Producer: Bristol-Myers Squibb Comp. (Bristol-Myers Skvibb Komp.) USA
Code of automatic telephone exchange: N05AX12, N05AX
Release form: Firm dosage forms. Tablets.
General characteristics. Structure:
Active ingredient: 5 mg, 10 mg, 15 mg or 30 mg of an aripiprazol.
Excipients: lactoses monohydrate, cellulose microcrystallic, starch corn, hypro rod, magnesium stearate; dyes: indigo carmine aluminum varnish (tablet of 5 mg), dye ferrous oxide red (tablets of 10 mg), dye ferrous oxide yellow (tablets of 15 mg), dye ferrous oxide red (tablets of 30 mg).
It is supposed that therapeutic action of an aripiprazol at schizophrenia bipolar disorder of the I type is caused by a combination of partial agonistic activity concerning D2-of dopamine and 5nt1a-serotoninovy receptors and antagonistic activity concerning 5HT2-serotoninovy receptors.
Pharmacodynamics. Aripiprazol has high affinity of ip vitro to D2-and D3 - dopamine receptors, 5nt1a-and to 5nt2a-serotoninovy receptors and moderate affinity to D4 - dopamine, 5NT2S-and 5HT7-serotoninovy, to alfa1-adrenoceptors and H1-histamine receptors.
Aripiprazol is characterized by also moderate affinity to sites of the return serotonin reuptake and lack of affinity to m-holinoretseptoram. Aripiprazol in experiments on animals showed antagonism concerning a dofaminergichesky hyperactivity and an agonizm concerning dofaminergichesky hypoactivity. Some clinical effects of an aripiprazol can be explained with interaction with other types of receptors (not dopamine and serotoninovy).
Pharmacokinetics. Activity of the drug Abilifay® is mainly caused by availability of initial substance - an aripiprazola. The average elimination half-life of an aripiprazol makes about 75 hours. Equilibrium concentration is reached in 14 days. Cumulation of an aripiprazol at multiple dose is predictable. Indicators of pharmacokinetics of an aripiprazol in an equilibrium state - are proportional to a dose. Daily allowance - fluctuations of distribution of an aripiprazol and its metabolite of a degidroaripiprazol is noted. It is established that the main metabolite of an aripiprazol in plasma of the person, дегидроарипипразол, has the same affinity to D2-to dopamine receptors, as well as арипипразол.
Aripiprazol is quickly soaked up after drug Abilifay® intake, at the same time the maximum concentration of drug in plasma is reached in 3-5 hours. Absolute; bioavailability of tablets of the drug Abilifay® makes 87%. Meal does not influence bioavailability of an aripiprazol.
Aripiprazol is intensively distributed in fabrics, and the seeming volume of distribution makes 4,9 l/kg. At therapeutic concentration more than 99% of an aripiprazol contact proteins of serum, mainly albumine. Aripiprazol is exposed to presistemny metabolism only in the minimum degree. Aripiprazol is metabolized in a liver in three ways: dehydrogenation, hydroxylation and N-dealkylation. According to in vitro experiments, dehydrogenation and a hydroxylation of an aripiprazol happens under the influence of isoenzymes of CYP3A4 and CYP2D6, and N-dealkylation is catalyzed by CYP3A4 isoenzyme. Aripiprazol is the main component of medicine in blood. At an equilibrium state the area under a curve, "concentration of medicine - time" makes (AUC) of a degidroaripiprazol about 39% of AUC of an aripiprazol in plasma.
The average time of semi-removal of an aripiprazol is made by about 75 hours at patients with a high speed of metabolism at means of an isoenzyme of CYP2D6 and about 146 hours at patients with a low speed of metabolism with the participation of this isoenzyme. The general clearance of an aripiprazol makes 0.7 ml/min., mainly due to removal by a liver.
After a single dose in marked [14C] aripiprazol about 27% and 60% of radioactivity is defined in urine and Calais, respectively. Less than 1% of not changed aripiprazol are defined in urine and about 18% of the accepted dose in not changed look are removed with a stake.
