MIRIUM - instructions for use, doses, side effects, contraindications

tablets 5 mg: sodium starch glycolate - 2.85 mg, microcrystalline cellulose - 5.00 mg, lactose monohydrate - 33.25 mg, hydroxypropyl cellulose - 1.00 mg, magnesium stearate - 0.40 mg;

tablets 10mg: sodium starch glycolate 5.68 mg, microcrystalline cellulose - 10.00 mg, lactose monohydrate - 66.50 mg, hydroxypropyl cellulose - 2.00 mg, iron oxide red (E 172) 0.02 mg, magnesium stearate 0.80 mg;

tablets 15 mg: sodium starch glycollate - 8.26 mg, microcrystalline cellulose - 15.00 mg, lactose monohydrate - 99.75 mg, hydroxypropylcellulose - 3.00 mg, iron oxide yellow (E 172) - 0.29 mg, magnesium stearate - 1.20 mg;

tablets 20 mg: sodium starch glycolate - 11.40 mg, microcrystalline cellulose - 20, .00 mg, lactose monohydrate - 133.00 mg, hydroxypropylcellulose - 4.00 mg, magnesium stearate - 1.60 mg;

tablets 30 mg: sodium starch glycolate 17.04 mg, microcrystalline cellulose 30.00 mg, lactose monohydrate 199.50 mg, hydroxypropylcellulose 6.00 mg, iron oxide red (E 172) 0.06 mg, magnesium stearate 2, 40 mg.

Description:

Tablets 5 mg: round biconvex tablets of white color with depressed inscriptions "ARZ" on one side and "5" on the other side.

Tablets 10 mg: oblong biconvex tablets of pink color with possible presence of lighter and more terrestrial inclusions, with depressed inscriptions "ARZ" and "10" on one side.

Tablets 15 mg: round biconvex tablets of yellow color with depressed inscriptions "ARZ" and "15" on one side.

Tablets of 20 mg: round biconvex tablets of white color with depressed inscriptions "ARZ" and "20" on one side.

Tablets 30 mg: round biconvex tablets of pink color with possible presence of single inclusions, with depressed inscriptions "ARZ" and "30" on one side. Perhaps a small round dent in the middle of the tablet on the side without engraving.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.12 Aripiprazole

Pharmacodynamics:

It is assumed that the therapeutic effect of aripiprazole in schizophrenia and bipolar disorder type 1 is due to a combination of partial agonistic activity in relation to D₂dopamine and 5-HT_1A-serotonin receptors and antagonistic activity against 5-HT_2A-serotonin receptors. Aripiprazole in animal experiments, exhibited antagonism with respect to dopaminergic hyperactivity and agonism with respect to dopaminergic hypoactivity.

Aripiprazole has high affinity in conditions in vitro to D₂- and D₃-dopamine receptors. 5-HT_1A- and 5-HT_2Aserotonin receptors and moderate affinity for D₄dopamine. 5-HT_2C- and 5-HT₇-serotonin, α₁adrenoceptors and H₁-histamine receptors. Aripiprazole is also characterized by moderate affinity for the sites of serotonin reuptake and lack of significant affinity for m-holinoretseptoram. Some clinical effects of aripiprazole can be explained by interaction with other types of receptors, in addition to dopamine and serotonin.

Taking aripiprazole orally at doses of 0.5 to 30 mg once a day by healthy volunteers for 2 weeks results in a dose-dependent decrease in binding ¹¹C-raclopride, ligand D₂/D₃dopamine receptors, with a caudate nucleus and a fence according to positron emission tomography.

Pharmacokinetics:

Suction

Aripiprazole is rapidly absorbed after ingestion, with the maximum concentration in the blood plasma achieved in 3-5 hours. Aripiprazole is minimally subjected to pre-systemic metabolism. The absolute bioavailability of aripiprazole tablets is 87%. Eating high in fat does not affect the pharmacokinetics of aripiprazole.

Distribution

Aripiprazole is intensively distributed in tissues, the apparent volume of distribution is 4.9 l / kg, indicating a significant extravascular distribution. At therapeutic concentrations of aripiprazole and dehydroaripiprazole more than 99% are associated with blood plasma proteins, mainly with albumins.

Metabolism

Aripiprazole is largely metabolized in the liver in three ways: dehydrogenation, hydroxylation and N-dealkylation. According to experiments in vitro, dehydrogenation and hydroxylation of aripiprazole occurs under the action of isoenzymes CYP3A4 and CYP2D6, a N-dealkylation is catalyzed by isoenzyme CYP3A4. Aripiprazole is the main active substance in the blood. In the equilibrium state, the area under the curve "concentration-time" (AUC) of dehydroaripiprazole, the main metabolite, is approximately 40% AUC aripiprazole in blood plasma.

