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Active ingredients
Aripiprazole
Release form
Pills
Composition
Aripiprazole 15 mg. Excipients: lactose monohydrate - 91.53 mg, corn starch - 15.675 mg, microcrystalline cellulose - 15.675 mg, hyprolosis - 2.85 mg, magnesium stearate - 1.425 mg, iron dye yellow oxide (E172) - 0.345 mg.
Pharmacological effect
Antipsychotic (neuroleptic). The therapeutic effect of aripiprazole in schizophrenia is assumed to be due to a combination of partial agonistic activity against dopamine D2 and serotonin 5-HT1-receptors and antagonistic activity against serotonin 5-HT2 receptors. Aripiprazole possesses high in vitro affinity for dopamine D2- and D3-receptors, serotonin 5-HT1a- and 5-HT2a-receptors and moderate affinity for dopamine D4-, serotonin 5-HT2c- and 5-HT7-, α1-adrenoceptors and histamine H1 receptors. Aripiprazole is also characterized by moderate affinity for serotonin reuptake sites and lack of affinity for muscarinic receptors.
Pharmacokinetics
After oral administration, aripiprazole is rapidly absorbed from the gastrointestinal tract. Cmax in plasma is reached in 3-5 hours. Absolute bioavailability is 87%. Eating does not affect the bioavailability of aripiprazole. Css is reached after 14 days. The cumulation of the drug with repeated use is predictable. Indicators of pharmacokinetics of aripiprazole in the equilibrium state are proportional to the dose. There were no diurnal variations in the distribution of aripiprazole and its metabolite dehydroaripiprazole. Aripiprazole is intensively distributed in the tissues, Vd is 4.9 l / kg. At a therapeutic concentration of more than 99%, aripiprazole binds to serum proteins, mainly albumin. Dehydroaripiprazole, the main metabolite in human plasma, has been found to have the same affinity for dopamine D2 receptors as aripiprazole. Aripiprazole undergoes a presystemic metabolism only to a minimal extent. Aripiprazole is metabolized 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. In the equilibrium state, the AUC of dehydroaripiprazole is about 39% of the AUC of aripiprazole in plasma. The average T1 / 2 of aripiprazole is about 75 hours. After a single dose of 14C-labeled 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 about 18% of the dose taken is excreted unchanged in the feces. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to elimination by the liver.
Indications
Treatment of acute attacks of schizophrenia, supportive therapy of schizophrenia. Treatment of acute manic episodes of bipolar I disorder and for maintenance therapy in patients with bipolar I disorder who have recently had a manic or mixed episode.
Contraindications
Senile dementia, lactation, childhood and adolescence to 18 years, hypersensitivity to aripiprazole.
Use during pregnancy and lactation
Adequate and strictly controlled clinical studies of the safety of use during pregnancy have not been conducted. Aripirazole can be used during pregnancy in cases where the potential benefit of therapy for the mother outweighs the possible risk to the fetus. It is not known whether aripirazole is excreted in human breast milk. The use of aripiprazole during lactation (breastfeeding) is contraindicated. Experimental studies have shown that aripiprazole is excreted in milk in lactating rats.
Dosage and administration
Individual, depending on the indications, the course of the disease, tolerability of therapy. The dose is 10-30 mg 1 time / day.