Pharmacokinetics at special groups of patients. Children of 13 - 17 years. Parameters of pharmacokinetics of an aripiprazol and degidroaripiprazol at children of 13-17 years do not differ from those at adults therefore dose adjustment of drug is not required.
Patients of the senior age group. Age distinctions of parameters of pharmacokinetics of an aripiprazol at adult patients with schizophrenia, and also at healthy volunteers are not revealed.
Floor. The distinctions of parameters of pharmacokinetics of an aripiprazol caused by a gender of adult patients with schizophrenia, and also at healthy volunteers are not revealed.
Race. Clinically significant differences of pharmacokinetics of an aripiprazol depending on race are noted.
Smoking. Smoking does not exert impact on pharmacokinetics of an aripiprazol.
Renal failure. Parameters of pharmacokinetics of an aripiprazol and degidroaripiprazol at patients with a serious illness of kidneys do not differ from those at healthy volunteers.
Abnormal liver function. After a single dose of an aripiprazol persons with varying severity of cirrhosis did not reveal significant influence of an abnormal liver function on pharmacokinetics of an aripiprazol and a degidroaripiprazol. However only 3 patients with dekompensirovanny cirrhosis participated in a research (A class C on classification of Chayld-Pyyu) in this connection it is impossible to make final conclusions about metabolic activity of a liver at patients with dekompensirovanny cirrhosis.
Indications to use:
- schizophrenia: bad attacks and maintenance therapy;
- bipolar disorder of the I type: maniacal episodes and a maintenance therapy for the purpose of prevention of a recurrence at the patients with bipolar disorder of the I type who recently transferred the maniacal or mixed episode;
- addition to therapy with drugs of lithium or valproic acid for treatment of the maniacal or mixed episodes within bipolar disorder of the I type in the presence of psychotic symptoms or without them and a maintenance therapy for the purpose of prevention of a recurrence at patients with bipolar disorder of 1 type;
- addition to antidepressive therapy at big depressive frustration.
Route of administration and doses:
Schizophrenia. The recommended initial dose - from 10 to 15 mg once a day, irrespective of meal. A maintenance dose - usually 15 mg a day. In clinical trials efficiency of drug in doses from 10 to 30 mg/days is shown.
Maniacal episodes at bipolar disorder. Monotherapy. The recommended initial dose - 15 mg once a day, irrespective of meal. Change of a dose, if necessary, is made with an interval not less than 24 hours. In clinical trials at maniacal episodes efficiency of drug in doses of 15-30 mg/day at reception within 3-12 weeks is shown. Safety of doses higher than 30 mg/days in clinical trials was not estimated.
At observation of the patients with bipolar disorder of the I type who transferred the maniacal or mixed episode at which stabilization of symptoms against the background of administration of drug of Abilifay® (15 mg/days or 30 mg/days was noted at an initial dose of 30 mg/days) within 6 weeks, then - 6 months and further - within 17 months, the favorable effect of such maintenance therapy is established. It is necessary to inspect periodically patients for definition of need of continuation of a maintenance therapy.
Additional therapy. As addition to therapy with drugs of lithium or valproic acid at bipolar disorder. The recommended initial dose from 10 mg to 15 mg once a day, irrespective of meal. A maintenance dose - usually 15 mg a day. The dose can be increased to 30 mg a day depending on clinical indications.
At observation of patients with bipolar disorder of the I type the favorable effect of a maintenance therapy by the drug Abilifay® (from 10 mg/days to 30 mg/days) as addition to therapy with drugs of lithium or valproic acid is established. It is necessary to inspect periodically patients for definition of need of continuation of a maintenance therapy.
Additional therapy at big depressive frustration. As addition to treatment with antidepressants it is recommended to appoint the drug Abilifay® in an initial dose of 5 mg a day; if necessary and good tolerance of therapy the daily dose of the drug Abilifay® can be increased weekly by 5 mg to the maximum no more than 15 mg a day.
