ABILIFY (Page 5 of 14)
6.1 Clinical Trials Experience
Adult Patients with Schizophrenia
The following findings are based on a pool of five placebo-controlled trials (four 4 week and one 6 week) in which oral ABILIFY was administered in doses ranging from 2 to 30 mg/day.
Commonly Observed Adverse Reactions
The only commonly observed adverse reaction associated with the use of ABILIFY in patients with schizophrenia (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) was akathisia (ABILIFY 8%; placebo 4%).
Adult Patients with Bipolar Mania
Monotherapy
The following findings are based on a pool of 3-week, placebo-controlled, bipolar mania trials in which oral ABILIFY was administered at doses of 15 or 30 mg/day.
Commonly Observed Adverse Reactions
Commonly observed adverse reactions associated with the use of ABILIFY in patients with bipolar mania (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) are shown in Table 16.
| Preferred Term | Percentage of Patients Reporting Reaction | |
|---|---|---|
| ABILIFY(n=917) | Placebo(n=753) | |
| Akathisia | 13 | 4 |
| Sedation | 8 | 3 |
| Restlessness | 6 | 3 |
| Tremor | 6 | 3 |
| Extrapyramidal Disorder | 5 | 2 |
Less Common Adverse Reactions in Adults
Table 17 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks in schizophrenia and up to 3 weeks in bipolar mania), including only those reactions that occurred in 2% or more of patients treated with ABILIFY (doses ≥2 mg/day) and for which the incidence in patients treated with ABILIFY was greater than the incidence in patients treated with placebo in the combined dataset.
| Percentage of Patients Reporting Reaction * | ||
|---|---|---|
| System Organ ClassPreferred Term | ABILIFY(n=1,843) | Placebo(n=1,166) |
| ||
| Eye Disorders | ||
| Blurred Vision | 3 | 1 |
| Gastrointestinal Disorders | ||
| Nausea | 15 | 11 |
| Constipation | 11 | 7 |
| Vomiting | 11 | 6 |
| Dyspepsia | 9 | 7 |
| Dry Mouth | 5 | 4 |
| Toothache | 4 | 3 |
| Abdominal Discomfort | 3 | 2 |
| Stomach Discomfort | 3 | 2 |
| General Disorders and Administration Site Conditions | ||
| Fatigue | 6 | 4 |
| Pain | 3 | 2 |
| Musculoskeletal and Connective Tissue Disorders | ||
| Musculoskeletal Stiffness | 4 | 3 |
| Pain in Extremity | 4 | 2 |
| Myalgia | 2 | 1 |
| Muscle Spasms | 2 | 1 |
| Nervous System Disorders | ||
| Headache | 27 | 23 |
| Dizziness | 10 | 7 |
| Akathisia | 10 | 4 |
| Sedation | 7 | 4 |
| Extrapyramidal Disorder | 5 | 3 |
| Tremor | 5 | 3 |
| Somnolence | 5 | 3 |
| Psychiatric Disorders | ||
| Agitation | 19 | 17 |
| Insomnia | 18 | 13 |
| Anxiety | 17 | 13 |
| Restlessness | 5 | 3 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||
| Pharyngolaryngeal Pain | 3 | 2 |
| Cough | 3 | 2 |
An examination of population subgroups did not reveal any clear evidence of differential adverse reaction incidence on the basis of age, gender, or race.
Adult Patients with Adjunctive Therapy with Bipolar Mania
The following findings are based on a placebo-controlled trial of adult patients with bipolar disorder in which ABILIFY was administered at doses of 15 or 30 mg/day as adjunctive therapy with lithium or valproate.
Adverse Reactions Associated with Discontinuation of Treatment
In a study of patients who were already tolerating either lithium or valproate as monotherapy, discontinuation rates due to adverse reactions were 12% for patients treated with adjunctive ABILIFY compared to 6% for patients treated with adjunctive placebo. The most common adverse drug reactions associated with discontinuation in the adjunctive ABILIFY-treated compared to placebo-treated patients were akathisia (5% and 1%, respectively) and tremor (2% and 1%, respectively).
