Expiration date: 01/2026
Composition
Description pharmaceutical form
Tablets white or almost white, round, lenticular, on one side engraved. For dosage 10 mg "N74", 15 mg — "N75", 20 mg "N76", 30 mg — "N77".
Pharmacological action
Drugs, the neuroleptic, antipsihoticescoe.
Pharmacodynamics
Therapeutic effect of aripiprazole in schizophrenia due to a combination of partial agonist activity for D2-dopamine and 5HT1a-serotonin receptors and antagonist activity against 5HT2-serotonin receptors.
Aripiprazole has a high affinity in vitro to the D2 - and d said-dofaminove receptors, 5HT1a and 5HT2a-serotonin receptors and moderate affinity for D4-dofaminove, 5HT2c and 5HT7-serotonin, ?l-adrenergic receptors and H1-histamine receptors. Aripiprazole is also characterized by a moderate affinity to parts of serotonin reuptake and no affinity for muskarinovykh receptors. In animal experiments aripiprazole showed antagonism against dopaminergic hyperactivity and agonism in respect of dopaminergic hypoactivity. Interaction not only with dopamine and serotonin receptors explains some of the clinical effects of aripiprazole.
Pharmacokinetics
Suction
Aripiprazole is rapidly absorbed after ingestion. Eating does not affect the bioavailability of aripiprazole. The absolute oral bioavailability is 87%. Cmax of aripiprazole in plasma is reached after 3-5 h, the Css is reached after 14 days.
Distribution
Aripiprazole rapidly distributed in the tissues, Vd — 4, 9 l/kg. the pharmacokinetics of aripiprazole at steady state are proportional to dose. At therapeutic concentrations over 99% aripiprazole binds to plasma proteins, mainly to albumin. The main metabolite of aripiprazole — dihydroimidazole — has the same affinity for D2-dofaminove receptors, as aripiprazole. Not marked diurnal fluctuations distribution of aripiprazole and its metabolite of dihydroimidazole. AUC at steady state of dihydroimidazole 39% of aripiprazole AUC in plasma.
Metabolism
Slightly undergoes first-pass metabolism. Aripiprazole is a major component of the drug in the blood plasma. Aripiprazole is metabolized in the liver by dehydrogenation, hydroxylation, and N-dezalkilirovania. In vitro dehydrogenation and hydroxylation of aripiprazole occurs with the participation of isozymes CYP3A4 and CYP2D6, and N-dezalkilirovania with the participation of isoenzyme CYP3A4.
Excretion
T1/2 is approximately 75 h in the fast metabolization isoenzyme CYP2D6 and approximately 146 hours at slow metabolization. Total clearance of aripiprazole — 0, 7 ml/min/kg, mainly through excretion by the liver. After a single dose of 14C-labeled aripiprazole, approximately 27% of the dose was allocated by the kidneys and approximately 60% through the intestine. Less than 1% of unchanged aripiprazole determined in urine and about 18% of the dose in unchanged form excreted via the gut.
Special groups of patients
Children. With adjustment for body weight, the pharmacokinetics of aripiprazole and dihydroimidazole in adolescents 13-17 years resembled that of adults.
Elderly. There were no differences in the pharmacokinetics of aripiprazole in elderly adults and healthy volunteers. Also revealed no effect of age on the pharmacokinetics in patients with schizophrenia.
Paul. There are no differences in the pharmacokinetics in healthy men and women. Also revealed no effect of gender on the pharmacokinetics of aripiprazole in patients with schizophrenia.
Smoking and ethnicity. In the study there was no clinically significant effect of racial differences or effects of Smoking on the pharmacokinetics of aripiprazole.
Of kidney disease. Were identified the same the pharmacokinetic parameters of aripiprazole and dihydroimidazole in patients with severe kidney diseases and of young healthy volunteers.
Diseases of the liver. In patients with liver cirrhosis of various degrees (classes A, b and C child-Pugh) after a single dose of aripiprazole revealed no significant effect of liver dysfunction on the pharmacokinetics of aripiprazole and dihydroimidazole. In connection with the lack of data in patients with decompensated cirrhosis (class C according to child-Pugh) it is impossible to draw definitive conclusions about the metabolic activity.
