Instruction for use: Aripiprazole

Dosage form: substance powder

Active substance: Aripiprazole *

Composition

1 tablet contains:

Active substance

Aripiprazole 10.00 mg / 15.00 mg / 30.00 mg;

Excipients:

microcrystalline cellulose (Avicel PH 102) 40.75 mg / 61.13 mg / 122.25 mg; cellulose microcrystalline silicified (mixture of 98% microcrystalline cellulose and 2% silicon dioxide) (Prosolv HD 90) 55.00 mg / 82.50 mg / 165.00 mg; silicon dioxide colloidal anhydrous 3.00 mg / 4.50 mg / 9.00 mg; carmellose (NS 300) 20.00 mg / 30.00 mg / 60.00 mg; crospovidone (Polyplasdone XL) 5.00 mg / 7.50 mg / 15.00 mg; xylitol (Xylisorb 300) 5.00 mg / 7.50 mg / 15.00 mg; aspartame 3.00 mg / 4.50 mg / 9.00 mg; potassium acesulfame 3.00 mg / 4.50 mg / 9.00 mg; tartaric acid 3.00 mg / 4.50 mg / 9.00 mg; flavor of pineapple 501085 AR0551 0.75 mg / 1.12 mg / 2.25 mg; magnesium stearate 1.50 mg / 2.25 mg / 4.50 mg.

Description of dosage form

Tablets with a dosage of 10 mg.

Round flat tablets with a chamfer from white to light yellow with a rough surface. On one side of risk. A slight fruity odor is allowed.

Tablets with a dosage of 15 mg.

Round flat tablets with a chamfer from white to light yellow with a rough surface. On one side of risk. A slight fruity odor is allowed.

Tablets with a dosage of 30 mg.

Round biconvex from white to light yellow tablets with a rough surface. On one side of risk. A slight fruity odor is allowed.

Pharmacological group

Antipsychotic agent (antipsychotic)

Pharmacodynamics

It is assumed that the therapeutic effect of aripiprazole in schizophrenia and bipolar disorder type I caused by a combination of partial agonistic activity on dopamine D 2 and 5 -nt1a -serotoninovyh receptors and antagonistic activity against 5 -nt2 -serotoninovyh receptors. Aripiprazole possesses high in vitro affinity for D 2 - D 3 and - dopamine receptors, 5- HTia - and 5 - HT 2a -serotoninovym receptors and moderate affinity for the D 4 - dopamine and 5-HT2C - and 5 -NT7 -serotoninovym, α 1-adrenoreceptors and H1-

Aripiprazole is intensively distributed in tissues, with an apparent volume of distribution of 4.9 l / kg. At therapeutic concentrations in the blood, aripiprazole and its main metabolite are almost completely bound (more than 99%) with blood plasma proteins, mainly with albumins.

Biotransformation.

Aripiprazole undergoes pre-systemic metabolism only to a minimal extent. Aripiprazole is metabolized in the liver in three ways: dehydrogenation, hydroxylation and N-dealkylation. According to in vitro experiments, dehydrogenation and hydroxylation of aripiprazole occurs under the action of CYP 3 A 4 and CYP 2 D 6 isoenzymes, and N-dealkylation is catalyzed by the CYP 3 A 4 isoenzyme. Aripiprazole is the main active substance in the blood (metabolites have low pharmacological activity). In the equilibrium state, the area under the concentration-time curve (AUC) of dehydroaripiprazole is approximately 40% of the aripiprazole AUC in plasma.

Elimination.

After a single administration of labeled [14C] aripiprazole, approximately 25% and 55% of radioactivity is determined in urine and feces, respectively. Less than 1% of unchanged aripiprazole is determined in urine, and approximately 18%) of the accepted dose is unchanged in the intestine. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to excretion by the liver. In patients with a low activity of the CYP 2 D 6 isoenzyme, compared to patients with high CYP2D6 isoenzyme activity, the aripiprazole concentration is increased by 80%, but the concentration of dehydroaripiprazole is reduced by 30%. The mean half-life of aripiprazole is approximately 75 hours in patients with a high CYP2 D6 isoenzyme activity and 146 hours in patients with low isopyrenal activity. The equilibrium concentration is achieved after 14 days. With multiple administration, aripiprazole cumulates. 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.

