How Effective Is Aripiprazole for Schizophrenia?

Aripiprazole tablets are indicated for the treatment of schizophrenia. The efficacy of aripiprazole in the treatment of schizophrenia has been established in short-term (4 and 6-week) controlled trials in patients with schizophrenia. Physicians who choose aripiprazole for long-term treatment should periodically re-evaluate the long-term efficacy of the drug in individual patients.

Drug Name: Aripiprazole tablets

Drug type: Prescription medicines, essential medicines, medicines for medical workers' injuries
Use classification: Other antipsychotics

Aripiprazole Tablets Caution

Deaths from Alzheimer's-related psychosis increase.
Compared with placebo, atypical antipsychotics for patients with dementia-related psychosis increase the risk of death. Seventeen placebo-controlled studies of the same drug found that the mortality rate in the drug-treated group was 1.6 to 1.7 times that of the placebo group. Compared to the 2.6% mortality rate in the placebo group, the drug treatment group had a mortality rate of about 4.5% in a typical 10-week placebo-controlled trial. Although the causes of death vary, most appear to be related to cardiovascular disease (such as heart failure or sudden death) or infection (such as pneumonia). Aripiprazole cannot be used to treat dementia-related psychosis.

Aripiprazole tablets ingredients

The main ingredient of this product is aripiprazole, the chemical name is: 7- {4- [4- (2,3-dichlorophenyl) -1-piperazinyl] butoxy} -3,4-dihydro -2 (1H) -quinolinone chemical structural formula:

Molecular formula: C ₂₃ H ₂₇ N ₃ O ₂ Cl ₂
Molecular weight: 448.38

Aripiprazole Tablet Properties

5mg tablets are blue tablets;
10mg tablets are pink tablets;
15mg tablets are yellow tablets.

Aripiprazole tablets specifications

5mg, 10mg, 15mg

Aripiprazole tablets dosage

Adults: Orally, once daily.
The recommended starting and therapeutic doses of commonly used aripiprazole are 10 or 15 mg / day and are not affected by eating. A systematic review showed that the clinically effective dose of aripiprazole ranges from 10 to 30 mg / day. The efficacy of high doses is not better than low doses of 10 mg or 15 mg / day. The dose should not be increased within 2 weeks (the time required for the drug to reach a steady state). After 2 weeks, it can be appropriately adjusted according to the individual's efficacy and tolerance, but the rate of addition should not be too fast.
Dosages for special populations generally do not need to be adjusted based on age, gender, ethnicity, or renal or hepatic impairment.
Dosage adjustment for concomitant CYP3A4 inhibitors: When taking ketoconazole at the same time, the dose of aripiprazole should be reduced to half of the usual amount. When stopping CYP3A4 inhibitors, the dose of aripiprazole should be increased.
Dose adjustments for concurrent CYP2D6 inhibitors: When taking CYP2D6 inhibitors (such as quinidine, fluoxetine, or paroxetine) at the same time, the dose of aripiprazole should be reduced to at least half its usual amount. When stopping CYP2D6 inhibitors, the dose of aripiprazole should be increased.
Dosing adjustments for concomitant CYP3A4 inducers: When taking CYP3A4 inducers (such as carbamazepine) at the same time, the dose of aripiprazole should be doubled (to 20 or 30 mg). Additional doses should be based on clinical evaluation. When carbamazepine is discontinued, the dose of aripiprazole should be reduced to 10-15 mg.
The change from taking other antipsychotics to this product has not yet been systematically evaluated in patients with schizophrenia who switch from other antipsychotics to aripiprazole or aripiprazole in combination with other antipsychotics. Although some patients may accept immediate discontinuation of previous medications, gradual discontinuation may be more appropriate. In any case, the overlap between antipsychotics should be minimized.

Aripiprazole tablets adverse reactions

The safety of aripiprazole was evaluated in a multi-dose, premarketing clinical trial of 7,951 patients with schizophrenia, bipolar disorder, manic episodes, and Alzheimer's dementia; the exposure was approximately 5,235 case-years . A total of 2,280 aripiprazole users had been treated for at least 180 days, and 1,558 aripiprazole patients had been treated for at least 1 year.
Conditions and duration of aripiprazole treatment include (overlapping categories) double-blind, controlled and non-controlled open trials, trials for inpatient and outpatients, fixed- and variable-dose trials, and short- and long-term drug trials.
Adverse events during dosing were obtained through spontaneous reporting and results of physical examination, vital signs, weight, laboratory analysis, and electrocardiogram (ECG).
The incidence of adverse events refers to the proportion of cases of adverse events in the category that have experienced at least one treatment. An event is considered to be caused by treatment if it occurs for the first time or worsens than the baseline assessment at the time of treatment. No consideration was given to selecting adverse events by investigating causality, ie all reported adverse events were included in the statistics.
1. Adverse results observed in short-term, placebo-controlled clinical trials in patients with schizophrenia. In 5 placebo-controlled clinical trials (4-6 weeks), the daily dose of aripiprazole was 2-30mg / kg.
Overall, the incidence of discontinuation of treatment due to adverse events did not differ between aripiprazole-treated patients (7%) and placebo-treated patients (9%). The types of adverse events that led to discontinuation of treatment were similar between aripiprazole-treated and placebo-treated patients.
2. Adverse results observed in short-term placebo-controlled clinical trials in patients with bipolar disorder manic episodes. In a placebo-controlled clinical trial of 3 weeks, the daily dose of aripiprazole was 15 or 30 mg / kg.
Overall, the incidence of discontinuation of treatment due to adverse events in patients with bipolar disorder mania did not differ between patients treated with aripiprazole (11%) and patients treated with placebo (9%). The types of adverse events that led to discontinuation were similar between aripiprazole-treated and placebo-treated patients.
3. Common adverse events in patients with bipolar disorder manic episodes in short-term placebo-controlled clinical trials. Aripiprazole used in patients with bipolar disorder manic episodes. Common adverse events (incidence rate 5%. (The incidence of the Lipiprazole group is at least twice that of the placebo group.) See Table 1. In short-term clinical trials of schizophrenia, there were no adverse events that met these criteria.

