Instructions Ariprazole tablets 10 mg blister No. 30
Composition
active ingredient: aripiprazole;
1 tablet contains 10 mg or 15 mg of aripiprazole (calculated as 100% dry aripiprazole);
Excipients: hydroxypropylmethylcellulose; croscarmellose sodium; lactose, monohydrate; microcrystalline cellulose; citric acid, monohydrate; colloidal anhydrous silicon dioxide; magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
10 mg tablets: white or almost white tablets, with a flat surface, round shape with a bevel, with a score on one side;
15 mg tablets: white or almost white, flat-surfaced, round, bevelled-edge tablets, marked “15” on one side.
Pharmacotherapeutic group
Psycholeptics. Other antipsychotics.. ATX code N05A X12.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
It has been suggested that the efficacy of aripiprazole in schizophrenia and bipolar I disorder is due to its partial agonism at dopamine D2 and serotonin 5-HT1a receptors, and antagonism at serotonin 5-HT2a receptors. Aripiprazole is known to have 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 dopamine D2 and D3 receptors, serotonin 5-HT1a and 5-HT2a receptors, and moderate affinity for dopamine D4, serotonin 5-HT2c and 5-HT7, alpha-1 adrenergic receptors, and histamine H1 receptors. Aripiprazole also has moderate affinity for serotonin receptors and no appreciable affinity for muscarinic receptors. Interactions with receptors other than the dopamine and serotonin receptor subtypes noted above may explain some of the other clinical effects of aripiprazole.
When aripiprazole was administered once daily to healthy volunteers for two weeks at doses ranging from 0.5 to 30 mg, the drug dose-dependently reduced the binding of 11C-raclopride, a D2/D3 dopamine receptor ligand, to the caudate nucleus and putamen as determined by positron emission tomography.
Clinical efficacy and safety:
Adults
Schizophrenia
In three short-term (4 to 6 weeks) placebo-controlled studies involving 1228 adult patients with schizophrenia with positive and negative symptoms, aripiprazole showed statistically significant improvements in psychiatric symptoms compared to placebo.
Aripiprazole is effective in maintaining clinical improvement during continuation of therapy in adult patients who have shown an initial response to treatment. In a controlled trial with haloperidol as the control, the number of patients who responded to treatment and remained responsive at week 52 was similar in both groups (77% in the aripiprazole group and 73% in the haloperidol group). The overall completion rate was significantly higher in patients taking aripiprazole (43%) compared to patients taking haloperidol (30%). Actual scores on rating scales, including the PANSS (Positive and Negative Syndrome Scale) and the Montgomery-Asberg Depression Rating Scale, used as secondary endpoints, demonstrated significant improvement compared to haloperidol.
In a 26-week placebo-controlled study in patients with chronic, stable schizophrenia, aripiprazole was significantly more effective in reducing relapse rates: 34% in the aripiprazole group and 57% in the placebo group.
Weight gain
In clinical trials, no clinically significant weight gain was observed with aripiprazole. In a 26-week, controlled (olanzapine as the control drug), double-blind, multinational study of schizophrenia in 314 patients with weight gain as the primary endpoint, significantly fewer patients gained at least 7% of their baseline weight (i.e., at least 5.6 kg from a mean baseline weight of 80.5 kg) with aripiprazole (N=18, or 13% of evaluable patients) compared with olanzapine (N=45, or 33% of evaluable patients).
Lipid indicators
In a pooled analysis of lipid parameters obtained from placebo-controlled clinical trials in adult patients, no clinically meaningful changes in total cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) concentrations were observed due to aripiprazole.
Prolactin
The incidence of hypoprolactinemia or decreased serum prolactin levels was 0.4% in patients treated with aripiprazole and 0.02% in patients treated with placebo. In patients treated with aripiprazole, the median time to onset was 30 days and the median duration was 194 days.