Therapy duration is not established by the drug Abilifay® according to all indications stated above; it is regularly necessary to conduct examination of the patient regarding a possibility of cancellation of therapy.
To patients with a liver failure the dose of 30 mg is appointed with care.
Use for special groups of patients. Patients with a renal failure. Dose adjustment at purpose of drug is not required to patients with a renal failure.
Patients with a liver failure. Dose adjustment at purpose of drug is not required to patients with a liver failure.
Use for patients is more senior than 65 years. Dose adjustment is not required.
Influence of a sex of the patient on the dosing mode. The drug dosing mode is identical to patients of both sexes.
Influence of smoking on the dosing mode. The drug dosing mode to smokers and non-smoking patients is identical.
The dosing mode at the accompanying therapy. At simultaneous use of the drug Abilifay® and powerful inhibitors of an isoenzyme CYP3A4 (кетоконазол, кларитромицин), the dose of the drug Abilifay® has to be reduced half. At cancellation of inhibitors of an isoenzyme of CYP3A4, the dose of the drug Abilifay® has to be increased.
At simultaneous use of the drug Abilifay® and powerful inhibitors of an isoenzyme CYP2D6 (quinidine, fluoxetine, пароксетин) the dose of the drug Abilifay® has to be reduced at least half. At cancellation of inhibitors of an isoenzyme of CYP2D6 the dose of the drug Abilifay® has to be increased.
Абилифай® it is necessary to apply without change of the mode of dosing if it is appointed as additional therapy at patients with big depressive frustration.
At simultaneous use of the drug Abilifay® and powerful inhibitors of isoenzymes CYP2D6 (quinidine, fluoxetine, пароксетин) and CYP3A4 (кетоконазол, кларитромицин), the dose of the drug Abilifay® has to be reduced by 3/4% (that is to 25% usual, doses). At cancellation of inhibitors of isoenzymes of CYP2D6 and/or CYP3A4, the dose of the drug Abilifay® has to be increased.
At simultaneous use of the drug Abilifay® and powerful, moderate or weak inhibitors of isoenzymes of CYP2D6 and CYP3A4, the dose of the drug Abilifay® can be originally reduced by 3/4% (that is to 25% of a usual dose), and then is increased for achievement of optimum clinical result.
At purpose of the drug Abilifay® to patients with low activity of an isoenzyme of CYP2D6 originally the dose of the drug Abilifay® has to be reduced half, and then is increased for achievement of optimum clinical result. At simultaneous use of the drug Abilifay® and powerful inhibitor of an isoenzyme CYP3A4 to patients with low activity of an isoenzyme of CYP2D60 the dose of the drug Abilifay® has to be reduced by 3/4% (that is to 25% of a usual dose).
At simultaneous use of the drug Abilifay® and potential inductors of an isoenzyme of CYP3A4 (carbamazepine), a dose of the drug Abilifay® it has to be increased twice. At cancellation of inductors of an isoenzyme of CYP3A4, the dose of the drug Abilifay® has to be reduced to 10-15 mg.
Features of use:
Pregnancy and lactation: adequate and well controlled researches at pregnant women were not conducted. It is unknown whether drug use by the pregnant woman can make harmful effects on a fruit or cause disturbances of reproductive function. It is known that newborns whose mothers accepted neuroleptics during the 3rd trimester of pregnancy in a puerperal period have a risk of development of extrapyramidal frustration and/or a syndrome of "cancellation". They noted the excitement increased or the lowered arterial pressure, a tremor, drowsiness, a respiratory distress syndrome, disturbances when feeding. These symptoms had varying severity; sometimes they passed without treatment whereas in other cases newborns needed an intensive care and long hospitalization. At use of an aripiprazol development in newborns of similar symptomatology was noted very seldom.
