Ariprizole, tablets 10 mg 30 pcs

Schizophrenia, Mental Disorders, Manic Depressive Psychosis

• Schizophrenia: acute attacks and maintenance therapy
• Bipolar disorder type I: Manic episodes and maintenance therapy to prevent relapses in patients with type I bipolar disorder who have recently had a manic or mixed episode
• Addition to antidepressant therapy for major depressive disorder

Active ingredient

Composition

One tablet contains:

Active ingredient:

aripiprazole 10.00 / 15.00 / 30.00 mg.

Associates:

Lactose monohydrate – 61.23 / 91.53 / 183.69 mg,

Corn starch – 10.45 / 15.675 / 31.35 mg,

microcrystalline cellulose – 10.45 / 15.675 / 31.35 mg,

hyprolose – 1.90 / 2.85 / 5.70 mg,

magnesium stearate – 0.95 / 1.425 / 2.85 mg,

red iron oxide dye (E172) (for 10 mg and 30 mg doses) – 0.02 / 0.06 mg,

Iron oxide yellow dye (E172) (for 15 mg dosage) – 0.345 mg.

How to take, the dosage

Schizophrenia
The recommended starting dose is 10 mg to 15 mg once daily, regardless of meals. The maintenance dose is 15 mg per day. In clinical trials, the effectiveness of the drug in doses from 10 mg to 30 mg per day has been shown. The maximum daily dose should not exceed 30 mg.

Manic episodes in bipolar disorder
As monotherapy, the recommended starting dose is 15 mg once daily, regardless of meals. If necessary, the dose should be changed at intervals of at least 24 hours. In clinical trials, the effectiveness of the drug in doses from 15 to 30 mg daily for 3 to 12 weeks has been shown. Safety of the preparation in doses greater than 30 mg daily has not been evaluated in clinical trials.
In observing patients with type I bipolar disorder who have experienced a manic or mixed episode, in whom stabilization of symptoms was observed on aripiprazole for 6 weeks at a dose of 15 mg daily or 30 mg daily at an initial dose of 30 mg daily, then 6 months and further for 17 months, favorable effects of such maintenance therapy were established. Patients should be periodically evaluated to determine whether continuation of maintenance therapy is necessary.

Addition to therapy with lithium or valproic acid in bipolar disorder type I
The recommended initial dose is 10 mg to 15 mg once daily, regardless of meals. The maintenance dose is 15 mg per day. The dose may be increased up to 30 mg per day depending on clinical indications.
When observing patients with bipolar disorder type I, a favorable effect of maintenance therapy with aripiprazole at a dose of 10 mg to 30 mg per day has been established as an adjunct to therapy with lithium or valproic acid.
Patients should be evaluated periodically to determine the need for continued maintenance therapy.

Adjuvant therapy for major depressive disorder
The recommended initial dose is 5 mg daily, regardless of meals.
If necessary and well tolerated, the daily dose can be increased weekly by 5 mg up to a maximum of 15 mg per day.
The duration of therapy for all the above indications has not been established. The patient should be evaluated regularly to see if the therapy can be discontinued.

Application of the drug in special patient groups

Patients with impaired renal function. No adjustment of the drug dose is required.

Patients with impaired liver function.
No dose adjustment is required.
Patients with severe hepatic impairment are prescribed the dose of 30 mg with caution.

Patients over 65 years of age.
No adjustment of the drug dose is required.

Influence of patient gender on dosing regimen.
The dosing regimen of the drug is the same for patients of both sexes.

Influence of smoking on dosing regimen.
The dosing regimen of the drug is the same for smoking and non-smoking patients.

Dosing regimen in concomitant therapy
In concomitant use of aripiprazole and potent CYP3A4 isoenzyme inhibitors (ketoconazole, clarithromycin) the drug dose should be halved; when CYP3A4 isoenzyme inhibitors are cancelled, the drug dose should be increased.

In concomitant use of aripiprazole and potent CYP2D6 isoenzyme inhibitors (quinidine, fluoxetine, paroxetine), the drug dose should be reduced by half; if CYP2D6 isoenzyme inhibitors are cancelled, the drug dose should be increased.
If the drug is prescribed as adjunctive therapy for major depressive disorder, the drug should be used without changing the dosing regimen.