Pharmacokinetics in specific patient groups

Patients of the older age group

Age differences in the parameters of pharmacokinetics of aripiprazole have not been established.

Floor

Differences in the parameters of pharmacokinetics in men and women have not been revealed.

Race

Clinical differences in pharmacokinetic parameters, depending on race, are not established. Smoking does not affect the pharmacokinetics. Parameters of pharmacokinetics of aripiprazole and its metabolite in patients with severe renal dysfunction do not differ from those in healthy volunteers.

Impaired liver function

After a single administration of aripiprazole by patients with cirrhosis, there was no significant effect of liver dysfunction on the pharmacokinetics of aripiprazole and dehydroaripiprazole. However, the study was small, which does not allow for an unambiguous conclusion.

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.

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 that is part of the drug.

Age to 18 years.

Breastfeeding period.

Carefully

In patients with cardiovascular diseases (with coronary heart disease or with myocardial infarction, with heart failure and conduction disorders), cerebrovascular diseases and conditions predisposing to arterial hypotension (dehydration, hypovolemia and taking antihypertensive drugs) in connection with the possibility of developing orthostatic hypotension , in patients with convulsions or with diseases in which cramps 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 impaired motor function of the esophagus and aspiration; in patients with obesity and in the presence of diabetes in a family history; in patients with high risk of suicide (psychotic diseases, bipolar disorders, major depressive disorder); at persons in the age of 18-24 years in connection with risk of development of suicidal behavior.

If you have any of these diseases, consult a doctor before taking the drug.

Application in pregnancy and lactation

Adequate and well-controlled studies in pregnant women have not been conducted. 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 OD-Teva may be taken during pregnancy only if the potential benefit to the mother is greater than the potential risk to the fetus. It is known that in newborns whose mothers took antipsychotics 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 passed without treatment, in other cases, newborns needed intensive care and continued hospitalization. Aripiprazole penetrates into breast milk. If necessary, breast-feeding is canceled.

Dosing and Administration

Aripiprazole OD-Teva tablets are dispersible in the oral cavity intended for oral administration. A tablet dispersible in the oral cavity should be placed in the oral cavity on the tongue where it quickly dissolves in the saliva. It can be taken with or without a liquid. The extraction of a tablet dispersible in the oral cavity from the oral cavity in an unchanged form is difficult. Since the tablet dispersible in the oral cavity is brittle, it must be taken immediately after opening the blister. Alternatively, the tablet dispersible in the oral cavity is dissolved in water and the resulting suspension is drunk.

Schizophrenia

The recommended initial dose is 10-15 mg once a day, regardless of food intake. The effectiveness of the drug is confirmed in the dose range from 10 to 30 mg / day. However, 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 usual maintenance dose is 15 mg per day. It is recommended to regularly examine patients for the need to continue therapy.

Manic or mixed episodes in bipolar disorder

Monotherapy.

The recommended initial dose is 15 mg once a day, regardless of food intake. 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 per day for 3-12 weeks was demonstrated. Safety of doses above 30 mg / day in clinical trials was not evaluated.

When observing patients with type I bipolar disorder who have had a manic or mixed episode who have had symptom stabilization against therapy with drugs at doses of 15 or 30 mg / day at an initial dose of 30 mg / day for 6 weeks and then for 6 months and further 17 months, a favorable profile of such maintenance therapy is 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 initial dose is 15 mg once a day, regardless of food intake. The dose may be increased to 30 mg per day, depending on the indications.