4. In short-term placebo-controlled clinical trials, the incidence of aripiprazole-treated patients was 2% and adverse events were higher than placebo. Table 2 lists acute treatment periods (maximum 6 weeks for schizophrenia, bipolar disorder) The maximum incidence of adverse events is 3 months. The combined incidence of adverse events should be rounded up to a whole number. It is only included in patients treated with aripiprazole (daily dose 2mg / day). Placebo adverse events.

Subpopulation studies have not found any clear evidence of differences in the incidence of adverse events based on age, gender, or ethnicity.
Dose-related adverse events: Schizophrenia was evaluated in 4 placebo-controlled clinical trials of schizophrenia patients at different fixed doses (2, 10, 15, 20, and 30 mg / day). Dose-response relationship of adverse event rates. Stratified analysis showed that the only adverse event that was likely to have a dose-response relationship and only at 30 mg was drowsiness (placebo: 7.7%; 15 mg: 8.7%; 20 mg: 7.5%; 30 mg: 15.3%).
Extrapyramidal Syndrome In short-term placebo-controlled trials of schizophrenia, the incidence of extrapyramidal syndrome (EPS) was reported by patients in both the aripiprazole and placebo groups at 6%. In a short-term placebo-controlled trial of bipolar disorder manic episodes, the incidence of EPS-related events (excluding events related to meditation inability) in aripiprazole-treated patients was 17% compared to 12% in placebo. In short-term placebo-controlled trials of bipolar disorder manic episodes, the incidence of seizure-inability-related events in aripiprazole-treated patients was 15% compared to 4% in placebo. The data were collected objectively based on the Simpson Angus evaluation quantitative scale (evaluation EPS), the Barnes meditation disability energy scale (evaluation of meditation inability), and the involuntary movement evaluation scale (evaluation of movement disorders). In the schizophrenia trial, with the exception of Barnes Sedation Failure Score (Aripiprazole: 0.08, Placebo: -0.05), the other scores did not show a difference between Aripiprazole and placebo. In the bipolar disorder manic episode test, the Simpson-Angus score and the Barnes sedation failure score showed a significant difference between aripiprazole and placebo (Aripiprazole: 0.61, placebo: 0.03; A Lipiprazole: 0.25, placebo: -0.06). Aripiprazole and placebo have similar changes in involuntary exercise scores.
Similarly, in a long-term (26-week) placebo-controlled trial of schizophrenia, the Simpson-Angus score (evaluating EPS), the Barnes sedation inability (evaluating meditation inability), and the involuntary movement score (evaluating dyskinesia) No difference was shown between aripiprazole and placebo.
A comparison of placebo-controlled trials with abnormal laboratory tests for 3 to 6 weeks showed that the aripiprazole group and placebo were in terms of the proportion of subjects with potentially clinically significant changes in blood biochemical, hematological, and urine test parameters. There were no significant differences between the groups. Similarly, there was no difference between aripiprazole and placebo in terms of discontinuation rates due to changes in blood biochemistry, hematology, and urine test parameters.
In a long-term (26-week) placebo-controlled trial, there were no clinical changes in prolactin, fasting blood glucose, triglycerides, HDL, LDL, and total cholesterol compared with baseline in aripiprazole-treated and placebo-treated patients. significance.
Weight gain In the 4- to 6-week trials with schizophrenia patients, the average weight gain between aripiprazole-treated and placebo-treated patients was slightly different (+ 0.7kg and -0.05kg, respectively), consistent with There was also a difference in the proportion of patients with a weight gain of 7% (8% in the aripiprazole group and 3% in the placebo group). In a 3-week trial of patients with bipolar disorder manic episodes, the average weight gain of aripiprazole-treated and placebo-treated patients was 0.0 kg and -0.2 kg, respectively. The proportion of patients with 7% weight gain in the aripiprazole and placebo groups was 3% and 2%, respectively.
Table 3 shows the results of body weight change by baseline body mass index (BMI) in a long-term (26-week) placebo-controlled trial of aripiprazole, including the average change in body weight based on baseline and the proportion of patients who gained 7% of baseline weight.

Table 4 shows the results of body weight changes by baseline BMI in long-term (52 weeks) clinical studies of aripiprazole, including the average change in body weight based on baseline and the proportion of patients who gained 7% of baseline body weight.