Excretion

The mean half-life (T₁/₂) of aripiprazole is approximately 75 hours in patients with high isoenzyme activity CYP2D6 and about 146 hours in patients with low isoenzyme activity CYP2D6. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to excretion by the liver.

After a single oral administration of the labeled [¹⁴C] aripiprazole, approximately 27% of the radioactivity is determined in urine and about 60 % in the stool. Less than 1% of unchanged aripiprazole is excreted in the urine, and approximately 18% of the dose taken unchanged is excreted with feces.

Pharmacokinetics in specific patient groups

Use in children

The pharmacokinetics of aripiprazole and dehydroaripiprazole in children aged 10 to 17 years was the same as in adults after adjusting the difference in body weight.

Elderly patients

Differences in the parameters of aripiprazole pharmacokinetics in healthy elderly and adult volunteers have not been revealed. Population pharmacokinetics analysis also showed no significant effect of age in patients with schizophrenia.

Floor

Differences in the parameters of aripiprazole pharmacokinetics in healthy men and women have not been revealed. Population analysis of pharmacokinetics also did not reveal a significant effect of sex in patients with schizophrenia.

Smoking

Population analysis of pharmacokinetics showed no clinically significant effects of smoking on the parameters of aripiprazole pharmacokinetics.

Race

Population analysis of pharmacokinetics showed no effect of racial differences on the pharmacokinetics of aripiprazole.

Patients with impaired renal function

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

Patients with impaired hepatic function

In a single-dose study in patients with varying degrees of severity of liver cirrhosis (class A. B and C according to the Child-Pugh classification), there was no significant effect of liver dysfunction on the pharmacokinetics of aripiprazole and dehydroaripiprazole.However, the study involved only three patients with class C liver cirrhosis according to the Child-Pugh classification, and therefore it is impossible to draw definitive conclusions on their metabolic activity.

Indications:

- 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 and / or to the excipients of the drug.

- Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome (because the preparation contains lactose).

- Breastfeeding period.

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

Carefully:

- Patients with cardiovascular diseases (coronary heart disease (CHD) or previous myocardial infarction, chronic heart failure (CHF) or conduction disorders);

- in patients with cerebrovascular diseases and conditions predisposing to the development of orthostatic hypotension;

- in patients with convulsive seizures with convulsions or with diseases in which convulsions are possible;

- in patients with an increased risk of hyperthermia, (for example, with intense physical exertion, overheating, m-holinoblokatorov, dehydration due to the ability of neuroleptics to disrupt thermoregulation);

- in patients with an increased risk of aspiration pneumonia due to the risk of developing a violation of the motor function of the esophagus and aspiration;

- in patients who are obese or have a history of diabetes mellitus;

- in patients with high risk of suicide (psychotic diseases, bipolar disorders, major depressive disorder);

- in persons aged 18-24 years due to 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 by a pregnant woman can have a harmful effect on the fetus or cause a violation of reproductive function.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 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, should also inform the doctor about the planned pregnancy.

Aripiprazole can be used during pregnancy only if the potential the use of the application for the mother exceeds the potential risk for the fetus.

Aripiprazole penetrates into the human breast milk. When applying the drug, breastfeeding is not recommended.

Dosing and Administration:

Schizophrenia

The recommended starting dose is 10 to 15 mg once a day, regardless of the intake of the poor. The maintenance dose is usually 15 mg per day. In clinical trials, the effectiveness of the drug in doses of 10 to 30 mg / day is shown.

Manic episodes with bipolar disorder

Monotherapy

The recommended initial dose is 15 mg once a day, regardless of meal time. Change the dose, if necessary, should be carried out with an interval of at least 24 hours. In clinical studies in manic episodes, the effectiveness of the drug in doses of 15-30 mg / day with a dose of 3-12 weeks was demonstrated. Safety of doses above 30 mg / day in clinical trials was not evaluated.

When observing patients with bipolar disorder type I who have had a manic or mixed episode who had a symptom stabilization against the background of taking the drug (15 mg / day 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 is established. Periodically, patients should be examined to determine if continuing maintenance therapy is necessary.

Additional therapy for major depressive disorder

As an adjunct to the treatment with antidepressants, it is recommended to prescribe the drug at an initial dose of 5 mg / day, if necessary and good tolerability of therapy, the daily dose of the drug can be increased every week by 5 mg to a maximum of 15 mg per day.

The duration of aripiprazole therapy for all of the above indications is not established; It is necessary to conduct a regular examination of the patient for the possibility of canceling therapy.

