Alembik Pipzol - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate 42.84 mg, cellulose microcrystalline 32.78 mg, giprolose 2.85 mg, corn starch 4.75 mg, crospovidone 2.85 mg, silicon dioxide colloid 0.48 mg, indigocarmine 2.50 mg, magnesium stearate 0.95 mg.

One 10 mg tablet contains: active substance: aripiprazole 10 mg;

Excipients: lactose monohydrate 39.51 mg, cellulose microcrystalline 32.78 mg, giprolose 2.85 mg, corn starch 4.75 mg, crospovidone 2.85 mg, silicon dioxide colloid 0.48 mg, pigment mixture PB-24880 pink * 0.83 mg, magnesium stearate 0.95 mg.

One 15 mg tablet contains: active substance: aripiprazole 15 mg;

Excipients: lactose monohydrate 58.01 mg, cellulose microcrystalline 49.17 mg, giprolose 4,275 mg, corn starch 7,125 mg, crospovidone 4,275 mg, silicon dioxide colloid 0,72 mg, pigment mixture PB-52290 yellow ** 2.50 mg, magnesium stearate 1.425 mg.

One 30 mg tablet contains: active substance: aripiprazole 30 mg;

Excipients: lactose monohydrate 118.52 mg, cellulose microcrystalline 98.34 mg, giprolase 8.55 mg, corn starch 14.25 mg, crospovidone 8.55 mg, silicon colloidal dioxide 1.44 mg, a mixture of pigments RV-24880 pink * 2.50 mg, magnesium stearate 2.85 mg.

* Mixture of pigments РВ-24880 pink: lactose monohydrate 90.0%, iron dye red oxide (E172) 10.0%.

** Pigment mixture PB-52290 yellow: lactose monohydrate 25.0%, iron dye oxide yellow (E172) 75.0%.

Description:

Dosage of 5 mg: rectangular flat with rounded edges of a tablet of blue color with impregnations, on one side engraving "250".

Dosage of 10 mg: rectangular flat with rounded edges pills of light pink color with impregnations, on one side engraving "252".

Dosage of 15 mg: round flat-cylindrical with a bevel of a yellow colored tablet with inclusions, on one side an engraving "253".

Dosage of 30 mg: round planocylindrical with a bevel of a tablet of light pink color with impregnations, on one side engraving "L255".

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 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 D₃dopamine receptors, 5-HT1a- and 5-HT_2Aserotonin receptors and moderate affinity for D4-dopamine, 5-HT_2C- and 5-HT₇-serotonin, α₁adrenoceptors and H₁-histamine receptors. Aripiprazole is characterized also moderate affinity for serotonin reuptake sites and a lack of significant affinity for m-cholinergic receptors.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, while its maximum concentration in the blood plasma is reached in 3-5 hours. Aripiprazole is minimally subjected to pre-systemic metabolism. Absolute bioavailability of tablets is 87%. Foods high in fat do 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 aripiprazole and dehydroaripiprazole more than 99% bind to 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 concentration-time curve (AUC) dehydroaripiprazole, the main metabolite, is about 40% AUC aripiprazole in blood plasma.

Excretion

The mean half-life (T_1/2) of aripiprazole is approximately 75 hours in patients with high isoenzyme activity CYP2D6 and approximately 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 feces. Less than 1% of unchanged aripiprazole is excreted in the urine, and approximately 18% of the accepted dose is excreted unchanged from the faeces.

Pharmacokinetics in specific patient groups

Application the 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 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, only three patients with cirrhosis class C according to the Child-Pugh classification, in connection with which it is impossible to draw definitive conclusions on their metabolic activity.

Indications:

- Schizophrenia: acute attacks and maintenance therapy;

- manic episodes in 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;

- Supplement to therapy with lithium or valproic acid for the treatment of manic or mixed episodes in the first type of bipolar disorder with or without psychotic symptoms and maintenance therapy to prevent relapse in patients with type I bipolar disorder;

- addition to antidepressant therapy for major depressive disorder.

Contraindications:

- Hypersensitivity to aripiprazole or any other component in the formulation;

- hereditary galactosemia, lactase deficiency, glucose-galactose malabsorption;

- age 18 years (efficacy and safety not established);

- the period of breastfeeding.