If the drug and potent CYP2D6 isoenzyme inhibitors (quinidine, fluoxetine, paroxetine) and CYP3A4 (ketoconazole, clarithromycin) are used simultaneously, the drug dose should be reduced to 25% of the usual dose. If CYP3A4 and/or CYP2D6 isoenzyme inhibitors are cancelled, the drug dose should be increased.

When concomitant use of the drug and potent, moderate or weak CYP3A4 and CYP2D6 isoenzyme inhibitors, the drug dose may initially be reduced to 25% of the usual dose and then increased to achieve optimal clinical results.

When administering the drug to patients with low CYP2D6 isoenzyme activity, the drug dose should initially be reduced by half and then increased to achieve optimal clinical results. In concomitant use of the drug and a potent CYP3A4 isoenzyme inhibitor in patients with low CYP2D6 isoenzyme activity, the drug dose should be reduced to 25% of the usual dose.

In case of concomitant use of the drug and potential inducers of CYP3A4 isoenzyme (carbamazepine), the drug dose should be doubled. After discontinuation of CYP3A4 isoenzyme inducers, the drug dose should be reduced to the recommended dose.

Interaction

Aripiprazole may increase the effect of antihypertensive drugs because it has an antagonistic effect on alpha1-adrenoreceptors.

The mechanism of action of aripiprazole is related to the effect on the central nervous system; this must be considered when using with other drugs with central action.

Caution should be exercised when using aripiprazole concomitantly with drugs that cause prolongation of QT interval or disturb electrolyte balance.

Special Instructions

The therapeutic effect of antipsychotic drugs develops over several days to several weeks. During this period, the patient’s condition should be monitored.

Suicidal attempts.
Suicidal behavior is common in psychosis and mood swings, and in some cases it occurs immediately after starting or changing treatment with antipsychotic medications, including treatment with aripiprazole. Patients at high risk should be monitored when treated with antipsychotics. Results from one epidemiologic study showed that patients with schizophrenia or bipolar disorder had no increased risk of suicide when treated with aripiprazole compared with other antipsychotics. There is insufficient clinical data to assess this risk in younger patients (under 18 years of age), but there is evidence to suggest that the risk persists after 4 weeks of treatment with antipsychotics, including aripiprazole.

Cardiovascular disease.
. Aripiprazole should be used with caution in patients with cardiovascular disease (myocardial infarction, coronary heart disease, heart failure, history of cardiac conduction disorders), cerebrovascular disorders, conditions predisposing to arterial hypotension (dehydration, hypovolemia, antihypertensive therapy) or hypertension, including essential or malignant.

In cases of venous thromboembolism have been reported with the use of antipsychotic drugs. Because patients treated with antipsychotics often have acquired risk factors for venous thromboembolism, all possible risk factors for venous thromboembolism should be identified before and during treatment with Ariprizol® with preventive measures.

Conduction disorders.
In clinical studies of aripiprazole, the incidence of QT interval prolongation was comparable to the placebo group. Aripiprazole, like other antipsychotics, should be used with caution in patients with a family history of QT interval prolongation.

Late dyskinesia.
In clinical trials lasting less than 1 year, infrequent cases of dyskinesia requiring urgent treatment have been observed during treatment with aripiprazole. If a patient develops signs and symptoms of tardive dyskinesia during treatment with aripiprazole®, consideration should be given to reducing the dose or discontinuing treatment.

The symptoms of dyskinesia may worsen temporarily or even appear for the first time after discontinuation of therapy.

Other extrapyramidal disorders.
Akathisia and parkinsonism have been observed in children in clinical studies of aripiprazole. If signs and symptoms of other extrapyramidal disorders occur, reduction of the dose of aripiprazole should be considered, with follow-up monitoring of the patient.

Malignant neuroleptic syndrome (MNS).
Malignant neuroleptic syndrome is a potentially life-threatening set of symptoms associated with the use of antipsychotic drugs. Rare cases of MNS have been observed in clinical studies during treatment with aripiprazole, which is manifested by hyperpyrexia, muscle rigidity, mental disturbances and instability of autonomic nervous system (irregular pulse and blood pressure, tachycardia, sweating, cardiac arrhythmia). In addition, in some cases there are increased CPK activity, myoglobinuria (rhabdomyolysis) and acute renal failure. If symptoms of MNS or unexplained fever occur, all neuroleptics, including Ariprizole®, should be discontinued.

Convulsions.
Seizures have been observed infrequently in clinical studies during treatment with aripiprazole. Therefore, aripiprazole should be used with caution in patients with a history of seizures and risk of seizures.

