Abilify Tablet Adverse Reactions

Aripiprazole has been evaluated for safety in 7951 patients who participated in multiple-dose, premarketing trials in schizophrenia, bipolar mania and dementia of the Alzheimer's type, and who had approximately 5235 patient-years of exposure. A total of 2280 aripiprazole-treated patients were treated for at least 180 days and 1558 aripiprazole-treated patients had at least 1 year of exposure.
The conditions and duration of treatment with aripiprazole 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.
Adverse events during exposure were obtained by collecting volunteered adverse events, as well as results of physical examinations, vital signs, weights, laboratory analyses and ECG. Adverse experiences were recorded by clinical investigators using terminology of their own choosing. In the tables and tabulations that follow, modified COSTART dictionary terminology has been used initially to classify reported adverse events into a smaller number of standardized event categories, in order to provide a meaningful estimate of the proportion of individuals experiencing adverse events.
The stated frequencies of adverse events represent the proportion of individuals who experienced at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. There was no attempt to use investigator causality assessments ie, all reported events are included.
The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatment, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse event incidence in the population studied.
Adverse Findings Observed in Short-Term, Placebo-Controlled Trials of Patients with Schizophrenia: The following findings are based on a pool of 5 placebo-controlled trials (four 4-week and one 6-week) in which aripiprazole was administered in doses ranging from 2-30 mg/day.
Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials: Overall, there was no difference in the incidence of discontinuation due to adverse events between aripiprazole-treated (7%) and placebo-treated (9%) patients. The types of adverse events that led to the discontinuation were similar between the aripiprazole- and placebo-treated patients.
Adverse Findings Observed in Short-Term, Placebo-Controlled Trials of Patients with Bipolar Mania: The following findings are based on a pool of 3-week, placebo-controlled, bipolar mania trials in which aripiprazole was administered at doses of 15 or 30 mg/day.
Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials: Overall, in patients with bipolar mania, there was no difference in the incidence of discontinuation due to adverse events between aripiprazole-treated (11%) and placebo-treated (9%) patients. The types of adverse events that led to discontinuation were similar between the aripiprazole and placebo-treated patients.
Commonly Observed Adverse Events in Short-Term, Placebo-Controlled Trials of Patients with Bipolar Mania: Commonly observed adverse events associated with the use of aripiprazole in patients with bipolar mania (incidence of ≥5% and aripiprazole incidence at least twice that for placebo) are shown in Table 1. There were no adverse events in the short-term trials of schizophrenia that met these criteria (see Table 1).


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Adverse Events Occurring at an Incidence of ≥2% Among Aripiprazole-Treated Patients and Greater Than Placebo in Short-Term Placebo-Controlled Trials: Table 2 enumerates the pooled incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during acute therapy (up to 6 weeks in schizophrenia and up to 3 weeks in bipolar mania), including only those events that occurred in ≥2% of patients treated with aripiprazole (doses ≥2 mg/day) and for which the incidence in patients treated with aripiprazole was greater than the incidence in patients treated with placebo in the combined dataset (see Table 2).


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An examination of population subgroups did not reveal any clear evidence of differential adverse event incidence on the basis of age, gender or race.
Dose-Related Adverse Events: Schizophrenia: Dose response relationships for the incidence of treatment-emergent adverse events were evaluated from 4 trials in patients with schizophrenia comparing various fixed doses (2, 10, 15, 20 and 30 mg/day) of aripiprazole to placebo. This analysis, stratified by study, indicated that the only adverse event to have a possible dose response relationship, and then most prominent only with 30 mg, was somnolence (placebo, 7.7%; 15 mg, 8.7%; 20 mg, 7.5%; 30 mg, 15.3%).
Extrapyramidal Symptoms (EPS): In the short-term, placebo-controlled trials of schizophrenia, the incidence of reported EPS for aripiprazole-treated patients was 6% versus 6% for placebo. In the short-term, placebo-controlled trials in bipolar mania, the incidence of reported EPS-related events excluding events related to akathisia for aripiprazole-treated patients was 17% versus 12% for placebo. In the short-term, placebo-controlled trials in bipolar mania, the incidence of akathisia-related events for aripiprazole-treated patients was 15% versus 4% for placebo. Objectively collected data from those trials was collected on the Simpson Angus Rating Scale (for EPS), the Barnes Akathisia Scale (for akathisia), and the Assessments of Involuntary Movement Scales (for dyskinesias). In the schizophrenia trials, the objectively collected data did not show a difference between aripiprazole and placebo, with the exception of the Barnes Akathisia Scale (aripiprazole, 0.08; placebo, -0.05). In the bipolar mania trials, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between aripiprazole and placebo (aripiprazole, 0.61; placebo, 0.03 and aripiprazole, 0.25; placebo, -0.06). Changes in the Assessments of Involuntary Movement Scales were similar for the aripiprazole and placebo groups.
Similarly, in a long-term (26-week), placebo-controlled trial of schizophrenia, objectively collected data on the Simpson Angus Rating Scale (for EPS), the Barnes Akathisia Scale (for akathisia), and the Assessments of Involuntary Movement Scales (for dyskinesias) did not show a difference between aripiprazole and placebo.
Laboratory Test Abnormalities: A between group comparison for 3- to 6-week placebo-controlled trials revealed no medically important differences between the aripiprazole and placebo groups in the proportions of patients experiencing potentially clinically significant changes in routine serum chemistry, hematology or urinalysis parameters. Similarly, there were no aripiprazole/placebo differences in the incidence of discontinuations for changes in serum chemistry, hematology or urinalysis.
In a long-term (26-week), placebo-controlled trial, there were no medically important differences between the aripiprazole and placebo patients in the mean change from baseline in prolactin, fasting glucose, triglyceride, HDL, LDL and total cholesterol measurements.
Weight Gain: In 4- to 6- week trials in schizophrenia, there was a slight difference in mean weight gain between aripiprazole and placebo patients (+0.7 kg vs -0.05 kg, respectively), and also a difference in the proportion of patients meeting a weight gain criterion of ≥7% of body weight [aripiprazole (8%) compared to placebo (3%)]. In 3-week trials in mania, the mean weight gain for aripiprazole and placebo patients was 0 kg versus -0.2 kg, respectively. The proportion of patients meeting a weight gain criterion of ≥7% of body weight was aripiprazole (3%) compared to placebo (2%).
Table 3 provides the weight change results from a long-term (26-week), placebo-controlled study of aripiprazole, both mean change from baseline and proportions of patients meeting a weight gain criterion of ≥7% of body weight relative to baseline, categorized by body mass index (BMI) at baseline (see Table 3).


