Zylaxera pills 10mg №28

Indications for use

• Treatment of schizophrenia.
• Treatment of manic episodes in bipolar disorder

Type I moderate and severe and the prevention of a new manic episode in adults who have predominantly manic episodes, which can be treated with aripiprazole.

• As an adjunct to antidepressant therapy for major depressive disorder.

Dosage and Administration

The drug should be taken orally, 1 time per day, regardless of the meal.

Schizophrenia

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

Maintenance dose - 15 mg / day.

In clinical studies, the effectiveness of the drug in doses of 10 to 30 mg / day.

The maximum daily dose is 30 mg / day.

Manic Episodes in Type I Bipolar Disorder

The initial dose of 15-30 mg / day.

If necessary, dose adjustment is carried out with an interval of at least 24 hours.

In clinical studies demonstrated the effectiveness of the drug in doses of 15-30 mg / day with manic episodes when taken for 3-12 weeks.

The safety of the dose above 30 mg / day has not been evaluated in clinical studies.

When monitoring patients with type I bipolar disorder who underwent a manic or mixed episode, they had stabilized symptoms while taking aripiprazole (15 mg / day or 30 mg / day) for 6 weeks, then 6 months and beyond, for 17 months - the beneficial effect of such maintenance therapy has been established.

Patients should be examined periodically to determine the need for continued maintenance therapy.

Supplementary Therapy for Major Depressive Disorder

As an additional therapy for treatment with antidepressants, it is recommended to use the drug Zilaxer® in the initial dose of 5 mg / day. If necessary and good tolerance of therapy, the daily dose of the drug Zilaxer® can be weekly increased by 5 mg to the maximum - no more than 15 mg / day.

The duration of therapy with Zilaxer® for all the above indications has not been established, it is necessary to regularly examine the patient for possible cancellation of therapy.

Contraindications

• Hypersensitivity to aripiprazole or other components of the drug.
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (as the composition contains lactose).
• Age up to 18 years (efficacy and safety have not been established).
• Breastfeeding period.

With care: cardiovascular diseases (coronary heart disease (CHD) or previous myocardial infarction, chronic heart failure (CHF) or conduction disturbances), cerebrovascular diseases, conditions predisposing to the development of arterial hypotension (dehydration, hypovolemia, use of antihypertensive drugs) in connection with the possibility of the development of orthostatic hypotension, convulsive seizures or diseases in which seizures are possible,increased risk of hyperthermia (eg, intense physical exertion, overheating, use of m-holinoblokatorov, dehydration, because neuroleptics can interfere with thermoregulation, patients with an increased risk of aspiration pneumonia because of the risk of development of motor function of the esophagus and aspiration, obesity or sugar diabetes in the family history; patients with a high risk of suicide (psychotic diseases, bipolar disorders, major depressive disorder), in people aged 18-24 years due to the risk of developing uicidal behavior.

Special patient groups

Dose adjustment in patients with renal insufficiency is not required.

In patients with mild and moderate hepatic insufficiency, dose adjustment is not required. In patients with severe hepatic insufficiency, dosing should be carried out with caution. However, in patients with severe hepatic insufficiency, the maximum daily dose of 30 mg should be used with caution.

Dose adjustment is not required.

The dosage regimen of the drug for patients of both sexes is the same.

The dosage regimen for smoking and non-smoking patients is the same.

With the simultaneous use of potent inhibitors of the CYP3A4 isoenzyme (ketoconazole, clarithromycin), the dose of Zilaxer® should be reduced by half. Accordingly, when canceling CYP3A4 isoenzyme inhibitors, the dose of Zilaxer® should be increased.

With the simultaneous use of potent inhibitors of the CYP2D6 isoenzyme (quinidine, Fluoxetine, paroxetine), the dose of Zilaxer® should be reduced by at least half. Accordingly, when canceling CYP2D6 isoenzyme inhibitors, the dose of Zilaxer® should be increased.

