Ariprizol, tablets 15 mg 30 pcs

An antipsychotic (neuroleptic).

The therapeutic effects of aripiprazole in schizophrenia are thought to be due to a combination of partial agonist activity against dopamine D₂– and serotonin 5-HT_1a– receptors and antagonistic activity against serotonin 5-HT₂– receptors.

Aripiprazole has high in vitro affinity for dopamine D₂– and D₃-receptors, serotonin 5-HT_1a– and 5-HT_2a-receptors and moderate affinity for dopamine D₄-, serotonin 5-HT_2c– and 5-HT₇-, α₁-adrenoreceptors and histamine H₁-receptors.

Aripiprazole is also characterized by moderate affinity for serotonin reuptake sites and no affinity for muscarinic receptors.

Indications

Treatment of acute episodes of schizophrenia, maintenance therapy for schizophrenia.

The treatment of acute manic episodes of bipolar disorder type I and for maintenance therapy in patients with bipolar disorder type I who have recently had a manic or mixed episode.

Active ingredient

Composition

How to take, the dosage

Interaction

There are different pathways of aripiprazole metabolism, including those involving CYP2D6 and CYP3A4 enzymes. In studies in healthy people potent CYP2D6 (quinidine) and CYP3A4 (ketoconazole) inhibitors decreased clearance of aripiprazole by 52% and 38% accordingly when administered orally (the dose of aripiprazole should be decreased when administered simultaneously with CYP3A4 and CYP2D6 inhibitors).

The administration of aripiprazole at a dose of 30 mg concomitantly 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. Other potent inducers of CYP3A4 and CYP2D6 can be expected to have similar effects.

Special Instructions

With caution, use in patients with cardiovascular disease (CHD, including patients with myocardial infarction, chronic heart failure, conduction disorders), conditions predisposing to arterial hypotension (dehydration, hypovolemia and taking hypotensive drugs) due to the possibility of orthostatic hypotension; in patients with cerebrovascular disease, with seizures or suffering from diseases in which seizures are possible; in patients with an increased risk of hyperthermia (e.g., with intense physical activity, overheating, taking 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 esophageal motor function disorder and aspiration; in patients with obesity, indicating in the history of diabetes mellitus; taking agents with m-cholin-blocking activity.

The propensity for suicidal thoughts and attempts is characteristic of psychosis, so close medical observation is necessary during drug therapy.

The risk of tardive dyskinesia increases with duration of neuroleptic therapy, so if symptoms of tardive dyskinesia occur with aripiprazole, the dose should be reduced or the therapy stopped. After discontinuation of therapy, these symptoms may increase temporarily or even appear for the first time.

When treated with neuroleptics, including aripiprazole, it is possible to develop MNS, which is manifested by hyperpyrexia, muscle rigidity, mental disturbances and instability of autonomic nervous system (irregular pulse and BP, tachycardia, sweating and cardiac arrhythmias). In addition, sometimes there are increased CPK activity, myoglobinuria (rhabdomyolysis) and acute renal failure. If symptoms of MNS or unexplained fever occur, all neuroleptics, including aripirazole, should be discontinued.

Hyperglycemia, in some cases severe and associated with ketoacidosis, which can lead to hyperosmolar coma and even death, has been reported in patients taking atypical neuroleptics. Although the association between taking atypical neuroleptics and hyperglycemic disorders remains unclear, patients diagnosed with diabetes should have their blood glucose levels determined regularly while taking atypical neuroleptics. Patients who have risk factors for diabetes (obesity, family history of diabetes) when taking atypical neuroleptics should have their blood glucose measured at the beginning of the course and periodically during the course of the medication. In any patient taking atypical neuroleptics, continuous monitoring of symptoms of hyperglycemia, including increased thirst, frequent urination, polyphagia, and weakness, is necessary.

Influence on driving and operating machinery

As with other neuroleptics, the patient should be warned about the dangers of operating moving machinery and operating a motor vehicle when aripiprazole is prescribed.

Features

Aripiprazole is rapidly absorbed from the gastrointestinal tract after oral administration. Cmax in plasma is reached after 3-5 hours. Absolute bioavailability is 87%. Food intake does not affect the bioavailability of aripiprazole.

Css is reached after 14 days. Cumulation of the drug with repeated administration is predictable. The pharmacokinetic parameters of aripiprazole in equilibrium are proportional to the dose. No diurnal fluctuations in the distribution of aripiprazole and its metabolite dehydroapiprazole have been noted.

Aripiprazole is intensely distributed in tissues, Vd is 4.9 l/kg. At the therapeutic concentration, more than 99% of aripiprazole binds to serum proteins, mainly to albumin.

Dehydroapiprazole, the main metabolite in human plasma, has been found to have the same affinity for dopamine D2 receptors as aripiprazole.

Aripiprazole undergoes 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 CYP3A4 and CYP2D6 isoenzymes, N-dealkylation – CYP3A4.

In equilibrium AUC of dehydroapiprazole is about 39% of AUC of aripiprazole in plasma.

The mean T1/2 of aripiprazole is about 75 h.