Commonly Observed Adverse Reactions
The commonly observed adverse reactions associated with adjunctive ABILIFY and lithium or valproate in patients with bipolar mania (incidence of 5% or greater and incidence at least twice that for adjunctive placebo) were: akathisia, insomnia, and extrapyramidal disorder.
Less Common Adverse Reactions in Adult Patients with Adjunctive Therapy in Bipolar Mania
Table 18 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute treatment (up to 6 weeks), including only those reactions that occurred in 2% or more of patients treated with adjunctive ABILIFY (doses of 15 or 30 mg/day) and lithium or valproate and for which the incidence in patients treated with this combination was greater than the incidence in patients treated with placebo plus lithium or valproate.
| Percentage of Patients Reporting Reaction * | ||
|---|---|---|
| System Organ ClassPreferred Term | ABILIFY + Li or Val †(n=253) | Placebo + Li or Val †(n=130) |
| Gastrointestinal Disorders | ||
| Nausea | 8 | 5 |
| Vomiting | 4 | 0 |
| Salivary Hypersecretion | 4 | 2 |
| Dry Mouth | 2 | 1 |
| Infections and Infestations | ||
| Nasopharyngitis | 3 | 2 |
| Investigations | ||
| Weight Increased | 2 | 1 |
| Nervous System Disorders | ||
| Akathisia | 19 | 5 |
| Tremor | 9 | 6 |
| Extrapyramidal Disorder | 5 | 1 |
| Dizziness | 4 | 1 |
| Sedation | 4 | 2 |
| Psychiatric Disorders | ||
| Insomnia | 8 | 4 |
| Anxiety | 4 | 1 |
| Restlessness | 2 | 1 |
Pediatric Patients (13 to 17 years) with Schizophrenia
The following findings are based on one 6-week, placebo-controlled trial in which oral ABILIFY was administered in doses ranging from 2 to 30 mg/day.
Adverse Reactions Associated with Discontinuation of Treatment
The incidence of discontinuation due to adverse reactions between ABILIFY-treated and placebo-treated pediatric patients (13 to 17 years) was 5% and 2%, respectively.
Commonly Observed Adverse Reactions
Commonly observed adverse reactions associated with the use of ABILIFY in adolescent patients with schizophrenia (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) were extrapyramidal disorder, somnolence, and tremor.
Pediatric Patients (10 to 17 years) with Bipolar Mania
The following findings are based on one 4-week, placebo-controlled trial in which oral ABILIFY was administered in doses of 10 or 30 mg/day.
Adverse Reactions Associated with Discontinuation of Treatment
The incidence of discontinuation due to adverse reactions between ABILIFY-treated and placebo-treated pediatric patients (10 to 17 years) was 7% and 2%, respectively.
Commonly Observed Adverse Reactions
Commonly observed adverse reactions associated with the use of ABILIFY in pediatric patients with bipolar mania (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) are shown in Table 19.
| Percentage of Patients Reporting Reaction | ||
|---|---|---|
| Preferred Term | ABILIFY(n=197) | Placebo(n=97) |
| Somnolence | 23 | 3 |
| Extrapyramidal Disorder | 20 | 3 |
| Fatigue | 11 | 4 |
| Nausea | 11 | 4 |
| Akathisia | 10 | 2 |
| Blurred Vision | 8 | 0 |
| Salivary Hypersecretion | 6 | 0 |
| Dizziness | 5 | 1 |
Pediatric Patients (6 to 17 years) with Autistic Disorder
The following findings are based on two 8 week, placebo-controlled trials in which oral ABILIFY was administered in doses of 2 to 15 mg/day.
Adverse Reactions Associated with Discontinuation of Treatment
The incidence of discontinuation due to adverse reactions between ABILIFY-treated and placebo-treated pediatric patients (6 to 17 years) was 10% and 8%, respectively.