Comparison of placebo-controlled trials in patients with schizophrenia or bipolar disorder with manic episodes with mixed ECG changes showed that the proportion of patients with potentially significant changes in ECG parameters was not significant between the aripiprazole and placebo difference. The median increase in heart rate in the aripiprazole group was 5 beats / min, and the placebo group was 1 beat / min.
5. Other results observed in clinical trials. Adverse events reported in a 26-week double-blind clinical trial comparing aripiprazole and placebo in patients with schizophrenia compared with short-term placebo-controlled clinical trials. The reported adverse events were basically the same, except that the incidence of tremor was higher [Aripiprazole 9% (13/153)], and placebo 1% (2/153)]. In this study, most cases of tremor were mild (9/13 mild, 4/13 moderate), occurred early in the treatment (9/13 49 days), and had a limited duration (9/13 10 days). Tremors rarely cause aripiprazole discontinuation (<1%). In addition, in a long-term (52-week) active drug controlled study, the incidence of tremor in the aripiprazole group was 4% (34/859). A similar situation can be observed in long-term bipolar disorder studies.
6. Other adverse events observed during the pre-marketing evaluation of aripiprazole. Adverse events that occurred during treatment are listed below using revised COSTART terminology. These adverse events, previously mentioned, from a database of 7,951 patients, were reported by patients during their participation in aripiprazole 2 mg / day multidose clinical trials. Include all reported adverse events (exclude the following cases: those listed in Table 2 or other paragraphs, which have been considered in [Precautions], the event terms are too general to provide little information, the incidence rate is 0.05% And there are no emergency life-threatening possible, other as common as background events, and drug-related adverse events deemed impossible). It is important to emphasize that although the reported incidents occurred during treatment with aripiprazole, these events were not necessarily caused by aripiprazole.
Adverse events are categorized by the body system and listed in descending order of frequency as defined below: Common adverse events are those that occur in at least 1 in 100 patients (listed here are not included in placebo-controlled trials only) Events in the results table); Rare adverse events refer to adverse events occurring in 1/100 to 1 / 1,000 patients; Rare adverse events refer to adverse events occurring in less than 1 / 1,000 patients.
Whole body: commonflu syndrome, fever, chest pain, stiffness (including neck and limbs), neck pain, pelvic pain; rarefacial edema, suicidal tendency, discomfort, migraine, chills, light allergy, tightness (including abdomen , Back, extremities, head, jaw, neck and tongue), jaw pain, flatulence, bloating, chest urgency, sore throat; rare-candidiasis, weight loss, tight throat, Mendelson syndrome And heat stroke.
Cardiovascular system: commontachycardia (including ventricular and supraventricular), hypotension, bradycardia; rarepalpitations, bleeding, heart failure, myocardial infarction, cardiac arrest, atrial fibrillation, atrioventricular block, Prolonged QT interval, extraperitoneal contraction, myocardial ischemia, deep venous thrombosis, angina, pale, cardiopulmonary dysfunction, phlebitis; rare-bundle branch block, atrial flutter, vasovagal response, cardiac hypertrophy, thrombotic vein Inflammation, heart and lung failure.
Digestive system: common-nausea and vomiting; rare-increased appetite, difficulty swallowing, gastroenteritis, flatulence, caries, gastritis, gingivitis, gastrointestinal bleeding, hemorrhoids, gastroesophageal reflux, periodontal abscess, fecal incontinence, Rectal bleeding, gastritis, colitis, tongue edema, cholecystitis, oral ulcers, oral candidiasis, belching, fecal impaction, gallstones; rare-esophagitis, vomiting, intestinal obstruction, bleeding gums, hepatitis, peptic ulcer , Glossitis, black stool, duodenal ulcer, cheilitis, hepatomegaly, pancreatitis.
Endocrine system: rare-hypothyroidism; rare-goiter, hyperthyroidism.
Blood / lymphatic system: common-bruises, anemia; rare-hypochromic anemia, leukocytosis, leukocytopenia (including neutropenia), lymphadenopathy, eosinophilia, macrocytic anemia; rare- Thrombocytosis, thrombocytopenia, petechiae.
Metabolic and nutritional disorders: commonweight loss, elevated creatine phosphokinase, dehydration; rareedema, hyperglycemia, hypercholesterolemia, hypokalemia, diabetes, hypoglycemia, hyperlipidemia, serum alanine aminotransferase Elevated, thirst, increased blood urea nitrogen, hyponatremia, increased serum aspartate aminotransferase, increased creatinine, cyanosis, increased alkaline phosphatase, bilirubinemia, iron deficiency anemia, hyperkalemia, high Uric acidemia, obesity; rare-increased lactate dehydrogenase, hypernatremia, gout, hypoglycemic response.
Musculoskeletal system: commonmuscle painful spasms; rarejoint pain, muscle weakness, arthropathy, bone pain, arthritis, muscle weakness, cramps, bursitis, myopathy; rarerheumatoid arthritis, rhabdomyolysis, Tendonitis, tenosynovitis.
Nervous system: commondepression, nervousness, schizophrenic reaction, hallucinations, hostility, confusion, paranoid reaction, suicidal thoughts, abnormal gait, manic reaction, illusion, strange dreams; rareemotional instability, twitching , Gear-like rigidity, concentration loss, dystonia, vasodilation, paresthesia, impotence, limb tremor, dull feeling, dizziness, stiffness, slowness of movement, emotional apathy, panic attack, hyposexuality, excessive sleep, dyskinesia, manic Crazy depression, ataxia, hallucinations, cerebrovascular accidents, impaired motor function, disintegration of personality, memory loss, delirium, difficulty articulation, tardive dyskinesia, forgetfulness, hyperactivity, increased libido, myoclonus, Hyperactive legs, neuropathy, irritability, excessive exercise, cerebral ischemia, increased reflexes, inability to move, decreased consciousness, hypersensitivity, slow thinking; rare-insensitive, euphoric, dyskinesia, oculomotor crisis, obsessive-compulsive Thinking, hypotonia, buccal tongue syndrome, diminished reflexes, disintegration of reality, intracranial hemorrhage.
Respiratory system: commonsinusitis, dyspnea, pneumonia, asthma; rarenasal bleeding, hiccup, laryngitis, aspiration pneumonia; rarepulmonary edema, sputum, pulmonary embolism, hypoxia, respiratory failure, apnea, nasal cavity Dry and hemoptysis.
Skin and accessories: common-skin ulcers, sweating, dry skin; rare-itching, vesicular herpes, acne, eczema, skin discoloration, hair loss, seborrheic dermatitis, psoriasis; rare-maculopapular, exfoliative dermatitis, rubella.
Special sensory systems: common-conjunctivitis; rare-ear pain, dry eyes, eye pain, tinnitus, cataract, otitis media, taste change, blepharitis, eye bleeding, deafness; rare-diplopia, frequent blinking, ptosis , External otitis, amblyopia, photophobia.
Genitourinary system: common-interrupted urine flow; rare-frequent urination, leucorrhea, urinary retention, cystitis, hematuria, dysuria, amenorrhea, vaginal bleeding, abnormal ejaculation, kidney failure, vaginal candidiasis, urgency, male breast development, Kidney stones, proteinuria, breast pain, urethral burning; rare-nocturia, polyuria, menstruation, loss of sexual pleasure, diabetes, cervicitis, uterine bleeding, female lactation, urolithiasis, abnormal penile erection.
7. Other adverse events observed during the post-marketing evaluation of aripiprazole. Spontaneous reported adverse events, including rare allergies, reported by patients who have been taking aripiprazole since the aripiprazole market. (Such as allergic reactions, angioedema, laryngeal spasm, pruritus, or urticaria), elevated gamma-glutamyltransferase, and abnormal temperature regulation (such as fever, hypothermia) may not be causally related to the drug.

