Expiration date: 03/2025

release Form

pills

Composition

1 tablet contains 10 or 30 mg of aripiprazole

Packaging

28 pcs.

pharmachologic effect

It is assumed that the therapeutic effect of aripiprazole in schizophrenia is caused by a combination of partial agonistic activity on dopamine D2-and serotonin 5HT1A receptors and antagonistic activity against serotonin-5HT2A receptors.

Aripiprazole possesses high affinity in vitro for D2- and D3-dopamine receptor-5NT1a- and 5HT2A serotonin receptors and moderate affinity for the D1-dopamine, and 5NT2s- 5NT7-serotonin, ?1-adrenoceptors and histamine H1 receptors.

Aripiprazole is also characterized by a moderate affinity for serotonin reuptake sites and the lack of affinity for muscarinic. Aripiprazole in animal experiments showed antagonism against and agonism dopaminergic hyperactivity against dopaminergic hypoactivity. Some aripiprazole clinical effects can be attributed to interaction with other receptors in addition to dopamine and serotonin.

testimony

schizophrenia: acute attacks and supportive therapy,

1tipa bipolar disorder: manic episodes and maintenance treatment to prevent recurrence in patients with bipolar I disorder with recent manic or mixed episode.

Contraindications

• hereditary galactosemia, lactase deficiency, glucose-galactose malabsorption,
  
• age of 18 years (effectiveness and safety have been established),
  
• lactation,
  
• Hypersensitivity to aripiprazole Zylaksera or other components of the formulation.
  

Precautions: cardiovascular disease (coronary heart disease or myocardial infarction, chronic heart failure, or conduction disorders in the anamnesis), cerebrovascular disease, conditions that predispose to the development of arterial hypotension (dehydration, hypovolemia, antihypertensive drug therapy) in connection with the possibility of orthostatic hypotension or hypertension, including progressive or malignant, hereditary syndrome of elongated QT interval on the ECG, epilepsy, seizures, or diseases in which the possible convulsions, diabetes, or the presence of risk factors for diabetes (obesity, diabetes, family history), patients with an increased risk of aspiration pneumonia because of the risk of disturbances in motor function of the esophagus and aspiration, older patients, severe liver failure, patients at high risk of suicide (psychotic disorders, bipolar disorders), among persons aged 18-24 years due to the risk of suicidal behavior, pregnancy , the risk of hyperthermia (intense exercise, overheating, taking anticholinergics medicines, dehydration).

Pregnancy and breast-feeding

There are no adequate and well-controlled studies of aripiprazole in pregnant women have been conducted. It is recommended to inform the doctor about the occurrence of pregnancy or planning. Zylaksera The drug may be taken during pregnancy if the potential benefit to the mother outweighs the potential risk to the fetus.

During treatment with Zylaksera breastfeeding should be discontinued.

Dosing and Administration

Zylaksera taken orally, 1 time / day, regardless of meals.

Schizophrenia

The initial dose of 10-15 mg 1 time / day. Maintenance dose - 15 mg / day.

In clinical studies demonstrated the efficacy of the drug in doses of 10 to 30 mg / day.

The maximum daily dose - 30 mg / day.

Manic episodes in bipolar disorder

The initial dose of 15-30 mg / day.

If necessary, dose adjustment is carried out at intervals of not less than 24 hours. The effectiveness of the drug demonstrated in clinical studies at doses of 15-30 mg / day with manic episodes when administered within 3-12 weeks. Safety of doses above 30 mg / day in clinical studies has not been evaluated. When monitoring for 6 months and then, for 17 months for patients with bipolar disorder type 1, which have borne the manic or mixed episode who observed stabilization of symptoms in patients receiving aripiprazole (15 mg / day or 30 mg / day) - set a favorable effect such maintenance therapy. patients should be evaluated periodically to determine whether to continue maintenance therapy.

Side effects

Classification of the incidence of side effects: Very common (> 1/10), often (by> 1/100 to <1/10), uncommon (from> 1/1000 to <1/100), rarely ( by> 1 / 10,000 to <1/1000), very rare (from <1/10000, including isolated reports).

Since the cardiovascular system: often - orthostatic hypotension, tachycardia, rarely - bradycardia, palpitations, myocardial infarction, lengthening the interval QT, heart failure, hemorrhage, atrial fibrillation, heart failure, AV-blockade, myocardial ischemia, deep venous thrombosis, phlebitis, beats, decrease blood pressure, rarely - vasovagal syndrome, expansion of borders of the heart, atrial flutter, thrombophlebitis, intracranial hemorrhage, cerebral ischemia, very rarely - a faint.

From the digestive system: very often - nausea, anorexia, often - dry mucous membranes of the nose, indigestion, feeling of heaviness in the abdomen, vomiting, constipation, rarely - 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, ulceration of the oral mucosa, cholecystitis, fekaloma, candidiasis of the oral mucosa, cholelithiasis, belching, stomach ulcer, rarely - esophagitis, bleeding gums, glossitis, melena, gastrointestinal bleeding, ulcer 12 duodenal ulcer, cheilitis, hepatitis, enlarged liver, pancreatitis, perforation of the intestine, bloody vomiting, very rarely - increased activity of ALT and ACT, jaundice, dysphagia.