Application the special patient groups

Patients with renal insufficiency

Correction of dose in the appointment of aripiprazole to patients with renal insufficiency is not required.

Patients with hepatic insufficiency

Correction of dose in the administration of aripiprazole to patients with mild to moderate liver failure is not required.

Patients with severe hepatic insufficiency dose of 30 mg prescribe with caution.

Use in patients over the age of 65 years

Correction of the dose is not required.

Effect of the patient's sex on the dosing regimen

The dosage regimen of aripiprazole for patients of both sexes is the same.

Effect of smoking on the dosing regimen

The dosing regimen of aripiprazole for smokers and non-smokers is the same.

Dosing regimen with concomitant therapy

With the simultaneous use of aripiprazole and potent inhibitors of isoenzyme CYP3A4 (ketoconazole, clarithromycin) the dose of the drug should be reduced by half. When cancellation of isoenzyme inhibitors CYP3A4 dose of the drug should be increased.

With the simultaneous use of aripiprazole and potent inhibitors of isoenzyme CYP2D6 (quinidine. fluoxetine, paroxetine) the dose of aripiprazole should be reduced by at least half. When cancellation of isoenzyme inhibitors CYP2D6 dose of aripiprazole should be increased.

The dosage regimen should not be changed if aripiprazole prescribe as an additional therapy for patients with major depressive disorder.

With the simultaneous use of aripiprazole and potent inhibitors of isoenzymes CYP2D6 (quinidine, fluoxetine, paroxetine) and CYP3A4 (ketoconazole, clarithromycin), the dose of aripiprazole should be reduced by ¾ (that is, up to 25% of the usual dose). When cancellation of isozyme inhibitors CYP2D6 and / or CYP3A4 dose of aripiprazole should be increased.

With the simultaneous use of aripiprazole and powerful, moderate or weak inhibitors of isoenzymes CYP2D6 and CYP3A4, the dose of aripiprazole may initially be reduced by ¾ (that is, up to 25% of the usual dose), and then increased to achieve the optimal clinical outcome.

Patients with low isoenzyme activity CYP2D6 Initially, the dose of aripiprazole should be reduced by half, and then increased to achieve optimal clinical result. With the simultaneous use of aripiprazole and a potent inhibitor of isoenzyme CYP3A4 patients with low isoenzyme activity CYP2D6 dose of aripiprazole should be reduced by ¾ (that is, up to 25% of the usual dose).

With the simultaneous use of aripiprazole and potential isoenzyme inducers CYP3A4 (carbamazepine), the dose of aripiprazole should be increased 2 times. When cancellation of isoenzyme inducers CYP3A4 dose of aripiprazole should be reduced to 10-15 mg.

Side effects:

The most common side effects in placebo-controlled clinical trials are akathisia and nausea, each of which occurred in more than 3% of patients taking aripiprazole.

Undesirable reactions are classified according to organ and organ damage and the frequency of development as follows: 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) and the frequency is unknown (can not be estimated based on available data). Within the limits of each group, isolated depending on the incidence of the undesired reaction, undesirable reactions are presented in order of decreasing severity.

The incidence of adverse reactions in post-marketing studies can not be determined, since reports about them were spontaneous. Therefore, the frequency of these unwanted reactions is indicated as "frequency is unknown".

Violations of the blood and lymphatic system

The frequency is unknown: leukopenia, neutropenia, thrombocytopenia.

Immune system disorders

The frequency is unknown: allergic reactions (eg, anaphylactic reactions, angioedema, including swelling of the tongue, swelling of the tongue, face swelling, itching, or urticaria).

Disorders from the endocrine system

Infrequently: hyperprolactinemia.

The frequency is unknown: diabetic hyperosmolar coma, diabetic ketoacidosis, hyperglycemia.

Disorders of metabolism and nutrition

Often: diabetes mellitus.

Infrequently: hyperglycemia.

Frequency unknown: hyponatremia. anorexia, weight loss, weight gain.

Disorders of the psyche

Often: insomnia, anxiety, anxiety.

Infrequently: depression, increased sexuality.

The frequency is unknown: attempted suicide, suicidal thoughts and perfect suicide, pathological addiction to gambling, aggression, agitation, nervousness.

Disturbances from the nervous system

Often: akathisia, extrapyramidal disorders, tremor, headache, sedation, drowsiness, dizziness.

Infrequent: tardive dyskinesia, dystonia.

The frequency is unknown: malignant neuroleptic syndrome (CNS), large seizure, serotonin syndrome, speech impairment.

Disturbances on the part of the organ of sight

Often: blurred vision.

Infrequently: diplopia.