Zilaksera® drug should be used without changing the dosing regimen, if it is prescribed as an additional therapy in patients with major depressive disorder.

With the simultaneous use of potent inhibitors of CYP2D6 isoenzymes (quinidine, fluoxetine, paroxetine) and CYP3A4 (ketoconazole, clarithromycin), the dose of Zilaxer® should be reduced by ¾ (i.e. up to 25% of the usual dose). Accordingly, when canceling inhibitors of CYP2D6 and / or CYP3A4 isoenzymes, the dose of Zilaxer® should be increased.

With the simultaneous use of potent, moderate and mild inhibitors of CYP2D6 and / or CYP3A4 isoenzymes, the dose of Zilaxer® can be initially reduced by (that is, up to 25%) of the usual dose), and then increased to achieve an optimal clinical result.

For patients with low CYP2D6 isoenzyme activity, the dose of Zilaxer® should initially be reduced by half and then increased to achieve an optimal clinical outcome. With simultaneous use of a potent inhibitor of the CYP3A4 isoenzyme in patients with low activity of the CYP2D6 isoenzyme, the dose of Zilaxer® should be reduced by

3/4 (i.e. up to 25% of the usual dose).

With the simultaneous use of potential inducers of CYP3A4 isoenzyme (carbamazepine), the dose of the drug Zilaxer® should be increased in

2 times. Accordingly, when canceling CYP3A4 isoenzyme inductors, the dose of Zilaxer® should be reduced to 10-15 mg.

Use during pregnancy and lactation

Adequate and well-controlled studies in pregnant women have not been conducted. It is not known whether the use of aripiprazole in a pregnant woman can have a harmful effect on the fetus or cause a violation of the reproductive function. It is known that in newborns whose mothers took antipsychotics during the third trimester of pregnancy, in the postpartum period there is a risk of developing extrapyramidal disorders and / or "withdrawal" syndrome. They noted excitement, muscle hypertension or hypotension, tremor, drowsiness, respiratory distress syndrome, feeding disorders. These symptoms had varying degrees of severity, sometimes they passed without treatment, while in other cases newborns needed intensive care and prolonged hospitalization. With the use of aripiprazole, the development of new symptoms in newborns was very rare.

Patients should be warned that they should immediately inform the doctor about the occurrence of pregnancy during the treatment, they should also inform the doctor about the planned pregnancy.

Zilaxera® can be taken during pregnancy only if the potential benefit to the mother is greater than the potential risk to the fetus.

Drug Zilaksera® gets into female breast milk.It is not recommended to breastfeed when using the drug.

Side effects

The classification of the incidence of side effects recommended by the World Health Organization (WHO):

very often ≥1 / 10

often from ≥1 / 100 to <1/10

infrequently from ≥1 / 1000 to <1/100

rarely from ≥1 / 10,000 to <1/1000

very rarely <1/10000

frequency unknown cannot be estimated based on available data.

infrequently: iron deficiency anemia;

very rarely: leukopenia, neutropenia, thrombocytopenia.

Immune system disorders:

very rarely: allergic reactions (anaphylaxis, angioedema, pruritus, urticaria), laryngospasm.

Endocrine Disorders:

infrequently: hypoglycemia, diabetes;

very rarely: hyperglycemia, diabetic ketoacidosis, diabetic hyperosmolar coma.

Metabolic and nutritional disorders:

often: weight loss;

infrequently: dehydration, edema, hypercholesterolemia, hypokalemia, hyperlipidemia, thirst, elevated levels of urea in the blood plasma, increased alkaline phosphatase activity, increased lactate dehydrogenase activity, obesity;

rarely: gout, hypernatremia, cyanosis, acidification of urine;

very rarely: hyponatremia, anorexia.

Mental Disorders:

very often: insomnia;

often: psychomotor agitation, depression, nervousness, hostility, suicidal thoughts, manic thoughts;

infrequently: panic reactions, hyperactivity, depersonalization;

seldom: obsessive thoughts.