Side effects
Since the cardiovascular system: often - orthostatic hypotension, tachycardia; possible - bradycardia, palpitations, myocardial infarction, prolonged QT interval, cardiac arrest, hemorrhage, atrial fibrillation, heart failure, AV-blockade, myocardial ischemia, deep vein thrombosis, phlebitis, extrasystole; rarely - vasovagal syndrome, heart enlargement, atrial flutter, thrombophlebitis, intracranial bleeding, cerebral ischemia; very rarely - fainting. On the part of the digestive system: very often - nausea, loss of appetite; often - dyspepsia, vomiting; constipation; possible - increased appetite, gastroenteritis, difficulty swallowing, flatulence, gastritis, dental caries, gingivitis, hemorrhoids, gastroesophageal reflux disease, gastrointestinal bleeding, periodontal abscess, swelling of the tongue, faecal incontinence, colitis, rectal hemorrhage, stomatitis, ulcerations in the mouth , cholecystitis, fecalom,oral mucosa candidiasis, gallstone disease, belching, gastric ulcer; rarely - esophagitis, bleeding gums, inflammation of the tongue, hematemesis, intestinal bleeding, duodenal ulcer, cheilitis, hepatitis, liver enlargement, pancreatitis, intestinal perforation; very rarely - an increase in the activity of ALT, AST, ALP. Allergic reactions: very rarely - anaphylaxis, angioedema, pruritus and urticaria. From the musculoskeletal system: often - myalgia, cramps; possibly - pain in the joints and bones, myasthenia, arthritis, arthrosis, muscle weakness, spasms, bursitis; very rarely - an increase in CPK activity, 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 performance of passive movements (cogwheel syndrome); possibly - dystonia, muscle twitching, weakening of concentration, paresthesia, tremor of extremities, impotence, bradykinesia, decreased / increased libido, panic reactions, apathy, weakening of memory, stupor, amnesia, stroke, hyperactivity, depersonalization, dyskinesia, restless legs syndrome (akathisia), myoclonus, depressed mood, increased reflexes, slowed mental function, hypersensitivity to stimuli, hypotension, impaired oculomotor response; rarely - delirium, euphoria, buccoglossal syndrome, akinesia, depression of consciousness up to loss of consciousness, diminished reflexes, obsessive thoughts, ZNS. On the part of the respiratory system: often - shortness of breath, pneumonia; possible - asthma, nosebleeds, hiccups, laryngitis; rarely - hemoptysis, aspiration pneumonia, increased sputum production, dry nasal mucosa, pulmonary edema, pulmonary embolism, hypoxia, respiratory failure, apnea. Dermatological reactions: often - dry skin, itching, excessive sweating, skin ulceration; possibly - acne, vesicular (blistering) rash, eczema, alopecia, psoriasis, seborrhea; rarely - maculo-papular rash, exfoliative dermatitis, urticaria.From the senses: often - conjunctivitis, pain in the ears; possible - dry eyes, pain in the eyes, tinnitus, inflammation of the middle ear, cataracts, loss of taste, blepharitis; seldom - increased tearing, frequent flashing, external otitis, amblyopia, deafness, diplopia, eye hemorrhages, photophobia. On the part of the urinary system: often - incontinence; possible - cystitis, frequent urination, leukorrhea, urinary retention, hematuria, dysuria, amenorrhea, premature ejaculation, vaginal bleeding, vaginal candidiasis, renal failure, uterine bleeding, menorrhagia, albuminuria, kidney stones, anohypia, anohypia, anohype, uterine hemorrhage, menorrhagia, albuminuria, kidney stones, anohypia, anohype, uterine bleeding, menorrhagia, albuminuria, kidney stones. rarely - pain in the mammary gland, cervicitis, galactorrhea, anorgasmia, burning sensation in the urogenital system, glycosuria, gynecomastia (an increase in the mammary glands in men), urolithiasis, painful erection. On the part of the body as a whole: often - flu-like syndrome, peripheral edema, chest pain, neck pain; possible - pelvic pain, swelling of the face, malaise, photosensitivity, jaw pain, chills, jaw stiffness, abdominal distension, chest tension; rarely - sore throat, stiffness in the back, heaviness in the head, candidiasis, stiffness in the throat, Mendelssohn's syndrome, heat stroke. On the part of the metabolism: often - weight loss, increased levels of CPK; possible - dehydration, edema, hypercholesterolemia, hyperglycemia, hypokalemia, diabetes mellitus, hyperlipidemia, hypoglycemia, thirst, increased blood levels of urea, hyponatremia, iron deficiency anemia, elevated creatinine, bilirubinemia, elevated LDH, obesity; rarely - hyperkalemia, gout, hypernatraemia, cyanosis, acidification of urine, hypoglycemic reaction.