The testimony of the drug of Amdoal®
treatment of schizophrenia in adults
treatment of manic episodes within bipolar disorder type I and prevention of manic episodes in patients who have a history of manic episodes and the clinical response to treatment with aripiprazole.
Contraindications
- hypersensitivity to one of the components of the drug
- senile dementia,
- lactase deficiency, lactose intolerance, glucose-galactose malabsorption,
- lactation,
- the age of 18.
Caution: diseases of the cardiovascular system (ischemic heart disease, including myocardial infarction, congestive heart failure, conduction disorder, condition, predisposing to decrease blood pressure (dehydration, hypovolemia, intake of antihypertensive drugs) in regard to the possibility of orthostatic hypotension, cerebrovascular disease, epilepsy, diseases which may develop seizures, patients with risk of aspiration pneumonia (because of the risk of violation of motor function of the esophagus and aspiration), patients with an increased risk of hyperthermia, for example during intensive physical loads, overheating, receiving funds from m-holinoblokiruta activity, dehydration (due to the ability of neuroleptics disrupt thermoregulation), patients with obesity, diabetes mellitus in anamnesis, pregnancy.
Application of pregnancy and breastfeeding
Adequate and well-controlled studies in pregnant women have not been conducted. In connection with the lack of data on safety the product can be taken during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Patients should be warned about the need to immediately tell your doctor the occurrence of pregnancy during treatment with aripiprazole, and also about the planned pregnancy. Newborns whose mothers took antipsychotics during the third trimester of pregnancy, in the postpartum period there is a risk of extrapyramidal disorders and/or withdrawal symptoms. In newborns with marked agitation, high or low blood pressure, tremor, somnolence, respiratory distress syndrome, disturbance when feeding. Such newborns need careful supervision.
During treatment with aripiprazole should be breastfeeding. In animal studies provided data on the allocation of the drug with milk. Data on the penetration of aripiprazole in breast milk is not.
Side effects
The most frequently reported side effects in placebo-controlled studies were akathisia and nausea, each of them was observed more than 3% of patients treated with oral aripiprazole.
Given below side effects were found more often (?1/100) than placebo, or were identified as adverse reactions, possibly associated with the drug (*). The frequency of side effects is given in accordance with the following scale: very often — > 10% is often > 1 percent and < 10%, infrequently — >, 0, 1% and < 1%, rarely — >, 0, 01% and < 0, 1%, very rarely — <, 0, 01%.
On the part of the psyche: often — anxiety, insomnia, anxiety, rarely — depression*.
From the nervous system: often — extrapyramidal disorders, akathisia, tremor, dizziness, drowsiness, sedation, headache.
On the part of the organ of vision: often — blurred vision.
Of the heart and vascular system: rarely — tachycardia*, orthostatic hypotension*.
From the digestive system: often — dyspepsia, vomiting, nausea, constipation, salivation.
Systemic disorders and complications at the injection site: often — fatigue.
Other observations: in the treatment with aripiprazole schizophrenia, manic episodes and bipolar disorder type I was observed a lower incidence of extrapyramidal symptoms (EPS), including parkinsonism than patients treated with haloperidol was the same as that of patients receiving olanzapine. The frequency of EPS in patients treated with aripiprazole about manic episodes and bipolar disorder type I, was higher in comparison with the group treatment with lithium.
Post-marketing use of
Below are the spontaneous reports of adverse reactions. Based on available data, it is impossible to determine the frequency of occurrence of these effects.
Violations by the blood and lymphatic system: leukopenia, neutropenia, thrombocytopenia.
Immune disorders: allergic reactions (anaphylactic reaction, angioedema, including swelling and swelling of the tongue, swelling of the face, itching, hives).
From the endocrine system: hypercalcemia, diabetes mellitus, diabetic ketoacidosis, diabetic coma catesbeiana.
From the metabolic and nutrition: weight gain, weight loss, anorexia, hyponatremia.
Psychiatric disorders: agitation, nervousness, suicidal attempts, suicidal thoughts, committed suicide.
