Абилифай®

General characteristics. Structure:

Active ingredient: 10 mg of an aripiprazol.

Excipients: the tartaric acid granulated R-tsiklo-a dextrin sulfobutyl ether (Каптисол®), sodium hydroxide, water for injections.

* - Packing is made taking into account a rebookmark that is necessary for the guaranteed extraction 1,33 ml of the solution containing not less than 10 mg of active agent. At the same time the full volume of solution in a bottle makes 1,69 ml (total quantity of an aripiprazol in a bottle - 12,675 mg).

Pharmacological properties:

Indications to use:

The drug Abilifay® solution for intramuscular introduction is used for bystry stopping of a condition of excitement and behavioural disturbances at patients with schizophrenia and at patients with maniacal episodes at bipolar disorder of the I type at impossibility of administration of drug inside.

As soon as there is possible an administration of drug inside, therapy in the form of intramuscular injections is cancelled.

Route of administration and doses:

It is applied only to intramuscular injections. The recommended initial dose - 10 mg (1 bottle, 1,33 ml) in the form of a single intramuscular injection. Effective doses are in range from 5,25 to 15 mg in the form of a single injection. The reduced dose of 5,25 mg (0,7 ml) can be appointed on the basis of assessment of a clinical condition of the patient which has to consider the drugs which are already appointed to the patient for the supporting treatment or for emergency treatment. The second injection can be made 2 hours later after the first injection, depending on the individual clinical status of the patient. It is not necessary to appoint more than three, injections within 24 hours.

The maximum daily dose makes 30 mg of an aripiprazol, at the same time the doses entered in the form of solution for intramuscular injections and the doses accepted in the form of tablets are summed up.

If further treatment by means of the drug Abilifay® in the form of tablets is supposed, it is necessary to study the application instruction of tablets attentively.

For improvement of absorption it is necessary to administer the drug in deltoid or it is deep in a big muscle of a buttock, avoiding zones with the expressed hypodermic fatty tissue. Drug is not intended for intravenous or hypodermic administration.

Drug is used only in the form of a short course of therapy.

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 of weak or moderate degree. At a heavy liver failure it is necessary to be careful, especially at purpose of the maximum daily dose of 30 mg.

Use for patients is more senior than 65 years. Considering the increased risk of development of side reactions in this group of patients, it is necessary to consider a question of purpose of a reduced initial dose it.

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.

Use for children. Safety and efficiency at patients are younger than 18 years with psychomotor excitement at schizophrenia or a bipolar mania are not established.

Dose adjustment in connection with interactions. At co-administration of an aripiprazol and powerful inhibitors of isoenzymes - CYP3A4 and CYP2D6 a dose of an aripiprazol should be reduced. After cancellation of powerful inhibitors of isoenzymes of CYP3A4 and CYP2D6 the dose of an aripiprazol is increased.

At co-administration of an aripiprazol and powerful inductors of an isoenzyme CYP3A4 the dose of an aripiprazol should be increased. After cancellation of the powerful inductor of an isoenzyme of CYP3A4 the dose of an aripiprazol is reduced.

Features of use:

Pregnancy and lactation: adequate and well controlled researches at pregnant women were not conducted. Cases of congenital anomalies of newborns were noted, however their relationship of cause and effect is not established with reception of an aripiprazol. Researches on animals do not allow to exclude potential negative effect on fetation. The patient should be warned that it is necessary to inform the attending physician if she became pregnant or plans pregnancy during treatment aripiprazoly.

Due to insufficient information about safety of drug at inclusion in pregnancy time, and also considering results of studying on animals, it is necessary to appoint the drug Abilifay® during pregnancy only when the potential advantage of use for mother exceeds potential risk for a fruit.

Aripiprazol gets into milk of rats. There are no data on penetration of an aripiprazol into breast milk of the person. It is not recommended to nurse at drug use.

Suicide attempts - tendency to suicide thoughts and attempts is characteristic of patients with psychotic diseases and bipolar disorder therefore medicinal therapy has to be combined with careful medical observation. Cases of suicide behavior at the beginning of therapy were noted by neuroleptics; and also when changing a neuroleptic, including арипипразол.

Late dyskinesia - risk of development of late dyskinesia increases in process of increase in duration of therapy by neuroleptics therefore at emergence of symptoms of late dyskinesia against the background of administration of drug of Abilifay® it is necessary to reduce a dose of drug or to cancel it. After therapy cancellation these symptoms can temporarily amplify or even for the first time to appear.

