Aripiprazole may cause orthostatic hypotension, perhaps due to its α -adrenergic receptor antagonism. The incidence of orthostatic hypotension-associated events from short-term, placebo-controlled trials of adult patients on oral aripiprazole (n=2467) included (aripiprazole incidence, placebo incidence) orthostatic hypotension (1%, 0.3%), postural dizziness (0.5%, 0.3%), and syncope (0.5%, 0.4%); of pediatric patients 6 to 18 years of age (n=732) on oral aripiprazole included orthostatic hypotension (0.5%, 0%), postural dizziness (0.4%, 0%), and syncope (0.2%, 0%) . The incidence of a significant orthostatic change in blood pressure (defined as a decrease in systolic blood pressure ≥20 mmHg accompanied by an increase in heart rate ≥25 when comparing standing to supine values) for aripiprazole was not meaningfully different from placebo (aripiprazole incidence, placebo incidence): in adult oral aripiprazole-treated patients (4%, 2%), in pediatric oral aripiprazole-treated patients aged 6 to 18 years (0.4%, 1%). 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), cerebrovascular disease, or conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications) .
1 [see ADVERSE REACTIONS (6.1)]
[see DRUG INTERACTIONS (7.1)]
In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including aripiprazole. Agranulocytosis has also been reported.
Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC)/absolute neutrophil count (ANC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC/ANC or drug-induced leukopenia/neutropenia, perform a complete blood count (CBC) monitored frequently during the first few months of therapy. In such patients, consider discontinuation of aripiprazole at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue aripiprazole in patients with severe neutropenia (absolute neutrophil count <1000/mm3) and follow their WBC counts until recovery.
In short-term, placebo-controlled trials, seizures/convulsions occurred in 0.1% (3/2467) of adult patients treated with oral aripiprazole, in 0.1% (1/732) of pediatric patients (6 to 18 years). As with other antipsychotic drugs, aripiprazole should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.
Aripiprazole, like other antipsychotics, may have the potential to impair judgment, thinking, or motor skills. For example, in short-term, placebo-controlled trials, somnolence (including sedation) was reported as follows (aripiprazole incidence, placebo incidence): in adult patients (n=2467) treated with oral aripiprazole (11%, 6%), in pediatric patients ages 6 to 17 (n=611) (24%, 6%). Somnolence (including sedation) led to discontinuation in 0.3% (8/2467) of adult patients and 3% (20/732) of pediatric patients (6 to 18 years) on oral aripiprazole in short-term, placebo-controlled trials. Despite the relatively modest increased incidence of these events compared to placebo, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that therapy with aripiprazole does not affect them adversely.
Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing aripiprazole for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, (e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration) [see ADVERSE REACTIONS (6.2)].
The possibility of a suicide attempt is inherent in psychotic illnesses and close supervision of high-risk patients should accompany drug therapy. Prescriptions for aripiprazole should be written for the smallest quantity consistent with good patient management in order to reduce the risk of overdose [see ADVERSE REACTIONS (6.1, 6.2)].
Esophageal dysmotility and aspiration have been associated with antipsychotic drug use, including aripiprazole. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer’s dementia. Aripiprazole and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia . [see WARNINGS AND PRECAUTIONS (5.1) and ADVERSE REACTIONS (6.2)]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following adverse reactions are discussed in more detail in other sections of the labeling: •Increased Mortality in Elderly Patients with Dementia-Related Psychosis •Cerebrovascular Adverse Events, Including Stroke •Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults •Neuroleptic Malignant Syndrome (NMS) •Tardive Dyskinesia •Metabolic Changes •Orthostatic Hypotension •Leukopenia, Neutropenia, and Agranulocytosis •Seizures/Convulsions •Potential for Cognitive and Motor Impairment •Body Temperature Regulation •Suicide •Dysphagia The most common adverse reactions in adult patients in clinical trials (≥10%) were nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia, and restlessness.
[see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)]
[see WARNINGS AND PRECAUTIONS (5.2)]
[see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.3)]
[see WARNINGS AND PRECAUTIONS (5.4)]
[see WARNINGS AND PRECAUTIONS (5.5)]
[see WARNINGS AND PRECAUTIONS (5.6)]
[see WARNINGS AND PRECAUTIONS (5.7)]
[see WARNINGS AND PRECAUTIONS (5.8)]
[see WARNINGS AND PRECAUTIONS (5.9)]
[see WARNINGS AND PRECAUTIONS (5.10)]
[see WARNINGS AND PRECAUTIONS (5.11)]
[see WARNINGS AND PRECAUTIONS (5.12)]
[see WARNINGS AND PRECAUTIONS (5.13)]
The most common adverse reactions in the pediatric clinical trials (≥10%) were somnolence, headache, vomiting, extrapyramidal disorder, fatigue, increased appetite, insomnia, nausea, nasopharyngitis, and weight increased.
Aripiprazole has been evaluated for safety in 13,543 adult patients who participated in multiple-dose, clinical trials in schizophrenia, another indication, Dementia of the Alzheimer’s type, Parkinson’s disease, and alcoholism, and who had approximately 7619 patient-years of exposure to oral aripiprazole and 749 patients with exposure to aripiprazole injection. A total of 3390 patients were treated with oral aripiprazole for at least 180 days and 1933 patients treated with oral aripiprazole had at least 1 year of exposure.
Aripiprazole has been evaluated for safety in 1,686 patients (6 to 18 years) who participated in multiple-dose, clinical trials in schizophrenia or other indications and who had approximately 1,342 patient-years of exposure to oral aripiprazole. A total of 959 pediatric patients were treated with oral aripiprazole for at least 180 days and 556 pediatric patients treated with oral aripiprazole had at least 1 year of exposure.
The conditions and duration of treatment with aripiprazole tablets included (in overlapping categories) double-blind, comparative and noncomparative open-label studies, inpatient and outpatient studies, fixed- and flexible-dose studies, and short- and longer-term exposure.
Additional pediatric use information is approved for Otsuka America Pharmaceutical, Inc.’s ABILIFY® (aripiprazole) product. However, due to Otsuka America Pharmaceutical, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
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