INSTRUCTION
for medical use of a medicinal product
Mintegra
(Mintegra)
Composition:
active ingredient: aripiprazole;
1 orodispersible tablet contains 10 mg or 15 mg or 30 mg of aripiprazole;
excipients:
10 mg tablets: lactose monohydrate, microcrystalline cellulose (E 460), croscarmellose sodium, colloidal anhydrous silicon dioxide, magnesium stearate (E 470b), red iron oxide (E 172), aspartame (E 951), vanillin flavoring;
15 mg tablets: lactose monohydrate, microcrystalline cellulose (E 460), croscarmellose sodium, colloidal anhydrous silicon dioxide, magnesium stearate (E 470b), yellow iron oxide (E 172), aspartame (E 951), vanillin flavoring;
30 mg tablets: lactose monohydrate, microcrystalline cellulose (E 460), croscarmellose sodium, colloidal anhydrous silicon dioxide, magnesium stearate (E 470b), red iron oxide (E 172), aspartame (E 951), vanillin flavor.
Dosage form
Main physicochemical properties:
10 mg tablets – pink, round tablets with a flat surface, embossed with “10” on one side and smooth on the other;
15 mg tablets – yellow, round tablets with a flat surface, embossed with “15” on one side and smooth on the other;
30 mg tablets – pink, round tablets with a flat surface, embossed with “30” on one side and smooth on the other.
Pharmacotherapeutic group
Pharmacological properties.
Pharmacodynamics.
Mechanism of action.
The therapeutic effect of aripiprazole in the treatment of schizophrenia and bipolar I disorder is due to a combination of partial agonism at D2 dopamine and HT1A serotonin receptors, and antagonism at 5-HT2A serotonin receptors. Aripiprazole has shown antagonistic properties in animal models of dopaminergic hyperactivity and agonistic properties in animal models of dopaminergic hypoactivity. Aripiprazole has high binding affinity in vitro for D2 and D3 dopamine receptors, 5-HT1A and 5-HT2A serotonin receptors, and moderate affinity for D4 dopamine receptors, 5-HT2C and 5-HT7 serotonin, α-1 adrenergic, and histamine H1 receptors. Aripiprazole also has moderate affinity for serotonin reuptake sites and no appreciable affinity for muscarinic receptors. Interactions with receptors other than dopamine and serotonin subtypes may explain some of the other clinical effects of aripiprazole.
Aripiprazole at doses ranging from 0.5 to 30 mg once daily in healthy volunteers for 2 weeks showed a dose-dependent reduction in the binding of 11C-raclopride, a D2-D3 receptor ligand, to the caudate nucleus and shell, as measured by positron emission tomography.
Clinical efficacy and safety.
Adults.
Schizophrenia.
Aripiprazole is effective in maintaining clinical improvement during continued therapy in adult patients who have shown an initial response to treatment.
Weight gain.
Aripiprazole has not been shown to cause clinically significant weight gain.
Lipid indicators.
Aripiprazole does not cause clinically significant changes in total cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels.
Prolactin.
The incidence of hyperprolactinemia, or increased serum prolactin, in patients treated with aripiprazole (0.3%) was similar to placebo (0.2%).
Manic episodes in bipolar I disorder.
Aripiprazole demonstrated superior efficacy compared to placebo in reducing manic symptoms over 3 weeks.
Pharmacokinetics.
Absorption.
Aripiprazole is rapidly absorbed after oral administration, reaching peak plasma concentrations (Cmax) within 3–5 hours. Aripiprazole undergoes minimal first-pass metabolism. Absolute oral bioavailability is 87%. The pharmacokinetics of aripiprazole are not affected by fatty foods.
Distribution.
Aripiprazole is extensively distributed into body tissues. The volume of distribution is 4.9 l/kg, indicating extensive extravascular distribution. At therapeutic concentrations, more than 99% of aripiprazole and dehydroaripiprazole are bound to serum proteins, primarily albumin.
Biotransformation.
Aripiprazole is extensively metabolized in the liver, primarily by dehydrogenation, hydroxylation, and N-dealkylation. In vitro studies indicate that dehydrogenation and hydroxylation of aripiprazole occur mediated by CYP3A4 and CYP2D6, and N-dealkylation is catalyzed by CYP3A4. Aripiprazole is the major component of the drug in the systemic circulation. At steady state, dehydroaripiprazole, its active metabolite, accounts for approximately 40% of the plasma AUC of aripiprazole.
Breeding.