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Table 4 provides the weight change results from a long-term (52-week) study of aripiprazole, both mean change from baseline and proportions of patients meeting a weight gain criterion of ≥7% of body weight relative to baseline, categorized by BMI at baseline (see Table 4).


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Electrocardiogram (ECG) Changes: Between group comparisons for a pooled analysis of placebo-controlled trials in patients with schizophrenia or bipolar mania revealed no significant differences between aripiprazole and placebo in the proportion of patients experiencing potentially important changes in ECG parameters. Aripiprazole was associated with a median increase in heart rate of 5 bpm compared to a 1 bpm increase among placebo patients.
Additional Findings Observed in Clinical Trials: Adverse Events in a Long-Term, Double-Blind, Placebo-Controlled Trial: The adverse events reported in a 26-week, double-blind trial comparing Abilify and placebo in patients with schizophrenia were generally consistent with those reported in the short-term, placebo-controlled trials, except for a higher incidence of tremor [9% (13/153) for Abilify vs 1% (2/153) for placebo]. In this study, the majority of the cases of tremor were of mild intensity (9/13 mild and 4/13 moderate), occurred early in therapy (9/13 ≤49 days) and were of limited duration (9/13 ≤10 days). Tremor infrequently led to discontinuation (<1%) of Abilify. In addition, in a long-term (52-week), active-controlled study, the incidence of tremor for Abilify was 4% (34/859). A similar adverse event profile was observed in a long-term study in bipolar disorder.
Other Adverse Events Observed During the Premarketing Evaluation of Aripiprazole: Following is a list of modified COSTART terms that reflect treatment-emergent adverse events as defined in the introduction to this section reported by patients treated with aripiprazole at multiple doses ≥2 mg/day during any phase of a trial within the database of 7951 patients. All reported events are included except those already listed in Table 2 or other parts of this section, those considered in the Warnings or Precautions, those event terms which were so general as to be uninformative, events reported with an incidence of ≤0.05% and which did not have a substantial probability of being acutely life-threatening, events that are otherwise common as background events, and events considered unlikely to be drug-related. It is important to emphasize that, although the events reported occurred during treatment with aripiprazole, they were not necessarily caused by it.
Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse events are those occurring in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.
Body as a Whole: Frequent: Flu syndrome, fever, chest pain, rigidity (including neck and extremity), neck pain, pelvic pain. Infrequent: Face edema, suicide attempt, malaise, migraine, chills, photosensitivity, tightness (including abdomen, back, extremity, head, jaw, neck, and tongue), jaw pain, bloating, enlarged abdomen, chest tightness, throat pain. Rare: Moniliasis, head heaviness, throat tightness, Mendelson's syndrome, heat stroke.
Cardiovascular System: Frequent: Tachycardia (including ventricular and supraventricular), hypotension, bradycardia. Infrequent: Palpitation, hemorrhage, heart failure, myocardial infarction, cardiac arrest, atrial fibrillation, AV block, prolonged QT interval, extrasystoles, myocardial ischemia, deep vein thrombosis, angina pectoris, pallor, cardiopulmonary arrest, phlebitis. Rare: Bundle branch block, atrial flutter, vasovagal reaction, cardiomegaly, thrombophlebitis, cardiopulmonary failure.
Digestive System: Frequent: Nausea and vomiting. Infrequent: Increased appetite, dysphagia, gastroenteritis, flatulence, tooth caries, gastritis, gingivitis, gastrointestinal hemorrhage, hemorrhoids, gastroesophageal reflux, periodontal abscess, fecal incontinence, rectal hemorrhage, stomatitis, colitis, tongue edema, cholecystitis, mouth ulcer, oral moniliasis, eructation, fecal impaction, cholelithiasis. Rare: Esophagitis, hematemesis, intestinal obstruction, gum hemorrhage, hepatitis, peptic ulcer, glossitis, melena, duodenal ulcer, cheilitis, hepatomegaly, pancreatitis.
