Composition, form of production and packaging
Tablets of blue color, rectangular, with rounded edges, marked "A-007" and "5" on one side.
1 tab.
aripiprazole 5 mg
Excipients: lactose monohydrate, microcrystalline cellulose, corn starch, giprolose, magnesium stearate, aluminum blue lacquer.
7 pcs. - blisters (4) - packs of cardboard.
Tablets of pink color, rectangular, with rounded edges, marked "A-008" and "10" on one side.
1 tab.
aripiprazole 10 mg
Excipients: lactose monohydrate, microcrystalline cellulose, corn starch, giprolase, magnesium stearate, iron dye red oxide.
7 pcs. - blisters (4) - packs of cardboard.
Tablets are yellow, round, with a bevel, marked "A-009" and "15" on one side.
1 tab.
aripiprazole 15 mg
Excipients: lactose monohydrate, microcrystalline cellulose, corn starch, giprolose, magnesium stearate, iron oxide, yellow oxide.
7 pcs. - blisters (4) - packs of cardboard.
Tablets are white or slightly yellow, round, with a bevel, labeled "A-010" and "20" on one side.
1 tab.
aripiprazole 20 mg
Excipients: lactose monohydrate, microcrystalline cellulose, corn starch, giprolose, magnesium stearate.
7 pcs. - blisters (4) - packs of cardboard.
Tablets of pink color, round, with a facet, marked "A-011" and "30" on one side.
1 tab.
aripiprazole 30 mg
Excipients: lactose monohydrate, microcrystalline cellulose, corn starch, giprolase, magnesium stearate, iron dye red oxide.
7 pcs. - blisters (4) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Antipsychotic drug (antipsychotic). It is assumed that the therapeutic effect of aripiprazole in schizophrenia is due to a combination of partial agonistic activity against dopamine D 2 and serotonin 5HT1 a receptors and antagonistic activity against serotonin 5HT 2 receptors.
Aripiprazole has a high in vitro affinity for dopamine D 2 - and D 3 receptors, serotonin 5HT1 a - and 5HT2 a receptors and moderate affinity for dopamine D 4 -, serotonin 5HT2 c - and 5HT7-,? 1- adrenoreceptors and histamine H 1 -receptors. Aripiprazole is also characterized by moderate affinity for the sites of serotonin reuptake and lack of affinity for muscarinic receptors. In experimental animal studies, aripiprazole exhibited antagonism with respect to dopaminergic hyperactivity and agonism with respect to dopaminergic hypoactivity. Some clinical effects of aripiprazole can be explained by interaction with dopamine and serotonin receptors.
PHARMACOKINETICS
Suction
After ingestion, aripiprazole is rapidly absorbed from the digestive tract. C max in plasma is achieved in 3-5 hours. Absolute bioavailability is 87%. Eating food does not affect the bioavailability of aripiprazole.
Distribution and Metabolism
C ss is achieved after 14 days. Cumulation of the drug with multiple admission is predictable. The pharmacokinetics of aripiprazole in the equilibrium state are proportional to the dose. There were no daily fluctuations in the distribution of aripiprazole and its metabolite dehydroaripiprazole.
Aripiprazole is intensively distributed in tissues, V d is 4.9 l / kg. At a therapeutic concentration of more than 99%, aripiprazole binds to serum proteins, mainly with albumin.
It has been established that dehydroaripiprazole, the main metabolite in human plasma, has the same affinity for dopamine D 2 receptors as aripiprazole.
Aripiprazole undergoes pre-systemic metabolism only to a minimal extent. Metabolised in the liver in three ways: dehydrogenation, hydroxylation and N-dealkylation. In vitro dehydrogenation and hydroxylation of aripiprazole occurs under the action of isoenzymes CYP3A4 and CYP2D6, N-dealkylation - CYP3A4.
The activity of Abilifae is mainly due to the presence of unchanged aripiprazole.
In the equilibrium state, the AUC of dehydroaripiprazole in plasma is about 39% of the aripiprazole AUC.
Excretion
The mean T 1/2 of aripiprazole is about 75 hours.
After a single administration of 14 C labeled aripiprazole, approximately 27% and 60% of radioactivity is determined in urine and feces, respectively. Less than 1% of unchanged aripiprazole is determined in urine and approximately 18% of the dose taken is unchanged in the form of feces. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to excretion by the liver.