The mean elimination half-life of aripiprazole is approximately 75 hours in CYP2D6 extensive metabolizers and approximately 146 hours in CYP2D6 poor metabolizers. The total clearance of aripiprazole is 0.7 mL/min/kg, primarily due to hepatic clearance.
Pharmacokinetics in special patient groups.
Elderly patients.
There are no differences in the pharmacokinetics of aripiprazole between healthy elderly volunteers and younger patients. There are also no apparent differences in pharmacokinetics between different age groups of patients with schizophrenia.
Sex.
There are no differences between the pharmacokinetics of aripiprazole in healthy men and women. There is also no effect of gender on the pharmacokinetics of aripiprazole in patients with schizophrenia.
Smoking.
Population pharmacokinetic evaluation revealed no clinically significant effect of smoking on the pharmacokinetics of aripiprazole.
Race.
Population pharmacokinetic evaluation revealed no clinically significant race-related differences in the pharmacokinetics of aripiprazole.
Kidney dysfunction.
The pharmacokinetic characteristics of aripiprazole and dehydroaripiprazole were found to be similar in both patients with severe renal disease and young healthy volunteers.
Liver dysfunction.
In studies involving patients with varying degrees of liver cirrhosis (Child-Pugh Class A, B, and C) after a single dose of aripiprazole, there was no significant effect of impaired hepatic function on the pharmacokinetics of aripiprazole and dehydroaripiprazole. Due to the lack of data, it is not possible to draw definitive conclusions about metabolic activity in patients with decompensated liver cirrhosis (Child-Pugh Class C).
Clinical characteristics.
Indication
Treatment of schizophrenia in adults.
Treatment of moderate to severe manic episodes in bipolar I disorder, and for the prevention of new manic episodes in adults who have previously had a manic episode and have responded to aripiprazole treatment.
Contraindication
Hypersensitivity to aripiprazole or to any other component of the drug.
Interaction with other medicinal products and other types of interactions
Due to antagonism at α1-adrenergic receptors, aripiprazole may enhance the effect of some antihypertensive drugs.
Since aripiprazole affects the central nervous system (CNS), caution should be exercised when alcohol or CNS-active drugs are taken concomitantly due to the potential for cross-reactions, such as sedation (see section 4.8).
Aripiprazole should be used with caution in combination with other drugs that prolong the QT interval or disrupt electrolyte balance.
Potential effects of other drugs on the action of aripiprazole.
No clinically significant effect of the histamine H2-receptor blocker famotidine, which inhibits gastric acid secretion, on aripiprazole was found, despite a decrease in the rate of absorption of aripiprazole.
Aripiprazole is metabolized by multiple pathways involving CYP2D6 and CYP3A4 enzymes, but not CYP1A enzymes, so no dose adjustment is necessary for smokers.
Quinidine and other CYP2D6 inhibitors.
In studies in healthy volunteers, a potent inhibitor of the CYP2D6 isoenzyme (quinidine) increased the AUC of aripiprazole by 107%, while Cmax remained unchanged. The AUC and Cmax of dehydroaripiprazole, the active metabolite, were reduced by 32% and 47%, respectively. In this regard, it is necessary to reduce the dose of aripiprazole by approximately 2 times when it is prescribed with quinidine. Other potent inhibitors of CYP2D6, such as fluoxetine and paroxetine, are likely to have a similar effect, therefore, a similar dose reduction is required.
Ketoconazole and other CYP3A4 inhibitors.
In studies in healthy volunteers, a strong CYP3A4 inhibitor (ketoconazole) increased the AUC and Cmax of aripiprazole by 63% and 37%, respectively. The AUC and Cmax of dehydroaripiprazole increased by 77% and 43%, respectively. In individuals who are poor metabolizers of CYP2D6, concomitant administration of strong CYP3A4 inhibitors may result in higher plasma concentrations of aripiprazole compared to those in patients who are extensive metabolizers of CYP2D6.
If concomitant use of ketoconazole or other potent CYP3A4 inhibitors with aripiprazole is necessary, the potential benefits should outweigh the potential risks to the patient. When aripiprazole and ketoconazole are co-administered, the aripiprazole dose should be reduced by approximately half. Other potent CYP3A4 inhibitors, such as itraconazole and HIV protease inhibitors, could theoretically have similar effects and therefore doses should be reduced accordingly (see section 4.2).
After discontinuation of the CYP2D6 or CYP3A4 inhibitor, the aripiprazole dose should be increased to the level used prior to initiation of concomitant therapy.