From the nervous system: speech disorder, neuroleptic malignant syndrome, epileptic seizure.
Of the heart and vascular system: prolongation of QT interval, ventricular arrhythmias, sudden death for unknown reasons, angina, polymorphic ventricular tachycardia type "pirouette", bradycardia, syncope, increased blood pressure, venous thromboembolism (including thromboembolism of pulmonary artery branches and deep vein thrombosis).
The respiratory system, chest and mediastinum disorders: oropharyngeal spasm, laryngospasm, aspiration pneumonia,
From the digestive system: pancreatitis, dysphagia, abdominal discomfort, stomach discomfort, diarrhea.
Hepatobiliary system: jaundice, hepatitis, increased ALT activity, AST, GGT, alkaline phosphatase.
From the side of musculoskeletal system and connective tissue: rhabdomyolysis, myalgia, stiffness.
From the urinary system: urinary incontinence, urinary retention.
From the reproductive system and mammary glands: priapism.
Pregnancy, puerperium and perinatal status: a syndrome of drug withdrawal in newborns.
Systemic disorders and complications at the injection site: disorders of temperature regulation (hypothermia, pyrexia), chest pain, peripheral edema.
Laboratory tests: increased activity of KFK, the increase in the concentration of sugar in the blood, fluctuations in the concentration of sugar in the blood, increasing the concentration of glycosylated hemoglobin.
Interaction
In connection with the peculiar aripiprazole antagonism to the ?l-adrenergic receptors there is likely to enhance the effect of some antihypertensive drugs. As aripiprazole has an effect on the Central nervous system, should be wary of concurrent use of alcohol or drugs affecting the Central nervous system, as this may lead to increased side effects, such as sedation. Revealed no significant effect of H2-blocker of histamine receptor famotidine causing a powerful inhibition of secretion of hydrochloric acid in the stomach, on the pharmacokinetics of aripiprazole.
Care should be taken when using aripiprazole with drugs that may cause QT prolongation.
Known various ways of metabolism of aripiprazole, including with the participation of isoenzymes CYP2D6 and CYP3A4. Studies in healthy humans potent inhibitors of isoenzyme CYP2D6 (quinidine) and CYP3A4 (ketoconazole) decreased clearance of aripiprazole ingestion by 52 and 38%, respectively. Therefore, you should reduce the dose of aripiprazole when used in combination with inhibitors of isoenzyme CYP3A4 (Itraconazole and HIV protease inhibitors), and CYP2D6. After the cancellation of inhibitors of isoenzymes CYP3A4 and CYP2D6 dose of aripiprazole should be returned to the source.
When using aripiprazole with weak inhibitors of CYP3A4 isoenzymes (diltiazem, ESCITALOPRAM) or CYP2D6 should expect a small increase in the concentration of aripiprazole in serum.
Receiving 30 mg of aripiprazole with carbamazepine, a potent inducer of CYP3A4, accompanied by a decrease by 68 and 73% in Cmax and AUC of aripiprazole, respectively, and a decrease of 69 and 71% Cmax and AUC of its active metabolite dihydroimidazole respectively. When using aripiprazole together with carbamazepine should double the dose of aripiprazole. We can expect similar actions and other powerful inducers of CYP3A4 isozyme (rifampicin, rifabutin, phenytoin, phenobarbital, primidon, efavirenz, nevirapine, St. John's wort) and CYP2D6. After the abolition of the powerful inducers of isoenzymes CYP3A4 and CYP2D6 dose of aripiprazole should be reduced to recommended. In the metabolism of aripiprazole not involved in vitro isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2E1, in connection with his unlikely interactions with drugs and other factors (such as Smoking), able to inhibit or activate these enzymes.
Concomitant use of lithium or valproate with aripiprazole had no clinically significant effect on the pharmacokinetics of aripiprazole.
In clinical trials aripiprazole doses of 10-30 mg/day had no significant effect on the metabolism of substrates isoenzymes CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin), and CYP3A4 (dextromethorphan). In addition, aripiprazole and its major metabolite dihydroimidazole did not change the metabolism with participation of isoenzyme CYP1A2 in vitro. It is unlikely a clinically significant effect of aripiprazole on drugs, metaboliziruemah with participation of these isoenzymes.