Commonly Observed Adverse Reactions
Commonly observed adverse reactions associated with the use of ABILIFY in pediatric patients with autistic disorder (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) are shown in Table 20.
| Percentage of Patients Reporting Reaction | ||
|---|---|---|
| Preferred Term | ABILIFY(n=212) | Placebo(n=101) |
| Sedation | 21 | 4 |
| Fatigue | 17 | 2 |
| Vomiting | 14 | 7 |
| Somnolence | 10 | 4 |
| Tremor | 10 | 0 |
| Pyrexia | 9 | 1 |
| Drooling | 9 | 0 |
| Decreased Appetite | 7 | 2 |
| Salivary Hypersecretion | 6 | 1 |
| Extrapyramidal Disorder | 6 | 0 |
| Lethargy | 5 | 0 |
Pediatric Patients (6 to 18 years) with Tourette’s Disorder
The following findings are based on one 8 week and one 10 week, placebo-controlled trials in which oral ABILIFY was administered in doses of 2 to 20 mg/day.
Adverse Reactions Associated with Discontinuation of Treatment
The incidence of discontinuation due to adverse reactions between ABILIFY-treated and placebo-treated pediatric patients (6 to 18 years) was 7% and 1%, respectively.
Commonly Observed Adverse Reactions
Commonly observed adverse reactions associated with the use of ABILIFY in pediatric patients with Tourette’s disorder (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) are shown in Table 21.
| Percentage of Patients Reporting Reaction | ||
|---|---|---|
| Preferred Term | ABILIFY(n=121) | Placebo(n=72) |
| Sedation | 13 | 6 |
| Somnolence | 13 | 1 |
| Nausea | 11 | 4 |
| Headache | 10 | 3 |
| Nasopharyngitis | 9 | 0 |
| Fatigue | 8 | 0 |
| Increased Appetite | 7 | 1 |
Less Common Adverse Reactions in Pediatric Patients (6 to 18 years) with Schizophrenia, Bipolar Mania, Autistic Disorder, or Tourette’s Disorder
Table 22 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks in schizophrenia, up to 4 weeks in bipolar mania, up to 8 weeks in autistic disorder, and up to 10 weeks in Tourette’s disorder), including only those reactions that occurred in 2% or more of pediatric patients treated with ABILIFY (doses ≥2 mg/day) and for which the incidence in patients treated with ABILIFY was greater than the incidence in patients treated with placebo.
| Percentage of Patients Reporting Reaction * | ||
|---|---|---|
| System Organ ClassPreferred Term | ABILIFY(n=732) | Placebo(n=370) |
| ||
| Eye Disorders | ||
| Blurred Vision | 3 | 0 |
| Gastrointestinal Disorders | ||
| Abdominal Discomfort | 2 | 1 |
| Vomiting | 8 | 7 |
| Nausea | 8 | 4 |
| Diarrhea | 4 | 3 |
| Salivary Hypersecretion | 4 | 1 |
| Abdominal Pain Upper | 3 | 2 |
| Constipation | 2 | 2 |
| General Disorders and Administration Site Conditions | ||
| Fatigue | 10 | 2 |
| Pyrexia | 4 | 1 |
| Irritability | 2 | 1 |
| Asthenia | 2 | 1 |
| Infections and Infestations | ||
| Nasopharyngitis | 6 | 3 |
| Investigations | ||
| Weight Increased | 3 | 1 |
| Metabolism and Nutrition Disorders | ||
| Increased Appetite | 7 | 3 |
| Decreased Appetite | 5 | 4 |
| Musculoskeletal and Connective Tissue Disorders | ||
| Musculoskeletal Stiffness | 2 | 1 |
| Muscle Rigidity | 2 | 1 |
| Nervous System Disorders | ||
| Somnolence | 16 | 4 |
| Headache | 12 | 10 |
| Sedation | 9 | 2 |
| Tremor | 9 | 1 |
| Extrapyramidal Disorder | 6 | 1 |
| Akathisia | 6 | 4 |
| Drooling | 3 | 0 |
| Lethargy | 3 | 0 |
| Dizziness | 3 | 2 |
| Dystonia | 2 | 1 |
| Respiratory, Thoracic, and Mediastinal Disorders | ||
| Epistaxis | 2 | 1 |
| Skin and Subcutaneous Tissue Disorders | ||
| Rash | 2 | 1 |
Adult Patients Receiving ABILIFY as Adjunctive Treatment of Major Depressive Disorder
The following findings are based on a pool of two placebo-controlled trials of patients with major depressive disorder in which ABILIFY was administered at doses of 2 to 20 mg as adjunctive treatment to continued antidepressant therapy.