Endocrine System: Infrequent: Hypothyroidism. Rare: Goiter, hyperthyroidism.
Hemic/Lymphatic System: Frequent: Ecchymosis, anemia. Infrequent: Hypochromic anemia, leukocytosis, leukopenia (including neutropenia), lymphadenopathy, eosinophilia, macrocytic anemia. Rare: Thrombocythemia, thrombocytopenia, petechiae.
Metabolic and Nutritional Disorders: Frequent: Weight loss, increased creatine phosphokinase, dehydration. Infrequent: Edema, hyperglycemia, hypercholesteremia, hypokalemia, diabetes mellitus, hypoglycemia, hyperlipemia, increased SGPT, thirst, increased BUN, hyponatremia, increased SGOT, increased creatinine, cyanosis, increased alkaline phosphatase, bilirubinemia, iron deficiency anemia, hyperkalemia, hyperuricemia, obesity. Rare: Increased lactic dehydrogenase, hypernatremia, gout, hypoglycemic reaction.
Musculoskeletal System: Frequent: Muscle cramp. Infrequent: Arthralgia, bone pain, myasthenia, arthritis, arthrosis, muscle weakness, spasm, bursitis, myopathy. Rare: Rhabdomyolysis, tendonitis, tenosynovitis, rheumatoid arthritis.
Nervous System: Frequent: Depression, nervousness, schizophrenic reaction, hallucination, hostility, confusion, paranoid reaction, suicidal thought, manic reaction, abnormal gait, delusions, abnormal dream. Infrequent: Emotional lability, twitch, cogwheel rigidity, impaired concentration, dystonia, vasodilation, paresthesia, impotence, extremity tremor, hypesthesia, vertigo, stupor, bradykinesia, apathy, panic attack, decreased libido, hypersomnia, dyskinesia, manic depressive reaction, ataxia, visual hallucination, cerebrovascular accident, hypokinesia, depersonalization, impaired memory, delirium, dysarthria, tardive dyskinesia, amnesia, hyperactivity, increased libido, myoclonus, restless leg, neuropathy, dysphoria, hyperkinesia, cerebral ischemia, increased reflexes, akinesia, decreased consciousness, hyperesthesia, slowed thinking. Rare: Blunted affect, euphoria, incoordination, oculogyric crisis, obsessive thought, hypotonia, buccoglossal syndrome, decreased reflexes, derealization, intracranial hemorrhage.
Respiratory System: Frequent: Sinusitis, dyspnea, pneumonia, asthma. Infrequent: Epistaxis, hiccup, laryngitis, aspiration pneumonia. Rare: Pulmonary edema, increased sputum, pulmonary embolism, hypoxia, respiratory failure, apnea, dry nasal passages, hemoptysis.
Skin and Appendages: Frequent: Skin ulcer, sweating, dry skin. Infrequent: Pruritus, vesiculobullous rash, acne, eczema, skin discoloration, alopecia, seborrhea, psoriasis. Rare: Maculopapular rash, exfoliative dermatitis, urticaria.
Special Senses: Frequent: Conjunctivitis. Infrequent: Ear pain, dry eye, eye pain, tinnitus, cataract, otitis media, altered taste, blepharitis, eye hemorrhage, deafness. Rare: Diplopia, frequent blinking, ptosis, otitis externa, amblyopia, photophobia.
Urogenital System: Frequent: Urinary incontinence. Infrequent: Urinary frequency, leukorrhea, urinary retention, cystitis, hematuria, dysuria, amenorrhea, abnormal ejaculation, vaginal hemorrhage, kidney failure, vaginal moniliasis, urinary urgency, gynecomastia, kidney calculus, albuminuria, breast pain, urinary burning. Rare: Nocturia, polyuria, menorrhagia, anorgasmy, glycosuria, cervicitis, uterus hemorrhage, female lactation, urolithiasis, priapism.
Other Events Observed During the Post-Marketing Evaluation of Aripiprazole: Voluntary reports of adverse events in patients taking aripiprazole that have been received since market introduction and not listed previously that may have no causal relationship with the drug include very rare occurrences of allergic reaction (eg, anaphylactic reaction, angioedema, laryngospasm, pruritis, or urticaria), temperature regulation disorder (eg, pyrexia, hypothermia), increased γ-GTP, increased blood glucose, blood glucose fluctuation, increased glycosylated hemoglobin, increased weight, grand mal convulsion, jaundice.