Description of the active substance :.
This information is a reference and it is not enough that the drug was prescribed by a doctor. .
PHARMACHOLOGIC EFFECT
Antipsychotic agent (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 5-HT 1a receptors and antagonistic activity against serotonin 5-HT 2receptors.
Aripiprazole has a high affinity in vitro to dopamine D 2 - and D 3 receptors, serotonin 5-HT 1a - and 5-HT 2a receptors and moderate affinity for dopamine D 4 -, serotonin 5-HT 2c - and 5-HT 7 -,? 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.
PHARMACOKINETICS
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.
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. Aripiprazole is metabolized in the liver in three ways: by dehydrogenation, hydroxylation and N-dealkylation. In vitro dehydrogenation and hydroxylation of aripiprazole occurs under the action of isoenzymes CYP3A4 and CYP2D6, N-dealkylation - CYP3A4.
In the equilibrium state, the AUC of dehydroaripiprazole is about 39% of the aripiprazole AUC in plasma.
The mean T 1/2 of aripiprazole is about 75 hours.
After a single administration of labeled 14C aripiprazole, approximately 27% and 60% of radioactivity is determined in urine and feces, respectively. Less than 1% of unchanged aripiprazole is detected in the urine and approximately 18% of the dose taken is unchanged with feces. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to excretion by the liver.
INDICATIONS
Treatment of acute attacks of schizophrenia, supporting the therapy of schizophrenia.
Treatment of acute manic episodes of type I bipolar disorder and for maintenance therapy in patients with type I bipolar disorder who have recently undergone a manic or mixed episode.
DOSING MODE
Individual, depending on the indications, the course of the disease, the tolerability of therapy. The dose is 10-30 mg 1 time / day.
SIDE EFFECT
From the cardiovascular system: often - orthostatic hypotension, tachycardia; possibly 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, enlargement of the heart, atrial flutter, thrombophlebitis, intracranial bleeding, cerebral ischemia; very rarely - fainting.
From the side of the digestive system: very often - nausea, loss of appetite; often - indigestion, vomiting; constipation; possibly - increased appetite, 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 in the mouth , cholecystitis, fecaloma, candidiasis of the oral mucosa, cholelithiasis, belching, stomach ulcer; rarely - esophagitis, gum bleeding, tongue inflammation, bloody vomiting, intestinal bleeding, duodenal ulcer, cheilitis, hepatitis, liver enlargement, pancreatitis, perforation of the intestine; very rarely - increased activity of ALT, AST, APF.
Allergic reactions: very rarely - anaphylaxis, angioedema, itching and urticaria.
From the musculoskeletal system: often - myalgia, convulsions; possibly - pain in the joints and bones, myasthenia gravis, arthritis, arthrosis, muscle weakness, spasms, bursitis; very rarely - increased activity of CK, rhabdomyolysis, tendenitis, tenobursitis, rheumatoid arthritis, myopathy.
From the side of the central nervous system and peripheral nervous system: very often - insomnia, drowsiness, akathisia; often - dizziness, tremor, extrapyramidal syndrome, psychomotor agitation, depression, nervousness, increased salivation, hostility, suicidal thoughts, manic thoughts, unsteady gait, confusion, resistance to the implementation of passive movements (cogwheel syndrome); dystonia, muscle twitching, weakening of concentration, paresthesia, limb tremor, impotence, bradykinesia, low / increased libido, panic reactions, apathy, memory loss, stupor, amnesia, stroke, hyperactivity, depersonalization, dyskinesia, restless legs syndrome (akathisia), myoclonus, depressed mood, increased reflexes, slowing of mental function, hypersensitivity to irritants, hypotension, violation of oculomotor reaction; rarely - delirium, euphoria, bucco-glossal syndrome, akinesia, depression of consciousness down to loss of consciousness, decreased reflexes, obsessive thoughts, ZNS.
On the part of the respiratory system: often - shortness of breath, pneumonia; possibly - asthma, epistaxis, hiccough, laryngitis; rarely hemoptysis, aspiration pneumonia, increased sputum production, dry nasal mucosa, pulmonary edema, pulmonary embolism, hypoxia, respiratory insufficiency, apnea.
Dermatological reactions: often - dry skin, itching, excessive sweating, skin ulceration; possibly - acne, vesiculobuleznaya (bubble) rash, eczema, alopecia, psoriasis, seborrhea; rarely - maculopapular rash, exfoliative dermatitis, urticaria.
From the senses: often - conjunctivitis, pain in the ears; possibly - 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, eye hemorrhage, photophobia.
