Ariprazol 15 mg 60 tablets — Made in Ukraine — Free Delivery

Pharmacological properties

Pharmacodynamics. Mechanism of action. The therapeutic effect of aripiprazole in the treatment of schizophrenia and bipolar I disorder is due to a combination of partial agonism for dopamine d2 and serotonin 5-ht1a receptors, as well as antagonism for serotonin 5-ht2a receptors. aripiprazole is known to exhibit antagonistic properties in animal models of dopaminergic hyperactivity and agonistic properties in animal models of dopaminergic hypoactivity. aripiprazole has a high in vitro binding affinity for dopamine d2 and d3 receptors, serotonin receptors 5-ht1a and 5-ht2a, as well as moderate affinity for dopamine d4 receptors, serotonin 5-ht2c and 5-ht7, adrenergic receptors histamine and h1. aripiprazole also exhibits moderate affinity for serotonin receptors and has no discernible affinity for muscarinic receptors. interactions with receptors other than the dopamine and serotonin subtypes may explain some of the other clinical effects of aripiprazole.

Pharmacokinetics. Suction. Aripiprazole is well absorbed, and its Cmax in blood plasma is reached 3-5 hours after administration. Aripiprazole undergoes minimal first-pass metabolism. The oral bioavailability of the preparation is 87%. Aripiprazole pharmacokinetics are not affected by high fat intake.

Distribution. Aripiprazole is widely distributed in body tissues. The volume of distribution is 4.9 L / kg, which indicates a large extravascular distribution. When administered in therapeutic doses, aripiprazole and dehydroaripiprazole bind by more than 99% to blood plasma proteins, mainly albumin.

Biotransformation. Aripiprazole is extensively metabolized in the liver, mainly by dehydrogenation, hydroxylation, and N-dealkylation. According to in vitro studies, the enzymes CYP 3A4 and CYP 2D6 are responsible for the dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP 3A4. Aripiprazole is the main substance of the preparation found in the systemic circulation. In the equilibrium state, dehydroaripiprazole, its active metabolite, is about 40% of the AUC of aripiprazole in blood plasma.

Excretion. T1 / 2 of aripiprazole is approximately 75 hours in individuals with an active metabolism of CYP 2D6 and approximately 146 hours in individuals with a slow metabolism of CYP 2D6.

The total clearance of aripiprazole is 0.7 ml / min / kg, mainly hepatic clearance. After a single oral administration of 14C-labeled aripiprazole, approximately 27% was excreted in the urine and about 60% in the feces. Less than 1% of unchanged aripiprazole was excreted in the urine, about 18% of unchanged aripiprazole was excreted in the feces.

Pharmacokinetics in special patient groups. Children. The pharmacokinetics of aripiprazole and dehydroaripiprazole in patients aged 10–17 years were similar to those in adults after correction with a difference in body weight.

Elderly patients. There are no differences between the pharmacokinetics of aripiprazole in healthy elderly volunteers and younger patients.

Floor. There are no differences between the pharmacokinetics of aripiprazole in healthy men and women.

Smoking and race. Population pharmacokinetic evaluations did not reveal clinically significant race-related differences or effects of smoking on the pharmacokinetics of aripiprazole.

Impaired renal function. It was revealed that the pharmacokinetic characteristics of aripiprazole and dehydroaripiprazole are the same both in patients with severe kidney disease and in young healthy volunteers.

Liver dysfunction. There are insufficient data on the metabolic characteristics of aripiprazole in patients with impaired liver function.

Indications

Ariprazole is indicated for the treatment of schizophrenia in adults.

Ariprazole is also indicated for the treatment of moderate to severe manic episodes in type I bipolar disorder, and for the prevention of new manic episodes in adults who have had previous manic episodes and have responded to treatment with aripiprazole.

Application

Adults. schizophrenia: the recommended initial dose of ariprazole is 10 or 15 mg / day, and the maintenance dose is 15 mg / day. this dose is taken 1 time per day, regardless of food intake.

Ariprazole is effective over a dose range of 10–30 mg / day. No improvement in efficacy has been demonstrated with doses in excess of a daily dose of 15 mg, although an increased dose may be beneficial in some patients.

The maximum daily dose should not exceed 30 mg.