Manic episodes in bipolar I disorder
Aripiprazole was superior to placebo in two 3-week, dose-titration, monotherapy studies in patients with manic or mixed episodes of bipolar I disorder. Efficacy was measured by reductions in manic symptoms over 3 weeks of treatment. These studies included patients with and without psychotic symptoms, and patients with and without rapid cycling.
In one 3-week, placebo-controlled, fixed-dose monotherapy study in patients with manic or mixed episodes of bipolar I disorder, aripiprazole did not demonstrate superior efficacy compared to placebo.
In two 12-week monotherapy studies (one placebo-controlled and the other active-controlled) in patients with manic or mixed episodes of bipolar I disorder with or without psychotic symptoms, aripiprazole demonstrated superior efficacy at week 3 and maintained efficacy comparable to lithium or haloperidol at week 12. The number of patients with mania in whom aripiprazole induced symptom remission was comparable to the number of patients receiving lithium or haloperidol at week 12.
In a 6-week placebo-controlled study in patients with manic or mixed episodes of bipolar I disorder with or without psychotic symptoms, 2 weeks of monotherapy with lithium or valproate at therapeutic doses was partially ineffective. However, aripiprazole, as add-on therapy, resulted in an effective reduction in manic symptoms compared with lithium or valproate monotherapy.
A 26-week, placebo-controlled study with a 74-week extension enrolled patients with manic disorder who had achieved remission on aripiprazole during the stabilization phase prior to randomization. In this study, aripiprazole was superior to placebo in preventing recurrence of bipolar disorder (primarily mania) but did not differ from placebo in preventing recurrence of depression.
In a 52-week placebo-controlled trial of patients with manic or mixed episodes in bipolar I disorder who were in sustained remission (total Young's MRS and Montgomery-Asberg Rating Scale (MADRS) ≤ 12 weeks), aripiprazole (10 mg/day and 30 mg/day) to lithium or valproate for 12 weeks was superior to the addition of aripiprazole to placebo, with a 46% reduction in the risk of bipolar episode recurrence (relative risk RR 0.001) and a 65% reduction in the risk of manic episode recurrence (RR 0.35). However, the combination was not superior to placebo in preventing depressive relapse. The addition of aripiprazole was superior to placebo on the secondary endpoint of the Clinical Global Impression Scale for Bipolar I Disorder Severity Score. (CGI-BP).
In this open-label study, patients were randomized to receive lithium or valproate monotherapy in order to identify patients who were partially refractory to therapy. Patients were stabilized for at least 12 weeks by adding aripiprazole to the same mood stabilizers. Stabilized patients were randomized to continue therapy with the same mood stabilizers plus aripiprazole or placebo in a double-blind manner. The randomized phase consisted of 4 subgroups: aripiprazole + lithium; aripiprazole + valproate; placebo + lithium; placebo + valproate.
The recurrence rate of any mood change was determined by the Kaplan-Meier method and was: 16% in the aripiprazole + lithium group and 18% in the aripiprazole + valproate group, compared with 45% in the placebo + lithium group and 19% in the placebo + valproate group.
Pharmacokinetics.
Absorption
Aripiprazole is well absorbed, with peak plasma concentrations (Cmax) occurring 3-5 hours after administration. Aripiprazole undergoes minimal first-pass metabolism. Absolute oral bioavailability is 87%. High-fat meals do not affect the pharmacokinetics of aripiprazole.
Distribution
Biotransformation Aripiprazole is extensively metabolized in the liver, primarily by dehydrogenation, hydroxylation, and N-dealkylation. In vitro studies indicate that CYP3A4 and CYP2D6 are responsible for the dehydrogenation and hydroxylation of aripiprazole, with N-dealkylation catalyzed by CYP3A4. Aripiprazole is the major systemic drug. At steady state, dehydroaripiprazole, its active metabolite, accounts for approximately 40% of the area under the plasma concentration-time curve (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, and is primarily due to hepatic clearance. Following a single oral dose of 14C-labeled aripiprazole, approximately 27% was excreted in the urine and approximately 60% in the feces. Less than 1% of unchanged aripiprazole was excreted in the urine, and approximately 18% of unchanged aripiprazole was excreted in the feces.