Aripiprazole tablets contraindications

Disabled in patients known to be allergic to this product.

Aripiprazole tablets precautions

General precautions 1. Orthostatic hypotension Aripiprazole has an antagonistic effect on a1-adrenergic receptors and may cause orthostatic hypotension. In five short-term placebo-controlled trials of aripiprazole for schizophrenia (n = 926), the incidence of orthostatic hypotension-related events included orthostatic hypotension (1% of placebo, aripiprazole 1.9%), orthostatic dizziness (1% placebo, 0.9% aripiprazole), and syncope (1% placebo, 0.6% aripiprazole). In a short-term placebo-controlled trial of aripiprazole for bipolar disorder manic episodes (n = 597), the incidence of orthostatic hypotension-related events included: orthostatic hypotension (0% placebo, aripipr 0.7%), orthostatic dizziness (0.5% placebo, aripiprazole 0.5%), and syncope (0.9% placebo, 0.5% aripiprazole).
The incidence of significant changes in orthostatic blood pressure (defined as a reduction in systolic blood pressure from supine to upright of at least 30 mmHg), with no statistical difference between aripiprazole and placebo (schizophrenia: 14% of patients treated with aripiprazole , 12% of patients treated with placebo; manic episodes of bipolar disorder: 3% of patients treated with aripiprazole and 2% of patients treated with placebo).
Aripiprazole should be used with caution in patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), patients with cerebrovascular disease, or conditions that induce hypotension (dehydration, hypovolemia, and hypotension) Medication).
2. Seizures In short-term placebo-controlled clinical trials, 0.1% (1/926) of aripiprazole-treated patients experienced seizures. In short-term placebo-controlled clinical trials in patients with bipolar disorder manic episodes, 0.3% (2/597) of aripiprazole-treated patients and 0.2% of placebo-treated patients experienced seizures. As with other antipsychotics, aripiprazole should be used with caution in patients with a history of epilepsy or in patients with low epilepsy thresholds (such as Alzheimer's dementia). Lower epileptic thresholds are more common in people over 65 years of age.
3. Potential Cognitive and Exercise Impairment In short-term placebo-controlled trials of schizophrenia, 11% of aripiprazole-treated patients report drowsiness compared to 8% of placebo-treated patients; in short-term placebo-controlled clinical trials Of these, 0.1% (1/926) of aripiprazole-treated schizophrenia patients discontinued due to drowsiness. In a short-term placebo-controlled trial of bipolar disorder manic episodes, 14% of aripiprazole-treated patients had drowsiness compared to 7% of placebo-treated patients; but drowsiness did not discontinue patients with bipolar disorder. . Although the incidence of drowsiness is higher in patients treated with aripiprazole compared to placebo, like other antipsychotics, aripiprazole may affect judgment, thinking, or motor skills. Patients should be warned to operate certain dangerous machines, including automobiles, until they are confident that aripiprazole treatment will not adversely affect them.
4. Body temperature regulation interferes with the body's temperature reduction mechanism is a feature of antipsychotics. When aripiprazole is prescribed to patients who may have elevated body temperature (such as strenuous exercise, overheating, taking anticholinergic drugs or dehydration), appropriate care is recommended.
5. Swallowing disorders Esophageal motor dysfunction and aspiration are related to the use of antipsychotics. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, especially elderly patients with progressive Alzheimer's dementia. In patients at risk for aspiration pneumonia, aripiprazole and other antipsychotics should be used with caution.
6. Suicidal suicidal tendencies are inherent in mental illness and bipolar disorder, and high-risk patients should be closely monitored during medication. To reduce the risk of drug overdose, aripiprazole doses should be kept to a minimum and patients should be well managed.
7. Medication for patients with other diseases For patients with certain systemic diseases, there is no clinical experience in the use of aripiprazole.
Aripiprazole was not evaluated or used in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were excluded from premarketing clinical studies.
Safety Experience for Elderly Psychiatric Patients with Alzheimer's Disease: Treatment of 3 10-week-old aripiprazole patients with Alzheimer's disease with elderly Alzheimer's disease (n = 938, mean age: 82.4 years) (Age range: 56 to 99 years old). In placebo-controlled trials, adverse events including 3% in treatment and at least twice as frequent in the aripiprazole group as in the placebo group included weakness (placebo 3%, aripiprazole 8%), drowsiness (3% placebo, 9% aripiprazole) and urinary incontinence (1% placebo, 5% aripiprazole 5%), salivary (0% placebo, Aripiprazole 4%), dizziness (1% placebo, 4% aripiprazole).
The safety and effectiveness of aripiprazole in the treatment of patients with dementia-related psychosis have not been established. Physicians should be especially cautious if they choose to treat these patients with aripiprazole, especially those with difficulty swallowing or excessive drowsiness, which may induce accidental injury or aspiration.
8. Antipsychotic Malignant Syndrome (NMS)
A potentially fatal syndrome has been reported to be related to the use of antipsychotics, including aripiprazole, and is known as the antipsychotic malignant syndrome (NMS). Two cases of suspected NMS appeared in the global clinical database of aripiprazole before marketing. The clinical manifestations of NMS are high fever, myotonia, altered mental state, and signs of autonomic instability (irregular pulse or blood pressure fluctuations, tachycardia, sweating, and arrhythmia). Other signs may include elevated creatine phosphokinase, myoglobinuria (striated rhinolysis), and acute renal failure.