Aripiprazole does not affect the pharmacokinetics and pharmacodynamics of warfarin, i.e. does not displace warfarin from its association with blood proteins.
INDICATIONS
- schizophrenia: acute attacks and maintenance therapy;
- type I bipolar disorder: manic episodes and maintenance therapy to prevent relapse in patients with type I bipolar disorder who have recently undergone a manic or mixed episode;
- as an adjunct to the therapy with lithium or valproic acid for the treatment of manic or mixed episodes with or without psychotic symptoms;
- as a supplement to antidepressant therapy for major depressive disorder.
DOSING MODE
When schizophrenia is recommended to appoint Abilifai in the initial dose of 10-15 mg 1 time / day, regardless of food intake. The maintenance dose is 15 mg / day. In clinical trials, the effectiveness of the drug in doses of 10 to 30 mg / day is shown.
In manic episodes with bipolar disorder as a monotherapy, the recommended initial dose is 15 mg 1 time / day, regardless of food intake.The dose change, if necessary, should be carried out with an interval of at least 24 hours. In clinical trials, the efficacy of the drug at doses of 15-30 mg / day with a dose of 3-12 weeks was demonstrated. Safety of the drug in doses more than 30 mg / day in clinical trials was not evaluated.
When observing patients with type I bipolar disorder and manic or mixed episodes that had stabilized symptoms against the background of taking Abilifai for 6 weeks at a dose of 15 mg / day or 30 mg / day at an initial dose of 30 mg / day, then - 6 months and further - within 17 months, the favorable effect of such maintenance therapy is established. Periodically, patients should be examined to determine whether to continue supporting therapy.
As a supplement to therapy with lithium or valproic acid, the recommended initial dose of the drug Abilifai is 15 mg 1 time / day, regardless of food intake. Depending on the clinical indications, the dose can be increased to 30 mg / day.
In case of major depressive disorder, it is recommended to prescribe Abilifai in an initial dose of 5 mg / day as an additional therapy for the treatment with antidepressants. If necessary and good tolerability of therapy, the daily dose of the drug Abilifai can be weekly increased by 5 mg to a maximum - not more than 15 mg / day.
Patients with renal insufficiency, hepatic insufficiency, patients over the age of 65 do not need a dose adjustment.
Dosage regimen for patients of both sexes is the same.
The dosing regimen for smokers and non-smokers is the same.
Dosing regimen with concomitant therapy
With the simultaneous administration of Abilifai and powerful inhibitors of isoenzymes CYP2D6 or CYP3A4, the dose of Abilifai should be reduced by a factor of 2. When the inhibitors of isoenzymes CYP2D6 or CYP3A4 are abolished, the dose of Abilifai should be increased. Abilipha should be used without changing the dose, if it is prescribed as an adjunctive therapy for a major depressive disorder .
With the simultaneous use of the drug Abilifai and inducers of the isoenzyme CYP3A4, the dose of Abilifai should be doubled. An additional increase in the dose of Abilifai should be done taking into account the clinical indications. With the cancellation of inducers of the isoenzyme CYP3A4, the dose of Abilifai should be reduced.
When administering several drugs that inhibit the isoenzymes CYP3A4 and CYP2D6, the possibility of reducing the daily dose of Abilifai should be considered.
SIDE EFFECT
Determination of the frequency of side effects: very often (? 10%), often (? 1% and <10%), sometimes (? 0.1% and <1%), rarely (? 0.01% and <0.1%), very rarely (? 0.01%).
From the cardiovascular system: often - orthostatic hypotension, tachycardia; sometimes bradycardia, palpitations, myocardial infarction, QT interval prolongation, cardiac arrest, hemorrhages, atrial fibrillation, heart failure, AV blockade, myocardial ischemia, deep vein thrombosis, phlebitis, extrasystole; rarely - vasovagal syndrome, atrial flutter, thrombophlebitis, intracranial hemorrhage, cerebral ischemia;very rarely - fainting, raising blood pressure.