Pharmacokinetics in special patient groups
Children
The pharmacokinetics of aripiprazole and dehydroaripiprazole in patients 10 to 17 years of age were similar to those in adults after adjusting for differences in body weight.
Elderly patients
There are no differences in the pharmacokinetics of aripiprazole between healthy elderly volunteers and younger patients. There is also no significant effect of age in a population pharmacokinetic analysis in patients with schizophrenia.
Gender There are no differences in the pharmacokinetics of aripiprazole between healthy males and females, and there is no discernible effect of gender in a population pharmacokinetic analysis of 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 effect of ethnic differences on 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
A single-dose study in patients with varying degrees of liver cirrhosis (Child-Pugh classes A, B, and C) did not reveal a significant effect of hepatic impairment on the pharmacokinetics of aripiprazole and dehydroaripiprazole, however, the study included only three patients with class C liver cirrhosis, which is insufficient to draw conclusions about metabolic capacity.
Indication
Ariprazole® is indicated for the treatment of schizophrenia in adults.
Aripiprazole® is also indicated for the treatment of moderate to severe manic episodes in bipolar I disorder, as well as for the prevention of new manic episodes in adults who have previously experienced manic episodes and who have responded to treatment with aripiprazole.
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.
Given the primary effects of aripiprazole on the central nervous system (CNS), caution should be exercised when prescribing aripiprazole with alcohol or other CNS-active drugs due to possible cross-adverse reactions, such as sedation (see section 4.4).
Aripiprazole should be used with caution with other drugs that prolong the QT interval or disrupt electrolyte balance.
Potential effects of other medicinal products on the action of aripiprazole
The inhibitor of hydrochloric acid secretion, H2-histamine receptor antagonist famotidine reduces the rate of absorption of aripiprazole, but this effect is not considered clinically significant.
Aripiprazole is metabolized by multiple pathways involving CYP2D6 and CYP3A4, but not CYP1A. Therefore, no dose adjustment is necessary for smokers.
Quinidine and other CYP2D6 inhibitors
In a clinical study in healthy volunteers, a potent inhibitor of the CYP2D6 enzyme (quinidine) increased the AUC of aripiprazole by 107%, while Cmax remained unchanged. The AUC and Cmax of dehydroaripiprazole, the active metabolite of aripiprazole, were decreased by 32% and 47%, respectively. The dose of aripiprazole should be reduced by approximately half when co-administered with quinidine. Other potent inhibitors of CYP2D6, such as fluoxetine and paroxetine, are likely to have a similar effect, and the dose reduction should be similar if they are used.
In a clinical study 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 were increased by 77% and 43%, respectively. In CYP2D6 poor metabolizers, concomitant administration of strong CYP3A4 inhibitors may result in higher plasma concentrations of aripiprazole compared to CYP2D6 extensive metabolizers. If ketoconazole or other strong CYP3A4 inhibitors are co-administered with aripiprazole, the potential benefit should outweigh the potential risk to the patient. When aripiprazole and ketoconazole are co-administered, the dose of aripiprazole should be reduced by approximately half. Other potent CYP3A4 inhibitors, such as itraconazole and HIV protease inhibitors, could theoretically have similar effects and therefore require similar dose reductions (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 concentrations is possible with concomitant use of weak inhibitors of CYP3A4 (diltiazem) or CYP2D6 (escitalopram).