Concomitant use of lithium, lamotrigine or valproate with aripiprazole does not lead to clinically significant changes in the concentrations of lithium, lamotrigine or valproate.
Method of application and doses
Inside, 1 times per day regardless of the meal.
Schizophrenia. The recommended initial dose of 10-15 mg 1 time a day. Maintenance dose — 15 mg per day. The drug is effective in doses of 10 to 30 mg/day. Increase the effectiveness of doses above 15 mg/day has not been proven, but may be required by some patients. The maximum daily dose should not exceed 30 mg.
Manic episodes in bipolar disorder. Initial dose of 15 mg/day in monotherapy or in combination. Some patients may require higher doses. The maximum daily dose should not exceed 30 mg.
Prevention of manic episodes in bipolar disorder type I. For the prevention of manic episodes in patients who had previously taken aripiprazole as monotherapy or in combination, continue treatment at previous dose. Correction daily dose, including its reduction, shall be in accordance with the patient's condition.
Special groups of patients
Patients with renal insufficiency. Dosage adjustment when administering the drug to patients with renal insufficiency is not required.
Patients with hepatic insufficiency. Dosage adjustment when administering the drug to patients with renal insufficiency is not required. However, patients with severe hepatic insufficiency should be used with caution in the daily dose of 30 mg.
Patients older than 65 years. Dose adjustment is not required.
The effect of sex on the mode. The dosage regimen of the drug for patients of both sexes the same.
Dosage with concomitant therapy. While the use of the drug Amdoal® and potent inhibitors of CYP2D6 or CYP3A4 isoenzymes dose of Amdoal® should be reduced in 2 times. If you cancel inhibitors of CYP2D6 or CYP3A4 isoenzymes dose of Amdoal® should be increased. Amdoal® should be applied without changing the dosage, if he is appointed as additional therapy in patients with major depressive disorder. While the use of the drug Amdoal® and inducers of CYP3A4 dose of Amdoal® should be increased in 2 times. A further increase in the dose of Amdoal® should be based on clinical indications. If you cancel the CYP3A4 isoenzyme inducers dose of Amdoal® should be reduced. When assigning several drugs that inhibit the isoenzyme CYP2D6 and CYP3A4, should consider the possibility of reducing the daily dose of Amdoal®.
Overdose
During clinical trials and post-marketing use cases were identified intentional or unintentional use of the drug in adult patients at doses up to 1260 mg, accompanied not fatal.
Symptoms: lethargy, increased blood pressure, tachycardia, nausea, vomiting, diarrhea, drowsiness.
Described cases of overdose of aripiprazole in children (up to 195 mg), is not accompanied by death.
Symptoms: drowsiness, transient loss of consciousness, extrapyramidal disorders.
Treatment: the appointment of activated charcoal (50 g, inserted through 1 h after administration of aripiprazole, decreased the AUC and Cmax of aripiprazole by 51 and 41%, respectively), supportive therapy, ensuring adequate airway, oxygenation, effective ventilation and symptomatic treatment, monitoring of indicators of function of SSS with the registration of ECG to detect arrhythmias. Should be careful medical supervision until the disappearance of all symptoms.
The effectiveness of hemodialysis is unlikely (virtually not excreted by the kidney in unchanged form and is largely bound to plasma proteins).
Special instructions
Since the improvement of the condition of the patient with neuroleptic treatment may require several days, patients should be closely monitored. Tendency to suicidal thoughts and attempts is characteristic of psychosis, may occur in a short time after starting treatment or changing medication. Therefore, such patients should be carefully monitored.
Violations of the CCC. Aripiprazole should be used with caution in patients with diseases of the CVS (myocardial infarction or coronary heart disease history, heart failure, conduction disorders), cerebrovascular disorders, risk factors for hypotension (dehydration, hypovolemia, use of antihypertensive drugs), hypertension, including progressive and malignant.