Carefully:

Cardiovascular diseases (coronary heart disease (CHD) or previous myocardial infarction, chronic heart failure (CHF) or conduction disorders); cerebrovascular diseases and conditions predisposing to the development of arterial hypotension (dehydration, hypovolemia, use of antihypertensive drugs) in connection with the possibility of developing orthostatic hypotension; patients with convulsions or with diseases in which cramps are possible; increased risk of hyperthermia (for example, intense physical exertion, overheating, use of m-holinoblokatorov, dehydration, as 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 the familyanamnesis; 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.

Pregnancy and lactation:

Adequate and well-controlled studies in pregnant women have not been conducted. It is not known whether the use of the drug by 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, increased or decreased blood pressure, 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.

The drug can be taken during pregnancy only if the potential benefit to the mother is greater than the potential risk to the fetus.

Aripiprazole penetrates into breast milk. When applying the drug, breastfeeding should be discontinued.

Dosing and Administration:

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

Schizophrenia

The recommended initial dose is 10-15 mg once daily.

The maintenance dose is usually 15 mg / day.

The effectiveness of the drug is confirmed in the dose range from 10 to 30 mg / day. Increasing the dose more than 15 mg / day does not increase the effectiveness of the drug. The dose is increased not earlier than in 2 weeks.

The maximum daily dose is 30 mg.

Manic episodes with type I bipolar disorder

Monotherapy

The recommended initial dose is 15 mg once a day.

The dose change, if necessary, is carried out with an interval of at least 24 hours. In manic episodes, the effectiveness of the drug in doses of 15-30 mg / day with a dose of 3-12 weeks was demonstrated. The maximum daily dose is 30 mg.

When observing patients with type I bipolar disorder who have had a manic or mixed episode, who had a symptom stabilization against the background of taking the drug 15 or 30 mg / day at an initial dose of 30 mg / day for 6 weeks, and then for 6 months and beyond - 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.

As an adjunct to therapy with lithium or valproic acid The recommended starting dose is 10 mg to 15 mg once a day, regardless of food intake. The maintenance dose is usually 15 mg / day. The dose can be increased to 30 mg / day, depending on the clinical indications.

When observing patients with type I bipolar disorder, a favorable effect of maintenance therapy with a drug from 10 mg to 30 mg per day was added as a supplement to therapy with lithium or valproic acid. Periodically, patients should be examined to determine whether to continue supporting therapy.

Additional therapy for major depressive disorder

As an additional therapy to treatment with antidepressants, it is recommended to prescribe the drug in 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 no more than 15 mg per day.

The duration of drug 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.

Use in special patient groups

Patients with renal insufficiency

Correction of the dose is not required.

Patients with hepatic insufficiency

Patients with mild and moderate hepatic insufficiency do not need dose adjustment. 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 administered with caution.

Patients over 65 years of age

Correction of the dose is not required.

Effect of the patient's sex on the dosing regimen

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 aripiprazole and potent inhibitors of isoenzyme CYP3A4 (ketoconazole, clarithromycin), the dose of aripiprazole should be reduced 2 times. When cancellation of isoenzyme inhibitors CYP3A4, the dose of aripiprazole 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 2 times. When cancellation of isoenzyme inhibitors CYP2D6 the dose of aripiprazole should be increased.

The drug should be used without changing the dosage regimen if it is prescribed as an adjunctive therapy in 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% (that is, up to 25% of the usual dose). When cancellation of isozyme inhibitors CYP2D6 and / or CYP3A4, the dose of aripiprazole should be increased.

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

Patients with low isoenzyme activity CYP2D6 Initially, the dose of aripiprazole should be reduced 2-fold, and then increased to achieve the optimal clinical outcome. With the simultaneous use of aripiprazole and a potent inhibitor of isoenzyme CYP3A4 patients with low isoenzyme activity CYP2D60 the dose of aripiprazole should be reduced by% (that is, up to 25 % 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, the 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 of adverse reactions were spontaneous. Therefore, the frequency of these undesired reactions is indicated as "frequency unknown ".