Carbamazepine and other CYP3A4 inhibitors
When carbamazepine, a potent CYP3A4 inducer, was co-administered with aripiprazole in patients with schizophrenia or schizoaffective disorder, the geometric mean Cmax and AUC of aripiprazole were decreased by 68% and 73%, respectively, compared to aripiprazole (30 mg) alone. Similarly, when carbamazepine was co-administered with dehydroaripiprazole, the geometric mean Cmax and AUC of the latter were decreased by 69% and 71%, respectively, compared to aripiprazole alone. The dose of aripiprazole should be doubled when co-administered with carbamazepine. Concomitant use of aripiprazole with other potent CYP3A4 inducers (rifampicin, rifabutin, phenytoin, phenobarbital, primidone, efavirenz, nevirapine and St. John's wort), which theoretically have similar effects to the potent CYP3A4 inhibitors mentioned above, requires an appropriate dose increase. After discontinuation of the potent CYP3A4 inducer, the aripiprazole dose 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, therefore no dose adjustment is required when valproate or lithium is co-administered with aripiprazole.
Serotonin syndrome
Cases of serotonin syndrome have been reported in patients taking aripiprazole, particularly when used concomitantly with other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs)/selective serotonin/norepinephrine reuptake inhibitors (SNRIs), or with drugs that increase aripiprazole concentrations (see section 4.4).
Potential effects of aripiprazole on the effects of other medicinal products
In clinical studies, aripiprazole at a dose of 10-30 mg/day did not affect the metabolism of substrates of the enzyme CYP2D6 (dextromethorphan/3-methoxymorphinan ratio), CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A. In addition, in vitro studies did not show the ability of aripiprazole and dehydroaripiprazole to affect metabolic pathways mediated by the enzyme CYP1A2. Therefore, it is unlikely that aripiprazole is capable of causing clinically important drug interactions mediated by these enzymes.
No clinically significant changes in valproate, lithium or lamotrigine concentrations were observed when aripiprazole was co-administered with valproate, lithium or lamotrigine.
Application features
When treated with antipsychotics, clinical improvement may take from several days to several weeks. During this period, patients should be closely monitored.
Suicidality: The emergence of suicidal behaviour is common in patients with psychotic illnesses and affective disorders and has been observed in some cases shortly after initiation or change of antipsychotic treatment, including aripiprazole. Treatment with antipsychotic drugs 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 hypotension (dehydration, hypovolemia, use of antihypertensive drugs), or hypertension, including progressive or malignant hypertension.
QT prolongation: In clinical trials with aripiprazole, the incidence of QT prolongation was comparable to placebo. Aripiprazole should be used with caution in patients with a family history of QT prolongation (see section 4.8).
Tardive dyskinesia: In clinical trials of one year or less duration, dyskinesia was reported infrequently with aripiprazole. If symptoms of tardive dyskinesia develop in a patient taking aripiprazole, consideration should be given to reducing the dose or discontinuing treatment. These symptoms may temporarily worsen or even recur after discontinuation of treatment.
Other extrapyramidal symptoms: Akathisia and parkinsonism have been observed in children with aripiprazole. If signs of other extrapyramidal symptoms appear, dose reduction should be considered and the patient should be closely monitored clinically.
Neuroleptic malignant syndrome (NMS). NMS is a symptom complex associated with the use of antipsychotics that can be potentially fatal. NMS was rarely observed in clinical trials of aripiprazole.
Clinical manifestations of NMS include hyperpyrexia (very high body temperature), muscle rigidity, altered mental status, and signs of autonomic 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 reported, 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 medicinal products, including aripiprazole, should be discontinued.
Seizures: Rare cases of seizures have been reported with aripiprazole. Therefore, aripiprazole should be used with caution in patients with a history of epilepsy or conditions associated with seizures.
Elderly patients with psychosis on the background of dementia
Increased mortality. In three placebo-controlled trials (n = 938; mean age: 82.4 years; range: 56 to 99 years), aripiprazole was associated with an increased risk of death compared with placebo in elderly patients with psychosis due to Alzheimer's disease. The mortality rate in patients treated with aripiprazole was 3.5% compared with 1.7% in the placebo group. 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.