It is necessary to warn patients that they have to report immediately to the doctor about approach of pregnancy against the background of treatment, it is necessary to inform the doctor on the planned pregnancy also. Абилифай® can be accepted during pregnancy, only if the potential advantage of use for mother exceeds potential risk for a fruit.
Aripiprazol gets into female breast milk. It is not recommended to nurse at drug use.
Suicide attempts. Tendency to suicide thoughts and attempts is characteristic of patients with psychosis, bipolar disorder and big depressive frustration therefore medicinal therapy has to be combined with careful medical observation. The drug Abilifay® should be prescribed in the minimum quantity sufficient for treatment of the patient; it will reduce risk of overdose.
Reception of antidepressants, according to clinical trials, increases risk of emergence of suicide thoughts and attempts at children, teenagers and young patients with a depression and other mental disorders. In this regard it is necessary to observe extra care at use of antidepressants, including in the form of a combination therapy antidepressants and drug
Абилифай®, for treatment of children, teenagers and young patients. At patients is more senior 24 strengthening of suicide thoughts and behavior under the influence of antidepressants is not revealed, and at patients is more senior 65 decrease in frequency of this side effect was noted.
Late dyskinesia. The risk of development of late dyskinesia increases in process of increase in duration of therapy by neuroleptics therefore at emergence against the background of administration of drug of Abilifay® of symptoms of late dyskinesia it is necessary to reduce a dose of this drug or to cancel it. After therapy cancellation these symptoms can temporarily amplify or even for the first time to appear.
Malignant antipsychotic syndrome. At treatment neuroleptics, including aripiprazoly, described a life-threatening symptom complex, the malignant antipsychotic syndrome (MAS), known under the name. This syndrome is shown by a hyper pyrexia, muscular rigidity, disturbances of mentality and instability of the autonomic nervous system (irregular pulse and arterial pressure, tachycardia, perspiration and cardiac arrhythmias). Besides, sometimes there are an increase in activity of a kreatinfosfokinaza, a myoglobinuria (рабдомиолиз) and an acute renal failure. In a case, emergence of symptoms of ZNS or inexplicable fever all neuroleptics, including the drug Abilifay®, have to be cancelled.
Spasms. As well as other neuroleptics, арипипразол it is necessary to apply with care at patients with spasms in the anamnesis and risk of their development.
The psychoses connected with senile dementia and Alzheimer's disease. At patients with the psychoses caused by senile dementia at treatment by atypical neuroleptics the risk of a lethal outcome increases. At psychoses at patients 65 years with Alzheimer's disease are more senior disturbances from cardiovascular system were noted: a heart attack, passing ischemic disturbance of cerebral circulation, including with a lethal outcome. Use of the drug Abilifay® at the psychoses caused by senile dementia and at elderly patients with Alzheimer's disease is not recommended.
Hyperglycemia and diabetes mellitus. The hyperglycemia in some cases expressed and which is followed by ketoacidosis or a giperosmolyarny coma with a lethal outcome was noted at the patients accepting atypical neuroleptics. Though communication between reception of atypical neuroleptics and disturbances of hyper glycemic type remains not clear, patients for whom the diabetes mellitus is diagnosed have to carry out regularly definition of concentration of glucose to blood at reception of atypical neuroleptics. Patients who have risk factors of emergence of a diabetes mellitus (obesity, existence of a diabetes mellitus in the family anamnesis) at reception of atypical neuroleptics have to carry out definition of concentration of glucose to blood at the beginning of a course and periodically in the course of administration of drug. At the patients accepting atypical neuroleptics continuous monitoring of symptoms of a hyperglycemia, including the increased thirst, the speeded-up urination, a polyphagia, weakness is necessary; special attention should be paid to patients, with a diabetes mellitus and risk factors of its development.