Manic episodes in bipolar I disorder: The recommended starting dose of Ariprazole is 15 mg. This dose is taken 1 time per day, regardless of food intake. The preparation  can be prescribed as monotherapy or as part of a combination treatment. Increasing the dose may be effective in some patients. The maximum daily dose should not exceed 30 mg.

Prevention of new manic episodes in bipolar I disorder: To prevent recurrence of manic episodes in patients taking aripiprazole as monotherapy or as part of a combination treatment, the preparation should be continued at the same dose. Due to the patient's clinical condition, it is possible to correct the daily dose, including its reduction.

Patients with impaired liver function: No dose adjustment is required in patients with mild or moderate hepatic impairment. There is insufficient data available to provide advice to patients with severely impaired liver function. The dose for these patients should be carefully selected. In patients with severe liver dysfunction, the maximum daily dose of 30 mg should be used with caution.

Patients with impaired renal function: No dose adjustment is required in patients with impaired renal function.

Elderly patients: the effectiveness of the preparation Ariprazole in the treatment of schizophrenia and bipolar I disorder in patients aged 65 years and older has not been established. Given the higher sensitivity of this patient population, consideration should be given to using lower initial doses of the preparation if other clinical factors permit.

Gender: No dose adjustment is required based on the patient's gender.

Smoking: Given the metabolic pathway of aripiprazole, no dose adjustment is required for smokers.

Dose adjustment as a result of interactions: in the case of the simultaneous administration of potent inhibitors of CYP 3A4 or CYP 2D6 with aripiprazole, the dose of aripiprazole should be reduced. If a CYP 3A4 or CYP 2D6 inhibitor is excluded from the combination regimen, the dose of aripiprazole should be increased.

In the case of the simultaneous administration of powerful inducers of CYP 3A4 with aripiprazole, the dose of aripiprazole should be increased. If the CYP 3A4 inducer is excluded from the combination treatment regimen, the dose of aripiprazole should be reduced to the recommended dose.

Contraindications

Hypersensitivity to aripiprazole or any other component of the preparation.

Side effects

The most common adverse reactions were akathisia and nausea.

The frequency indicated below is determined by the following conditional parameters: often (≥1 / 100-1 / 10) and infrequently (≥1 / 1000-1 / 100):

on the part of the psyche: often - agitation, insomnia, anxiety; infrequently - depression, hypersexuality.

From the nervous system: often - extrapyramidal disorders, akathisia, tremor, dizziness, drowsiness, sedation, headache.

From the side of the organ of vision: often - blurred vision; infrequently - diplopia.

From the side of the cardiovascular system: infrequently - tachycardia, orthostatic hypotension.

From the digestive system: often - dyspepsia, nausea, vomiting, constipation, excessive salivation.

General disorders: often - fatigue.

The frequency of the following reactions is considered unknown (cannot be estimated from the available data):

from the endocrine system: hyperprolactinemia.

On the part of the blood and lymphatic system: leukopenia, neutropenia, thrombocytopenia.

From the immune system: allergic reactions (for example, anaphylactic reactions, angioedema, tongue edema, facial edema, itching, urticaria).

From the endocrine system: hyperglycemia, diabetes mellitus, diabetic ketoacidosis, diabetic hyperosmolar coma.

From the side of metabolism: increase or decrease in body weight, anorexia, hyponatremia.

From the side of the psyche: agitation, nervousness, pathological passion for gambling, aggressiveness, attempts at suicide, suicidal thinking and completed suicide.

From the nervous system: speech impairment, neuroleptic malignant syndrome (MNS), large seizure, serotonin syndrome.

From the side of the heart: prolongation of the Q – T interval, ventricular arrhythmia, sudden death, cardiac arrest, pirouette-type ventricular tachycardia, bradycardia.

From the side of the vessels: fainting, hypertension, venous thromboembolism (VTE; including pulmonary embolism and deep vein thrombosis).

From the respiratory system, chest and mediastinal organs: oropharyngeal spasm, laryngospasm, aspiration pneumonia.

From the digestive system: pancreatitis, dysphagia, gastrointestinal discomfort, diarrhea.

From the liver and biliary tract: liver failure, jaundice, hepatitis, increased levels of ALT, ASAT, gamma-glutamyltransferase, alkaline phosphatase.

