Aripiprazole-Teva - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 31.05 mg / 62.10 mg / 93.15 mg / 186.30 mg; microcrystalline cellulose (Avicel PH 101) 5.00 mg / 10.00 mg / 15.00 mg / 30.00 mg; corn starch 5.00 mg / 10.00 mg / 15.00 mg / 30.00 mg; giprolase (Klucel ExF) 2.00 mg / 4.00 mg / 6.00 mg / 12.00 mg; sodium croscarmellose (AC-D1-SOL) 1.50 mg / 3.00 mg / 4.50 mg / 9.00 mg; magnesium stearate 0.40 mg / 0.80 mg / 1.20 mg / 2.40 mg; ferric oxide yellow oxide (E 172) 0.05 mg / 0.10 mg / 0.15 mg / 0.30 mg.

Description:

Tablets 5 mg: round light yellow colored tablets with bevelled edges.

Tablets 10 mg: oblong light yellow colored pills with a risk on one side.

Tablets 15 mg: round light yellow colored tablets with bevelled edges with a risk on one side.

Tablets 30 mg: round biconvex light yellow colored pills with a risk on one side.

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 a partial agonist activity against D2-dopamine and 5-HT1a-serotonin receptors and antagonistic activity against 5-HT2-serotonin receptors. Aripiprazole has a high affinity in vitro to D₂- and D₃- dopamine receptors, 5-HT_1A- 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 also characterized by moderate affinity for the sites of serotonin reuptake and lack of affinity for m-holinoretseptoram. Aripiprazole in animal experiments showed antagonism with respect to dopaminergic hyperactivity and agonism in relation to dopaminergic hypoactivity.Some clinical effects of aripiprazole may be due to interactions with other than dopamine and serotonin receptors.

When aripiprazole is administered internally in healthy volunteers at a dose of 0.5 to 30 mg once a day for 2 weeks, a dose-dependent decrease in the binding of 11C-rakloprid, ligand D2/D3dopamine receptors, with a caudate nucleus and a fence (according to positron emission tomography data).

Pharmacokinetics:

Absorption. After taking the drug Aripiprazole-Teva inside aripiprazole quickly absorbed, while its maximum concentration in blood plasma is reached after 3-5 hours. Absolute bioavailability of tablets is about 85-90%. Food intake for the bioavailability of aripiprazole is not affected, but it slows the time to reach the maximum concentration of aripiprazole and dehydroaripiprazole (active metabolite) in blood plasma at 3 and 12 hours, respectively.

Distribution. Aripiprazole 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 almost completely bind (more than 99%) with plasma proteins, mainly - with albumins.

Biotransformation. Aripiprazole is subjected to presystemic metabolism only to a minimal extent. Aripiprazole metabolized in the liver in three ways: dehydrogenation, hydroxylation and N-dealkylation. According to 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 (metabolites have low pharmacological activity). At equilibrium the area under the concentration-time curve (AUC) dehydroaripiprazole is about 40% of AUC aripiprazole in plasma.

Elimination. After a single dose of labeled [¹⁴C] aripiprazole of about 27% and 60% of radioactivity is determined in urine and feces, respectively. Less than 1% of unchanged aripiprazole is determined in urine, and approximately 18% of the dose taken is unchanged in the intestine. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to excretion by the liver.

In patients with low isoenzyme activity CYP2D6 compared with patients with high isoenzyme activity CYP2D6 the concentration of aripiprazole 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 high isoenzyme activity CYP2D6 and 146 hours in patients with low activity. The equilibrium concentration is achieved after 14 days. With multiple reception 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.
Rare hereditary galactosemia, lactase deficiency, glucose-galactose malabsorption.
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 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 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.

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-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 neuroleptics during the III trimester of pregnancy, there is a risk of development of extrapyramidal disorders and / or withdrawal syndrome in the postpartum period. 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:

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 were symptomatically stabilized against therapy with drugs at doses of 15 or 30 mg / day at an initial dose of 30 mg / day in from 6 weeks, and then 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 isoenzyme CYP3A4 (eg, ketoconazole or clarithromycin) the dose of aripiprazole is reduced by 2 times. When cancellation of isoenzyme inhibitors CYP3A4, the dose of aripiprazole is increased.

With the simultaneous use of the drug and potent inhibitors of the isoenzyme CYP2D6 (eg, quinidine, fluoxetine or aripiprazole), the dose of aripiprazole is reduced by 2 times.

When cancellation of isoenzyme inhibitors CYP2D6 or CYP3A4, the dose of aripiprazole is increased. If Aripiprazole-Teva is prescribed as an adjunctive therapy in patients with major depressive disorder, no dosage adjustment is required.

With the simultaneous use of the drug and potent inhibitors of isoenzymes CYP3A4 (eg, ketoconazole or clarithromycin) and CYP2D6 (eg, quinidine, fluoxetine or aripiprazole), the dose of aripiprazole is reduced 4-fold. With the cancellation of potent inhibitors of isoenzymes CYP3A4 and / or CYP2D6, the dose of aripiprazole is increased.