A slight increase in aripiprazole plasma concentrations is possible with concomitant use of weak inhibitors of CYP3A4 (e.g. diltiazem) or CYP2D6 (escitalopram).
Carbamazepine and other CYP3A4 inhibitors.
The dose of aripiprazole should be doubled when co-administered with carbamazepine. Co-administration of aripiprazole with other potent CYP3A4 inducers (such as rifampicin, rifabutin, phenytoin, phenobarbital, primidone, efavirenz, nevirapine, and St. John's wort) is expected to have a similar effect, and an appropriate dose increase is therefore required. After discontinuation of potent CYP3A4 inducers, the dose of aripiprazole should be reduced to the recommended dose.
Valproate and lithium.
No clinically significant changes in aripiprazole concentrations were observed when valproate or lithium were co-administered with aripiprazole, and therefore no dose adjustment is required.
Potential effects of aripiprazole on the effects of other drugs.
In clinical studies, aripiprazole at a dose of 10-30 mg/day did not cause clinically important drug interactions mediated by the enzymes CYP2D6 (dextromethorphan/3-methoxymorphine ratio), CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A4 (dextromethorphan). In addition, aripiprazole and dehydroaripiprazole have not been shown to affect CYP1A2-mediated metabolism in vitro. Therefore, it is unlikely that aripiprazole has a clinically significant effect on substances metabolized by this enzyme.
No clinically significant changes in valproate, lithium, or lamotrigine concentrations were observed during concomitant administration of aripiprazole with valproate, lithium, or lamotrigine.
Serotonin syndrome.
Cases of serotonin syndrome have been reported in patients taking aripiprazole, particularly when used concomitantly with other serotonergic medicinal products, such as selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs), or with medicinal products that increase aripiprazole concentrations (see section 4.8).
Application features
With antipsychotic treatment, it may take several days to several weeks for the patient to improve their clinical condition. During this period, the patient should be closely monitored.
Suicide.
The emergence of suicidal behaviour is common in patients with psychotic and mood disorders and has been observed in some cases early in antipsychotic treatment, including aripiprazole (see section 4.8). Antipsychotic treatment should be accompanied by close monitoring of patients at increased risk.
Cardiovascular disorders.
Aripiprazole should be used with caution in patients with a history of cardiovascular disease (myocardial infarction or ischemic heart disease, heart failure or conduction disorders), cerebrovascular disorders, conditions that predispose patients to arterial hypotension (dehydration, hypovolemia, use of antihypertensive drugs), arterial hypertension, including progressive or malignant hypertension.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients taking neuroleptics often have acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with aripiprazole and all preventive measures should be taken.
QT prolongation.
The incidence of QT prolongation with aripiprazole was comparable to that with placebo. However, caution should be exercised when using aripiprazole in patients with a family history of QT prolongation (see section 4.8).
Tardive dyskinesia.
Symptoms of tardive dyskinesia have been reported rarely in patients taking aripiprazole for up to 1 year. If symptoms of tardive dyskinesia develop in a patient taking aripiprazole, dose reduction or discontinuation of treatment should be considered (see section 4.8). These symptoms may temporarily worsen or even recur after discontinuation of treatment.
Neuroleptic malignant syndrome (NMS).
NMS is a symptom complex associated with the use of antipsychotic drugs that can be potentially fatal. In clinical studies with aripiprazole, cases of NMS were rare. Clinical manifestations of NMS include hyperpyrexia (very high body temperature), muscle rigidity, altered mental status, and signs of autonomic nervous system dysfunction (irregular pulse or blood pressure, tachycardia, increased sweating, and cardiac arrhythmia). Additional features may include elevated creatine kinase, myoglobinuria (rhabdomyolysis), and acute renal failure. However, isolated cases of elevated creatine kinase and rhabdomyolysis have been observed, not necessarily associated with NMS. If a patient develops symptoms of NMS or an unexplained very high body temperature without additional clinical manifestations of NMS, all neuroleptic active substances, including aripiprazole, should be discontinued.
Epileptic seizures.
Seizures have been reported uncommonly with aripiprazole. Therefore, aripiprazole should be used with caution in patients with a history of epilepsy or conditions associated with seizures.
Increased mortality: Aripiprazole has been associated with an increased risk of death in elderly patients with psychosis due to Alzheimer's disease. Although the causes of death varied, the majority of deaths were cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature (see Adverse Reactions).
Cerebrovascular adverse reactions: Cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatal outcomes, have been observed in elderly patients (mean age 84 years; range 78-88 years). A strong dose-response relationship has also been observed for cerebrovascular adverse reactions in patients taking aripiprazole.