Adverse Reactions Associated with Discontinuation of Treatment
The incidence of discontinuation due to adverse reactions was 6% for adjunctive ABILIFY-treated patients and 2% for adjunctive placebo-treated patients.
Commonly Observed Adverse Reactions
The commonly observed adverse reactions associated with the use of adjunctive ABILIFY in patients with major depressive disorder (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) were: akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision.
Less Common Adverse Reactions in Adult Patients with Major Depressive Disorder
Table 23 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks), including only those adverse reactions that occurred in 2% or more of patients treated with adjunctive ABILIFY (doses ≥2 mg/day) and for which the incidence in patients treated with adjunctive ABILIFY was greater than the incidence in patients treated with adjunctive placebo in the combined dataset.
| Percentage of Patients Reporting Reaction * | ||
|---|---|---|
| System Organ ClassPreferred Term | ABILIFY + ADT †(n=371) | Placebo + ADT †(n=366) |
| Eye Disorders | ||
| Blurred Vision | 6 | 1 |
| Gastrointestinal Disorders | ||
| Constipation | 5 | 2 |
| General Disorders and Administration Site Conditions | ||
| Fatigue | 8 | 4 |
| Feeling Jittery | 3 | 1 |
| Infections and Infestations | ||
| Upper Respiratory Tract Infection | 6 | 4 |
| Investigations | ||
| Weight Increased | 3 | 2 |
| Metabolism and Nutrition Disorders | ||
| Increased Appetite | 3 | 2 |
| Musculoskeletal and Connective Tissue Disorders | ||
| Arthralgia | 4 | 3 |
| Myalgia | 3 | 1 |
| Nervous System Disorders | ||
| Akathisia | 25 | 4 |
| Somnolence | 6 | 4 |
| Tremor | 5 | 4 |
| Sedation | 4 | 2 |
| Dizziness | 4 | 2 |
| Disturbance in Attention | 3 | 1 |
| Extrapyramidal Disorder | 2 | 0 |
| Psychiatric Disorders | ||
| Restlessness | 12 | 2 |
| Insomnia | 8 | 2 |
Patients with Agitation Associated with Schizophrenia or Bipolar Mania (Intramuscular Injection)
The following findings are based on a pool of three placebo-controlled trials of patients with agitation associated with schizophrenia or bipolar mania in which ABILIFY injection was administered at doses of 5.25 to 15 mg.
Commonly Observed Adverse Reactions
There was one commonly observed adverse reaction (nausea) associated with the use of ABILIFY injection in patients with agitation associated with schizophrenia and bipolar mania (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo).
Less Common Adverse Reactions in Patients with Agitation Associated with Schizophrenia or Bipolar Mania
Table 24 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (24-hour), including only those adverse reactions that occurred in 2% or more of patients treated with ABILIFY injection (doses ≥5.25 mg/day) and for which the incidence in patients treated with ABILIFY injection was greater than the incidence in patients treated with placebo in the combined dataset.
| Percentage of Patients Reporting Reaction * | ||
|---|---|---|
| System Organ ClassPreferred Term | ABILIFY(n=501) | Placebo(n=220) |
| ||
| Cardiac Disorders | ||
| Tachycardia | 2 | <1 |
| Gastrointestinal Disorders | ||
| Nausea | 9 | 3 |
| Vomiting | 3 | 1 |
| General Disorders and Administration Site Conditions | ||
| Fatigue | 2 | 1 |
| Nervous System Disorders | ||
| Headache | 12 | 7 |
| Dizziness | 8 | 5 |
| Somnolence | 7 | 4 |
| Sedation | 3 | 2 |
| Akathisia | 2 | 0 |
Dose-Related Adverse Reactions
Schizophrenia
Dose response relationships for the incidence of treatment-emergent adverse events were evaluated from four trials in adult patients with schizophrenia comparing various fixed doses (2, 5, 10, 15, 20, and 30 mg/day) of oral ABILIFY to placebo. This analysis, stratified by study, indicated that the only adverse reaction to have a possible dose response relationship, and then most prominent only with 30 mg, was somnolence [including sedation]; (incidences were placebo, 7.1%; 10 mg, 8.5%; 15 mg, 8.7%; 20 mg, 7.5%; 30 mg, 12.6%).