Skin and subcutaneous tissue disorders: rash, photosensitivity, alopecia, increased sweating.

Musculoskeletal and connective tissue disorders: rhabdomyolysis, myalgia, muscle stiffness.

Pregnancy, postpartum and perinatal conditions: preparation withdrawal syndrome in newborns.

From the kidneys and urinary tract: urinary incontinence, urinary retention.

On the part of the genitals and mammary gland: priapism.

Complications of a general nature and reactions at the injection site: violation of temperature regulation (for example, hypothermia, hyperthermia), chest pain, peripheral edema.

Laboratory tests: an increase in the level of CPK, an increase in the level of glucose in the blood, fluctuations in the level of glucose in the blood, an increase in the level of glycated hemoglobin.

Special instructions

When treated with antipsychotics, the improvement of the patient's clinical condition can take from several days to several weeks. during this period, close monitoring of the patient's condition should be carried out.

Suicidal tendencies: The emergence of suicidal behavior is inherent in patients with psychotic illnesses and mood disorders. In some cases, it was noted soon after the start of the use of antipsychotics or the transition from one antipsychotic to another, including treatment with aripiprazole. Treatment with antipsychotics should be accompanied by careful monitoring of patients at high risk.

It is known that there is no increased risk of suicidal tendencies with the use of aripiprazole compared with the use of other antipsychotics.

Cardiovascular disorders: aripiprazole should be used with caution in patients with a history of cardiovascular diseases (myocardial infarction or coronary artery disease, heart failure or conduction disturbances), cerebrovascular disorders, conditions that make patients prone to arterial hypotension (dehydration, hypovolemia, the use of antihypertensive preparations) or hypertension, including progressive or malignant hypertension.

Cases of VTE have been reported during treatment with antipsychotics. Since patients taking antipsychotics often have acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with aripiprazole and all preventive measures taken.

Prolongation of the Q – T interval: Like other antipsychotics, aripiprazole should be used with caution in patients with a family history of lengthening of the Q – T interval.

Tardive dyskinesia: if symptoms of tardive dyskinesia appear in a patient taking aripiprazole, the appropriateness of reducing the dose of the preparation or discontinuing treatment should be considered. These symptoms may worsen temporarily or even occur after stopping treatment.

Other extrapyramidal symptoms: with the use of aripiprazole in children, akathisia and parkinsonism have occurred. In the event of signs of other extrapyramidal symptoms, the possibility of reducing the dose should be considered and careful clinical monitoring of the patient's condition should be carried out.

NNS: NNS is a complex of symptoms associated with the use of antipsychotic preparations, which can potentially be fatal.

Clinical manifestations of NMS are hyperpyrexia (extremely high body temperature), muscle rigidity, altered mental status, and signs of autonomic nervous system disorder (irregular heart rate or blood pressure, tachycardia, increased sweating, and cardiac arrhythmia). Additional signs may include elevated CPK levels, myoglobinuria (rhabdomyolysis), and acute renal failure. However, there were also some cases of increased CPK and rhabdomyolysis, not necessarily associated with NNS. If a patient develops symptoms of NNS or unexplained very high body temperature without additional clinical manifestations of NNS, all antipsychotic preparations, including aripiprazole, should be discontinued.

Epileptic seizures: There have been rare cases of epileptic seizures during treatment with aripiprazole. Therefore, aripiprazole should be used with caution in patients with a history of epilepsy or seizure-related conditions.

Elderly patients with dementia-related psychosis. Increased mortality: with the use of aripiprazole in elderly patients with psychosis associated with Alzheimer's disease, the risk of death is increased. Although the causes of death were different, most of them were of cardiovascular (eg heart failure, sudden death) or infectious (eg pneumonia) nature.

Adverse reactions of a cerebrovascular nature: in elderly patients with psychosis against the background of Alzheimer's disease, undesirable reactions of the cerebrovascular type (for example, stroke, transient ischemic attack), including fatal ones, have developed.

There was a pronounced relationship between the doses of the preparation and the occurrence of undesirable reactions of the cerebrovascular type in patients taking aripiprazole.

Aripiprazole is not indicated for the treatment of psychosis associated with dementia.