With the simultaneous use of the drug and powerful, moderate or weak inhibitors of isoenzymes CYP3A4 and CYP2D6 The dose of aripiprazole is reduced 4-fold and subsequently titrated to achieve the optimal therapeutic effect.

Patients with low isoenzyme activity CYP2D6 the dose is reduced by a factor of 2 and subsequently titrated to achieve the optimal therapeutic effect. If patients with low isoenzyme activity CYP2D6 Simultaneously with aripiprazole, powerful inhibitors CYP3A4, in such cases, a four-fold decrease in the dose of aripiprazole is shown.

With the simultaneous use of the drug and potential isoenzyme inducers CYP3A4 (eg, carbamazepine), the dose of Aripiprazole-Teva is increased 2-fold. Additional increase in the dose of the drug is carried out taking into account the clinical indications. When cancellation of isoenzyme inducers CYP3A4, 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%.

On the part of the organs of hematopoiesis: rarely - Lakopenia, neutropenia, thrombocytopenia.

From the side of the cardiovascular system: often - orthostatic hypotension, tachycardia; infrequently - bradycardia, palpitations, myocardial infarction, lengthening of the interval QT, heart failure, 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; rarely - fainting, high blood pressure (BP); frequency not defined - thromboembolism (including pulmonary embolism and deep vein thrombosis of the lower extremities).

From the nervous system: 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 the implementation of 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 the function of thought, increased sensitivity to irritants, violation of the oculomotor reaction; rarely - delirium, euphoria, bucco-glossal syndrome, akinesia,depression of consciousness (down to loss of consciousness), decreased reflexes, obsessive thoughts, malignant neuroleptic syndrome; rarely - Speech disorder, convulsions.

From the digestive system: Often - nausea, loss of appetite; often - increased appetite (in the treatment of depression in combination with antidepressants), indigestion, vomiting, constipation, hypersecretion of saliva, dry mouth, abdominal heaviness, diarrhea; infrequently Gastroenteritis, difficulty swallowing, flatulence, gastritis, dental caries, gingivitis, hemorrhoids, gastroesophageal reflux, gastrointestinal hemorrhages, periodontal abscess, swelling of the tongue, fecal incontinence, colitis, rectal hemorrhage, stomatitis, ulceration of the oral mucosa, cholecystitis , fecal matter, mucous candidiasis of the oral cavity, belching, stomach ulcer; rarely - esophagitis, gum bleeding, tongue inflammation, vomiting of blood, intestinal bleeding, duodenal ulcer, cheilitis, enlargement of the liver, perforation of the intestine; rarely - Hepatitis, jaundice, pancreatitis, dysphagia, increased activity of ALT and ACT.

From the immune system: rarely - allergic reactions (including anaphylaxis, angioedema, pruritus and urticaria), laryngospasm.

From the musculoskeletal system: often - arthralgia, muscle rigidity; infrequently - myasthenia gravis, arthritis, arthrosis, muscle weakness, muscle spasms, bursitis; rarely - an increase in the activity of creatine phosphokinase, rhabdomyolysis, tendonitis, tenobursitis, myalgia.

Respiratory system: often - shortness of breath, pneumonia; infrequently - nosebleeds, hiccough, laryngitis; rarely - hemoptysis, increased sputum, dry mucous nasal membranes, pulmonary edema, pulmonary embolism, hypoxia, respiratory insufficiency, apnea; 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; infrequently - dry eyes, eye pain, ringing in the ears, inflammation of the middle ear, cataracts, loss of taste, blepharitis, eyelid edema, photopsy, diplopia; rarely - increased lacrimation, frequent blinking, otitis externa, amblyopia, deafness, intraocular hemorrhages.

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; rarely - urinary incontinence, urinary retention, priapism.

Common violations: often - asthenia, fatigue, flu-like syndrome, sensation of trembling in the body; infrequently - peripheral edema, edema of the face, 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, a feeling of "lump" in the throat, heat stroke; rarely - violation of the regulation of body temperature (including hyperthermia), pain in the chest, in the neck.

Metabolic disorders and disorders, related to nutrition: often - weight loss; infrequently - dehydration, edema, hypercholesterolemia, hypokalemia, hyperlipidemia, hypoglycemia, thirst, increasing concentrations of urea in the blood, elevated alkaline phosphatase, lactate dehydrogenase, iron deficiency anemia, obesity; rarely - Hyperkalemia, hypernatremia, gout, cyanosis, lower urinary pH; rarely - hyponatremia, increased alanine aminotransferase activity, increased aspartate aminotransferase activity, increased activity creatine phosphokinase, anorexia, hyperglycemia, diabetic ketoacidosis, diabetic hyperosmolar coma.

Adverse events that occur when taking antipsychotics were also noted, and during therapy with aripiprazole, including rare cases of neuroleptic malignant syndrome as well as infrequent cases of tardive dyskinesia and seizures.

For some sensitive patients during the first days of treatment may experience symptoms of dystonia manifested by spasm of the neck muscles,with a feeling of sagging 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.