Cerebrovascular adverse reactions. In the same clinical trials, cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, were reported (mean age of patients was 84 years, range 78-88 years). Overall, in these trials, cerebrovascular adverse reactions occurred in 1.3% of patients treated with aripiprazole compared with 0.6% of patients treated with placebo. This difference was not statistically significant. However, in one of these trials (a fixed-dose trial), a significant dose-response relationship was observed in patients treated with aripiprazole.
Aripiprazole is not indicated for the treatment of psychosis in dementia.
Hyperglycemia and Diabetes Mellitus. Hyperglycemia, in some cases extremely severe and associated with ketoacidosis or hyperosmolar coma, including fatal outcomes, has been reported in patients taking atypical antipsychotics, including aripiprazole. Risk factors for severe complications include obesity and a family history of diabetes. In clinical trials of aripiprazole, there were no significant differences in the incidence of adverse reactions related to hyperglycemia (including diabetes mellitus) or in the incidence of abnormal laboratory values of glucose compared to placebo.
There is no precise comparative assessment of the risks of adverse reactions related to hyperglycemia in patients taking aripiprazole and other atypical antipsychotics. Patients taking any antipsychotic, including aripiprazole, should be closely monitored for symptoms of hyperglycemia (polydipsia, polyuria, polyphagia, and weakness), and patients with diabetes mellitus or risk factors for diabetes mellitus should be regularly monitored for elevated glucose levels.
Weight gain: Patients with schizophrenia and bipolar mania often experience weight gain due to comorbid conditions, the use of neuroleptics known to cause weight gain, and the disruption of healthy lifestyles that can lead to serious complications. Cases of weight gain with aripiprazole have generally been reported in patients with significant risk factors such as diabetes, thyroid disorders, or a history of pituitary adenoma.
In clinical studies, aripiprazole did not cause clinically significant weight gain in adults. In clinical studies in adolescent patients with bipolar mania, aripiprazole was associated with weight gain after 4 weeks of treatment. Weight gain in adolescent patients with bipolar mania should be monitored. If weight gain becomes clinically significant, a dose reduction should be considered (see Adverse Reactions).
Dysphagia: Neuroleptics, including aripiprazole, may cause esophageal motility disorders and aspiration of gastric contents. Aripiprazole and other neuroleptics should be used with caution in patients at increased risk of aspiration pneumonia.
Pathological gambling and other impulse control disorders. Pathological gambling and the inability to control this impulse have been reported in patients treated with aripiprazole. Hypersexuality, compulsive shopping, binge eating or eating disorders, and other impulsive and compulsive behaviors have also been reported. It is important that patients and their caregivers report any new or worsening symptoms of the above-mentioned disorders to their physician during treatment with aripiprazole. Symptoms of impulse control disorders may be related to the underlying disorder, but sometimes the symptoms resolve with dose reduction or discontinuation of treatment. Impulse control disorders can be harmful to the patient and others if they are not recognized. If such symptoms develop while taking aripiprazole, consideration should be given to reducing the dose or discontinuing treatment.
Lactose: Ariprazole® tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Patients with comorbid ADHD (attention deficit hyperactivity disorder): Despite the high comorbidity of bipolar I disorder and ADHD, there is very limited safety data on the concomitant use of aripiprazole and stimulants, and extreme caution should be exercised when these agents are co-administered.
Falls: Aripiprazole may cause drowsiness, orthostatic hypotension, and motor and sensory instability, which may lead to falls. Caution should be exercised when treating patients at increased risk and treatment should be initiated at lower initial doses (e.g., elderly or debilitated patients).
Use during pregnancy or breastfeeding
Pregnancy
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 exclude the possibility of embryofetotoxicity. Patients should inform their physician if they become pregnant or intend to become pregnant while taking aripiprazole. Due to the lack of safety data on aripiprazole in humans and the inconclusive results of animal studies, the drug should be used during pregnancy only if the expected 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, increased or decreased muscle tone, tremor, drowsiness, respiratory distress, or feeding difficulties. Therefore, close observation of such neonates is necessary.