From the urinary system: often - urinary incontinence; possibly - cystitis, frequent urination, leukorrhea, urinary retention, hematuria, dysuria, amenorrhea, premature ejaculation, vaginal bleeding, vaginal candidiasis, renal failure, uterine bleeding, menorrhagia, albuminuria, kidney stones, nocturia, polyuria, urination; rarely - pain in the mammary gland, cervicitis, galactorrhea, anorgasmia, burning in the genitourinary system, glycosuria, gynecomastia (enlargement of mammary glands in men), urolithiasis, painful erection.
On the part of the body as a whole: often - the flu-like syndrome, peripheral edema, pain in the chest, in the neck; possibly - pelvic pain, face swelling, malaise, photosensitivity, jaw pain, chills, stiffness of the jaw, bloating, 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.
From the side of metabolism: often - weight loss, increase in the level of CK; possibly - dehydration, edema, hypercholesterolemia, hyperglycemia, hypokalemia, diabetes mellitus, hyperlipidemia, hypoglycemia, thirst, increased urea in the blood, hyponatremia, iron deficiency anemia, elevated creatinine, bilirubinemia, elevated LDH, obesity; rarely - hyperkalemia, gout, hypernatremia, cyanosis, urine acidification, hypoglycemic reaction.
CONTRAINDICATIONS
Senile dementia, lactation, children and adolescents under 18, hypersensitivity to aripiprazole.
PREGNANCY AND LACTATION
Adequate and strictly controlled clinical studies of safety of use in pregnancy have not been conducted. Aripirazole can be used in 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. The use of aripiprazole during lactation (breastfeeding) is contraindicated.
In experimental studies, it has been shown that aripiprazole is secreted with milk in lactating rats.
APPLICATION FOR CHILDREN
Contraindication: children and adolescence under 18 years.
SPECIAL INSTRUCTIONS
Use with caution in patients with cardiovascular diseases (IHD, including myocardial infarction, chronic heart failure, conduction disorders), conditions predisposing to arterial hypotension (dehydration, hypovolemia and taking antihypertensive drugs) in connection with the possibility of development orthostatic hypotension; in patients with cerebrovascular disease, with convulsive seizures or suffering from diseases in which convulsions 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 with obesity, with a history of diabetes mellitus; reception of funds with m-cholinoblocking activity.
Propensity to suicidal thoughts and attempts is characteristic for psychoses, therefore at carrying out of medicinal therapy careful medical observation is necessary.
The risk of developing tardive dyskinesia increases with the duration of therapy with antipsychotics, so when aripiprazole arises with symptoms of tardive dyskinesia, you should reduce its dose or cancel it. 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 hyperpyrexia, muscle rigidity, mental disorders and instability of the autonomic nervous system (irregular heartbeats and blood pressure, tachycardia, sweating and cardiac arrhythmias). 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. aripyrazole, it is necessary to cancel.
Hyperglycemia, sometimes expressed and associated with ketoacidosis, which can lead to hyperosmolar coma and even death, has been noted in patients taking atypical antipsychotics. Although the association between the admission of atypical antipsychotics and hyperglycemic disorders is unclear, patients who have diabetes mellitus should regularly perform a blood glucose test when taking atypical antipsychotics. Patients who are at risk for diabetes (obesity, having diabetes in the family) should take the blood glucose level at the beginning of the course and periodically during the administration of the drug when taking atypical antipsychotics. Any patient taking atypical antipsychotics needs constant monitoring of symptoms of hyperglycemia, including increased thirst, frequent urination, polyphagia, and weakness.
Impact on the ability to drive vehicles and manage mechanisms
As with the appointment of other neuroleptics, when appointing aripiprazole, the patient should be warned about the dangers of working with moving mechanisms and driving.
DRUG INTERACTION
There are different ways of metabolism of aripiprazole, including. with the participation of enzymes CYP2D6 and CYP3A4. In studies in healthy humans, potent inhibitors of CYP2D6 (quinidine) and CYP3A4 (ketoconazole) reduced aripiprazole clearance when ingested by 52% and 38%, respectively (the dose of aripiprazole should be reduced while being used with CYP3A4 and CYP2D6 inhibitors).
Receipt of aripiprazole at a dose of 30 mg concomitantly with carbamazepine, a powerful inducer of CYP3A4, was accompanied by a decrease in C max and AUC of aripiprazole by 68% and 73%, respectively, and by a decrease of C max and AUC of its active metabolite dehydroaripiprazole by 69% and 71%, respectively. You can expect a similar effect on other powerful inductors CYP3A4 and CYP2D6.