Leukopenia, neutropenia, agranulocytosis. It is known that neuroleptics, including Abilifay®, can cause temporary changes of a picture of blood - a leukopenia, a neutropenia, and also an agranulocytosis. Risk factors is low concentration of white blood cells at the patient prior to treatment, and also caused by other medicines; leukopenia and neutropenia. It is regularly necessary to control a blood pattern at such patients, especially in the first months of treatment by the drug Abilifay®. At clinically significant decrease in concentration of white blood cells of not clear etiology it is necessary to consider a question of drug withdrawal of Abilifay®.
It is necessary to control carefully a condition of patients with clinically significant neutropenia regarding identification of the increased temperature or other symptoms of an infection for the purpose of the immediate beginning of the corresponding treatment. At a heavy neutropenia (number of neutrophils less than 1000/mm3) treatment with the drug Abilifay® is interrupted before normalization of a picture of blood.
Cardiovascular diseases. Due to the risk of development orthostatic" hypotensions арипипразол should be applied with care at patients with cardiovascular diseases (a myocardial infarction, ischemic, a heart trouble; heart failure, disturbances of cordial conductivity in the anamnesis), the disturbances of cerebral circulation or states contributing. to arterial hypotension (dehydration, a hypovolemia, therapy by anti-hypertensive means).
Cognitive and motive frustration. As well as other neuroleptics, the drug Abilifay® can cause cognitive and motive frustration. In particular, in clinical trials of the drug Abilifay® cases of drowsiness and block were noted. During treatment patients should refrain from driving and dangerous mechanisms.
Thermal control disturbance. It is known that neuroleptics can cause thermal control disturbance. It patients who have an increased risk of overheating owing to the intensive exercise stress, high temperature of the environment, administration of drugs possessing m-holinoblokiruyushchey activity, dehydration should consider the drug Abilifay® at appointment.
Dysphagy. At use of neuroleptics cases of disturbances of a vermicular movement of a gullet and, as a result, aspiration pneumonia were noted. It is necessary to be careful at appointment to patients with risk factors of development of aspiration pneumonia.
Risk of development of a venous thromboembolism. Use of neuroleptics, including the drug Abilifay®, can be connected with risk of development of a venous thromboembolism. In this regard it is necessary to reveal risk factors of development of the given complication before purpose of the drug Abilifay®, and also during treatment by this drug. In case of need it is necessary to apply measures for prevention of development of a venous thromboembolism.
Influence on ability to manage vehicles and mechanisms. As well as at purpose of other neuroleptics, at purpose of an aripiprazol the patient has to be warned about danger of work with moving mechanisms and driving.
Frequency of side effects is specified according to the following scale: very often:> 10%, are frequent:> 1% and <10%, infrequently:> 0,1% and <1%, are rare:> 0,01% and <0,1%, are very rare: <0,01%, frequency is unknown (it cannot be estimated by means of available data).
Cardiovascular system. Often: orthostatic hypotension, tachycardia; infrequently: bradycardia, heart consciousness, myocardial infarction, lengthening of an interval of QT, cardiac standstill, hemorrhages, fibrillation of auricles, heart failure, AV blockade, myocardium ischemia, deep vein thrombosis, phlebitis, premature ventricular contraction; seldom: vazovagalny syndrome, atrial flutter, thrombophlebitis, intracraneal hemorrhage, brain ischemia; very seldom: syncope, increase in arterial pressure; frequency is unknown: a thromboembolism (including an embolism of a pulmonary artery and a deep vein thrombosis).
Alimentary system. Very often: nausea, appetite loss; often: appetite strengthening *, dyspepsia, vomiting, a lock, saliva hypersecretion, dryness in a mouth, weight in a stomach, diarrhea; * at treatment of a depression in a combination with antidepressants. Infrequently: a gastroenteritis, the complicated swallowing, a meteorism, gastritis, tooth caries, an ulitis, hemorrhoids, a gastroesophagal reflux, gastrointestinal hemorrhages, periodontal abscess, a paraglossa, an incontience a calla, colitis, rectal hemorrhages, stomatitis, ulcerations of a mucous membrane of an oral cavity, cholecystitis, a fekaloma, candidiasis of a mucous membrane of an oral cavity, an eructation, stomach ulcer; seldom: esophagitis, bleeding of gums, language inflammation, hematemesis, intestinal bleedings, duodenum ulcer, cheilitis, increase in a liver, intestines perforation; very seldom: increase in activity of alaninaminotranspherase (ALT), and aspartate aminotransferase (ACT), hepatitis, jaundice, pancreatitis, dysphagy.