	Often	Infrequently	Frequency unknown
Violations of the blood and lymphatic system			Leukopenia Neutropenia Thrombocytopenia
Immune system disorders			Allergic reactions (for example, anaphylactic reactions, angioedema, including swelling of the tongue, swelling of the tongue, swelling of the face, itching or urticaria)
Disorders from the endocrine system		Hyperprolactinemia	Diabetic hyperosmolar coma Diabetic ketoacidosis Hyperglycemia
Disorders of metabolism and nutrition	Diabetes	Hyperglycaemia	Hyponatremia Anorexia Decreased body weight Weight gain
Violations psyche	Insomnia Anxiety Anxiety	Depression Increased sexuality	Attempted suicide, suicidal thoughts and perfect suicide Pathological addiction to gambling games Aggression Excitation Nervousness
Disturbances from the nervous system	Akathisia Extrapyramidal disorders Tremor Headache Sedative Effect Drowsiness Dizziness	Late dyskinesia Dystonia	Malignant neuroleptic syndrome (CNS) Great seizure Serotonin syndrome Violation of speech
Disturbances on the part of the organ of sight	Unclear view	Diplopia
Heart Disease		Tachycardia	Sudden Death Polymorphic ventricular tachycardia of the type "pirouette" QT interval prolongation Ventricular arrhythmia Cardiac arrest Bradycardia
Vascular disorders		Orthostatic hypotension	Venous thromboembolism (including pulmonary embolism and deep vein thrombosis) Increased blood pressure Fainting
Disturbances from the respiratory system, chest and mediastinal organs		Hiccups	Aspiration pneumonia Laryngospasm Oral arterial spasm
Disorders from the gastrointestinal tract	Constipation Dyspepsia Nausea Hyper secretion saliva Vomiting		Pancreatitis Dysphagia Diarrhea Discomfort in the abdomen Discomfort in the stomach
Disturbances from the liver and bile ducts			Liver failure Hepatitis Jaundice Increased activity alanine aminotransferase (ALT) Increase in activity of aspartate aminotransferase (ACT) Increase in activity of gamma glutamyl transferase (GGT) Increased activity of alkaline phosphatase
Disturbances from the skin and subcutaneous tissues			Rash Photosensitivity Alopecia Hyperhidrosis
Disturbances from musculoskeletal and connective tissue			Rhabdomyolysis Muscle Pain Rigidity
Disorders from the kidneys and urinary tract			Urinary Incontinence Urinary retention
Pregnancy, postpartum and perinatal conditions			The syndrome of "cancellation" in newborns
Violations of the genitals and mammary gland			Priapism
Are common disorders and disorders at the site of administration	Fatigue		Disturbances in temperature regulation (eg, hypothermia, pyrexia) Pain in the chest Peripheral edema
Laboratory and instrumental data			Increased blood glucose levels Increase in the level of glycated hemoglobin Fluctuations in blood glucose Increased activity of creatinine phosphokinase

Overdose:

Symptoms: lethargy, increased blood pressure, drowsiness, tachycardia, nausea, vomiting, loss of consciousness. Hospitalized patients showed no clinically significant changes in the basic physiological parameters, laboratory parameters and electrocardiogram (ECG).

Potentially dangerous symptoms of overdose include drowsiness, 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 all symptoms disappear.

Drug reactions should be considered.

Activated charcoal (50 g), administered 1 hour after administration of aripiprazole, reduced AUC and C_m_Oh aripiprazole at 51 and 41%, respectively, which allows us to recommend its use in overdose.

Data on the use of hemodialysis in case of an overdose of aripiprazole are absent; The favorable effect of this method is unlikely, since aripiprazole is not excreted by the kidneys in an unchanged form and is largely associated with plasma proteins.

Interaction:

Aripiprazole can enhance the effect of certain antihypertensive drugs, since it has antagonistic action against α₁adrenoreceptors. The mechanism of action of aripiprazole is associated with influence on the central nervous system (CNS), therefore caution should be exercised when aripiprazole is used together with alcohol or drugs having a central effect, as this may exacerbate a side effect such as sedation. Caution should be exercised with the simultaneous use of aripiprazole and drugs that cause lengthening of the interval QT or disturb the electrolyte balance.