From the side of the digestive system: very often - nausea, loss of appetite; often - increased appetite (when treating depression in combination with antidepressants), indigestion, vomiting, constipation, hypersecretion of saliva, dry mouth, abdominal heaviness, diarrhea;sometimes - gastroenteritis, difficulty swallowing, flatulence, gastritis, dental caries, gingivitis, hemorrhoids, gastroesophageal reflux, gastrointestinal hemorrhage, periodontal abscess, swelling of the tongue, stool incontinence, colitis, rectal hemorrhage, stomatitis, ulceration of the oral mucosa, cholecystitis, fecaloma, candidiasis of the oral mucosa, belching, stomach ulcer; rarely - esophagitis, gum bleeding, tongue inflammation, bloody vomiting, intestinal bleeding, duodenal ulcer, cheilitis, enlarged liver, perforation of the intestine;very rarely - increased activity of ALT, AST and AF, hepatitis, jaundice, pancreatitis, dysphagia.
From the musculoskeletal system: often - arthralgia, rigidity of muscles; sometimes - myasthenia gravis, arthritis, arthrosis, muscle weakness, muscle spasms, bursitis; very rarely - increased activity of CK, rhabdomyolysis, tendonitis, tenobursitis, myalgia.
From the side of the central nervous system and peripheral nervous system: very often - insomnia, headache, akathisia (in patients with bipolar disorder and in the treatment of depression in combination with antidepressants); often drowsiness, dizziness, tremor, extrapyramidal syndrome, psychomotor agitation, depression, nervousness, hostility, suicidal thoughts, manic thoughts, confusion, resistance to performing passive movements (cogwheel syndrome), lethargy, decreased concentration, sedation; sometimes dystonia, muscle twitching, paresthesia, limb tremor, impotence, bradykinesia, decreased / increased libido, panic reactions, apathy, memory impairment, stupor, amnesia, stroke, hyperactivity, depersonalization, dyskinesia, restless legs syndrome, myoclonus, depressed mood, increased reflexes, slowing of mental function, increased sensitivity to irritants, violation of oculomotor reaction; rarely - delirium, euphoria, bucco-glossal syndrome, akinesia, depression of consciousness down to loss of consciousness, decreased reflexes, obsessive thoughts, ZNS; very rarely - speech disorder, convulsions.
On the part of the respiratory system: often - shortness of breath, pneumonia; sometimes - nosebleeds, hiccoughs, laryngitis; rarely - hemoptysis, increased sputum production, dryness of the nasal mucosa, pulmonary edema, pulmonary embolism, hypoxia, respiratory insufficiency, apnea.
From the senses: often - blurred vision, photophobia, pain in the ears; sometimes - dry eyes, pain in the eyes, ringing in the ears, inflammation of the middle ear, cataracts, loss of taste, blepharitis; rarely - increased lacrimation, frequent flashing, external otitis media, amblyopia, deafness, diplopia, intraocular hemorrhage.
From the urinary system: sometimes - cystitis, frequent urination, leukorrhea, hematuria, dysuria, renal insufficiency, albuminuria, kidney stones, nocturia, polyuria, urge to urinate; rarely burning in the urethra; very rarely - urinary incontinence, urinary retention.
On the part of the reproductive system: sometimes - amenorrhea, premature ejaculation, vaginal bleeding, vaginal candidiasis, uterine bleeding, menorrhagia; rarely - pain in the mammary gland, cervicitis, galactorrhea, anorgasmia, burning in the external genital area, gynecomastia (enlargement of mammary glands in men), painful erection; very rarely - priapism.
From the side of metabolism: often - weight loss; sometimes - dehydration, edema, hypercholesterolemia, hypokalemia, hyperlipidemia, hypoglycemia, thirst, increased urea in the blood, iron deficiency anemia, increased LDH, obesity; rarely - hyperkalemia, gout, hypernatremia, glucosuria, cyanosis, urine acidification; very rarely - hyponatremia, hyperglycemia, diabetic ketoacidosis, diabetic hyperosmolar coma.
Dermatological reactions: often - dry skin, itching, skin ulceration; sometimes - acne, vesiculobuleznaya (pemphigus) rash, eczema, alopecia, psoriasis, seborrhea; rarely - maculopapular rash, exfoliative dermatitis, hyperhidrosis.