Diagnostic evaluation of patients with this syndrome is complex. In order to obtain this diagnosis, it is important to exclude clinical manifestations that are accompanied by severe medical diseases (such as pneumonia, systemic infections, etc.) and untreated or inappropriately treated extrapyramidal signs and symptoms (EPS). Another important consideration in differential diagnosis includes central anticholinergic toxicity, heat stroke, drug-induced fever, and primary central nervous system disease.
The management of NMS should include: 1) immediately stop antipsychotics and other currently unnecessary treatment drugs; 2) strengthen symptomatic treatment and medical monitoring; 3) treatment of serious medical problems accompanied by specific treatment methods. For uncomplicated NMS, there is currently no generally accepted specific drug treatment option.
If the patient still needs antipsychotic therapy after recovering from NMS, the possibility of drug therapy causing NMS again should be carefully considered. Patients should be closely monitored as there have been reports of recurrence of NMS.
9. Tardive dyskinesia In patients treated with antipsychotics, irreversible unconscious dyskinesia syndrome may occur. Although the syndrome has the highest incidence among older people, especially older women, it is not possible to predict which patients may develop the syndrome based on epidemiological estimates alone at the beginning of antipsychotic treatment. It is unclear whether antipsychotics differ in their effects on tardive dyskinesia.
It has been determined that with the extension of the course of treatment and the increase in the patient's total cumulative dose of antipsychotics, the risk of tardive dyskinesia and its likelihood of becoming irreversible also increase. However, the syndrome may also occur after short-term treatment with low-dose antipsychotics, but it is generally rare.
Although the syndrome resolves partially or completely after discontinuation of antipsychotic treatment, no known treatment is currently available for cases diagnosed with tardive dyskinesia. However, antipsychotic treatment itself may inhibit (or partially inhibit) the signs and symptoms of this syndrome, which may obscure the progression of the disease. It is unclear whether symptom suppression has an effect on the long-term course of the syndrome.
Based on the above considerations, aripiprazole should be used in a way to minimize the occurrence of tardive dyskinesia. For patients with chronic diseases, long-term antipsychotic treatment should be reserved. These patients include: (1) known to be effective with antipsychotics, and (2) alternative equivalents, but with less potential harm Treatment is not available or appropriate. In patients who need long-term treatment, the lowest therapeutic dose and the shortest treatment time to achieve satisfactory results should be sought. The need for continuous treatment should be re-evaluated regularly.
If aripiprazole-treated patients show signs and symptoms of tardive dyskinesia, discontinuation should be considered. However, some patients may require aripiprazole despite this syndrome.
10. Cerebrovascular adverse events in patients with dementia-related dementia, including stroke In a placebo-controlled clinical trial of dementia-related psychosis, aripiprazole was used to treat elderly patients (mean age: 84 years; age range: 78-88 years) ) Cerebrovascular adverse events (such as stroke, transient ischemic attack), including increased incidence of death. The fixed-dose test results showed that there was a statistically significant dose-response relationship between cerebrovascular adverse events and drugs in patients treated with aripiprazole. Aripiprazole cannot be used to treat patients with dementia-related psychosis.
11. Hyperglycemia and Diabetes There are reports of patients with atypical antipsychotics who have severe hyperglycemia with ketoacidosis or hypertonic coma or death. There is almost no report of hyperglycemia in aripiprazole-treated patients, and although few patients have been treated with aripiprazole, it is unclear whether these very limited experiences are the only reason for this rare report. Assessing the relationship between the use of atypical antipsychotics and blood glucose abnormalities is complex because of the increased risk of diabetic background in patients with schizophrenia and the increased incidence of diabetes in the general population. Under the influence of these confounding factors, the relationship between the use of atypical antipsychotics and adverse events related to hyperglycemia is completely unclear. However, epidemiological studies that do not include aripiprazole suggest that patients treated with atypical antipsychotics in these studies have an increased risk of developing hyperglycemia-related adverse events during treatment. Because aripiprazole was not available at the time of these studies, it is unclear whether aripiprazole is associated with this increased risk. In patients treated with atypical antipsychotics, no clear risk assessment for hyperglycemia-related adverse events is available.
Patients with a clear diagnosis of diabetes at the start of atypical antipsychotics should be monitored regularly for worsening glycemic control. Patients with risk factors for diabetes (such as obesity, family history of diabetes) should receive a fasting blood glucose test regularly before and during treatment with atypical antipsychotics. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia, including thirst, polyuria, polyphagia and fatigue. Patients who develop symptoms of hyperglycemia during atypical antipsychotic treatment should receive a fasting blood glucose test. In some cases, when the atypical antipsychotic treatment is stopped, the hyperglycemia disappears on its own; however, some patients need to continue their hypoglycemic treatment despite discontinuation of the suspicious drug.