When observing patients with bipolar disorder type I, a favorable effect of maintenance therapy with aripiprazole at doses of 10 to 30 mg per day as an additional therapy for lithium or valproic acid was established. Periodically, patients should be examined to determine whether to continue supporting therapy.

Additional therapy for major depressive disorder

As a supplement to the treatment with antidepressants, it is recommended to prescribe the drug at an initial dose of 5 mg per day; if necessary and good tolerability of therapy, the daily dose can be increased by 5 mg a week to a maximum, but not more than 15 mg per day. Periodically, patients should be examined to determine whether to continue supporting therapy.

Use in special patient groups

Patients with renal insufficiency. Dose adjustments for prescribing patients with renal insufficiency are not required.

Patients with hepatic insufficiency.

Dose adjustments for prescribing patients with liver failure are not required, but a dose of 30 mg should be administered with caution.

Use in patients older than 65 years.

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.

The effect of smoking on the dosing regimen.

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

Correction of dose with concomitant therapy.

With the simultaneous use of the drug and potent inhibitors of the CYP 3 A 4 isoenzyme (eg, ketoconazole, clarithromycin), the dose of aripiprazole is reduced by a factor of 2. With the cancellation of CYP 3A4 isoenzyme inhibitors, the dose of aripiprazole is increased. With the simultaneous use of the drug and potent inhibitors of the CYP 2 D 6 isoenzyme (eg, quinidine, fluoxetine), the dose of aripiprazole is reduced by a factor of 2. With the cancellation of inhibitors of the isoenzyme CYP 2 D 6 or CYP 3 A 4, the dose of aripiprazole is increased. If Aripiprazole OD-Teva is prescribed as an adjunctive therapy in patients with major depressive disorder, no dosage adjustment is required. With simultaneous use of the drug and potent inhibitors of CYP 3 A 4 isoenzymes (eg, ketoconazole, clarithromycin) and CYP 2 D 6 (eg, quinidine, fluoxetine), dozearipiprazole is reduced 4-fold. With the cancellation of potent CYP 3 A 4 and / or CYP 2 D 6 isoenzymes inhibitors, the dose of aripiprazole is increased. With the simultaneous use of the drug and powerful, moderate or weak inhibitors of CYP 3 A 4 and CYP 2 D 6 isoenzymes, the dose of aripiprazole is reduced 4-fold and then titrated until the optimal therapeutic effect is achieved. Patients with a low activity of the isoenzyme CYP 2 D 6 dose are reduced by 2 times and subsequently titrated to achieve the optimal therapeutic effect. If patients with a low activity of the CYP 2 D 6 isoenzyme simultaneously with aripiprazole use powerful inhibitors of CYP 3 A 4, in such cases a four-fold reduction in the dose of aripiprazole is indicated.

With the simultaneous use of the drug and potential inducers of the CYP 3 A 4 isoenzyme (eg, carbamazepine), the dose of Aripiprazole OD-Teva is doubled. Additional increase in the dose of the drug is carried out taking into account the clinical indications. When the inducers of the CYP 3 A 4 isoenzyme are canceled, the dose of aripiprazole can be reduced to 10-15 mg / day.

Side effects

The frequency of side effects is given in accordance with the following gradation: very often:> 10%; often:> 1% and <10%; infrequently:> 0.1% and <1%; rarely:> 0.01% and <0.1%; very rarely: <0.01%.

From the hematopoiesis:

rarely - leukopenia, neutropenia, thrombocytopenia.

From the cardiovascular system:

often - orthostatic hypotension, tachycardia;

infrequent bradycardia, palpitations, myocardial infarction, QT interval prolongation, cardiac arrest, hemorrhages, atrial fibrillation, heart failure, atrioventricular blockade, myocardial ischemia, deep vein thrombosis, phlebitis, extrasystole; rarely - vasovagal syndrome, atrial flutter, supraventricular tachycardia, ventricular tachycardia, thrombophlebitis, intracranial hemorrhage, cerebral ischemia;

very rarely - fainting, high blood pressure (BP);

frequency is not defined - thromboembolism (including pulmonary embolism and deep vein thrombosis of the lower limbs).