Nervous system disorders:

very often: drowsiness, headache, akathisia;

often: dizziness, tremor, extrapyramidal syndrome, confusion, resistance to the performance of passive movements ("cogwheel" syndrome), lethargy, decreased concentration, sedation;

infrequently: dystonia, muscle twitching, paresthesia, limb tremor, impotence, bradykinesia, lowered / increased libido, apathy, memory loss, stupor, amnesia, stroke, dyskinesia, restless legs syndrome, myoclonus, depressed mood, increased reflexes, slow thinking, slowed thinking functions, hypersensitivity to stimuli, impaired oculomotor reaction;

seldom: delirium, euphoria, buccoglossal syndrome, akinesia, depression of consciousness up to loss of consciousness, reduced reflexes, neuroleptic malignant syndrome;

very rarely: speech disorder, convulsions.

Violations by the organ of vision:

often: blurred vision, photophobia;

infrequently: dry eyes, eye pain, blepharitis;

seldom: increased lacrimation, frequent blinking, amblyopia, diplopia, intraocular hemorrhages.

Disturbances from an organ of hearing and labyrinth disturbances:

often: ear pain;

infrequently: tinnitus, inflammation of the middle ear;

seldom: external otitis, deafness.

Heart disorders:

often: tachycardia;

infrequently: bradycardia, palpitations, myocardial infarction, prolongation of the QT interval, sudden cardiac arrest, atrial fibrillation, heart failure, atrioventricular block, myocardial ischemia, extrasystole;

seldom: expansion of borders of heart, an atrial flutter;

very rarely: fainting.

Vascular disorders:

often: orthostatic hypotension;

infrequently: deep vein thrombosis, phlebitis, hemorrhage, decrease in blood pressure;

rarely: vasovagal syndrome, thrombophlebitis, intracranial hemorrhage, cerebral ischemia;

very rarely: increased blood pressure;

frequency unknown: thromboembolism (including pulmonary embolism and deep vein thrombosis).

Disorders of the respiratory system, organs of the chest and mediastinum:

often: shortness of breath, pneumonia;

infrequently: nasal bleeding, hiccups, laryngitis;

rarely: hemoptysis, increased sputum production, dry nasal mucosa, pulmonary edema, hypoxia, respiratory failure, apnea;

very rarely: aspiration pneumonia.

Violations of the gastrointestinal tract:

very often: nausea, loss of appetite;

often: increased appetite *, dyspepsia, vomiting, constipation, salivary hypersecretion, dryness of the oral mucosa, heaviness in the abdomen, diarrhea;

* in the treatment of depression in combination with antidepressants

infrequently: gastroenteritis, difficulty swallowing, flatulence, gastritis, dental caries, gingivitis, hemorrhoids, gastro-esophageal reflux, gastrointestinal hemorrhages,periodontal abscess, swelling of the tongue, fecal incontinence, colitis, rectal hemorrhage, stomatitis, ulceration of the oral mucosa, fecalom, candidiasis of the oral mucosa, belching, stomach ulcer, loss of taste;

rarely: esophagitis, bleeding gums, inflammation of the tongue, hematemesis, intestinal bleeding, duodenal ulcer, cheilitis, perforation of the intestine;

very rarely: pancreatitis, dysphagia.

Disorders of the liver and biliary tract:

infrequently: cholecystitis;

rarely: enlarged liver;

very rarely: hepatitis, jaundice, increased activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Violations of the skin and subcutaneous tissues:

often: dry skin, pruritus, skin ulceration;

infrequently: acne, vesiculobullous (blistering) rash, eczema, alopecia, psoriasis, seborrhea, photosensitivity;

seldom: maculopapular rash, exfoliative dermatitis, urticaria, hyperhidrosis.

Disorders of the musculoskeletal and connective tissue:

often: arthralgia, muscle stiffness;

infrequently: myasthenia gravis, arthritis, arthrosis, muscle weakness, muscle spasms, bursitis;

very rarely: rhabdomyolysis, tendonitis, tenobursitis, myalgia.