In the application of neuroleptics may develop venous thrombosis. Because patients receiving antipsychotics, may be predisposing factors for venous thromboembolism should be a thorough examination of patients before treatment with aripiprazole and preventive measures should be taken during treatment.
Of conduction disorders. The frequency of QT interval prolongation during treatment with aripiprazole is similar to the same when taking a placebo. However, patients with a family history of QT prolongation should observe the same caution in the appointment of aripiprazole, like other antipsychotics.
Tardive dyskinesia. The risk of developing tardive dyskinesia increases with duration of neuroleptic therapy, so when prompted during the treatment of symptoms of tardive dyskinesia should reduce the dose or stop the drug. After the therapy, these symptoms may temporarily worsen or even appear for the first time.
Neuroleptic malignant syndrome. When neuroleptic treatment may develop life-threatening neuroleptic malignant syndrome (or hyperpyrexia, muscle rigidity, mental disorders and instability of the autonomic nervous system, including the instability of pulse and blood pressure, tachycardia, sweating, and arrhythmias). In addition, it is sometimes possible increase in the activity of KFK, the occurrence of myoglobinuria (rhabdomyolysis) and acute renal failure. In the event of symptoms of neuroleptic malignant syndrome or unexplained fever, the drug should be withdrawn.
Seizures. In the treatment with aripiprazole was marked by the development of seizures. Therefore, caution should be exercised when treating patients with convulsive seizures in history or suffering from disorders in which they can develop.
Elderly patients suffering from senile dementia. The drug is not approved for the treatment of senile psychosis, because it increases the risk of mortality and development of cerebrovascular complications.
Hyperglycemia and diabetes. Hyperglycemia (in some cases severe, with ketoacidosis), which can lead to hyperosmolar coma and even death, was observed in patients treated with atypical antipsychotics. While the relationship between taking atypical antipsychotics and hyperglycemia remains unclear, patients diagnosed with diabetes mellitus requires regular monitoring of glucose concentration in the blood while taking atypical antipsychotics. In patients with risk factors for diabetes (obesity, presence of diabetes in the family history) when taking atypical neuroleptics it is necessary to determine the concentration of glucose in the blood at the beginning of the course and periodically in the process of taking the drug. All patients taking atypical antipsychotics, requires constant monitoring of symptoms of hyperglycemia, including increased thirst, frequent urination, polyphagia, and weakness.
Hypersensitivity. Like other drugs, aripiprazole may cause hypersensitivity reactions.
Increase in body weight. Had no effect of aripiprazole to the weight gain.
Dysphagia. Use of neuroleptics, including aripiprazole, causes a disturbance of motility of the esophagus and aspiration. In patients with risk of aspiration pneumonia aripiprazole and other antipsychotic drugs should be used with caution.
Lactose intolerance. The drug contains lactose, therefore it should not be taken by patients with rare hereditary diseases such as galactose intolerance, Lapp lactase insufficiency, or syndrome of glucose-galactose malabsorption.
Effects on ability to drive vehicles and operate machinery. During the period of treatment must be careful when doing activities that require high concentration and psychomotor speed reactions.
Release form
Tablets, 10 mg, 15 mg, 20 mg and 30 mg. In a contour acheikova packing from the combined three-layer material polyamide/aluminium/PVC (PA/Al/PVC) and aluminum foil for 15 PCs of 1 or 2 blisters per cardboard pack.
Storage conditions of the drug Amdoal®
In a dry, protected from light place, at temperature not exceeding 30 °C.
Keep out of reach of children.
The shelf life of the drug Amdoal®
3 years.
| Tablets | 1 tablets |
| active substance: | |
| Aripiprazole | 10 mg |
| 15 mg | |
| 20 mg | |
| 30 mg | |
| excipients: lactose monohydrate— 63, 077/94, 615/126, 153/189, 23 mg, MKC — 10/15/20/30 mg, corn starch— 6, 983/10, 475/13, 967/20, 95 mg hyprolose— 3, 8/5, 7/7, 6/11, 4 mg, magnesium stearate— 1, 14/1, 71/2, 28/3, 42 mg | |