From the nervous system:

very often - insomnia, drowsiness, headache, akathisia (in patients with bipolar disorder and in the treatment of depression in combination with antidepressants);

often - dizziness, tremor, extrapyramidal syndrome, psychomotor agitation, depression, nervousness, hostility, suicidal thoughts, manic thoughts, confusion, resistance to performing passive movements ("cogwheel" syndrome), lethargy, decreased concentration, sedation;

infrequently - dystonia, muscle twitching, paresthesia, limb tremor, bradykinesia, low / high libido, impotence, panic reactions, apathy, memory loss, stupor, amnesia, stroke, hyperactivity, depersonalization, dyskinesia, restless legs syndrome, myoclonus, depressed mood, increased reflexes, slowing of mental function, increased sensitivity to irritants, violation of oculomotor reaction; rarely - delirium, euphoria, bucco-glossal syndrome, akinesia, depression of consciousness (down to loss of consciousness), decreased reflexes, obsessive thoughts, malignant neuroleptic syndrome; very rarely - speech disorder, convulsions.

From the digestive system:

very often - nausea, loss of appetite;

often - increased appetite (when treating depression in combination with antidepressants), indigestion, vomiting, constipation, hypersecretion of saliva, dry mouth, abdominal heaviness, diarrhea;

infrequent gastroenteritis, difficulty swallowing, flatulence, gastritis, dental caries, gingivitis, hemorrhoids, gastroesophageal reflux, gastrointestinal hemorrhages, periodontal abscess, swelling of the tongue, fecal incontinence, colitis, rectal hemorrhages, stomatitis, ulceration of the oral mucosa, cholecystitis, fecaloma, mucous candidiasis of the oral cavity, belching, stomach ulcer;

rarely - esophagitis, gum bleeding, tongue inflammation, vomiting of blood, intestinal bleeding, duodenal ulcer, cheilitis, enlarged liver, perforation of the intestine;

very rarely - hepatitis, jaundice, pancreatitis, dysphagia, increased activity of ALT and ACT.

From the immune system:

very rarely - allergic reactions (including

anaphylaxis, angioedema, itching and urticaria), laryngospasm.

From the musculoskeletal system:

often - arthralgia, rigidity of muscles;

infrequently - myasthenia gravis, arthritis, arthrosis, muscle weakness, muscle spasms, bursitis;

very rarely - an increase in the activity of creatine phosphokinase, rhabdomyolysis, tendinitis, tenobursitis,

myalgia.

Respiratory system :

often shortness of breath, pneumonia;

infrequently - epistaxis, hiccough, laryngitis;

rarely - hemoptysis, increased sputum discharge, dry nasal mucosa, pulmonary edema, pulmonary embolism, hypoxia, respiratory insufficiency, apnea;

very rarely - aspiration pneumonia.

From the skin and subcutaneous tissue:

often - dry skin, itching, skin ulceration;

infrequently - acne, vesicle-bullous rash, eczema, alopecia, psoriasis, seborrhea;

rarely - maculopapular rash, exfoliative dermatitis, urticaria, hyperhidrosis.

From the sense organs:

often - blurred vision, photophobia, pain in the ears;

infrequent - dry eyes, pain in the eyes, ringing in the ears, inflammation of the middle ear, cataracts, loss of taste,

blepharitis, edema of the eyelids, photopsy, diplopia;

rarely - increased lacrimation, frequent blinking, external otitis, amblyopia, deafness, intraocular hemorrhage.