Effect of the use of other drugs on aripiprazole

Block H₂-gistaminovyh receptors famotidine reduces the rate of absorption of aripiprazole, however, it is believed that this has no clinically significant effect. Aripiprazole metabolized by various routes, including with the participation of isoenzymes CYP2D6 and CYP3A4, However, it is not metabolized with the participation of isoenzyme CYP1A. Therefore, adjusting the dose to smokers is not required.

Quinidine and other isoenzyme inhibitors CYP2D6

The results of a clinical study involving healthy patients showed that a potent inhibitor of the isoenzyme CYP2D6 (quinidine) increases AUC aripiprazole by 107%, while the index C_m_Oh remains unchanged. Indicators AUC and C_m_Ohdehydroaripiprazole, an active metabolite, were reduced by 32% and 47%, respectively. It is necessary to reduce the dose of aripiprazole by approximately half of the prescribed dose while using aripiprazole with quinidine. Other potent inhibitors of isoenzyme CYP2D6, such as fluoxetine and paroxetine, can have a similar effect, so a similar reduction in the dose of aripiprazole in the case of their simultaneous application is recommended.

Ketoconazole and other isoenzyme inhibitors CYP3A4

The results of a clinical study involving healthy patients showed that a potent inhibitor of the isoenzyme CYP3A4 (ketoconazole) increases the indicators AUC and C_m_Oh aripiprazole at 63 % and 37%, respectively. Indicators AUC and C_m_Ohdehydroaripiprazole increased by 77% and 43%, respectively. In slow isoenzyme metabolizers CYP2D6 simultaneous application of powerful inhibitors of isoenzyme CYP3A4 can lead to a higher concentration of aripiprazole in the blood plasma compared to fast metabolizers of the isoenzyme CYP2D6.

When considering the simultaneous use of ketoconazole or other potent inhibitors of isoenzyme CYP3A4 with aripiprazole, the possible benefit should exceed the possible risk to the patient. With the simultaneous use of ketoconazole and aripiprazole, the dose of aripiprazole should be reduced by approximately half the prescribed dose. With the combined use of aripiprazole with other potent inhibitors of isoenzyme CYP3A4, such as itraconazole and HIV protease inhibitors, a similar action can be expected, so the dose of aripiprazole should also be reduced.

In the event of discontinuation of the isoenzyme inhibitor CYP2D6 or CYP3A4, The dose of aripiprazole should be increased to a level appropriate for the level before the start of the joint application.

With the simultaneous use of aripiprazole and weak inhibitors of isoenzymes CYP3A4 (such as diltiazem or escitalopram) or CYP2D6 one can expect a slight increase in the concentration of aripiprazole in the blood plasma.

Carbamazepine and other isoenzyme inducers CYP3A4

With the simultaneous use of carbamazepine, a powerful isoenzyme inducer CYP3A4, geometric means C_m_Oh and AUC aripiprazole decreased 68% and 73%, respectively, compared with the use of aripiprazole (30 mg) as monotherapy. Similarly, with the simultaneous use of dehydroaripiprazole and carbamazepine, the geometric mean C_m_Ohand AUC decreased by 69% and 71%, respectively, compared with the use of aripiprazole in the form of monotherapy.

When combined with carbamazepine, the dose of aripiprazole should be increased 2-fold. With the combined use of aripiprazole with other powerful isoenzyme inducers CYP3A4 (such as rifampicin, rifabutin, phenytoin, phenobarbital, primidon, efavirenz, nevirapine and St. John's wort), you can expect a similar effect, so the dose of aripiprazole should be increased. In the event of termination of reception of powerful isoenzyme inducers CYP3A4, the dose of aripiprazole should be reduced to the recommended dose.

Valproic acid and lithium preparations

With the simultaneous use of aripiprazole with preparations of valproic acid or lithium, there were no significant clinical changes in the concentration of aripiprazole in the blood plasma.

Serotonin syndrome

Cases of serotonin syndrome were recorded in patients taking aripiprazole, and the possible signs and symptoms of this condition may appear especially when used with other serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSRIs), or with drugs that increase the aripiprazole concentration in the plasma blood.

Effect of aripiprazole on other drugs

In clinical trials aripiprazole in doses of 10-30 mg / day had no significant effect on the metabolism of substrates of isoenzymes CYP2D6 (dextromethorphan / 3-methoxymorphinan), CYP2C9 (warfarin), CYP2C19 (omeprazole) and CYP3A4 (dextromethorphan). Besides, aripiprazole and dehydroaripiprazole did not change the biotransformation of drugs metabolized by isoenzyme CYP1A2 in vitro. Thus, it is unlikely that aripiprazole can cause a clinically significant effect on the interaction of drugs metabolized with the participation of these isoenzymes.