Heart Disease

Infrequently: tachycardia.

The frequency is unknown: sudden death, polymorphic ventricular tachycardia as pirouette, lengthening of the interval QT, ventricular arrhythmia, cardiac arrest, bradycardia.

Vascular disorders

Infrequent: orthostatic hypotension.

The frequency is unknown: venous thromboembolism (including pulmonary embolism and deep vein thrombosis), increased blood pressure, fainting.

Disturbances from the respiratory system, organs of the thoracic cue and mediastinum

Infrequently: hiccough.

The frequency is unknown: aspiration pneumonia, laryngospasm, oropharyngeal spasm.

Disorders from the gastrointestinal tract

Often: constipation, indigestion, nausea, hypersecretion of saliva, vomiting.

The frequency is unknown: pancreatitis, dysphagia, diarrhea, discomfort in the abdomen, discomfort in the stomach.

Disturbances from the liver and bile ducts

The frequency is unknown: hepatic insufficiency, hepatitis, jaundice, increased activity of alanine aminotransferase (ALT), increased activity of aspartate aminotransferase (ACT), an increase in the activity of gamma-glutamyl transferase (GGT), an increase in the activity of alkaline phosphatase.

Disturbances from the skin and subcutaneous tissues

The frequency is unknown: rash, photosensitivity, alopecia, hyperhidrosis.

Disturbances from musculoskeletal and connective tissue

The frequency is unknown: rhabdomyolysis, muscle pain, stiffness.

Disorders from the kidneys and urinary tract

The frequency is unknown: urinary incontinence, urinary retention.

Pregnancy, postpartum and perinatal conditions

The frequency is unknown: the syndrome of "cancellation" in newborns.

Violations of the genitals and mammary gland

The frequency is unknown: priapism.

General disorders and disorders at the site of administration

Often: fatigue.

The frequency is unknown: violations of temperature regulation (eg, hypothermia, pyrexia), chest pain, peripheral edema.

Laboratory and instrumental data

The frequency is unknown: increased blood glucose levels, increased glycated hemoglobin levels, fluctuations in blood glucose levels, increased activity of creatinine phosphokinase.

Overdose:

In clinical trials, random and 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 electrocardiogram (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 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 It is not excreted by the kidneys in an unchanged form and binds to a considerable extent with the proteins of the blood plasma.

Interaction:

The mechanism of action of aripiprazole is associated with an effect on the central nervous system (CNS), 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 drugs that cause lengthening of the interval QT 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.

Block H₂-gistaminovyh receptors 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.

Various routes of metabolism of aripiprazole are known, including with the participation of isoenzymes CYP2D6 and CYP3A4. In studies in healthy volunteers, powerful inhibitors of 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 isozyme inhibitors CYP3A4 and CYP2D6 (see "Method of administration and dose").With the simultaneous use of aripiprazole and weak inhibitors of isoenzymes CYP3A4 (diltiazem. escitalopram) or CYP2D6 one can expect a slight increase in the concentration of aripiprazole in the blood plasma.

Due to the fact that the isoenzyme CYP1And does not participate in the metabolism of aripiprazole, smoking does not affect the pharmacokinetics and the effect of aripiprazole.

When taking aripiprazole together with carbamazepine. powerful isoenzyme inducer CYP3A4. the metabolism of aripiprazole is enhanced, so the dose of aripiprazole should be adjusted (see "Method of administration and dose"). It is possible to expect a similar effect on other powerful inductors of isoenzymes CYP3A4 and CYP2D6.

In the metabolism of aripiprazole under conditions in vitro does not participate isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2E1, in this connection, it is unlikely that it interacts with drugs and other factors (for example, smoking) that can inhibit or activate these enzymes.

In clinical trials aripiprazole in doses of 10-30 mg / day did not have a significant effect on the metabolism of substrates of isoenzymes CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin) and CYP3A4 (dextromethorphan). Besides, aripiprazole and its main metabolite dehydroaripiprazole did not change the metabolism involving isoenzyme CYP1A2 in conditions in vitro. The clinically significant effect of aripiprazole on drugs metabolized with the participation of these isoenzymes is unlikely.

At simultaneous application of aripiprazole (10-30 mg / day) and lamotrigine (100-400 mg / day) in patients with bipolar disorder there were no changes in the pharmacokinetics of lamotrigine, so correction of its dose is not required. Aripiprazole did not affect the pharmacokinetics of escitalopram and venlafaxine in healthy volunteers, so correction of the doses of these drugs is not required when combined with aripiprazole.

When used in patients with major depressive disorder, aripiprazole concomitantly 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 was not detected.