Overdose
Symptoms: lethargy, increased blood pressure, drowsiness, tachycardia, loss of consciousness, nausea, vomiting, diarrhea. In hospitalized patients, there were no clinically significant changes in the main physiological parameters, laboratory parameters, and ECG. In clinical studies described cases of accidental or deliberate overdose of aripiprazole with a single dose of up to 1260 mg, not accompanied by a fatal outcome. There are cases of overdose of aripiprazole in children (up to 195 mg) without death.Potentially dangerous symptoms of overdose are drowsiness, extrapyramidal disorders, and transient loss of consciousness. Treatment: monitoring of vital functions, ECG to detect possible arrhythmias, supportive therapy, airway management, oxygenation, effective ventilation of the lungs, activated carbon, symptomatic treatment, careful medical observation until all symptoms disappear. There are no data on the use of hemodialysis in overdose of aripiprazole; the favorable effect of this method is unlikely, since aripiprazole is not excreted by the kidneys unchanged and is largely bound to plasma proteins.
Interaction with other drugs
There are various metabolic pathways of aripiprazole, incl. with the participation of CYP2D6 and CYP3A4 enzymes. In studies in healthy people, potent inhibitors of CYP2D6 (quinidine) and CYP3A4 (ketoconazole) reduced the clearance of aripiprazole when taken orally by 52% and 38%, respectively (a dose of aripiprazole should be reduced while used with CYP3A4 and CYP2D6 inhibitors). Acceptance of aripiprazole at a dose of 30 mg simultaneously with carbamazepine, a potent inducer of CYP3A4, was accompanied by a decrease in Cmax and AUC of aripiprazole by 68% and 73%, respectively, and a decrease in Cmax and AUC of its active metabolite dehydroaripiprazole by 69% and 71%, respectively. You can expect a similar effect and other powerful inducers CYP3A4 and CYP2D6.
special instructions
Use with caution in patients with cardiovascular diseases (coronary artery disease, including myocardial infarction, chronic heart failure, conduction disturbance), conditions predisposing to arterial hypotension (dehydration, hypovolemia and taking antihypertensive drugs) due to the possibility of development orthostatic hypotension; in patients with cerebrovascular diseases, with convulsive seizures or suffering from diseases in which seizures are possible; in patients with an increased risk of hyperthermia (for example, with intense physical exertion, overheating, taking anticholinergic drugs, with dehydration due to the ability of neuroleptics to violate 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; receiving funds with m-anticholinergic activity.Tendency to suicidal thoughts and attempts is characteristic of psychosis, therefore, when conducting drug therapy requires careful medical supervision. The risk of tardive dyskinesia increases as the duration of neuroleptic therapy increases, therefore, when symptoms of tardive dyskinesia appear on the background of aripiprazole intake, reduce its dose or cancel it. After discontinuation of therapy, these symptoms may temporarily worsen or even appear for the first time. When treating neuroleptics, incl. aripiprazole may develop ZNS, which is manifested by hyperpyrexia, muscle rigidity, mental disorders and instability of the autonomic nervous system (irregular pulse and blood pressure, tachycardia, sweating, and cardiac arrhythmias). In addition, sometimes there is an increase in the activity of CPK, myoglobinuria (rhabdomyolysis) and acute renal failure. In the event of symptoms of ZNS or unexplained fever, all neuroleptics, including Aripirazole, you must cancel. Hyperglycemia, in some cases severe and associated with ketoacidosis, which can lead to hyperosmolar coma and, even death, was noted in patients taking atypical antipsychotics. Although the relationship between taking atypical antipsychotics and hyperglycemic type disorders remains unclear, patients diagnosed with diabetes should regularly determine blood glucose levels when taking atypical antipsychotics. Patients who have risk factors for diabetes (obesity, the presence of diabetes in the family) while taking atypical neuroleptics should determine the level of glucose in the blood at the beginning of the course and periodically in the process of taking the drug. In all patients taking atypical antipsychotics, constant monitoring of the symptoms of hyperglycemia, including increased thirst, frequent urination, polyphagy, weakness, is necessary. Effect on ability to drive vehicles and control mechanisms As with the appointment of other neuroleptics, when prescribing aripiprazole, the patient must be warned about the dangers of working with moving mechanisms and driving.