, difficulty swallowing, difficulty breathing, and / or protrusion of the tongue. These symptoms can also occur with the use of high doses of neuroleptics of the first generation.

Patients at high risk for developing dystonia are men and young people.

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. Hospitalized patients showed no clinically significant changes in the basic physiological parameters, laboratory parameters and electrocardiogram (ECG). 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 carbon, symptomatic treatment, careful medical observation until the symptoms disappear. Data on the use of hemodialysis in case of an overdose of aripiprazole are absent, a favorable effect of this method is unlikely, since aripiprazole is not excreted by the kidneys unchanged and largely binds to blood plasma proteins.

Interaction:

The mechanism of action of aripiprazole is associated with 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.

Care should be taken when the use of aripiprazole and drugs 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 the connection with the proteins of the blood plasma.

The H2-histamine receptor blocker - famotidine, causing a powerful inhibition of the secretion of hydrochloric acid in the stomach, reduces the rate of absorption of aripiprazole, but this has no effect on the clinical effect of aripiprazole.

There are various ways of metabolism of aripiprazole, including those involving isoenzymes CYP2D6 and CYP3A4.In studies in healthy volunteers, potent inhibitors of CYP2D6 isoenzymes (quinidine) and CYP3A4 (ketoconazole) had an effect on the pharmacokinetics of aripiprazole, therefore, doses of aripiprazole should be reduced when applied simultaneously with potent inhibitors of the CYP3A4 and CYP2D6 isoenzymes (see the "Dosage and Administration" section). At simultaneous application of aripiprazole and weak inhibitors of isoenzymes CYP3A4 (diltiazem, escitalopram) or CYP2D6, a small increase in the concentration of aripiprazole in the blood plasma can be expected.

Due to the fact that the CYP1A isoenzyme is not involved in the metabolism of aripiprazole, smoking has no effect on 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 section "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 therefore its interaction with drugs and other factors is unlikely(eg, smoking) capable of inhibiting or inducing these enzymes.

In clinical trials aripiprazole in doses of 10-30 mg / day had no significant effect on the metabolism of substrates of isoenzymes CYP2D6 (dextramethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin) and CYP3A4 (dextromethorphan). Besides, aripiprazole and its main metabolite dehydroaripiprazole did not change metabolism with the participation of 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 the 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, therefore no dosage adjustments for these drugs are 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) and 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.

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 Zilaxera® 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 antidepressants, including in the form of combination therapy with antidepressants and Zilaxera®, for the treatment of young patients.Patients over 24 years of age showed no increase in the incidence of suicidal ideation and behavior with antidepressants, and a decrease in the incidence of this side effect was noted in patients older than 65 years.

Late dyskinesia

The risk of developing tardive dyskinesia increases with the duration of therapy with antipsychotics, therefore, if the symptoms of tardive dyskinesia appear on the background of taking the drug, 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.

Malignant neuroleptic syndrome

In the treatment of neuroleptics, including aripiprazole, a life-threatening symptom complex, known as malignant neuroleptic syndrome (CNS), is described. 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 the activity of creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.In the event of symptoms of NSA or unexplained fever, all antipsychotics, including Zilaxera®, should be withdrawn.

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

Increased Mortality: Based on placebo-controlled studies in elderly patients (56 to 99 years old, mean age 82.4 years) with psychoses due to Alzheimer's disease, there was an increased risk of death compared with the placebo group 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. Despite the fact that the causes of death were different, most of them were cardiovascular (eg, heart failure, sudden cardiac death) or infectious (eg, pneumonia). Cerebrovascular side reactions: in the same studies, cerebrovascular adverse reactions (for example, stroke, transient ischemic attack), including fatal outcome, were reported in patients (78-88 years old, mean age: 84 years).In general, in patients treated with aripiprazole, Cerebrovascular side-effects were recorded in 1.3% of cases compared with 0.6% of patients receiving placebo. This difference was not statistically significant. Nevertheless, in one of these studies with a fixed dose, there was a pronounced dose-dependent effect on the increased incidence of cerebrovascular adverse reactions in patients who received aripiprazole. Zilaxera® 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-type disorders remains unclear, patients who are diagnosed with diabetes mellitus, should regularly determine the concentration of glucose in the blood when taking atypical antipsychotics. Patients who are at risk for diabetes (obesity,the presence of diabetes in a family history) when taking atypical antipsychotics should determine the concentration of glucose in the blood at the beginning of the course and periodically in the process of taking Zilaxera®. Patients taking atypical antipsychotics need constant monitoring of symptoms of hyperglycemia, including increased thirst, frequent urination, polyphagia, weakness. Particular attention should be paid to patients with diabetes mellitus and risk factors for its development.

Weight gain

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 weight gain, unhealthy lifestyles and can lead to serious complications. According to the post-marketing application of aripiprazole, weight gain reports have been reported, 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 antipsychotics, including the preparation Zilaxera®, can cause temporary changes in the blood picture - 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 Zilaxera®. With a clinically significant decrease in the concentration of white blood cells of unclear etiology, consideration should be given to the abolition of Zylaxer®. 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 Zylaxer® is interrupted until the blood picture is normalized.

Cardiovascular diseases

In connection with the risk of developing orthostatic hypotension aripiprazole It should be used with caution in patients with cardiovascular diseases (myocardial infarctionmyocardium, ischemic heart disease, heart failure, cardiac conduction abnormalities in the anamnesis), disorders of cerebral circulation or conditions predisposing to arterial hypotension (dehydration, hypovolemia, hypotensive therapy).

Violation of the conduction (prolongation of the QT interval)

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

Cognitive and motor disorders

Like other antipsychotics, Zilaxera® can cause cognitive and motor disorders. In particular, in the clinical studies of the drug Zilaxera® cases of drowsiness and inhibition were noted. During treatment, patients should refrain from driving and dangerous mechanisms.

Violation of thermoregulation

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

The risk of developing venous thromboembolism

The use of neuroleptics, including Zylaxer®, may be associated with a risk of venous thromboembolism. In this regard, it is necessary to identify the risk factors for the development of this complication before prescribing Zilaxer®, as well as during treatment with this drug. If necessary, measures should be taken to prevent the development of venous thromboembolism.

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 should be taken when using them simultaneously.

Effect on the ability to drive transp. cf. and fur:

Care should be taken when using Zilaxera® until patients are sure that aripiprazole does not have a negative impact on them.

Form release / dosage:

Tablets 5 mg, 10 mg, 15 mg and 30 mg.

Packaging:For 14 tablets in a contour mesh package made of a combined material (polyvinyl chloride film / polyvinylidene chloride film) and aluminum foil. 2 or 4 contour squares, together with instructions for use, are placed in a pack of cardboard.

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

Keep out of the reach of children.

Shelf life:2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008556/10

Date of registration:23.08.2010

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp19.02.2014

Illustrated instructions

Instructions

Zilaxera® (Zylaxera®)