Immune system: very rarely - allergic reactions: anaphylaxis, angioedema, laryngospasm, pruritus, urticaria.

From the musculoskeletal system: often - muscle stiffness, myalgia, muscle cramps, infrequently - ossalgia, arthralgia, myasthenia gravis, arthritis, arthrosis, muscle weakness, muscle spasms, bursitis, very rarely - activity increase in creatine kinase (CK), rhabdomyolysis, tendonitis , tenobursit, rheumatoid arthritis, myopathy,

From the nervous system: very often - insomnia, somnolence, akathisia, often - dizziness, tremor, extrapyramidal syndrome, agitation, depression, nervousness, excessive salivation, hostility, suicidal ideation, mania, unsteady gait, confusion, resistance to the implementation of passive movements (gear syndrome), sedation, infrequently - dystonia, muscle twitching, reduced concentration, paraesthesia, tremor of limbs, impotence, bradykinesia, decreased / increased libido, panic reaction, apathy, dyskinesia, loss of memory, stupor, amnesia, stroke, hyperactivity , depersonalization, myoclonus, depressed mood, hyperreflexia, slowing of mental function, increased sensitivity to stimuli, violation of oculomotor reactions, rarely - delirium, euphoria, bukkoglossalny syndrome, akinesia, depression of consciousness until he lost consciousness, hyporeflexia, obsessive thoughts, neuroleptic malignant syndrome, very rarely - the speech disorder.

With the respiratory system: often - shortness of breath, pneumonia, rarely - bronchospasm, epistaxis, hiccup, laryngitis, rare - hemoptysis, aspiration pneumonia, increased sputum, dry nasal mucosa, pulmonary edema, pulmonary embolism, hypoxia, respiratory failure , apnea.

For the skin: often - dry skin, itching, increased sweating, skin ulceration, infrequently - acne, vesiculobullous rash, eczema, alopecia, psoriasis, seborrhea, rarely - maculopapular rash, exfoliative dermatitis, urticaria.

From the senses: common - conjunctivitis, ear pain, rarely - dry eyes, eye pain, tinnitus, otitis media, cataracts, loss of taste, blepharitis, rarely - increased tearing, frequent blinking, otitis externa, amblyopia, deafness, diplopia, intraocular hemorrhage, photophobia.

With the genitourinary system: often - urinary incontinence, infrequent - cystitis, frequent urination, Leucorrhœa, urinary retention, hematuria, dysuria, amenorrhea, premature ejaculation, vaginal bleeding, vaginal candidiasis, renal insufficiency, uterine bleeding, menorrhagia, albuminuria, nocturia, polyuria , frequent urination, rarely - pain in the breast, cervicitis, galactorrhea, anorgasmia, burning of the external genitalia, glycosuria, gynecomastia, nephrolithiasis, painful erection, very rarely - priapism.

On the part of metabolism: often - weight loss, rarely - dehydration, edema, hypercholesterolemia, hyperlipidemia, hyperglycemia, hypokalemia, diabetes, thirst, elevated blood urea, hyponatremia, iron deficiency anemia, hypercreatininemia, hyperbilirubinemia, elevated lactate dehydrogenase (LDH) obesity, increased activity of alkaline phosphatase (ALP), rarely - hyperkalemia, gout, hypernatremia, cyanosis, acidification of urine, hypoglycemia,

Other: often - flu-like symptoms, peripheral edema, pain in the chest, neck, rarely - face edema, malaise, photosensitivity, pain in the jaw, fever, stiffness of the jaw, the tension in the chest, rarely - a sore throat, stiffness in the back, heaviness in the head, candidiasis, stiffness in the neck, Mendelson's syndrome, heat stroke.

special instructions

Suicide attempt - the propensity to suicidal thoughts and attempts characteristic of psychosis, so drug therapy must be combined with careful medical supervision. Zylaksera drug must be discharged in a minimum amount sufficient to treat the patient. Due to the risk of suicidal thinking and the development of suicidal behavior, drug Zylaksera should be used with extreme caution in patients aged 18-24 years. It is necessary to correlate the risk of suicide and the use of the drug.

Tardive dyskinesia - the risk of tardive dyskinesia increases with the duration of neuroleptic therapy, so when you see the background of the drug Zylaksera symptoms of tardive dyskinesia should reduce the dose of the drug or to cancel it. After discontinuation of these symptoms may temporarily worsen or even appear for the first time.

Neuroleptic malignant syndrome - neuroleptics in the treatment, including aripiprazole, described life-threatening syndrome known as neuroleptic malignant syndrome (NMS). This syndrome is manifested hyperpyrexia, muscle rigidity, mental disturbances and instability of the autonomic nervous system (irregular pulse and blood pressure, tachycardia, sweating and cardiac arrhythmias). In addition, sometimes there are an increase in activity of CK, myoglobinuria (rhabdomyolysis) and acute renal failure. In case of NMS symptoms or unexplained fever all antipsychotics, including Zylaksera drug should be abolished.