From the genitourinary system:

infrequently - cystitis, frequent urination, leukorrhea, hematuria, dysuria, amenorrhea, impotence, premature ejaculation, vaginal bleeding, vaginal candidiasis, renal failure, uterine bleeding, menorrhagia, albuminuria, nephrolithiasis, nocturia, polyuria, false urges to urinate;

rarely - pain in the mammary gland, cervicitis, galactorrhea, anorgasmia, burning in the area of the urethra and external genitalia, glycosuria, gynecomastia (enlargement of the mammary glands in men), painful erection;

very rarely - urinary incontinence, urinary retention, priapism.

Common violations:

often - asthenia, fatigue, flu-like syndrome, sensation of trembling in the body;

infrequent: peripheral edema, facial edema, malaise, photosensitivity, pain in the jaw, stiffness of the jaws, chills, bloating, tension in the chest;

rarely - sore throat, stiffness in the back, heaviness in the head, candidiasis, Mendelssohn's syndrome, sensation of a "lump" in the throat, heat stroke;

very rarely - a violation of the regulation of body temperature (including hyperthermia), pain in the chest, in the neck.

Metabolic disorders and disorders associated with diet:

often - weight loss; infrequently - dehydration, edema, hypercholesterolemia, hypokalemia, hyperlipidemia, hypoglycemia, thirst, increased urea concentration in the blood, increased activity of alkaline phosphatase, lactate dehydrogenase, iron deficiency anemia, obesity;

rarely - hyperkalemia, hypernatremia, gout, cyanosis, lower urinary pH;

very rarely - hyponatremia, increased activity of alanine aminotransferase, increased activity of aspartate aminotransferase, increased activity of creatine phosphokinase, anorexia, hyperglycemia, diabetic ketoacidosis, diabetic hyperosmolar coma. Adverse events occurring with the administration of antipsychotics have also been observed with aripiprazole therapy, including rare cases of malignant neuroleptic syndrome, as well as infrequent cases of late dyskinesia and convulsive seizures. Individual sensitive patients in the first days of treatment may have symptoms of dystonia manifested by spasm of the neck muscles, with a feeling of constriction in the throat, difficulty in swallowing, difficulty breathing, and / or protrusion of the tongue. These symptoms are most often manifested when high doses of neuroleptics of the first generation are prescribed. To the group of increased risk for the development of dystonia are men and young people.

Overdose

A random and deliberate overdose of aripiprazole with a single dose up to 1260 mg, not accompanied by a fatal outcome, is described.

Symptoms of overdose (including overdose with several substances):

vomiting, drowsiness, tremor, lethargy, increased blood pressure, tachycardia, loss of consciousness, acidosis, aggression, increased activity of aspartate aminotransferase, atrial fibrillation, bradycardia, coma, confusion, convulsions, increased activity of creatinine phosphokinase, depression of consciousness, hypokalemia, QRS, QT interval elongation, aspiration pneumonia, respiratory arrest, epileptic status and tachycardia. 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, maintenance therapy, airway patency, oxygenation, lung ventilation, activated charcoal (administration of 50 g of activated carbon 1 h after a single administration of 15 mg aripiprazole reduces the average AUC and C m aripiprazole by 50% ), symptomatic treatment, careful medical observation until all symptoms disappear. There are no data on the use of hemodialysis with aripiprazole overdose, but the effectiveness of this method is questionable, since aripiprazole is not excreted by the kidneys in unchanged form and binds to plasma proteins to a large extent.