Kidney and urinary tract disorders:

infrequently: cystitis, frequent urination, leukorrhea, hematuria, dysuria, renal failure, albuminuria, kidney stones, nocturia, polyuria, false urination;

seldom: burning in the urethra and external genital organs, glycosuria;

very rarely: urinary incontinence, urinary retention.

Violations of the genital and breast organs:

infrequently: amenorrhea, premature ejaculation, vaginal bleeding, vaginal candidiasis, uterine bleeding, menorrhagia;

rarely: pain in the mammary gland, cervicitis, galactorrhea, anorgasmia, gynecomastia, painful erection;

very rare: priapism.

General disorders and disorders at the site of administration:

often: asthenia, fatigue, flu-like syndrome, trembling feeling in the body;

infrequently: peripheral edema, swelling of the face, malaise, jaw pain, chills, jaw stiffness, chest pain;

seldom: sore throat, feeling of stiffness in the back, heaviness in the head, candidiasis, feeling of pressure in the throat, Mendelssohn's syndrome, heat stroke;

very seldom: violation of temperature regulation, pyrexia, pain in the chest, in the neck.

Laboratory and instrumental data:

very rare: increased activity of creatine phosphokinase.

Additional information on side effects of the drug

Adverse events occurring during treatment with neuroleptics have also been noted during aripiprazole therapy, including rare cases of the occurrence of a malignant neuroleptic syndrome, as well as infrequent cases of development of tardive dyskinesia and seizures.

In sensitive patients, in the first days of treatment, symptoms of dystonia may occur - prolonged pathological muscle spasms.

Symptoms of dystonia are: spasm of the neck muscles, sometimes with a feeling of pressure in the throat, difficulty in swallowing, difficulty breathing and / or protrusion of the tongue. These symptoms may appear when using high doses of first-generation antipsychotics.

For high-risk patients

Development of dystonia include men and young people.

Overdose

Symptoms: dizziness, tremor, agitation, drowsiness, serotonin syndrome, convulsions, depression of consciousness of varying severity (especially in combination with alcohol and / or other drugs that suppress the function of the central nervous system), nausea, vomiting, low blood pressure, tachycardia, ECG changes (change of ST segment, T wave, expansion of the QRS complex, prolongation of the QT interval), arrhythmias, respiratory depression, metabolic acidosis, rhabdomyolysis, hypokalemia, hyponatremia.

Treatment: symptomatic and supportive: gastric lavage, taking Activated carbon, ensuring the airway, adequate oxygenation, control functions of the cardiovascular and respiratory systems. There is no specific antidote.

Pharmacotherapeutic group: antidepressant

Pharmacodynamics

Aripiprazole possesses high affinity in vitro conditions for D2- and D3-dopamine receptors, 5HT1a- and serotonin 5HT2a-receptors and moderate affinity for D4-dopamine, 5HT2c- and serotonin 5HT7-, alpha1-adrenoceptors and H1-histamine receptors.Aripiprazole is also characterized by moderate affinity for serotonin reuptake sites and lack of affinity for muscarinic cholinergic receptors. Aripiprazole in animal experiments showed antagonism with respect to dopaminergic hyperactivity and agonism with respect to dopaminergic hypoactivity. Some of the clinical effects of aripiprazole can be explained by the interaction with other receptors besides dopamine and serotonin.

The use of aripiprazole orally in doses of 0.5 to 30 mg once a day in healthy volunteers for 2 weeks leads to a dose-dependent decrease in the binding of 11C-racloprid, D2 / D3 ligand - dopamine receptors, with the caudate nucleus and fencing (according to positron emission tomography).