Musculoskeletal system. Often: arthralgia, muscle tension; infrequently: myasthenia, arthritis, arthrosis, muscular weakness, muscular spasms, bursitis; very seldom: increase in activity of a kreatinfosfokinaza, рабдомиолиз, tendinitis, tenobursitis, mialgiya.
Nervous system. Very often: sleeplessness, drowsiness, headache, akathisia; often: dizziness, tremor, extrapyramidal syndrome, psychomotor excitement, depression, nervousness, hostility, suicide thoughts, maniacal thoughts, confusion of consciousness, resistance to performance of passive movements ("cogwheel syndrome"), lethargy, decrease in concentration of attention, sedation; infrequently: dystonia, muscular twitchings, paresthesia, a tremor of extremities, impotence, a bradykinesia, the lowered/raised libido, panic reactions, apathy, memory easing, a stupor, amnesia, a stroke, a hyperactivity, depersonalization, dyskinesia, a syndrome of "uneasy legs", a myoclonus, the suppressed mood, reinforced reflexes, delay of cogitative function, hypersensitivity to irritants, disturbance of oculomotor reaction; seldom: nonsense, euphoria, bukkoglossalny syndrome, akineziya, oppression of consciousness up to a loss of consciousness, reduced reflexes, the notions of compulsion, a malignant antipsychotic syndrome; very seldom: alalia, spasms.
Respiratory system. often: short wind, pneumonia; infrequently: nasal bleeding, hiccups, laryngitis; seldom: a pneumorrhagia, the strengthened expectoration, a xeromycteria, a fluid lungs, a pulmonary embolism, a hypoxia, respiratory insufficiency, an apnoea. Very seldom: aspiration pneumonia.
Skin and hypodermic cellulose. Often: xeroderma, itch, skin ulcerations; infrequently: acne, vezikulo-violent (bubbly) rash, eczema, alopecia (baldness), psoriasis, seborrhea; seldom: makulopapulezny rash, exfoliative dermatitis, small tortoiseshell, hyperhidrosis.
Sense bodys. Often: sight illegibility, photophobia, ear pain; Infrequently: a xerophthalmus, eye pain, a ring in ears, an inflammation of a middle ear, a cataract, taste loss, a blepharitis; seldom: the strengthened dacryagogue, frequent blinking, outside otitis, an amblyopia, deafness, a diplopia, intraocular hemorrhages.
Urinogenital system. Infrequently: cystitis, the speeded-up urination, a leukorrhea, a hamaturia, a dysuria, an amenorrhea, a premature ejaculation, vulval bleeding, vaginal candidiasis, a renal failure, uterine bleeding, a menorrhagia, an albuminuria, stones in kidneys, a nocturia, a polyuria, false desires to an urination; seldom: a mammary gland pains, a cervicitis, a galactorrhoea, an anorgazmiya, burning in an urethra and external genitals, a glucosuria, a gynecomastia (increase in chest glands at men), a painful erection; very seldom: urine incontience, ischuria, priapism.
Organism in general. Often: an adynamy, fatigue, a grippopodobny syndrome, feeling of a shiver in a body; infrequently: peripheral hypostasis, a face edema, an indisposition, a photosensitivity, maxillary pains, a fever, constraint of jaws, abdominal distention, tension in a breast; seldom: pharyngalgias, constraint in spin, weight in the head, candidiasis, feeling of a sdavlennost in a throat, Mendelssohn's syndrome, heatstroke; very seldom: a leukopenia, a neutropenia, thrombocytopenia, disturbances of temperature regulation, a pyrexia, thorax pains, in a neck.