Allergic reactions: very rarely - anaphylaxis, angioedema, itching, urticaria, laryngospasm.
On the part of the body as a whole: often - asthenia, fatigue, flu-like syndrome, sensation of trembling in the body; sometimes - peripheral edema, face swelling, malaise, photosensitivity, maxillary pain, chills, stiffness of the jaw, tension in the chest; rarely - sore throat, stiffness in the back, heaviness in the head, candidiasis, stiffness in the throat, Mendelssohn's syndrome, heat stroke; very rarely - violations of temperature regulation, pyrexia, pain in the chest, in the neck.
CONTRAINDICATIONS
- age up to 18 years;
- hypersensitivity to aripiprazole and other components of the drug.
Use with caution in patients with cardiovascular disease (with IHD or with myocardial infarction, heart failure and conduction disorders), cerebrovascular diseases and conditions predisposing to arterial hypotension (dehydration, hypovolemia and taking antihypertensive drugs) in connection with the possibility of orthostatic development hypotension; in patients with convulsive seizures or suffering from diseases in which cramps are possible; in patients with an increased risk of hyperthermia (for example, with intense physical exertion, overheating, anticholinergic drugs, dehydration due to the ability of neuroleptics to disrupt thermoregulation); in patients with an increased risk of aspiration pneumonia due to the risk of impaired motor function of the esophagus and aspiration; in patients suffering from obesity, and with a history of diabetes in the family history.
PREGNANCY AND LACTATION
Adequate and strictly controlled clinical studies of safety of use in pregnancy have not been conducted. Abilife can be used during pregnancy in cases where the potential benefit of therapy for the mother exceeds the possible risk to the fetus.
It is not known whether aripirazole is excreted in human milk. It is not recommended to use the drug during lactation (breastfeeding).
In experimental studies, it has been shown that aripiprazole is secreted with milk in lactating rats.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with renal insufficiency do not need a dose adjustment.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with hepatic insufficiency do not need a dose adjustment.
APPLICATION FOR CHILDREN
Contraindication: age to 18 years.
APPLICATION IN ELDERLY PATIENTS
Patients over the age of 65 do not need a dose adjustment.
SPECIAL INSTRUCTIONS
The tendency to suicidal thoughts and attempts is characteristic of patients with psychosis, bipolar disorder and major depressive disorder, so drug therapy must be combined with careful medical supervision. Abiliphas should be given at the lowest effective dose; this will reduce the risk of overdose.
The risk of developing tardive dyskinesia increases with the duration of therapy with antipsychotics, so when Abilafay appears on the background of symptoms of tardive dyskinesia, you should reduce the dose or cancel the drug. After the withdrawal of therapy, these symptoms may temporarily increase or even appear for the first time.
In the treatment of neuroleptics, incl. aripiprazole may develop ZNS, which manifests itself as hyperpyrexia, muscle rigidity, mental disorders and instability in the autonomic nervous system (irregular heartbeats and BP, tachycardia, sweating, arrhythmia). In addition, sometimes there is an increase in activity of CK, myoglobinuria (rhabdomyolysis) and acute renal failure. In case of symptoms of NSA or unexplained fever, all antipsychotics, incl. Abilifay, should be canceled.
Like other antipsychotics, Abilifai should be used with caution in patients with a history of seizures and the risk of their development.
In patients with psychoses due to senile dementia, the risk of a lethal outcome increases with the treatment of atypical neuroleptics. In psychosis in patients over 65 years of age with Alzheimer's disease were observed violations of the cardiovascular system: heart attack, transient ischemic cerebrovascular accident, including fatal. We do not recommend the use of Abilifay medication for psychosis caused by dementia in the elderly and patients with Alzheimer's disease.
Hyperglycemia, in some cases severe and accompanied by ketoacidosis, which can lead to hyperosmolar coma with fatal outcome, were observed in patients treated with atypical antipsychotics. While the relationship between the reception of atypical neuroleptics and type hyperglycemic disorders remains unclear, patients diagnosed with diabetes must regularly determining the blood glucose level when receiving atypical neuroleptics. Patients who present risk factors for diabetes (obesity, diabetes, family history), while taking atypical antipsychotics should be carried out to determine the level of blood glucose at the start of the course and periodically during drug administration. In patients treated with atypical antipsychotics, requires constant monitoring of symptoms of hyperglycemia (increased thirst,frequent urination, polyphagia, weakness). Particular attention should be given to patients with diabetes and risk factors for its development.