After a single dose of 14C-labeled aripiprazole, approximately 27% and 60% radioactivity is determined in urine and feces, respectively. Less than 1% of unchanged aripiprazole is detected in the urine and approximately 18% of the unchanged dose taken is excreted in the feces. Total clearance of aripiprazole is 0.7 ml/min/kg, mainly due to excretion by the liver.

Contraindications

Side effects

Cardiovascular system disorders: common – orthostatic hypotension, tachycardia; possibly – bradycardia, palpitations, myocardial infarction, prolongation of QT interval, cardiac arrest, hemorrhage, atrial fibrillation, heart failure, AV blockade, myocardial ischemia, deep vein thrombosis, phlebitis, extrasystole; rarely – vasovagal syndrome, dilated heart, atrial flutter, thrombophlebitis, intracranial hemorrhage, cerebral ischemia; very rarely – syncope.

Digestive system disorders: very often – nausea, loss of appetite; often – dyspepsia, vomiting; constipation; possibly – increased appetite, gastroenteritis, difficulty swallowing, flatulence, gastritis, dental caries, gingivitis, hemorrhoids, gastro-oesophageal reflux, gastrointestinal hemorrhage, periodontal abscess, tongue swelling, fecal incontinence, colitis, rectal hemorrhages, stomatitis, mouth ulcers, cholecystitis, fecaloma, oral candidiasis, cholelithiasis, belching, peptic ulcer; rarely – esophagitis, bleeding gums, inflamed tongue, bloody vomiting, intestinal bleeding, duodenal ulcer, cheilitis, hepatitis, liver enlargement, pancreatitis, intestinal perforation; very rare – increased ALT, AST, ALP activity.

Allergic reactions: very rare – anaphylaxis, angioedema, pruritus and urticaria.

Muscular system: often – myalgia, seizures; possibly – pain in joints and bones, myasthenia, arthritis, arthrosis, muscle weakness, spasms, bursitis; very rarely – increased CPK activity, rhabdomyolysis, tenenitis, tenobursitis, rheumatoid arthritis, myopathy.

CNS and peripheral nervous system disorders: very common – insomnia, somnolence, akathisia; common – dizziness, tremor, extrapyramidal syndrome, psychomotor agitation, depression, nervousness, increased salivation, hostility, suicidal thoughts, manic thoughts, unsteady gait, confusion, resistance to performing passive movements (cogwheel syndrome); dystonia, muscle twitching, loss of concentration, paresthesias, tremors in extremities, impotence, bradykinesia, decreased/increased libido, panic reactions, apathy, memory impairment, stupor, amnesia, stroke, hyperactivity depersonalization, dyskinesia, restless legs syndrome (akathisia), myoclonus, depressed mood, increased reflexes, slowed thinking function, increased sensitivity to stimuli, hypotonia, impaired eye movement response; Rarely – delirium, euphoria, buccoglossal syndrome, akinesia, depression of consciousness up to loss of consciousness, decreased reflexes, obsessive thoughts, ZNS.

Respiratory system: often – shortness of breath, pneumonia; possibly – asthma, nasal bleeding, hiccups, laryngitis; rarely – hemoptysis, aspiration pneumonia, increased sputum secretion, dry nasal mucosa, pulmonary edema, pulmonary embolism, hypoxia, respiratory failure, apnea.

Dermatological reactions: often – dry skin, itching, increased sweating, skin ulceration; possibly – acne, vesiculobular rash, eczema, alopecia, psoriasis, seborrhea; rarely – maculopapular rash, exfoliative dermatitis, urticaria.

Senses: often – conjunctivitis, ear pain; possibly – dry eyes, eye pain, ringing in the ears, middle ear inflammation, cataracts, loss of taste, blepharitis; rarely – increased lacrimation, frequent blinking, external otitis, amblyopia, deafness, diplopia, eye hemorrhage, photophobia.

With the urinary system: frequent – urinary incontinence; possibly – cystitis, frequent urination, leukorrhea, urinary retention, hematuria, dysuria, amenorrhea, premature ejaculation, vaginal bleeding, vaginal candidiasis, renal failure, uterine bleeding, menorrhea, albuminuria, kidney stones, nicturia, polyuria, urge to urinate; Rarely, breast pain, cervicitis, galactorrhea, anorgasmia, burning in the genitourinary system, glycosuria, gynecomastia (enlarged breasts in men), urolithiasis, painful erection.

In the body in general: Frequent – flu-like syndrome, peripheral edema, chest pain, neck pain; possibly – pelvic pain, facial swelling, malaise, photosensitivity, jaw pain, chills, jaw stiffness, abdominal bloating, chest tension; rarely – sore throat, back stiffness, heavy head, candidiasis, sore throat, Mendelson syndrome, heat stroke.

Metabolic side: frequent – weight loss, increased CPK levels; possibly – dehydration, edema, hypercholesterolemia, hyperglycemia, hypokalemia, diabetes, hyperlipidemia, hypoglycemia, thirst, increased blood urea, hyponatremia, iron deficiency anemia, increased creatinine, bilirubinemia, increased LDH levels, obesity; rarely – hyperkalemia, gout, hypernatriemia, cyanosis, urine acidification, hypoglycemic reaction.

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