Overdose Symptoms (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, oppression of consciousness, hypokalemia, decrease in blood pressure, expansion of the complex QRS, interval lengthening QT, 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, providing airway patency, oxygenation, ventilation, Activated carbon (application of 50 g of activated carbon 1 h after a single administration of 15 mg of aripiprazole reduces the average AUC and C_maxaripiprazole by 50%), symptomatic treatment, careful medical observation until all symptoms disappear. Data on the use of hemodialysis with an overdose of aripiprazole is not available, however, the effectiveness of this method is questionable, since aripiprazole is not excreted by the kidneys in an unchanged form and is largely associated with plasma proteins.

Interaction:

The mechanism of action of aripiprazole is associated with the effect on the central nervous system, which must be taken into account when used simultaneously with other drugs that have a central effect. Possessing antagonistic action in relation to α1β-adrenoreceptors, aripiprazole can enhance the effect of antihypertensive drugs.

The H2-histamine receptor blocker famotidine reduces the rate of absorption of aripiprazole, however,that this has no clinically significant effect. Various routes of metabolism of aripiprazole are known, including with the participation of isoenzymes CYP2D6 and CYP3A4. In studies in healthy volunteers, potent inhibitors of isoenzymes CYP2D6 (quinidine) and CYP3A4 (ketoconazole) decreased the clearance of aripiprazole for oral administration by 52% and 38%, respectively; so you should reduce the dose of aripiprazole when used in combination with inhibitors of isoenzymes CYP3A4 and CYP2D6.

With the joint use of other potent inhibitors of isoenzyme CYP3A4 (such as itraconazole and HIV protease inhibitors) with aripiprazole, a similar effect can be expected. In these cases, the dose of aripiprazole should also be reduced.

With the simultaneous use of aripiprazole and weak inhibitors of isoenzymes CYP3A4 (diltiazem, escitalopram) or CYP2D6 we can expect a small increase in the concentration of aripiprazole in the blood plasma.

Receiving 30 mg of aripiprazole together with carbamazepine (a powerful isoenzyme inducer CYP3A4) was accompanied by a decrease of 68% and 73% C_maxand AUC aripiprazole, respectively, and a decrease of 69% and 71% C_max and AUC its active metabolite dehydroaripiprazole, respectively. One can expect a similar effect for other powerful inductors of isoenzymes CYP3A4 and CYP2D6.

In the metabolism of aripiprazole in vitro does not participate isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2E1, and therefore its interaction with drugs and other factors (for example, smoking), which are capable of inhibiting or inducing these isoenzymes, is unlikely to interact.

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 trials aripiprazole in doses of 10-30 mg / day had no 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 biotransformation of drugs metabolized by isoenzyme CYP1A2 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 drugs that cause lengthening of the interval QT or disturb the electrolyte balance.

Special instructions:

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

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.

In three placebo-controlled clinical trials of aripiprazole in elderly 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 with the placebo group. Mortality with aripiprazole was 3.5% compared with 1.7% in the placebo group.Despite the fact that 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).

In the same clinical studies, 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 1.3% of patients with aripiprazole, cerebrovascular adverse 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 identified.

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-Teva is not recommended for use in patients with psychoses due to 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-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 case of symptoms of NSA or unexplained fever, all antipsychotics, including aripiprazole, should be abolished, 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, so if the symptoms of tardive dyskinesia appear on the background of taking Aripiprazol-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 signs and symptoms of other extrapyramidal disorders should consider a dose reduction of aripiprazole followed by observation of 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-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 the development of diabetes mellitus (obesity, the presence of diabetes in a family history) when taking atypical antipsychotics should make a determinationconcentration 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 development of orthostatic hypotension (due to blockade of α1-adrenergic receptors) 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 conditions predisposing to hypotension (dehydration, hypovolemia, hypotensive therapy).

Violation of the conduct (lengthening interval QT). 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.

Leukopenia, neutropenia and agranulocytosis. In clinical trials and post-registration experience, it has been established that 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 decrease in the white blood cell count aripiprazole cancel (if the given reaction can not be explained by other reasons).

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 1000 mm³) treatment of drugs stop.

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 (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 closely monitored whenuse of aripiprazole.

Patients with concomitant attention deficit hyperactivity disorder (ADHD). Despite the high frequency of the combination of type I bipolar disorder and ADHD, very limited data on the safety of simultaneous use of aripiprazole and psychostimulants are available, so care should be taken when they are used together.

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

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.

Form release / dosage:

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

Packaging:For 7 tablets in foil blisters (OPA / A1 / PVC-A1). For 4 or 8 blisters together with the instructions for use are placed 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 after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002557

Date of registration:04.08.2014

Expiration Date:04.08.2019

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVAPHARM INDIA, Pvt. Ltd. India

Representation: & nbspTeva Teva Israel

Information update date: & nbsp12.09.2017

Illustrated instructions

Instructions

Aripiprazole-Teva (Aripiprazole-Teva)