Because of the risk of orthostatic hypotension Abilifay should be used with caution in patients with cardiovascular diseases (myocardial infarction, coronary artery disease, heart failure, cardiac conduction disease), cerebrovascular disease or conditions predisposing to hypotension (dehydration, hypovolemia, antihypertensive drugs) therapy.
In the application of neuroleptics have been cases esophageal motility disorders and as a result, aspiration pneumonia. Precautions should be prescribed to patients with risk factors for aspiration pneumonia.
Impact on the ability to drive vehicles and manage mechanisms
As with other antipsychotics, the appointment Abilifaya patient should be warned of the dangers of working with moving machinery and driving.
OVERDOSE
In clinical studies described accidental or intentional overdose aripiprazole single dose up to 1260 mg, not accompanied by death.Symptoms: lethargy, increased blood pressure, somnolence, tachycardia, loss of consciousness. In hospitalized patients revealed no clinically significant changes in vital signs, laboratory parameters and ECG.
Cases of overdose of aripiprazole in children (reception of up to 195 mg). Potentially dangerous symptoms of overdose are extrapyramidal disorder and transient loss of consciousness.
Treatment:monitoring vital signs, ECG, supportive therapy, airway management, oxygen therapy, effective ventilation, activated carbon, symptomatic treatment, careful medical supervision until the disappearance of all symptoms. Data on the use of hemodialysis in overdose aripiprazole no; the beneficial effect of this method is unlikely, since Aripiprazole is not excreted by the kidneys in unchanged form and substantially bound to plasma proteins.
DRUG INTERACTION
There were no significant effect blocker histamine H 2 receptor antagonists famotidine inducing potent inhibition of acid secretion in the stomach, the pharmacokinetics of aripiprazole.
Various pathway aripiprazole including by CYP2D6 and CYP3A4 enzymes. In studies in healthy volunteers potent CYP2D6 inhibitors (quinidine) and CYP3A4 (ketoconazole) aripiprazole reduced clearance when administered by 52% and 38%, respectively (while the use of CYP3A4 and CYP2D6 inhibitor should reduce the dose of aripiprazole).
Receiving Aripiprazole 30 mg simultaneously with carbamazepine, a potent inducer of CYP3A4, accompanied by a decrease in C max and AUC aripiprazole 68% and 73%, respectively, and a decrease in C maxand its active metabolite AUC degidroaripiprazola 69% and 71% respectively. You can expect similar effects and other powerful inducers of CYP3A4 and CYP2D6.
The metabolism of aripiprazole in vitro do not participate isozymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP2E1, in connection with which it is unlikely its interaction with drugs and other factors (e.g., smoking), able to activate or inhibit these enzymes.
Simultaneous treatment with lithium or valproate aripiprazole 30 mg 1 time / day had no clinically significant effect on the pharmacokinetics of aripiprazole.
In clinical studies, aripiprazole at doses of 10-30 mg / day had no significant effect on the metabolism of substrates of CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin) and CYP3A4 (dextromethorphan). Furthermore, aripiprazole and its major metabolite degidroaripiprazol not alter metabolism involving CYP1A2 in vitro enzyme. It is unlikely aripiprazole clinically significant effect of medicines metabolized involving these isoenzymes.
With simultaneous use of aripiprazole (10-30 mg / day) and lamotrigine (100-400 mg / day) in patients with bipolar disorder were no changes in the pharmacokinetics of lamotrigine, however the dose adjustment is required.
Aripiprazole had no effect on the pharmacokinetics of escitalopram and venlafaxine in healthy volunteers, therefore dose adjustment of these drugs is not required with concomitant administration of aripiprazole.
When applied in patients with major depressive disorder aripiprazole simultaneously with fluoxetine (20-40 mg / day), paroxetine (37.5 -50 mg / day) and sertraline (2-20 mg / day), a significant change antidepressants concentrations were found in plasma.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be kept out of the reach of children, dry place at a temperature of from 15 В° to 30 В° C. Shelf life - 3 years.