Breastfeeding period
Aripiprazole/metabolites are 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 is known to have no adverse effect on fertility based on reproductive toxicity studies.
Ability to influence reaction speed when driving vehicles or other mechanisms
Aripiprazole, like other neuroleptics, has a moderate or minor influence on the ability to drive due to adverse reactions from the nervous system and visual organs, such as sedation, drowsiness, fainting, blurred vision, diplopia (see section "Adverse reactions").
Method of administration and doses
Method of administration: Ariprazole® is intended for oral administration.
Adults
Schizophrenia: The recommended starting dose of Ariprazole® is 10 or 15 mg/day, and the maintenance dose is 15 mg/day. This dose is taken once daily without regard to meals.
Ariprazole® is effective in the dose range of 10 to 30 mg/day. Increased efficacy has not been demonstrated with doses exceeding 15 mg/day, although individual patients may benefit from an increased dose.
The maximum daily dose should not exceed 30 mg.
Manic episodes in bipolar I disorder. The recommended starting dose of Ariprazole® is 15 mg. This dose is taken once daily with or without food. The drug can be prescribed as monotherapy or as part of combination therapy. For individual patients, dose escalation may be effective. The maximum daily dose should not exceed 30 mg.
Prevention of new manic episodes in bipolar I disorder. To prevent recurrence of manic episodes in patients who have been taking aripiprazole as monotherapy or as part of combination therapy, the drug should be continued at the same dose. Based on the clinical condition of the patient, correction of the daily dose, including its reduction, is possible.
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.
Patients with renal impairment: No dose adjustment is required for patients with renal impairment.
Elderly patients. The efficacy and safety of Ariprazole® in the treatment of schizophrenia and 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 if other clinical factors permit.
Gender: No dose adjustment is required based on the patient's gender.
Smoking: Given the metabolic pathway of aripiprazole, no dose adjustment is necessary for smokers.
Dose adjustments due to interactions: When potent CYP3A4 or CYP2D6 inhibitors are co-administered with aripiprazole, the aripiprazole dose should be reduced. If a CYP3A4 or CYP2D6 inhibitor is removed from the combination regimen, the aripiprazole dose should be increased.
When strong 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.
Children.
Ariprazole® in this dosage is not recommended for use in children.
Overdose
Signs and symptoms
In clinical trials and post-marketing experience, cases of intentional or accidental acute overdose of aripiprazole in adult patients have been reported, with doses up to 1260 mg, without subsequent fatal outcome. Potentially medically significant signs and symptoms observed included lethargy, increased blood pressure, somnolence, tachycardia, nausea, vomiting, and diarrhea.
In addition, there have been reports of accidental overdose of aripiprazole alone (up to 195 mg) in children without fatal outcomes. Potentially medically significant symptoms observed included drowsiness, transient loss of consciousness, and extrapyramidal symptoms.
Treatment
Treatment of overdose should include supportive care, airway management, oxygen therapy, mechanical ventilation, and symptom control. The possibility of multiple drug overdose should be considered. Therefore, immediate cardiovascular monitoring should be initiated, including continuous ECG monitoring for arrhythmias.
After a confirmed or suspected overdose with aripiprazole, close medical supervision and monitoring of the patient's condition are necessary until recovery.
Activated charcoal (50 g) administered 1 hour after aripiprazole administration reduced aripiprazole Cmax by approximately 41% and AUC by approximately 51%, indicating the potential efficacy of activated charcoal in the treatment of overdose.
Hemodialysis
Although information on the effect of hemodialysis on the treatment of aripiprazole overdose is lacking, it is unlikely that hemodialysis would be useful in the treatment of overdose because aripiprazole is highly bound to plasma proteins.
Side effects
Brief description of the safety profile
The most common adverse reactions reported in placebo-controlled trials were akathisia and nausea, each occurring in more than 3% of patients receiving