Pharmacokinetics

The activity of the drug Zilaksera®, mainly due to the presence of aripiprazole. The average half-life (T1 / 2) of aripiprazole is approximately 75 hours. Equilibrium concentration is reached after 14 days. The accumulation of aripiprazole with repeated use is predictable. Indicators of pharmacokinetics of aripiprazole in the equilibrium state are proportional to the dose. Daily fluctuations in the distribution of aripiprazole and its metabolite, dehydroaripiprazole, were not observed. It has been established that the main metabolite of the drug in human blood plasma, dehydroaripiprazole, has the same affinity for D2-dopamine receptors as aripiprazole.

Suction

Aripiprazole is rapidly absorbed after ingestion of the tablets of the drug Zilaksera®, while the maximum concentration of aripiprazole in the blood plasma is reached after 3-5 hours. Bioavailability of tablets of the drug Zilaksera® when administered orally is 87%. Eating does not affect the bioavailability of aripiprazole.

Distribution

Aripiprazole is well distributed in the tissues, with an apparent volume of distribution of 4.9 l / kg, which indicates an intense extravascular distribution. With a therapeutic concentration of more than 99%, aripiprazole binds to serum proteins, mainly albumin. Biotransformation (metabolism)

Aripiprazole undergoes a presystemic metabolism only to a minimal extent. Aripiprazole is metabolized in the liver in three ways: dehydrogenation, hydroxylation, and N-dealkylation. According to an in vitro study, dehydrogenation and hydroxylation of aripiprazole occurs under the action of CYP3A4 and CYP2D6 isoenzymes, and N-dealkylation is catalyzed by CYP3A4 isoenzyme. Aripiprazole is the main component of the drug in plasma. In the equilibrium state, the area under the concentration-time curve (AUC) of dehydroaripiprazole, an active metabolite, is approximately 40% of the plasma aripiprazole AUC. Inference. The average T1 / 2 of aripiprazole is about 75 hours in patients with high activity of the isoenzyme CYP2D6 and 146 hours in patients with low activity.After a single intake of labeled [14C] aripiprazole, approximately 27% and 60% of radioactivity is detected in urine and feces, respectively. Less than 1% of unchanged aripiprazole is determined in the urine and about 18% of the dose taken is excreted unchanged through the intestine with bile. The total clearance of aripiprazole is 0.7 ml / min / kg, mainly due to removal by the liver.

Pharmacokinetics of special groups of patients

Patients of the older age group

Age differences in pharmacokinetic parameters of aripiprazole in adult patients with schizophrenia, as well as in healthy volunteers were not identified.

Gender feature

Gender-related differences in the pharmacokinetic parameters of aripiprazole in adult patients with schizophrenia and in healthy volunteers were not detected.

Race

There were no clinically significant differences in the pharmacokinetics of aripiprazole depending on race.

Smoking has no effect on the pharmacokinetics of aripiprazole.

Renal dysfunction

The pharmacokinetic parameters of aripiprazole and dehydroaripiprazole in patients with severe kidney disease do not differ from those in healthy volunteers.

Liver dysfunction

After a single dose of aripiprazole in patients with varying degrees of severity of cirrhosis, there was no significant effect of impaired liver function on the pharmacokinetics of aripiprazole and dehydroaripiprazole.However, only 3 patients with decompensated liver cirrhosis (Child-Pugh class C) participated in the study, and therefore it is impossible to draw definitive conclusions about the metabolic activity of the liver in patients with decompensated liver cirrhosis.

List of excipients (excipients)

List of excipients: lactose monohydrate, corn starch, microcrystalline cellulose, hyprolosis, blue dye [patented blue dye (E131), diamond black dye (E151)],
Magnesium stearate.

Shelf life

2 years.

Special storage conditions

At temperatures not higher than 30 ° C, in the original packaging. Keep out of the reach of children.

Release form

Tablets 10 mg, 15 mg and 30 mg.
On 14 tablets in a blister strip packaging from the combined material (a film of polyvinyl chloride / a film of polyvinylidene chloride) and aluminum foil. 2 blister strip packagings together with the instruction for application are placed in a pack from a cardboard.