Hyperglycemia and diabetes mellitus: hyperglycemia, in some cases very severe and associated with ketoacidosis or hyperosmolar coma, including fatal ones, has been observed in patients taking atypical antipsychotics, in particular aripiprazole. Risk factors for severe complications include obesity and a family history of diabetes. There is no accurate comparative assessment of the risks of developing adverse reactions associated with hyperglycemia in patients taking aripiprazole and other atypical antipsychotics. It is necessary to carefully monitor the condition of patients taking any antipsychotics, including aripiprazole, fixing symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness), and the condition of patients with diabetes mellitus or risk factors for developing diabetes should be regularly monitored for an increase in glucose levels.

Hypersensitivity: As with other medicines, hypersensitivity reactions may develop when taking aripiprazole.

Increase in body weight. In patients with schizophrenia and bipolar mania, an increase in body weight is often noted due to concomitant diseases, the use of antipsychotics, which are known to cause an increase in body weight, as well as a lack of a healthy lifestyle; this phenomenon can lead to serious complications. When treated with aripiprazole, cases of weight gain are usually recorded in patients with significant risk factors, such as diabetes mellitus, thyroid disorders, or a history of pituitary adenoma.

Aripiprazole does not cause clinically significant weight gain in adults.

Dysphagia: Antipsychotics, including aripiprazole, can cause disturbances in esophageal motility and gastric aspiration. Aripiprazole and other antipsychotics should be used with caution in patients at increased risk of aspiration pneumonia.

Pathological gambling: Patients who were prescribed aripiprazole have had cases of pathological gambling, regardless of whether they have had a similar dependence in the past. Patients with a history of pathological gambling may be at increased risk and should be closely monitored.

Lactose: Ariprazole tablets contain lactose. Patients with rare hereditary disorders such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this preparation.

Patients with concomitant attention deficit hyperactivity disorder: despite the high incidence of concomitant diseases of type I bipolar disorder and attention deficit hyperactivity disorder, there are limited data on the safety of the concomitant use of aripiprazole and stimulants, therefore, extreme caution is required when these preparations are administered concurrently.

Use during pregnancy and lactation. Pregnancy. There have been no adequate controlled studies of aripiprazole in pregnant women. Congenital anomalies have been reported, but a causal relationship with aripiprazole has not been established. The known data from animal studies do not exclude the possibility of embryophetotoxicity. Patients should inform their healthcare provider if they are pregnant or intend to become pregnant while on treatment with aripiprazole. Due to insufficient information on the safety of the use of aripiprazole during pregnancy, it can be prescribed only when the expected benefit to the pregnant woman outweighs the potential risk to the fetus.

In newborns whose mothers took antipsychotics (including aripiprazole) in the third trimester of pregnancy, adverse reactions are possible, including extrapyramidal symptoms and / or withdrawal symptoms, which may vary in severity and duration. Known for agitation, increased or decreased muscle tone, tremors, drowsiness, breathing problems, or feeding problems. Therefore, it is necessary to carefully monitor the condition of such newborns.

Breast-feeding. Aripiprazole is excreted in breast milk. If necessary, taking the preparation, breastfeeding should be discontinued.

Children. The preparation Ariprazole in this dosage is not recommended for use in children.

The ability to influence the reaction rate when driving or working with other mechanisms. Aripiprazole, like other antipsychotics, can affect the ability to drive vehicles due to adverse reactions from the nervous system and the organ of vision (see SIDE EFFECTS). In the course of treatment, it is recommended to refrain from driving vehicles or working with other mechanisms until the sensitivity of patients to the preparation becomes known.

Interactions

Due to antagonism to α1-adrenergic receptors, aripiprazole may enhance the effect of some antihypertensive preparations.

Given the main effect of aripiprazole on the central nervous system, caution should be exercised when prescribing aripiprazole with other preparations that affect the central nervous system, due to possible cross-reactions, such as sedation.

It is also necessary to stop drinking alcohol during therapy with aripiprazole. Aripiprazole should be used with caution in combination with other preparations  that prolong the Q – T interval or disturb the electrolyte balance.

Potential effects of other preparations on the action of aripiprazole

An inhibitor of hydrochloric acid secretion, an antagonist of H2-receptors, famotidine reduces the rate of absorption of aripiprazole, but this effect is not considered clinically significant.

Aripiprazole is metabolized in several ways, involving the CYP 2D6 and CYP 3A4 enzymes, but not the CYP 1A enzymes. Thus, dose adjustment is not required for smokers.