With the simultaneous use of aripiprazole with valproic acid, lithium or lamotrigine, there was no clinically significant change in the concentration of valproic acid, lithium or lamotrigine in blood plasma.

Special instructions:

With the use of antipsychotic drugs, the therapeutic effect develops from several days to several weeks. During this period, it is necessary to carefully monitor the patient's condition.

Suicide attempts

The phenomenon of suicidal behavior is characteristic for psychoses and mood disorders, in some cases it is observed immediately after the beginning or change of treatment with antipsychotics, including treatment with aripiprazole. When treating with antipsychotic drugs, it is necessary to carefully monitor patients who are at high risk.

The results of the epidemiological study showed that patients with schizophrenia or bipolar disorder did not have an increased risk of suicidality when treated with aripiprazole, compared to other antipsychotics. There is insufficient clinical data,to assess this risk in younger patients (under the age of 18), but there is reason to believe that the risk persists after 4 weeks of treatment with antipsychotics, including aripiprazole.

Cardiovascular diseases

Aripiprazole should be used with caution in patients with cardiovascular disease (myocardial infarction or coronary heart disease, heart failure or cardiac conduction abnormalities in the anamnesis), disorders of cerebral circulation, conditions predisposing to arterial hypotension (dehydration, hypovolemia and antihypertensive therapy) or hypertension, including essential or malignant. When using antipsychotic drugs, cases of venous thromboembolism (VTE) have been reported. Since patients undergoing antipsychotic medications often have acquired risk factors for the development of VTE, it is necessary to identify all possible risk factors for developing VTE before and during treatment with aripiprazole with preventive measures.

Elongation is interesting FROM

In clinical studies of aripiprazole, the frequency of occurrence of lengthening interval QT was comparable to the placebo group. Aripiprazole, like other antipsychotics, should be used with caution in patients who have a family history of lengthening the interval QT.

Late dyskinesia

In clinical studies lasting 1 year or less, during the treatment with aripiprazole, infrequent cases of dyskinesia requiring urgent treatment were observed. If a patient exhibits signs and symptoms of tardive dyskinesia when treating aripiprazole, consider reducing the dose or stopping treatment. These symptoms may temporarily increase or even appear for the first time after the abolition of therapy.

Other extrapyramidal disorders

In clinical studies of aripiprazole in children, akathisia and parkinsonism were observed. In case of signs and symptoms of other extrapyramidal disorders in patients taking aripiprazole, the possibility of dose reduction and careful clinical observation of the patient should be considered.

Malignant neuroleptic syndrome (CNS)

Malignant neuroleptic syndrome is a potentially life-threatening combination of symptoms associated with the use of antipsychotics. In clinical studies during the treatment with aripiprazole, rare cases of CNS were observed. Clinical manifestations of CNS are hyperpyrexia, muscle rigidity, mental disorders and instability of the autonomic nervous system (irregular pulse or arterial pressure, tachycardia, increased sweating and cardiac arrhythmia). Additional signs may include an increase in the activity of creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Nevertheless, there have been cases of an increase in the activity of creatine phosphokinase and rhabdomyolysis, not associated with the NSA. In the event of signs and symptoms of CNS or unexplained fever without additional clinical manifestations of NSA, all antipsychotics, including aripiprazole, should be canceled.

Convulsions

In clinical studies during the treatment with aripiprazole, infrequent cases of seizures were observed. therefore aripiprazole should be used with caution in patients with a history of seizures or the risk of their development.

Psychoses, associated with senile dementia

Increased mortality

In three placebo-controlled clinical trials of aripiprazole in elderly patients (938 patients, mean age 82.4 years, age range 56-99 years) with psychosis due to Alzheimer's disease, there was an increased risk of death compared to the placebo group. Mortality at admission aripiprazole was 3.5% compared with 1.7% in the placebo group. Although the causes of death varied, the main causes of most deaths were either cardiovascular disorders (including heart failure, sudden death), or the development of infection (including pneumonia).