The metabolic disturbances and disturbances connected with food. Often: decrease in body weight; infrequently: dehydration, hypostasis, a hypercholesterolemia, a hypopotassemia, a lipidemia, a hypoglycemia, thirst, the increased content of urea in blood, increase in activity of an alkaline phosphatase, an iron deficiency anemia, increase in activity of a lactate dehydrogenase, obesity; seldom: hyperpotassemia, gout, hypernatremia, cyanosis, urine acidulation; very seldom: hyponatremia, increase in activity of alaninaminotranspherase, increase in activity of aspartate aminotransferase, increase in activity of a kreatinfosfokinaza, anorexia, hyperglycemia, diabetic ketoacidosis, diabetic giperosmolyarny coma.
Additional information on side effects of drug. The undesirable phenomena which are found at treatment by neuroleptics were noted as well at therapy by the drug Abilifay®, including exceptional cases of emergence of a malignant antipsychotic syndrome, and also infrequent cases of development of late dyskinesia and convulsive attacks.
At sensitive patients in the first days of treatment dystonia symptoms - long pathological muscular spasms can be noted.
Symptoms of dystonia are: a trachelism, sometimes with feeling of a sdavlennost in a throat; difficulties when swallowing, the complicated breath and/or a protrusion of language. These symptoms can appear also at purpose of low doses of drug, however they are more expressed and are more often noted purpose of high doses of neuroleptics of the first generation.
Men and persons of young age treat patients of group of the increased risk of development of dystonia.
Interaction with other medicines:
The mechanism of action of an aripiprazol is connected with influence on the central nervous system that needs to be considered at combined use with other medicines possessing the central action.
Possessing antagonistic action concerning alfa1-adrenoceptors, арипипразол can strengthen effect of anti-hypertensive drugs.
It is necessary to be careful at the simultaneous use of an aripiprazol and medicines causing lengthening of an interval of QT - or breaking electrolytic balance.
Aripiprazol does not influence pharmacokinetics and a pharmacodynamics of warfarin, it does not force out warfarin from communication with blood proteins.
The blocker of H2-histamine receptors the famotidine causing powerful oppression of secretion of hydrochloric acid in a stomach reduces the speed of absorption of an aripiprazol, however it does not exert impact on clinical effect of an aripiprazol.
Various ways of metabolism of an aripiprazol are known; including with participation of isoenzymes of CYP2D6 and CYP3A4. In researches at, healthy volunteers powerful inhibitors of isoenzymes of CYP2D6 (quinidine) and CYP3A4 (кетоконазол) exerted impact on pharmacokinetics of an aripiprazol therefore it is necessary to reduce doses of an aripiprazol when using it in various combinations to inhibitors - isoenzymes of CYP3A4 and CYP2D6 (see the section "Route of Administration and Doses"). At simultaneous use of an aripiprazol and weak inhibitors of isoenzymes CYP3A4 (diltiazem, estsitalopra) or CYP2D6 can expect small increase in concentration of an aripiprazol in blood.
Because the isoenzyme of CYP1A does not participate in metabolism of an aripiprazol, smoking does not exert impact on pharmacokinetics and effect of an aripiprazol.
At reception of an aripiprazol together with carbamazepine, the powerful inductor" CYP3A4 isoenzyme, metabolism of an aripiprazol amplifies therefore the dose of an aripiprazol has to be corrected (see the section "Route of Administration and Doses"). It is possible to expect similar action and other powerful inductors of isoenzymes of CYP3A4 and CYP2D6.
Isoenzymes of CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2E1 in this connection its interaction with drugs and other factors (for example, smoking), capable to inhibit or activate these enzymes is improbable do not participate in metabolism of an aripiprazol of in vitro.
The concomitant use of drugs of lithium or valproic acid from 30 mg of an aripiprazol did not exert clinically significant impact on pharmacokinetics of an aripiprazol.