Quinidine and other inhibitors of CYP 2D6. The dose of aripiprazole should be reduced by about half if taken simultaneously with quinidine. Other potent CYP 2D6 inhibitors such as fluoxetine and paroxetine are likely to have similar effects, so dose reductions should be the same if used.

Ketoconazole and other CYP 3A4 inhibitors. In individuals with a slow CYP 2D6 metabolism, concomitant use of potent CYP 3A4 inhibitors may result in higher plasma concentrations of aripiprazole compared to patients with an active CYP 2D6 metabolism. If necessary, the simultaneous use of ketoconazole or other potent inhibitors of CYP 3A4 with aripiprazole, the potential benefits should outweigh the possible risks to the patient. With the simultaneous use of aripiprazole and ketoconazole, the dose of aripiprazole must be reduced by about half. Other potent inhibitors of CYP 3A4, such as itraconazole and HIV protease inhibitors, could theoretically have the same effects, therefore, similar dose reductions should be made.

After discontinuation of a CYP 2D6 or CYP 3A4 inhibitor, the dose of aripiprazole should be increased to that used before commencing concomitant treatment.

A slight increase in the concentration of aripiprazole is possible in the case of the simultaneous use of weak inhibitors of CYP 3A4 (for example, diltiazem or escitalopram) or CYP 2D6.

Carbamazepine and other inhibitors of CYP 3A4. The dose of aripiprazole must be doubled if taken simultaneously with carbamazepine. Other potent inducers of CYP 3A4 (eg rifampicin, rifabutin, phenytoin, phenobarbital, primidone, efavirenz, nevirapine, and St. John's wort) theoretically have similar effects, so an appropriate dose increase is necessary. After discontinuation of potent inducers of CYP 3A4, the dose of aripiprazole should be reduced to the recommended dose.

Valproate and lithium. In the case of simultaneous administration of valproate or lithium with aripiprazole, there were no clinically significant changes in the concentration of aripiprazole.

Serotonin syndrome. Cases of serotonin syndrome have been reported in patients taking aripiprazole; especially when used simultaneously with other serotonergic preparations, such as selective serotonin reuptake inhibitor / selective serotonin / norepinephrine reuptake inhibitor, or with preparations  that increase the concentration of aripiprazole.

Potential effects of aripiprazole on the action of other preparations

It is unlikely that aripiprazole is capable of causing clinically important preparation interactions mediated by the enzymes CYP 2D6 (dextromethorphan / 3-methoxymorphine ratio), CYP 2C9 (warfarin), CYP 2C19 (omeprazole), and CYP 3A4 (dextromethorphan).

In the case of simultaneous administration of aripiprazole with valproate, lithium or lamotrigine, there were no clinically significant changes in the concentrations of valproate, lithium or lamotrigine.

Overdose

In patients, cases of deliberate or accidental acute overdose of aripiprazole with doses up to 1260 mg without further death have been described. potentially medically important observed symptoms were lethargy, increased blood pressure, drowsiness, tachycardia, nausea, vomiting, and diarrhea.

In addition, data were obtained on accidental overdose of aripiprazole only (at a dose of up to 195 mg) in non-lethal children. Drowsiness, transient loss of consciousness, and extrapyramidal symptoms were potentially medically important reported symptoms.

Overdose treatment should include supportive care, airway management, oxygen therapy, mechanical ventilation, and symptom control. The possibility of an overdose of numerous preparations should be taken into account. Therefore, it is necessary to immediately begin monitoring the state of the cardiovascular system, which should include continuous monitoring of the ECG to detect possible arrhythmias.

After a confirmed or probable overdose of aripiprazole, close medical supervision and monitoring of the patient's condition is necessary until recovery.

Activated charcoal (50 g), applied 1 hour after taking aripiprazole, reduced the Cmax of aripiprazole by about 41% and the AUC by about 51%, which indicates the possible efficacy of activated charcoal in the treatment of overdose.

Although there is no information on the effect of hemodialysis in the treatment of aripiprazole overdose, it is unlikely that hemodialysis could be useful in the treatment of overdose, since aripiprazole is highly associated with blood plasma proteins.

Storage conditions

In its original packaging at a temperature not exceeding 25 ° C.