The malignant antipsychotic syndrome - at treatment by neuroleptics, including aripiprazoly, is described the life-threatening symptom complex known under the name "malignant antipsychotic syndrome" (MAS). 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 case 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 anti-psychotics the risk of a lethal outcome increases. At psychoses at patients of 56-99 years with Alzheimer's disease in three placebos - controlled researches against the background of an aripiprazol the frequency of lethal outcomes increased (twice to comparison with placebo). The reasons of lethal outcomes were various, however, in most cases connected them with dysfunction of cardiovascular system (heart failure, sudden death) and infections (for example, pneumonia). In the same researches at patients of 79-88 years more often than at patients of younger age, side reactions concerning cardiovascular system were noted: a heart attack, ischemia attacks, including with a lethal outcome. Use of 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 appointment - atypical neuroleptics should carry out definition of concentration of glucose to blood at the beginning of a course and periodically in the course of treatment. 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.

Cardiovascular diseases. Due to the risk of development of orthostatic hypotension арипипразол it is necessary to apply with care at patients with cardiovascular diseases (a myocardial infarction, ischemia attacks, 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). At treatment neuroleptics noted cases of a venous thromboembolism therefore it is necessary to reveal patients of risk group concerning development of a venous thromboembolism prior to treatment by the drug Abilifay® and to apply preventively measures. In clinical trials of the drug Abilifay® cases of lengthening of an interval of Q-T were noted. As well as patients should appoint other neuroleptics, Abilifay® with care with lengthening of an interval of Q-T in the family anamnesis.

Dysphagy. At purpose of neuroleptics cases of disturbance 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.

Influence on body weight. At patients with schizophrenia and bipolar disorder excess body weight in connection with associated diseases, reception of neuroleptics and a non-optimal diet is often noted. Increase in body weight was noted against the background of therapy by the drug Abilifay®, is more often at the patients of risk group (having diabetes, dysfunctions of a thyroid gland, hypophysis adenoma). In clinical trials considerable influence of drug on body weight is not revealed.

Influence on ability to thermal control. It is known that neuroleptics, including арипипразол, can break ability to thermal control. It is necessary to be careful at purpose of an aripiprazol to patients concerning whom there is a probability of fervescence (for example, at the raised exercise stress, at temperature increase of the environment, at co-administration of anticholinergic drugs, at organism dehydration).

Alcohol intake. Efficiency and safety of use of an aripiprazol in the form of intramuscular injections at intoxication is not studied by alcohol or medicines. It is necessary to avoid alcohol intake during treatment aripiprazoly.

Influence on ability to manage vehicles and mkhanizm. As well as at purpose of other neuroleptics, at treatment aripiprazoly the patient has to be warned about danger of work with moving mechanisms and driving.

Side effects:

The most frequent side reactions noted in clinical trials of an aripiprazol of solution for injections (more than 3% of patients), had a nausea, dizziness and drowsiness.

The side reactions given below noted in clinical trials of an aripiprazol of solution for injections with a frequency> 1/100 or estimated as clinically significant, are noted by an asterisk (*). Frequency of the side effects given below is specified according to the following scale: frequent> 1/100 <1/10 infrequent> 1/1000 <1/100.

From the central nervous system. Often: drowsiness, dizziness, headache, akathisia

From cardiovascular system. Infrequently: tachycardia *, orthostatic hypotension *, increase in diastolic arterial pressure *

From the alimentary system. Often: nausea, vomiting. Infrequently: dryness of a mucous membrane oral полости*.

General reactions. Infrequently: усталость*.

The side reactions given below noted in clinical trials of an aripiprazol for intake with a frequency> 1/100 or estimated as clinically significant, are noted by an asterisk (*).

From mentality. Often: concern, sleeplessness, uneasiness. Infrequently: депрессия*.

From the central nervous system. Often: extrapyramidal frustration, akathisia, tremor, dizziness, drowsiness, sedation, headache.

From an organ of sight. Often: sight illegibility.

From cardiovascular system. Infrequently: tachycardia *, orthostatic гипотензия*.

From the alimentary system. Often: dyspepsia, nausea, vomiting, lock, hypersecretion of sialadens.

General reactions. Infrequently: усталость*.

Influence on indicators of laboratory researches. At 3,5% of the patients accepting арипипразол were noted increase in activity of a kreatinfosfokinaza (usually passing and symptomless).