Hyperglycemia and diabetes

Hyperglycemia, in some cases severe and accompanied by ketoacidosis, which can lead to hyperosmolar coma, and even death have been observed in patients treated with atypical antipsychotics. Although the association between atypical antipsychotics and violations of hyperglycemic type remains unclear, patients diagnosed with diabetes must regularly determination of blood glucose when receiving atypical antipsychotics. Patients who present risk factors for diabetes

(Obesity, diabetes mellitus family history) when receiving atypical neuroleptics should conduct determination of blood glucose concentration in the beginning of the course and periodically during treatment. In all patients treated with atypical antipsychotics, requires constant monitoring of the possible development of hyperglycemia symptoms, including increased thirst, frequent urination, polyphagia, and weakness.

The risk of venous thromboembolism

The use of antipsychotic drugs, including Aripiprazole may be associated with the risk of venous thromboembolism. In this connection it should identify the risk factors for this complication before administration of aripiprazole and during treatment with this drug. If necessary, apply measures to prevent the development of venous thromboembolism.

Psychosis associated with senile dementia and Alzheimer's disease

Patients with psychosis caused by dementia, for the treatment of atypical antipsychotic drugs increases the risk of death. When 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. The use of aripiprazole for psychosis caused by dementia in the elderly and patients with Alzheimer's disease is not recommended.

Drug interactions

There were no significant effects blocker histamine H2-receptor famotidine, causing strong inhibition of secretion of hydrochloric acid in the stomach, on the pharmacokinetics of aripiprazole.

Various aripiprazole pathway, including participation isoenzymes CYP2D6 and CYP3A4. In studies in healthy humans potent inhibitors isoenzyme CYP2D6 (quinidine) and isozymes CYP3A4 (ketoconazole) aripiprazole reduced clearance when administered by 52% and 38%, respectively. Therefore it is necessary to reduce the dose of aripiprazole when used in combination with inhibitors of CYP3A4 and isoenzymes CYP2D6.

Receiving 30 mg aripiprazole with carbamazepine, a potent inducer isoenzyme CYP3A4, accompanied by a decrease by 68% and 73% of Cmax and AUC of aripiprazole, respectively, and decreased by 69% and 71% of Cmax and AUC degidroaripiprazola its active metabolite, respectively. We can expect similar effects and other powerful inducers of isoenzymes CYP3A4 and CYP2D6.

In the metabolism of aripiprazole in vitro are not involved isozymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and of CYP2E1, and therefore it is unlikely its interaction with medications and other factors (eg, smoking), able to inhibit or induce these enzymes.

Simultaneous treatment with lithium or valproic acid and 30 mg of aripiprazole had no clinically meaningful effect on the pharmacokinetics of aripiprazole.

In clinical studies, aripiprazole at doses of 10-30 mg / day significantly affect the metabolism of CYP2D6 substrates (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin) and CYP3A4 (dextromethorphan). Furthermore, aripiprazole and its major metabolite degidroaripiprazol not alter metabolism involving isoenzyme CYP1A2 in vitro. It is unlikely clinically significant effect of aripiprazole on drugs metabolized with the participation of these enzymes.

Overdose

In clinical trials, cases of accidental or intentional overdose of aripiprazole described with a single dose up to 1080 mg, not accompanied by death.

Symptoms: depression of consciousness of varying degrees of severity up to coma, nausea, vomiting, fatigue, diarrhea, drowsiness. In hospitalized patients found no clinically significant changes in vital signs, laboratory parameters and indicators on the electrocardiogram (ECG). Post-marketing experience in adult patients receiving a single 450 mg aripiprazole suggests the possible development tachycardia. In addition, the described cases of accidental aripiprazole in children (receiving up to 195 mg). Potentially dangerous symptoms of overdose include extrapyramidal, convulsive, dystonic, cardiovascular (prolongation of the QT interval on the ECG, atrial fibrillation) disorders and transient loss of consciousness.

Treatment: supportive care, ensuring adequate airway patency, oxygen therapy, an effective ventilation and symptomatic treatment. Consideration should be given drug reactions. Immediately should be initiated monitoring of cardiac performance with the registration of ECG to detect arrhythmias. After confirmed or suspected overdose of aripiprazole requires careful medical supervision until the disappearance of all symptoms.

Activated charcoal (50 g) was injected 1 hour after aripiprazole, decreased Cmax and AUC aripiprazole 51 and 41%, respectively, which allows to recommend its use in overdose.

Although reliable data on the use of hemodialysis in overdose aripiprazole no beneficial effect of this method is unlikely because Aripiprazole appears almost kidneys unchanged and largely bound to plasma proteins.

Storage conditions

The preparation is stored at a temperature no higher than 30 ° C, in their original packaging. Keep out of the reach of children.

Shelf life

2 years.