Aripiprazole tablets for pregnant and lactating women

Appropriate and well-controlled studies have not been conducted in pregnant women. It is unclear whether aripiprazole can cause fetal damage or affect fertility in pregnant women. For pregnant women, use only if the potential benefits to the fetus outweigh the potential risks.
The effects of aripiprazole on human labor and labor are unclear.
Aripiprazole is secreted into the milk of lactating rats. It is unclear whether aripiprazole and its metabolites are secreted into human milk. Women who take aripiprazole are advised to stop breastfeeding.

Aripiprazole tablets for children

The safety and effectiveness of medications for children and adolescents have not been established.

Aripiprazole tablets for elderly

Of the 7,951 patients who received aripiprazole in premarketing clinical trials, 991 (12%) were 65 years of age and 789 (10%) were 75 years of age. Most (88%) of the 991 patients were diagnosed with Alzheimer's dementia.
A placebo-controlled trial of aripiprazole in the treatment of schizophrenia and bipolar disorder mania did not include enough patients aged 65 years or older to determine whether elderly patients would respond differently to treatment than young patients. Tester. Age had no effect on the pharmacokinetics of a single dose of 15 mg of aripiprazole. Aripiprazole clearance was reduced by 20% in older subjects (65 years) compared to young adult (18-64 years) subjects, but did not show in population pharmacokinetic analysis of schizophrenia The effect of age.
Studies of elderly patients with Alzheimer's-related psychosis suggest that this population may be more tolerated than younger patients with schizophrenia. The safety and effectiveness of aripiprazole in patients with Alzheimer's disease-related psychosis have not been established. Doctors should be careful if they choose to use aripiprazole to treat such patients.

Aripiprazole tablets drug interactions

Since this product mainly acts on the central nervous system, caution should be exercised when combined with other drugs and ethanol acting on the central nervous system. Because it antagonizes the a1-adrenergic receptor, aripiprazole may enhance the effect of some antihypertensive drugs.
Possibility of Other Drugs to Aripiprazole Aripiprazole is not a substrate for the CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2E1 enzymes. Neither is direct glucuronidation. This indicates that aripiprazole cannot interact with inhibitors or inducers of these enzymes, or other factors such as smoking.
CYP3A4 and CYP2D6 are involved in the metabolism of aripiprazole. CYP3A4 inducers (such as carbamazepine) can cause increased aripiprazole clearance and decreased plasma concentrations. CYP3A4 inhibitors (such as ketoconazole) or CYP2D6 inhibitors (such as quinidine, fluoxetine, paroxetine) can inhibit aripiprazole elimination and increase plasma concentrations.
Ketoconazole: When taking ketoconazole (200mg / day for 14 consecutive days) and 15mg a single dose of aripiprazole, the AUC of aripiprazole and its active metabolites increased by 63% and 77%, respectively. Higher doses (400 mg / day) of ketoconazole have not been studied. When taking ketoconazole and aripiprazole at the same time, the dose of aripiprazole should be reduced to half of the usual dose. Other strong inhibitors of CYP3A4 (Itraconazole, etc.) are expected to have similar effects, and the doses need to be reduced accordingly; no studies have been conducted on weak inhibitors of CYP3A4 (erythromycin, grapefruit juice, etc.). When stopping CYP3A4 inhibitors in combination therapy, the dose of aripiprazole should be increased.
Quinidine: Taking a single dose of 10mg aripiprazole and a potent CYP2D6 inhibitor, quinidine (166mg / day for 13 consecutive days), the AUC of aripiprazole increased by 112%, while its active metabolite, dehydrogenation Aripiprazole reduced the AUC by 35%. When taking quinidine and aripiprazole at the same time, the dose of aripiprazole should be reduced to half of the usual dose. Similar effects are expected from other strong CYP2D6 inhibitors (such as foroxetine or paroxetine), so doses need to be reduced accordingly. When stopping CYP2D6 inhibitors in combination therapy, the dose of aripiprazole should be increased.
Carbamazepine: Taking carbamazepine (200 mg, twice daily, a strong CYP3A4 inducer) and aripiprazole (30 mg, once daily) at the same time, leading to aripiprazole and its active metabolite, Both Cmax and AUC of hydroripiprazole were reduced by about 70%, respectively. When carbamazepine is used concurrently with aripiprazole, the dose of aripiprazole should be doubled. Additional doses should be based on clinical evaluation. When carbamazepine in combination therapy is discontinued, the aripiprazole dose should be reduced.
Possibility of aripiprazole affecting other drugs Important pharmacokinetic interactions between aripiprazole and drugs metabolized by cytochrome P450 enzymes are unlikely to occur. In vivo studies, aripiprazole at a daily dose of 10 to 30 mg against CYP2D6 substrate (dextromethorphan), CYP2C9 substrate (warfarin), CYP2C19 substrate (omeprazole, warfarin) and CYP3A4 The metabolism of the substrate (dextromethorphan) was not significantly affected. In addition, in vitro studies have shown that aripiprazole and dehydro aripiprazole do not affect the metabolism involved in CYP1A2.
Ethanol: Aripiprazole was taken in combination with ethanol in healthy volunteers, and the placebo and ethanol were taken in the control group. There was no significant difference between the two groups in general motor skills or stimulus response. As with most psychostimulants, patients should be advised to avoid alcohol while taking aripiprazole.
There is no clinically important interaction between aripiprazole and famotidine: aripiprazole (single dose of 15 mg) and a single dose of H2 receptor antagonist famotidine 40 mg (strongly acid-suppressing agent) ) Can reduce the solubility of aripiprazole, and therefore reduce the absorption of aripiprazole. The Cmax of aripiprazole and dehydro aripiprazole is reduced by 37% and 21%, and the absorption (AUC) is reduced by 13%, respectively. And 15%. When combined with famotidine, there is no need to adjust the dose of aripiprazole.
Valproate: When taking valproate (500-1500mg / day) and aripiprazole (30mg / day) at the same time, the Cmax and AUC of aripiprazole are reduced by 25% at steady state. When combined with valproate, there is no need to adjust the dose of aripiprazole.
Lithium salt: Because lithium does not bind to plasma proteins and is not metabolized, it is almost completely excreted into the urine in the form of the original drug, so pharmacokinetic interactions between aripiprazole and lithium salts are unlikely to occur. Taking a therapeutic amount of lithium salt (1200 1800mg / day) and aripiprazole (30mg / day) simultaneously for 21 consecutive days without causing pharmacoporation of aripiprazole or its active metabolite, dehydro aripiprazole Clinically significant changes in kinetics occur (Cmax and AUC increase less than 20%). When combined with lithium salts, there is no need to adjust the dose of aripiprazole.
Dextromethorphan: Take aripiprazole for 14 consecutive days, 10-30 mg / day, does not affect dextromethorphan O-dealkylation to produce its main metabolite, dexorphantane. This metabolic pathway is known to depend on CYP2D6 activity. Aripiprazole also has no effect on dextromethorphan through the N-demethylation metabolite 3-methoxymorphinane. This metabolic pathway is known to depend on CYP3A4 activity. No dose adjustment of dextromethorphan is required when combined with aripiprazole.
Warfarin: Taking aripiprazole at 10 mg / day for 14 consecutive days has no effect on the pharmacokinetics or internationally standardized ratios of pharmacodynamic endpoints of R and S warfarin, indicating that aripiprazole affects CYP2C9 and CYP2C19 metabolism and the binding of high protein-binding warfarin have little effect. When combined with aripiprazole, there is no need to adjust the dose of warfarin.
Omeprazole: Taking aripiprazole for 15 consecutive days, 15 mg / day, has no effect on the pharmacokinetics of healthy volunteers taking a single dose of 20 mg of omeprazole (CYP2C19 substrate). When combined with aripiprazole, there is no need to adjust the dose of omeprazole.