Psychosis associated with senile dementia.
In three placebo-controlled clinical trials of aripiprazole use in elderly patients (mean age 82.4 years, age range 56-99 years) with psychosis associated with Alzheimer’s disease, there was an increased risk of mortality compared with the placebo group. The mortality rate with aripiprazole was 3.5 percent compared with 1.7 percent in the placebo group. Although the causes of death varied, the main causes of most deaths were either cardiovascular disorders (including heart failure, sudden death) or the development of infection (including pneumonia).

The same clinical trials in elderly patients (mean age 84 years, age range 78-88 years) reported the development of cerebrovascular adverse reactions (including stroke, transient ischemic attack), including death. Overall, 1.3% of patients treated with aripiprazole had cerebrovascular adverse reactions compared to 0.6% of patients treated with placebo. This difference was not statistically significant. However, one of these fixed-dose aripiprazole studies found a significant dose-response relationship with cerebrovascular adverse reactions.

Aripiprazole® is not recommended for use in patients with psychosis due to dementia.

Hyperglycemia and diabetes mellitus.
Hyperglycemia, occasionally severe and accompanied by ketoacidosis or fatal hyperosmolar coma, has been reported in patients taking atypical neuroleptics. The relationship between atypical neuroleptics and hyperglycemic disorders remains unclear. In clinical trials of aripiprazole there was no significant difference in the incidence of adverse reactions accompanied by hyperglycemia (including diabetes) or in changes in laboratory glycemic values compared to the placebo group.
Patients diagnosed with diabetes mellitus should have their blood glucose concentrations determined regularly while taking atypical neuroleptics.
Patients with risk factors for diabetes mellitus (obesity, family history of diabetes mellitus) when taking atypical neuroleptics should have their blood glucose determined at the beginning of the course and periodically while taking the drug. In patients taking atypical neuroleptics, continuous monitoring of symptoms of hyperglycemia (increased thirst, frequent urination, polyphagia, weakness) is necessary. Special attention should be paid to patients with diabetes mellitus and risk factors for its development.

Hypersensitivity.
As with other drugs, hypersensitivity reactions in the form of allergic symptoms may develop when taking aripiprazole.

Elevation of body weight.
Body weight gain is commonly seen in patients with schizophrenia and bipolar mania due to comorbidities, use of antipsychotic medications that cause weight gain, unhealthy lifestyles that can lead to acute complications. Cases of weight gain have been reported in the post-marketing period in patients taking aripiprazole. Usually these adverse reactions were observed in patients with significant risk factors, such as diabetes mellitus, thyroid disease, or pituitary adenoma. In clinical trials, administration of aripiprazole did not cause a clinically significant increase in body weight.
In clinical studies of adolescent patients with bipolar mania, body weight increased after 4 weeks of treatment while taking aripiprazole. Continuous monitoring of body weight in adolescent patients with bipolar mania is necessary. If the increase in body weight is clinically significant, the dose of aripiprazole should be reduced.

Dysphagia.
In cases of esophageal peristalsis and, as a consequence, aspiration pneumonia have been reported with neuroleptics. The drug should be used with caution in patients with risk factors for aspiration pneumonia.

Pathological craving for gambling.
In the post-registration period, pathological gambling cravings have been reported in patients taking aripiprazole, regardless of whether these patients have a history of pathological gambling cravings. Patients with a history of pathological gambling cravings may be at increased risk of developing this disorder and should be closely monitored when using aripiprazole.

Lactose.
Aripiprazole® contains lactose, therefore it is not recommended for patients with rare hereditary conditions associated with galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Patients with concomitant attention deficit hyperactivity disorder (ADHD).
Despite the high incidence of the combination of type I bipolar disorder and ADHD, there are very limited data on the safety of concomitant use of aripiprazole and psychostimulants, so caution should be exercised if they are used together.

Effects on driving and operating machinery

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

Contraindications

Hypersensitivity to aripiprazole or to any component of the drug;
age under 18 years;
lactase deficiency, rare hereditary galactosemia, glucose-galactose malabsorption.