Aripiprazole is not indicated for the treatment of patients with psychosis in dementia.
Hyperglycemia and diabetes.
Hyperglycemia, in some cases extremely severe and associated with ketoacidosis or hyperosmolar coma, some of which have been fatal, has occurred in patients taking atypical antipsychotics, including aripiprazole. Obesity and a family history of diabetes are risk factors for serious complications. Studies of aripiprazole have not shown a significant difference in the incidence of hyperglycemic adverse reactions (including diabetes mellitus) or abnormal glucose levels compared with placebo. Based on the available data, it is not possible to make a precise comparative estimate of the incidence of hyperglycemic adverse reactions in patients taking aripiprazole and other atypical antipsychotics. Patients taking any neuroleptics, including aripiprazole, should be closely monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness), and patients with diabetes mellitus or risk factors for diabetes mellitus should be monitored regularly for elevated glucose levels.
Hypersensitivity.
Hypersensitivity reactions characterized by allergic symptoms may occur with aripiprazole (see section "Adverse reactions").
Weight gain.
Patients with schizophrenia and bipolar mania often experience weight gain due to comorbidities, the use of neuroleptics that cause weight gain, and an unhealthy lifestyle; this phenomenon can lead to serious complications. During post-marketing studies, the effect of aripiprazole on weight gain in patients has been identified. When treated with aripiprazole, cases of weight gain were usually observed in patients with significant risk factors, such as a history of diabetes mellitus, thyroid disorders, pituitary adenoma.
Dysphagia.
Neuroleptics, including aripiprazole, may cause esophageal motility disorders and aspiration of gastric contents. Aripiprazole should be used with caution in patients at increased risk of aspiration pneumonia.
Pathological gambling and other impulse control disorders.
Patients may experience increased episodes of pathological gambling, particularly gambling, and an inability to control these episodes while taking aripiprazole. Hypersexuality, compulsive shopping, binge eating or eating disorders, and other impulsive and compulsive behaviors have also been reported. It is important for physicians to inform patients of the development of new or previously mentioned disorders during treatment with aripiprazole. It should be noted that impulse control symptoms may be related to the underlying disorder, but sometimes the cessation of impulses has been reported when the dose of the drug is reduced or when treatment is discontinued. Impulse control disorders can cause harm to the patient and others if they are not identified. If a patient develops such tendencies while taking aripiprazole, the question of reducing the dose or discontinuing treatment should be considered.
Patients with concomitant attention deficit hyperactivity disorder (ADHD).
Despite the high frequency of comorbidities of bipolar I disorder and ADHD, data on the safety of concomitant use of aripiprazole and stimulants are very limited, so extreme caution is required when prescribing these drugs simultaneously.
Fall.
Aripiprazole may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls. Therefore, caution should be exercised when treating patients at higher risk (elderly or debilitated patients) or a lower starting dose should be considered (see section 4.2).
Important information about excipients.
Mintegra tablets contain lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Mintegra tablets contain 9.0 or 13.5 or 27.0 mg/dose of sodium, respectively. Caution should be exercised when administering the medicinal product to patients on a controlled sodium diet.
This medicine contains aspartame, which is a derivative of phenylalanine, which is dangerous for patients with phenylketonuria.
Use during pregnancy or breastfeeding.
There are no adequate and well-controlled studies of aripiprazole in pregnant women. Congenital anomalies have been reported, but a causal relationship to aripiprazole has not been established. Available animal data do not support the possibility of adverse effects on fetal development. Patients should be advised to inform their physician if they become pregnant or intend to become pregnant while taking aripiprazole. Due to insufficient information on the safety of aripiprazole during pregnancy, aripiprazole should be used only if the potential benefit to the mother justifies the potential risk to the fetus.
Neonates exposed to neuroleptics (including aripiprazole) during the third trimester of pregnancy may experience adverse reactions, including extrapyramidal symptoms and/or withdrawal syndrome, which may vary in severity and duration. There have been reports of agitation, hypertension, hypotension, tremor, somnolence, respiratory distress, or feeding difficulties. Therefore, close observation of such neonates is necessary.
Breastfeeding period.
Aripiprazole is excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from aripiprazole therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility.
Aripiprazole does not affect fertility based on reproductive toxicity studies.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
Aripiprazole has minor or moderate influence on the ability to drive or use machines due to potential effects on the nervous system and visual organs and the occurrence of adverse reactions such as sedation, drowsiness, fainting, blurred vision, diplopia (see section "Adverse reactions").