Aripiprazole tablets overdose

Adverse event classification using MedDRA terminology.
Clinical experience Currently, 76 cases of intentional or accidental aripiprazole overdose have been reported worldwide, including overdose of aripiprazole alone and in combination with other drugs, with no deaths. Of the 44 cases with known results, 33 recovered with no sequelae, and 1 recovered with sequelae (dilated pupils and paresthesia). The maximum acute intake of aripiprazole is known to be 1,080 mg (36 times the maximum recommended daily dose), and the patient has fully recovered. The 76 cases included 10 children (age 12 or younger) who had an intentional or accidental aripiprazole overdose, with a maximum aripiprazole intake of 195 mg and no deaths.
Regarding aripiprazole overdose (alone or in combination), common (at least 5% of all overdose) adverse events reported include vomiting, lethargy, and tremor. Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdose (single or combined) include acidosis, aggressive behavior, elevated aspartate aminotransferase, atrial fibrillation, heartbeat Bradycardia, coma, confusion, convulsions, elevated blood creatine phosphokinase, hypoconsciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, extended QRS complex duration, QT interval Prolonged period, aspiration pneumonia, status epilepticus, and tachycardia.
There is currently no specific way to overdose aripiprazole overdose. In case of overdose, the ECG should be checked; if the QTc interval is prolonged, close cardiac monitoring should be performed. At the same time, supportive therapy should be used to keep the airway open, oxygen and ventilation, and symptomatic treatment. Close monitoring should be continued until the patient recovers.
Activated carbon: If an aripiprazole overdose occurs, the early use of activated carbon may help prevent aripiprazole absorption to some extent. One hour after a single oral dose of 15 mg of aripiprazole, taking 50 g of activated carbon can reduce the average AUC and Cmax of aripiprazole by 50%.
Hemodialysis: Although there is no information on aripiprazole overdose for hemodialysis, hemodialysis may not have a significant effect on overdose due to its high plasma protein binding rate.