In clinical trials арипипразол in doses of 10-30 mg/days did not exert significant impact on metabolism of substrates of isoenzymes of CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (омепразол, warfarin) and CYP3A4 (dextromethorphan). Besides, арипипразол and its main metabolite дегидроарипипразол did not change metabolism with participation of an isoenzyme of CYP1A2 in vitro. Clinically significant influence of an aripiprazol on drugs, metaboliziruyemy with participation of these isoenzymes is improbable.
At simultaneous use of an aripiprazol (10 - 30 mg/days) and patients with bipolar disorder had no lamotridzhin (100 - 400 mg/days) of changes of pharmacokinetics of a lamotridzhin therefore correction of its dose is not required. Aripiprazol did not exert impact on pharmacokinetics of an estsitalopram, and a venlafaksin at healthy volunteers therefore correction of doses of these drugs is not required at simultaneous use aripiprazoly.
At use for patients with big depressive frustration of an aripiprazol along with fluoxetine (20-40 mg/days), paroksetiny (37,5 - 50 mg/days) and sertraline (2 - 20 mg/days) of considerable changes of concentration of antidepressants in plasma it is not revealed.
Alcohol intake during treatment aripiprazoly can strengthen sedative effect of drug therefore it should be avoided.
- hypersensitivity to the aripiprazol or any other component which is a part of drug;
- rare hereditary galactosemia, deficit of lactase, glyukozo-galaktozny malabsorption;
- age up to 18 years;
- breastfeeding period.
With care: use for patients with cardiovascular diseases (with coronary heart disease or the postponed myocardial infarction, with heart failure and disturbances of conductivity), the cerebrovascular diseases and states contributing to arterial hypotension (dehydration, a hypovolemia and reception of hypotensive drugs) in connection with a possibility of development of orthostatic hypotension at patients with convulsive attacks or with diseases at which spasms are possible; at patients with the increased risk of a hyperthermia, for example, at intensive exercise stresses, overheating, reception of m-holinoblokatorov, at dehydration because of ability of neuroleptics to break thermal control; at patients with the increased risk of aspiration pneumonia because of risk of disturbance of motor function of a gullet and aspiration; at patients with obesity and in the presence of a diabetes mellitus in a family; at patients with high risk of a suicide (psychotic diseases, bipolar disorders, big depressive frustration); persons at the age of 18-24 years in connection with risk have development of suicide behavior.
If at you one of the listed diseases, before administration of drug surely consult with the doctor.
In clinical trials the accidental or intentional overdoses of an aripiprazol with a single dose to 1260 mg which were not followed by a lethal outcome are described. Overdose symptoms: lethargy, increase in arterial pressure, drowsiness, tachycardia, loss of consciousness. At the hospitalized patients not - it is revealed clinically significant changes of the main physiological indicators, laboratory parameters and an ECG.
Cases of overdose of an aripiprazol at children are described (reception to 195 mg). Extrapyramidal frustration and a passing loss of consciousness belong to potentially dangerous symptoms of overdose.
Treatment: control of the vital functions, an ECG (for detection of possible arrhythmia), a maintenance therapy, ensuring passability of respiratory tracts, oxygenation, effective ventilation of the lungs, absorbent carbon, a symptomatic treatment, careful medical observation before disappearance of all symptoms.
There are no data on use of a hemodialysis at overdose of an aripiprazol; the favorable effect of this method is improbable as it арипипразол is not removed by kidneys in not changed look and considerably contacts proteins of plasma.
At a temperature from 15 to 30 °C in the dry place. To store in the place, unavailable to children. A period of validity - 3 years. Not to use drug after the expiry date specified on packaging.
According to the recipe
Tablets of 5 mg, 10 mg, 15 mg, 30 mg. Packaging: on 7 tablets in the AI/A1 blister laminated by a polyamide film and PVC. On 4 blisters together with the application instruction in a pack cardboard.