Method of administration and doses
The medicinal product is intended for oral use. The tablet should be placed on the tongue, where it quickly disperses in saliva. The tablet can be taken with or without liquid. It is difficult to remove the tablet from the oral cavity intact. Since the tablet is fragile, it should be taken immediately after opening the blister. Alternatively, the tablet can be dispersed in water and the resulting suspension drunk. Orodispersible tablets can be used as an alternative dosage form for patients who have difficulty swallowing.
Adults.
Schizophrenia: the recommended initial dose is 10 or 15 mg once daily, the maintenance dose is 15 mg once daily without regard to meals.
Aripiprazole is effective in the dose range of 10 to 30 mg per day. Increased efficacy has not been demonstrated with daily doses exceeding 15 mg, although individual patients may benefit from higher doses.
The maximum daily dose should not exceed 30 mg.
Manic episodes in bipolar I disorder: The recommended starting dose is 15 mg once daily without regard to meals (as monotherapy or as part of combination therapy). Individual patients may benefit from dose increases. The maximum daily dose should not exceed 30 mg.
Prevention of recurrence of new manic episodes in bipolar I disorder: To prevent recurrence of manic episodes in patients taking aripiprazole as monotherapy or as part of combination therapy, the drug should be continued at the same dose. The daily dose may be adjusted, including a decrease, based on the clinical condition of the patient.
Special patient groups.
Patients with hepatic impairment. No dose adjustment is required in patients with mild or moderate hepatic impairment. There are insufficient data to make recommendations for patients with severe hepatic impairment. The dose should be adjusted with caution in these patients. The maximum daily dose of 30 mg should be used with caution in patients with severe hepatic impairment (see section 5.1).
Patients with renal impairment: No dose adjustment is required for patients with renal impairment.
Elderly patients: The safety and efficacy of aripiprazole in the treatment of schizophrenia or manic episodes in bipolar I disorder in patients aged 65 years and older have not been established. Given the greater sensitivity of this patient population, lower starting doses should be considered unless other clinical factors preclude this (see section 4.4).
Gender: No dose adjustment is required based on the patient's gender (see section 5.1).
Smoking: Given the metabolic pathway of aripiprazole, no dosage adjustment is required for smokers (see section 4.5).
When potent CYP3A4 inducers are co-administered with aripiprazole, the aripiprazole dose should be increased. If the CYP3A4 inducer is removed from the combination regimen, the aripiprazole dose should be reduced to the recommended dose (see section 4.5).
Children.
The drug is not used in children, as it is impossible to provide the initial dose according to the treatment regimen.
Overdose
There have been reports of accidental or intentional overdose with aripiprazole with a single dose of up to 1260 mg, which was not accompanied by a fatal outcome. Medically significant symptoms included lethargy, increased blood pressure, drowsiness, tachycardia, nausea, vomiting and diarrhea. In addition, cases of overdose with aripiprazole in children (up to 195 mg) have been described, which did not lead to a fatal outcome. Potentially dangerous symptoms of overdose include drowsiness, transient loss of consciousness and extrapyramidal disorders.
Treatment: In case of overdose, supportive therapy, ensuring adequate airway patency, oxygenation, artificial ventilation of the lungs and symptomatic treatment are required. Monitoring of cardiac parameters with ECG recording for arrhythmias should be initiated immediately. After a confirmed or suspected overdose of aripiprazole, careful medical observation is necessary until all symptoms have resolved.
Activated charcoal (50 g) administered 1 hour after aripiprazole administration reduces the AUC and Cmax of aripiprazole in the blood by 51% and 41%, respectively, and is therefore recommended for use in overdose.
Although there is no reliable data on the use of hemodialysis in case of aripiprazole overdose, a beneficial effect of this method is unlikely, because aripiprazole is not excreted unchanged by the kidneys and is extensively bound to plasma proteins.
Adverse reactions
The most common adverse reactions were akathisia and nausea, each occurring in more than 3% of patients taking oral aripiprazole.
All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 - < 1/10), uncommon (≥ 1/1,000 - < 1/100), rare (< 1/10,000), frequency unknown (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
The frequency of adverse reactions during post-marketing use cannot be determined as information on adverse reactions is obtained from spontaneous reports. Therefore, the frequency of these adverse reactions is classified as “not known”.
On the part of the organs of vision: often - blurred vision; infrequently - diplopia; frequency unknown - oculogyric crisis.