The use of alcohol 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), the therapeutic effect develops over a period of a few days or weeks.During this period, it is necessary to carefully monitor the patient's condition.

Suicide attempts

Propensity to suicidal thoughts and attempts is characteristic for patients with psychosis, bipolar disorder and major depressive disorder, so drug therapy must be combined with careful medical supervision. Aripiprazole should be prescribed in a minimal 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 as a combination therapy with antidepressants and aripiprazole 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 neuroleptics, so if you experience aripiprazole symptoms of late 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.

Malignant neuroleptic syndrome (CNS)

In the treatment of neuroleptics, including aripiprazole. described a life-threatening symptom complex, known as malignant neuroleptic syndrome. This syndrome manifests itself as hyperpyrexia, muscle rigidity, mental disorders and instability of the autonomic nervous system (irregular heartbeats and blood pressure, tachycardia, sweating and arrhythmia). In addition, sometimes there is an increase in the activity of creatine phosphokinase in the blood plasma, myoglobinuria (rhabdomyolysis) and acute renal failure. In case of symptoms of NSA or unexplained fever, all antipsychotics, including aripiprazole. should be abolished.

Convulsions

Like other antipsychotics, aripiprazole should be used with caution in patients with a history of seizures or 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.

Mortality in the group of patients treated with aripiprazole. in comparison 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 effects

In the same studies, cerebrovascular adverse reactions have been reported (eg, stroke, transient ischemic attack), including fatal outcomes in patients (78-88 years, mean age 84 years). Cerebrovascular side-effects were registered in patients treated with aripiprazole 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. Aripiprazole is not indicated for the treatment of psychosis against a background of 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, who took atypical antipsychotics. Although the association between the administration of atypical antipsychotics and hyperglycemic-type disorders remains unclear, patients diagnosed with diabetes mellitus should regularly determine the blood glucose concentration when taking atypical antipsychotics. Patients who have risk factors for diabetes (obesity, history of diabetes in the family history), when taking atypical antipsychotics should determine the blood glucose concentration at the beginning of the course and periodically in the process of taking the drug. 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.

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, there are reports of increased 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 antipsychotics, including aripiprazole, can cause temporary changes in the blood picture - leukopenia, neutropenia, as well as agranulocytosis. Risk factors for development are a low number of white blood cells in a patient prior to treatment, as well as leukopenia and neutropenia caused by other drugs. It is necessary to regularly monitor the picture of blood in these patients, especially in the first months of treatment with aripiprazole.With a clinically significant decrease in the concentration of white blood cells of unclear etiology, consideration should be given to the abolition of the aripiprazole drug.

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. When severe neutropenia (neutrophil count less than 1000 / mm³) treatment with aripiprazole is interrupted until the blood picture is normalized.

Cardiovascular diseases

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

Violation of the conduct (lengthening interval QT)

In clinical trials, the incidence of lengthening of the interval QT in patients with aripiprazole was comparable to the placebo group.Patients with congenital syndrome of an elongated interval QT Aripiprazole, like other antipsychotics, should be used with caution.

Cognitive and motor disorders

Like other antipsychotics, aripiprazole can cause cognitive and motor disorders. In particular, clinical studies of aripiprazole reported cases of drowsiness and retardation. 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 administering aripiprazole to patients who have an increased risk of overheating due to intense physical exertion, high ambient temperature, medications with m-holin-blocking 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.

The risk of developing venous thromboembolism

The use of neuroleptics, including aripiprazole, may be associated with a risk of venous thromboembolism. In this regard, it is necessary to identify risk factors development of this complication before administration of aripiprazole, and 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 pathologies of type I bipolar disorder and ADHD, data on the safety of simultaneous administration of aripiprazole and psycho-stimulating agents. Therefore, special care should be taken when using them simultaneously.

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

When using aripiprazole, care should be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets 5 mg, 10 mg, 15 mg, 20 mg, 30 mg.

Packaging:

For 7 tablets in a planar cell pack of foil laminated aluminum and aluminum foil.

By 2, 4, 7, 8 or 14 contour mesh packages together with instructions for use in a pack of cardboard.

For 10 tablets in a planar cell box made of foil laminated aluminum and aluminum foil.

By 1, 3, 5 or 10 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-004452

Date of registration:12.09.2017

Expiration Date:12.09.2022

The owner of the registration certificate:GRINDEX, JSC GRINDEX, JSC Latvia

Manufacturer: & nbsp

SYNTHON HISPANIA, S.L. Spain

Representation: & nbspGrindeks Rus, Open CompanyGrindeks Rus, Open CompanyRussia

Information update date: & nbsp04.10.2017

Illustrated instructions

Instructions

MIRIUM (Mirium)