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. Various routes of metabolism of aripiprazole are known, including with the participation of CYP 2 D 6 and CYP 3 A 4 isoenzymes. In studies in healthy volunteers, potent inhibitors of CYP 2 D 6 (quinidine) and CYP 3 A 4 (ketoconazole) isoenzymes reduced aripiprazole clearance inside by 52% and 38%, respectively; therefore, the dose of aripiprazole should be reduced when used in combination with inhibitors of CYP 3 A 4 and CYP 2 D 6 isoenzymes. When using aripiprazole and weak CYP 3 A 4 (diltiazem, escitalopram) or CYP 2 D 6 isoenzymes concurrently, a small increase in concentration aripiprazole in blood plasma. The intake of 30 mg of aripiprazole together with carbamazepine (a potent inducer of the isoenzyme CYP 3A 4) was accompanied by a decrease in C m ax and AUC of aripiprazole by 68% and 73%, respectively, and a decrease in C max and AUC of its active metabolite (dehydroaripiprazole) by 69% and 71%, respectively. Similar effects can be expected for other potent inducers of CYP 3 A 4 and CYP 2 D 6 isoenzymes. In the metabolism of aripiprazole, the isoenzyme CYP 1 A 1, CYP 1 A 2, CYP 2 A 6, CYP 2 B 6, CYP 2 C 8, CYP 2 C 9, CYP 2 C 19 and CYP 2 E 1, and it is unlikely that it interacts with drugs and other factors (eg, smoking) that are capable of inhibiting or inducing these isoenzymes. Simultaneous administration of lithium or valproic acid with 30 mg of aripiprazole did not have a clinically significant effect on the pharmacokinetics of aripiprazole. In clinical studies, aripiprazole at doses of 10-30 mg / day had no significant effect on the metabolism of substrates of isoenzymes CYP 2 D 6 (dextromethorphan), CYP 2 C 9 (warfarin), CYP 2 C 19 (omeprazole, warfarin) and CYP 3 A 4 (dextromethorphan). In addition, aripiprazole and its main metabolite dehydroaripiprazole did not alter the biotransformation of drugs metabolized by the CYP 1 A 2 isoenzyme in vitro. The clinically significant effect of aripiprazole on drugs metabolized with the participation of these isoenzymes is unlikely. The use of alcohol during treatment with aripiprazole may increase the sedative effect of the drug. With the following drugs pharmacokinetic interaction is absent or has no clinical significance: famotidine, valproic acid, lithium preparations, lamotrigine, dextromethorphan, warfarin, omeprazole, lorazepam, venlafaxine, fluoxetine, paroxetine, sertraline. Caution should be exercised with the simultaneous use of aripiprazole and medications that cause prolongation of the QT interval or disturb the electrolyte balance.

Special instructions

Psychoses associated with senile dementia and Alzheimer's disease.

In patients with psychoses due to senile dementia, in the treatment of neuroleptics (predominantly atypical), the risk of a lethal outcome increases. The main cause of death was cardiovascular (heart failure, sudden death) and infectious (pneumonia) causes. In patients older than 65 years with psychoses due to Alzheimer's disease, the following undesirable drug reactions were noted: lethargy, drowsiness, incontinence (mostly urine), hypersalivation, pre-patch. Aripiprazole OD-Teva is not indicated for the treatment of patients with psychoses due to senile dementia. Suicide. 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. In children, adolescents and young people (under 24 years) with depression, other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when appointing aripiprazole or any other antidepressants in young people (aged 18-24 years), the risk of suicide and the benefits of their use should be correlated. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for early detection of abnormalities or behavioral changes, as well as suicidal tendencies. Aripiprazole OD-Teva should be prescribed in a minimal amount sufficient to treat the patient; this will reduce the risk of overdose.

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 arterial pressure, tachycardia, sweating and cardiac arrhythmias). In addition, in some cases 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 aripiprazole, should be discontinued and therapy immediately started to stop this condition.

Late dyskinesia.

The risk of developing tardive dyskinesia (potentially irreversible) increases with the duration of therapy with antipsychotics, therefore, if the symptoms of tardive dyskinesia appear on the background of taking Aripiprazole OD-Teva, you should reduce the dose of this drug or cancel it. Symptoms of dyskinesia may first appear or temporarily increase, even after the abolition of therapy. However, in some cases, despite the symptomatology, the continuation of the treatment is indicated.

Other extrapyramidal disorders

In clinical studies of aripiprazole in children, akathisia and parkinsonism were observed. In the case of the appearance of signs and symptoms of other extrapyramidal disorders, one should consider the possibility of reducing the dose of aripiprazole followed by monitoring the patient.