Cerebrovascular undesirable reactions

In the same clinical trials, elderly patients (mean age 84 years, age range 78-88 years) reported the development of cerebrovascular unwanted reactions (including stroke, transient ischemic attack), including fatal outcome.In general, in 1.3% of patients with aripiprazole treatment, cerebrovascular unwanted reactions were observed compared with 0.6% of patients receiving placebo. This difference was not statistically significant. Nevertheless, in one of these studies of a fixed dose of aripiprazole, a significant dose-to-cerebrovascular undesirable reaction was found. Aripiprazole It is not recommended for use in patients with psychoses due to dementia.

Hyperglycemia and diabetes mellitus

Hyperglycemia, sometimes expressed and accompanied by ketoacidosis or hyperosmolar coma with fatal outcome, was noted in patients taking atypical antipsychotics, including aripiprazole. The risk factors for serious complications in patients include obesity and diabetes in the family history. In clinical trials of aripiprazole, there was no significant difference in the incidence of adverse events associated with hyperglycemia (including diabetes) or in changing laboratory glucose values compared to the placebo group.There is no accurate comparative assessment of the risks of development of adverse reactions associated with hyperglycemia in patients taking aripiprazole and other atypical antipsychotics. In patients taking atypical antipsychotics, including aripiprazole, constant monitoring of symptoms of hyperglycemia (increased thirst, frequent urination, polyphagia and weakness) is necessary. Patients with diabetes mellitus or with risk factors for developing diabetes should regularly be assessed for blood glucose.

Hypersensitivity

As with other medications, hypersensitivity reactions may develop in the form of allergic symptoms when taking aripiprazole.

Weight gain

Weight gain is usually seen in patients with schizophrenia and bipolar mania due to the development of concomitant diseases, the use of antipsychotics that cause weight gain, unhealthy lifestyles, and can lead to serious complications. Reports of cases of weight gain were obtained in the postmarketing period in patients who took aripiprazole. Usually, these adverse reactions were observed in patients with significant risk factors, such as diabetes mellitus, thyroid disease or pituitary adenoma. In clinical trials, the administration of aripiprazole did not produce a clinically significant increase in body weight in adult patients. In clinical studies of adolescent patients with bipolar mania, when receiving aripiprazole, body weight increased after 4 weeks of treatment. It is necessary to continuously monitor body weight in adolescent patients with bipolar mania. If the increase in body weight is clinically significant, it is necessary to reduce the dose of aripiprazole.

Dysphagia

When using antipsychotics, including aripiprazole, cases of peristalsis of the esophagus and aspiration were noted. Aripiprazole and other antipsychotics should be used with caution in patients at risk of developing aspiration pneumonia.

Pathological attraction to gambling

In the post-registration period, there were reports of pathological attraction to gambling in patients taking aripiprazole, regardless of whether these patients had a pathological attraction to gambling in the anamnesis. Patients with an anamnesis pathological attraction to gambling may be at increased risk for developing this disorder and should be carefully monitored.

Lactose

The drug contains lactose, therefore it is not recommended for patients who have rare hereditary diseases associated with intolerance to galactose, deficiency of lactase or glucose-galactose malabsorption.

Patients with concomitant attention deficit hyperactivity disorder (ADHD)

Despite the high frequency of the combination of bipolar disorder type I and ADHD, there are very limited data on the safety of simultaneous use aripiprazole and psychostimulants, so caution should be exercised when using these medicines together.

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

During the treatment period, care must be taken when driving vehicles and engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets 5 mg, 10 mg, 15 mg, 30 mg.

Packaging:

For 10 tablets per blister of OPA / Al / PVC film and aluminum foil. 1 blister with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use at the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004135

Date of registration:13.02.2017

Expiration Date:13.02.2022

The owner of the registration certificate:Alembic Pharmaceuticals, LimitedAlembic Pharmaceuticals, Limited India

Manufacturer: & nbsp

Alembic Pharmaceutical Limited India

Representation: & nbspAlembic Pharmaceuticals, LimitedAlembic Pharmaceuticals, LimitedIndia

Information update date: & nbsp22.03.2017

Illustrated instructions

Instructions

Alepbik Pipzol (Alembik Pipzol)