Aripiprazole clinical trials

1. According to foreign literature reports:
In four short-term (4 to 6 weeks) placebo-controlled clinical trials, inpatients with acute relapsed schizophrenia who mainly met the DSM-III / IV criteria were evaluated as treatment subjects. Effectiveness. Three of the active control trials showed significant differences between aripiprazole and placebo. The active control drugs were risperidone and haloperidol. The comparison of aripiprazole with the active control drug was not considered in the study design.
In three aripiprazole-positive control trials, four major measures were used to evaluate signs and symptoms of psychosis. The Positive and Negative Symptoms Scale (PANSS) is a multi-item evaluation scale used in general psychopathology to evaluate the efficacy of drugs for schizophrenia. The PANSS Positive Symptom Scale is a subset of the 7 positive symptoms scale for schizophrenia (delusions, conceptual disturbances, hallucinations, excitement, exaggeration, suspicion / victimization, and hostility). The PANSS Negative Symptom Scale assesses Subsets of 7 symptoms of schizophrenia negative symptoms (bluntness, emotional withdrawal, emotional communication impairment, passive emotional avoidance of social interaction, difficulty in abstract thinking, lack of spontaneity and fluency in conversation, and stereotypes). The Clinical Comprehensive Impressions (CGI) assessment reflects the overall clinical status of a patient with a skilled observer who is very familiar with the performance of schizophrenia.
The effectiveness of aripiprazole at daily doses of 15 mg, 20 mg, and 30 mg was established in two studies, and the effectiveness of aripiprazole at a dose of 10 mg was established in one study. There is no evidence in any study that the high-dose group is superior to the lowest-dose group.
Population subgroup analysis did not show any differences in age, gender, or ethnicity.
In a long-term trial of 310 inpatients or outpatients who met the DSM-IV criteria for schizophrenia, patients treated with other antipsychotic medications had stable symptoms for 3 months or more, discontinuing the antipsychotic medications being used by these patients They were randomized to receive aripiprazole 15mg or placebo, and the recurrence was observed for up to 26 weeks. Relapse during double-blind treatment was defined as a CGI improvement score of 5 (minimal aggravation), a PANSS hostility or uncooperative score of 5 (moderate severity), or a PANSS total score increase of 20%. Compared with placebo, aripiprazole 15mg significantly prolonged the relapse time within 26 weeks.
2. According to domestic research data reports:
In a 6-week, double-blind, double-simulation, randomized, parallel, multicenter clinical trial of three doses of aripiprazole (10 mg, 15 mg, or 30 mg / day) compared with risperidone (2-6 mg / day) (N = 120), aripiprazole is effective in treating schizophrenia and acute schizophrenia. In the analysis of the efficacy of the ITT population, the total efficacy index of PANSS after 6 weeks of treatment was compared with the baseline, and the aripiprazole group and the risperidone group were significantly improved (both P [0.0001) in both groups. There was no statistical difference between the two groups in the effectiveness judged by the PANSS reduction rate 50% (P = 0.114).

Aripiprazole tablets pharmacology and toxicology

Pharmacological effects Aripiprazole has high affinity for D ₂ , D ₃ , 5-HT _1A , 5-HT _2A receptors, and D ₄ , 5-HT _2C , 5-HT ₇ , ₁ , H ₁ receptors, and The 5-HT reabsorption site has a moderate affinity. Aripiprazole is a partial agonist of the D ₂ receptor and the 5-HT _1A receptor and an antagonist of the 5-HT _2A receptor.
As with other anti-schizophrenia drugs, the mechanism of action of aripiprazole is unclear. However, it is currently thought to be caused by the partial agonism of D ₂ and 5-HT _1A receptors and the antagonism of 5-HT _2A receptors. Interaction with other receptors may produce some other clinical effects of aripiprazole, such as antagonism of ₁ receptors, which may explain its orthostatic hypotension.
Toxicology studies Repeated administration of toxicity in long-term toxicity studies in white rats at a dose of 60 mg / kg for 26 weeks and 2-year doses of 40 and 60 mg / kg [in mg / m ² are equivalent to the maximum human recommended dose (MRHD) (13 times and 19 times, in terms of AUC, equivalent to 7 to 14 times the exposure of humans at MRHD). In carcinogenicity studies, animals showed retinal degeneration. No retinal degeneration was observed in the evaluation of the white mouse and monkey retinas. No further studies have been conducted on the mechanism of action. The relevance of this result to human risk is unclear.
In the presence or absence of metabolic activation, aripiprazole and its metabolites (2,3-DCPP) exhibit gene fission in CHL cells in vitro chromosome aberration test, and 2,3-DCPP causes aberrations without metabolic activation The number increases. The in vivo mouse micronucleus test results were positive, but the results were thought to be produced by mechanisms unrelated to humans. Aripiprazole was negative in in vitro bacterial back mutation test, bacterial DNA repair test, mouse lymphocyte forward gene mutation test, and out-of-program DNA synthesis test.
272620mg/kg/ mg/m ²MRHD0.626620mg/kg20mg/kg9204060mg/kg/mg/m ²MRHD6131960mg/kg4060mg/kg
31030mg/kg/[mg/m ²MRHD1310]30mg/kg30mg/kg30mg/kg1030mg/kg-1030mg/kg30mg/kg30mg/kg1030mg/kg30mg/kg30mg/kg1030100mg/kg/AUCMRHD2311mg/m ²61965100mg/kg100mg/kg30100mg/kg30100mg/kg100mg/kg
172131030mg/kg/mg/m[sup]2[/sup]MRHD131030mg/kg
ICRSDF344ICR131030mg/kg/F3441310mg/kg/SD10204060mg2330mg/kgAUCMRHD0.10.9mg/m ²MRHD0.5510mg/kg/AUCMRHD0.1mg/m ²MRHD360mg/kg/AUCMRHD14mg/m ²MRHD19/
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D240%759414P450CYP2D6CYP3A4
3587%15mgCmaxAUCTmax312
404 L4.9 L/kg99%140.530mg/D2
N-CYP3A4CYP2D6CYP3A4N-AUC40%
8%CYP2D6PMEMEMPM80%30%PMEM60%EMCYP2D6112%EMPM75146CYP2D6
[ ¹⁴ C]25%55%1%18%

Child-PughABC15mgHIAUC31%HI8%HI20%
<30mL/min15mgCmax36%53%AUC15%AUC7%1%
15mg65186420%
CmaxAUC30%40%25%

CYP1A2

10mg30mgAUC0-tCmax2563~751456

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101141

36 months

YBH25342006 ^[1]