With caution

. In patients with cardiovascular disease (coronary heart disease or myocardial infarction, heart failure and conduction disorders), cerebrovascular disease and conditions predisposing to arterial hypotension (dehydration, hypovolemia and taking hypotensive drugs) due to the possibility of orthostatic hypotension; in patients with seizures or suffering from diseases that may lead to seizures; in patients with an increased risk of hyperthermia (e.g., with intense physical activity, overheating, taking m-cholinoblockers, dehydration due to the ability of neuroleptics to disrupt thermoregulation); in patients with an increased risk of aspiration pneumonia due to the risk of esophageal motor function failure and aspiration; in patients who are obese and have a family history of diabetes mellitus; in patients at high risk of suicide (psychotic illness, bipolar disorder, major depressive disorder); in persons aged 18-24 years due to the risk of suicidal behavior.

Side effects

The most common side effects in placebo-controlled clinical trials are akathisia and nausea, each of which was observed in more than 3% of patients taking aripiprazole.

The following side effects occur more frequently (≥ 1/100) compared to placebo or are identified as possible clinically significant side effects (*).
The following classification is used to indicate the frequency of side effects: frequent (˃ 1/100 and ˂ 1/10) and not frequent (˃ 1/1000 and ˂ 1/100):

Psychiatric disorders:
often – anxiety, insomnia, anxiety;
not infrequently -depression*, increased sexuality.

Nervous system disorders:
frequent – extrapyramidal disorders, akathisia, tremor, dizziness, somnolence, sedation, headache.

Visual disorders:
often – blurred vision; infrequently – diplopia.

Cardiovascular system disorders:
infrequent – tachycardia*, orthostatic hypotension*.

Gastrointestinal disorders:
frequent – dyspepsia, vomiting, nausea, constipation, hypersecretion of saliva.

General disorders:
often- fatigue.

Postmarketing surveillance

The following adverse reactions have been reported in post-marketing studies. The frequency of adverse reactions is considered unknown because it cannot be estimated from the available data.

Hematopoietic organs: leukopenia, neutropenia, thrombocytopenia.

From the immune system: allergic reactions (anaphylactic shock, angioedema, including, inflammation of the tongue, tongue swelling, facial swelling, itching or urticaria).

From the endocrine system: Hyperglycemia, diabetes mellitus, diabetic ketoacidosis, diabetic hyperosmolar coma.

From the side of metabolism and nutrition: increased body weight, decreased body weight, anorexia, hyponatremia.

Psychiatric disorders: excitement, nervousness, pathological gambling addiction, attempted suicide, suicidal thoughts, committed suicide.

From the nervous system: Speech disorders, malignant neuroleptic syndrome, seizures, serotonin syndrome.

Cardiovascular system side: QT interval prolongation, ventricular arrhythmias, sudden death, cardiac arrest, tachycardia, bradycardia, syncope, increased blood pressure, thromboembolism (including pulmonary embolism and deep vein thrombosis).

Involved respiratory system: oropharyngeal spasm, laryngospasm, aspiration pneumonia.

Gastrointestinal tract: pancreatitis, dysphagia, abdominal heaviness, diarrhea.

Hepatic and biliary tract disorders: hepatic failure, jaundice, hepatitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity.

Skin and subcutaneous tissues: rash, photosensitivity, alopecia, hyperhidrosis.

Muscular system disorders: Rhabdomyolysis, myaglia, muscle weakness.

Side of the urinary system: urinary incontinence, urinary retention.

From the reproductive system: priapism.

General disorders: disorders of temperature regulation (including hypothermia, pyrexia), chest pain, peripheral edema, increased creatine phosphokinase (CPK) activity, increased blood glucose levels, fluctuating blood glucose levels, increased glycohemoglobin levels.

Overdose

In clinical trials, cases of accidental or intentional overdose of aripiprazole with a single dose of up to 1260 mg have been described that were not fatal.

Symptoms:lethargy, increased blood pressure, drowsiness, tachycardia, loss of consciousness, nausea, vomiting, diarrhea. No clinically significant changes in basic physiological parameters, laboratory parameters and ECG were found in hospitalized patients.

There have been described cases of aripiprazole overdose in children (intake up to 195 mg) without fatal outcome. Potentially dangerous symptoms of overdose are somnolence, extrapyramidal disorders and transient loss of consciousness.

Treatment: monitoring of vital functions, ECG to detect possible arrhythmias, supportive therapy, ensuring airway patency, oxygenation, effective ventilation, activated charcoal, symptomatic treatment, close medical monitoring until all symptoms disappear. There are no data on hemodialysis for aripiprazole overdose; a favorable effect of this method is unlikely, since aripiprazole is not excreted unchanged by kidneys and is largely bound to plasma proteins.

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