Respiratory, thoracic and mediastinal disorders: infrequently - hiccups; unknown - aspiration pneumonia, laryngospasm, oropharyngeal spasm.
Gastrointestinal: often - constipation, dyspepsia, nausea, increased salivation, vomiting; unknown - pancreatitis, dysphagia, diarrhea, abdominal discomfort, gastric discomfort.
Hepatobiliary disorders: not known – hepatic failure, hepatitis, jaundice, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased gamma-glutamyltransferase (GGT), increased alkaline phosphatase.
Renal and urinary disorders: not known – urinary incontinence, urinary retention.
On the part of the endocrine system: infrequently - hyperprolactinemia; unknown - diabetic hyperosmolar coma, diabetic ketoacidosis.
Metabolism and metabolism: often - diabetes mellitus; infrequently - hyperglycemia; unknown - hyponatremia, anorexia, weight loss or increase.
Nervous system disorders: often - akathisia, extrapyramidal disorders, tremor, headache, sedation, drowsiness, dizziness; infrequently - dystonia, tardive dyskinesia; unknown - CNS depression, grand mal convulsions, serotonin syndrome, speech disorders.
On the part of the psyche: often - insomnia, anxiety, restlessness; infrequently - depression, hypersexuality; unknown - suicide attempts, suicidal thoughts and suicide, pathological gambling, impulse control disorders, compulsive overeating, compulsive shopping, dromomania, aggression, agitation, nervousness.
Cardiac disorders: infrequently - tachycardia; unknown - sudden death of unknown etiology, torsades de pointes, QT prolongation, ventricular arrhythmia, cardiac arrest, bradycardia.
Vascular disorders: uncommon - orthostatic hypotension; unknown - venous thromboembolism (including pulmonary embolism and deep vein thrombosis), hypertension, syncope.
Blood and lymphatic system disorders: not known – leukopenia, neutropenia, thrombocytopenia.
Immune system disorders: Not known: allergic reactions (e.g. anaphylactic reaction, angioedema including tongue swelling, facial swelling, pruritus or urticaria).
Skin and subcutaneous tissue disorders: not known – rash, photosensitivity reaction, alopecia, increased sweating.
Musculoskeletal and connective tissue disorders: not known – rhabdomyolysis, myalgia, stiffness.
Pregnancy, puerperium and perinatal conditions: not known – drug withdrawal syndrome in newborns.
General disorders: often - fatigue; unknown - thermoregulation disorders (hypothermia, pyrexia), chest pain, peripheral edema.
Laboratory indicators: unknown - increased blood glucose concentration, increased glycosylated hemoglobin level, fluctuations in blood glucose concentration, increased creatine phosphokinase level.
Description of selected adverse reactions.
Extrapyramidal disorders included parkinsonism, akathisia, dystonia, and dyskinesia.
Dystonia.
This class of drugs is characterized by symptoms of dystonia, a prolonged abnormal muscle contraction, which may occur in patients during the first days of treatment. Symptoms of dystonia include spasm of the neck muscles, sometimes progressing to throat constriction, difficulty swallowing, breathing, and/or tongue protrusion. While these symptoms may occur at low doses, they occur more frequently and with greater severity at high doses of first-generation neuroleptics. Males and younger patients are at increased risk of acute dystonia.
Prolactin.
In clinical trials for approved indications, both increases and decreases in serum prolactin from baseline were observed.
Laboratory parameters.
There were no clinically significant differences in routine laboratory parameters and lipid parameters between the aripiprazole and placebo groups. Elevations in creatine phosphokinase, usually transient and asymptomatic, occurred in 3.5% of patients treated with aripiprazole and 2.0% of patients treated with placebo.
Pathological gambling and other impulse control disorders.
Pathological gambling, hypersexuality, compulsive shopping, binge eating, or uncontrolled food cravings may occur in patients taking aripiprazole.
Other data.
Adverse reactions identified during treatment with aripiprazole include CNS depression, tardive dyskinesia, seizures, cerebrovascular adverse reactions and increased mortality in elderly patients with dementia, hyperglycemia and diabetes mellitus (see section "Special warnings and precautions for use").
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.
Expiration date
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging.
10 tablets in a blister; 3 blisters in a pack.
Release category. By prescription.
Applicant.
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the applicant and address of the place of business.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
Producer.
Rontis Hellas Medical and Pharmaceutical Products S.A.
Location of the manufacturer and address of its place of business.
P.O. Box 3012 Larisa Industrial Area, Larisa, 41004, Greece.