Hyperglycemia and diabetes mellitus.

Hyperglycemia, in some cases expressed and accompanied by ketoacidosis or hyperosmolar coma with a fatal outcome, was noted in patients taking atypical antipsychotics. Although the association between the administration of atypical antipsychotics and hyperglycemic disorders remains unclear, patients who have diabetes mellitus should regularly perform a blood glucose test when taking atypical antipsychotics. Patients who have risk factors for developing 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 the drug. Patients taking atypical antipsychotics need constant monitoring of symptoms of hyperglycemia, including increased thirst, frequent urination, polyphagia, weakness; special attention should be given to patients with diabetes mellitus and risk factors for its development.

Hypersensitivity.

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

Orthostatic hypotension.

In connection with the risk of orthostatic hypotension (due to blockade of α 1 -adrenoceptors), aripiprazole should be used with caution in patients with cardiovascular diseases (myocardial infarction, coronary heart disease, heart failure, cardiac conduction abnormalities in the anamnesis), cerebral circulation disorders or states predisposing to arterial hypotension (dehydration, hypovolemia, hypotensive therapy).

Leukopenia, neutropenia and agranulocytosis.

In the course of clinical trials and post-registration experience, neuroleptics, including aripiprazole, can cause leukopenia, neutropenia and agranulocytosis. A possible risk factor may be a low white blood cell count, drug leukopenia / neutropenia. Such patients show a regular general blood test with leukoformula (especially in the first months of therapy). At the first sign of a clinically significant reduction in the white blood cell count, aripiprazole is canceled (if this reaction can not be explained by other causes). Patients with clinically significant neutropenia should be carefully monitored for elevated temperature or other signs of infection with a view to initiating appropriate treatment immediately. In severe neutropenia (the number of neutrophils is less than 1OOO mm3), treatment of the drugs is discontinued.

Convulsions.

Like other antipsychotics, aripiprazole should be used with caution in patients with a history of seizures and the risk of their development (eg, dementia due to Alzheimer's disease). Such conditions often develop in people older than 65 years.

Violation of cognitive and motor abilities.

Aripiprazole, like other antipsychotics, can cause disturbances in thinking and motor skills, there have been cases of drowsiness and inhibition, which should be taken into account when driving vehicles and engaging in other potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Violation of body temperature regulation.

Neuroleptics can cause a violation of the regulation of body temperature. Patients who are at increased risk of thermoregulation disorders (increased physical activity, exposure to high temperatures, use of m-holinoblokatorov, hypohydration), it is necessary to provide appropriate care.

The risk of venous thromboembolism.

The use of neuroleptics, including aripiprazole, may be associated with a risk of venous thromboembolism. In this regard, risk factors for the development of this complication should be identified before administration of aripiprazole, as well as during treatment with this drug. If necessary, measures should be taken to prevent the development of venous thromboembolism. Dysphagia.

When using neuroleptics, cases of peristalsis of the esophagus and, as a consequence, aspiration pneumonia were noted. Caution should be exercised when prescribing to patients with risk factors for the development of aspiration pneumonia.

Alcohol consumption.

You should refrain from drinking alcohol during treatment with aripiprazole.

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 with aripiprazole.

Patients with concomitant attention deficit hyperactivity disorder (ADHD).

Despite the high frequency of combination of type I bipolar disorder and ADHD, very limited data on the safety of simultaneous use

aripiprazole and psychostimulants, so you should be careful if they are used together.

Impact on the ability to drive vehicles and mechanisms

Care should be taken when driving vehicles and engaging in other activities that require increased concentration and speed of psychomotor reactions, as it can cause drowsiness and dizziness. Patients should be warned about the need to be careful until patients are not sure that the drug does not adversely affect them.

Release form

Tablets are dispersible in the oral cavity 10 mg, 15 mg, 30 mg.

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 expiration date.

Conditions of leave from pharmacies

On prescription.