Side reactions characteristic of all neuroleptics. Dystonia: dystonia symptoms (long pathological reductions of groups of muscles) can be noted at some patients in the first days of treatment. Symptoms of dystonia are neck muscles spasms, sometimes up to feeling of squeezing of a throat, difficulty when swallowing, the complicated breath, a language protrusion. These symptoms are noted more often and are more intensively expressed at use of high doses of typical neuroleptics. The risk group is made by men and young patients.

ZNS, late dyskinesia, spasms, reactions from cardiovascular system and the increased mortality of patients with senile dementia, a hyperglycemia and a diabetes mellitus meet at use of all neuroleptics, including арипипразол.

During post-marketing use the following side reactions which frequency is not established were noted:

From the blood circulatory system and a lymphokinesis - a leukopenia, a neutropenia, thrombocytopenia.

From immune system - allergic reactions (an anaphylaxis, vascular hypostasis, including a paraglossa, a face edema, an itch, a small tortoiseshell).

From endocrine system - a hyperglycemia, a diabetes mellitus, diabetic ketoacidosis, a diabetic giperosmolyarny coma.

Disturbances of food and metabolism - increase in body weight, decrease in body weight, anorexia, a hyponatremia.

Disturbances from mentality - excitement, nervousness, suicide thoughts and attempts.

From a nervous system - an alalia, ZNS, a spasm (grand mal).

From cardiovascular system - lengthening of an interval of Q-T, ventricular arrhythmia, sudden death, a cardiac standstill, torsades de points, bradycardia, a syncope, increase in arterial pressure, a venous thromboembolism, (including an embolism of a pulmonary artery and a deep vein thrombosis).

From respiratory system, bodies of a thorax and a mediastinum - a stomatopharynx spasm, a laryngospasm, aspiration pneumonia.

From the alimentary system - pancreatitis, a dysphagy, discomfort in a stomach, discomfort in an abdominal cavity, diarrhea; jaundice, hepatitis.

From skin and skin appendages - rash, photosensitivity reactions, an alopecia, a hyperhidrosis.

From a musculoskeletal system - рабдомиолиз, a mialgiya, constraint.

From urinogenital system - an urine incontience, an ischuria, a priapism.

The general reactions - thermal control disturbance (a hypothermia, a pyrexia), a stethalgia, peripheral hypostases.

Change of laboratory indicators - increase in activity of alaninaminotranspherase, aspartate aminotransferase, a gammaglutamilaminotransferaza, alkaline phosphatase, kreatinfosfokinaza, increase in concentration of glikozilirovanny hemoglobin.

Interaction with other medicines:

Influence of other drugs on drug Abilifay® Pharmacokinetics. Aripiprazol shows antagonism to α1-адренорецепторам, in this regard it is possible to expect that it will strengthen action of anti-hypertensive means at simultaneous use.

Aripiprazol influences preferential TsNS, in this regard in order to avoid excess sedative action and suppression of functions of respiratory and serdechnoyososudisty systems it is necessary to show extra care at simultaneous use of other drugs influencing TsNS. At combined, therapies parenteral aripiprazoly and benzodiazepines (lorazepam) the risk of increase in sedation and development of orthostatic hypotension increases.

It is necessary to be careful at the simultaneous use of an aripiprazol and drugs capable to extend an interval of Q-T or to break electrolytic balance.

The blocker of H2-histamine receptors famotidine reduces the speed of absorption of an aripiprazol, however the clinical importance of this effect is not found out.

Various ways of metabolism of an aripiprazol, including with participation of isoenzymes of CYP2D6 and CYP3A4, but not isoenzyme of CYP1 A are known. In this regard dose adjustment for the smoking patients is not required.

In researches at healthy people powerful inhibitor of an isoenzyme CYP2D6 quinidine increased AUC of an aripiprazol by 107% whereas value of Smaks did not change. AUC values and СМакс a degidroaripiprazola (an active metabolite) decreased by 32% and 47%, respectively. In this regard the drug Abilifay® dose at use with quinidine has to be lowered approximately half. It is expected that similar effect can render also powerful inhibitors of an isoenzyme CYP2D6 fluoxetine and пароксетин.

In researches at healthy people .moshchny inhibitor of an isoenzyme CYP3A4 кетоконазол increased AUC values and Smaks of an aripiprazol by 63% and 37%, respectively. AUC values and Smaks of a degidroaripiprazol (an active metabolite) increased by 77% and 47%, respectively. At patients with low activity of metabolism by means of CYP2D6 isoenzyme simultaneous use of powerful CYP3A4 inhibitors can lead to increase in concentration of an aripiprazol, in plasma in comparison with patients at whom metabolism by means of CYP2D6 takes place more actively. Use of a ketokonazol or other powerful inhibitors of an isoenzyme CYP3A4 and the drug Abilifay® reasonably only when the potential advantage of therapy surpasses possible risk from its use. The drug Abilifay® dose at use with ketokonazoly has to be lowered approximately half. It is expected that also other powerful inhibitors of an isoenzyme of the drug Abilifay® can render similar effect, for example, итраконазол and HIV protease inhibitors in this connection it is necessary to carry out necessary dose adjustment of the drug Abilifay®. After the therapy termination by inhibitors of isoenzymes of CYP3A4 and CYP2D6 the dose of the drug Abilifay® is raised.

At simultaneous use of the drug Abilifay® and weak inhibitors of isoenzymes CYP3A4 (for example, diltiazem and an estsitalopram) and CYP2D6 can be expected small increase in concentration of an aripiprazol in a blood plasma.

Use of an aripiprazol (30 mg) together with carbamazepine, the powerful inductor of an isoenzyme CYP3A4, was followed by decrease by 68% and 73% of Cmax and AUC of an aripiprazol, respectively, and decrease by 69% and 71% of Cmax and AUC of its active metabolite of a degidroaripiprazol, respectively. The drug Abilifay® dose in such cases should be increased twice. It is possible to expect similar action and other powerful inductors of isoenzymes CYP3A4 (rifampicin, рифабутин, Phenytoinum, phenobarbital, Primidonum, эфавиренз, not Virapinum, drugs of the St. John's Wort which is made a hole) therefore it is necessary to carry out drug Abilifay® dose adjustment. After the therapy termination by the powerful inductors CYP3A4 the dose of the drug Abilifay® is reduced. Simultaneous use of drugs of lithium or valproic acid and an aripiprazol did not exert clinically significant impact on pharmacokinetics of an aripiprazol.

Influence of the drug Abilifay® on Pharmacokinetics of other drugs. At simultaneous use of solution of an aripiprazol for injections and lorazepam for injections the pharmacokinetics of lorazepam does not change. However, at single intramuscular introduction of an aripiprazol in a dose of 15 mg to healthy volunteers along with intramuscular administration of lorazepam in a dose of 2 mg the frequency of cases of orthostatic hypotension was higher, than at administration of one lorazepam.

In clinical trials it was shown that арипипразол in doses of 10-30 mg did not exert considerable impact on metabolism of substrates of isoenzymes of CYP2D6 (a ratio dextromethorphan / 3-метоксиморфинан), 2C9 (warfarin), 2C19 (омепразол) and ZA4 (dextromethorphan). Besides, арипипразол and degidro-aripiprazol in conditions ин витро do not change function of an isoenzyme CYP1A2 therefore it is improbable that арипипразол can have clinically significant influence on pharmacokinetics of medicines which metabolism is mediated by this isoenzyme.

At simultaneous use with valproic acid, drugs of lithium or lamotridzhiny clinically significant changes of concentration of these drugs in blood are not revealed.

Contraindications:

- hypersensitivity to an aripiprazol or any other component of drug;

- age up to 18 years;

- lactation period.

With care - at patients with cardiovascular diseases (coronary heart disease, the postponed myocardial infarction, heart failure and disturbance of conductivity); at patients with 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 diseases at which spasms are possible; at patients with the increased risk of a hyperthermia, for example, at intensive exercise stresses, overheating, at 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 a diabetes mellitus in the family anamnesis.

Overdose:

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 clinically significant changes of the main physiological indicators, laboratory parameters and an ECG are not revealed.

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, continuous an ECG, 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. It is necessary to consider possible influence of the accompanying therapy. The absorbent carbon accepted 1 hour later after an aripiprazol reduces the maximum concentration of Smaks-by 41% and the area under a curve concentration/time (AUC) approximately for 51% that can demonstrate advantage of purpose of absorbent carbon at overdose of an aripiprazol.

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.

Storage conditions:

At a temperature of 15-25 °C in the place protected from light. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Solution for intramuscular introduction of 7,5 mg/ml. Packaging: on 1,69 ml of drug in a bottle of colourless glass the type I corked by a rubber bung and an aluminum cap under a running in and a protective plastic cover (flip-off). On 1 bottle together with the application instruction in a cardboard pack.