In the study of pediatric patients (13 to 17 years of age) with schizophrenia, three common adverse reactions appeared to have a possible dose response relationship: extrapyramidal disorder (incidences were placebo, 5.0%; 10 mg, 13.0%; 30 mg, 21.6%); somnolence (incidences were placebo, 6.0%; 10 mg, 11.0%; 30 mg, 21.6%); and tremor (incidences were placebo, 2.0%; 10 mg, 2.0%; 30 mg, 11.8%).
Bipolar Mania
In the study of pediatric patients (10 to 17 years of age) with bipolar mania, four common adverse reactions had a possible dose response relationship at 4 weeks; extrapyramidal disorder (incidences were placebo, 3.1%; 10 mg, 12.2%; 30 mg, 27.3%); somnolence (incidences were placebo, 3.1%; 10 mg, 19.4%; 30 mg, 26.3%); akathisia (incidences were placebo, 2.1%; 10 mg, 8.2%; 30 mg, 11.1%); and salivary hypersecretion (incidences were placebo, 0%; 10 mg, 3.1%; 30 mg, 8.1%).
Autistic Disorder
In a study of pediatric patients (6 to 17 years of age) with autistic disorder, one common adverse reaction had a possible dose response relationship: fatigue (incidences were placebo, 0%; 5 mg, 3.8%; 10 mg, 22.0%; 15 mg, 18.5%).
Tourette’s Disorder
In a study of pediatric patients (7 to 17 years of age) with Tourette’s disorder, no common adverse reaction(s) had a dose response relationship.
Extrapyramidal Symptoms
Schizophrenia
In short-term, placebo-controlled trials in schizophrenia in adults, the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 13% vs. 12% for placebo; and the incidence of akathisia-related events for ABILIFY-treated patients was 8% vs. 4% for placebo. In the short-term, placebo-controlled trial of schizophrenia in pediatric patients (13 to 17 years), the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 25% vs. 7% for placebo; and the incidence of akathisia-related events for ABILIFY-treated patients was 9% vs. 6% 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 adult schizophrenia trials, the objectively collected data did not show a difference between ABILIFY and placebo, with the exception of the Barnes Akathisia Scale (ABILIFY, 0.08; placebo, –0.05). In the pediatric (13 to 17 years) schizophrenia trial, the objectively collected data did not show a difference between ABILIFY and placebo, with the exception of the Simpson Angus Rating Scale (ABILIFY, 0.24; placebo, –0.29).
Similarly, in a long-term (26 week), placebo-controlled trial of schizophrenia in adults, 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 ABILIFY and placebo.
Bipolar Mania
In the short-term, placebo-controlled trials in bipolar mania in adults, the incidence of reported EPS-related events, excluding events related to akathisia, for monotherapy ABILIFY-treated patients was 16% vs. 8% for placebo and the incidence of akathisia-related events for monotherapy ABILIFY-treated patients was 13% vs. 4% for placebo. In the 6 week, placebo-controlled trial in bipolar mania for adjunctive therapy with lithium or valproate, the incidence of reported EPS-related events, excluding events related to akathisia for adjunctive ABILIFY-treated patients was 15% vs. 8% for adjunctive placebo and the incidence of akathisia-related events for adjunctive ABILIFY-treated patients was 19% vs. 5% for adjunctive placebo. In the short-term, placebo-controlled trial in bipolar mania in pediatric (10 to 17 years) patients, the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 26% vs. 5% for placebo and the incidence of akathisia-related events for ABILIFY-treated patients was 10% vs. 2% for placebo.
In the adult bipolar mania trials with monotherapy ABILIFY, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between ABILIFY and placebo (ABILIFY, 0.50; placebo, –0.01 and ABILIFY, 0.21; placebo, –0.05). Changes in the Assessments of Involuntary Movement Scales were similar for the ABILIFY and placebo groups. In the bipolar mania trials with ABILIFY as adjunctive therapy with either lithium or valproate, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between adjunctive ABILIFY and adjunctive placebo (ABILIFY, 0.73; placebo, 0.07 and ABILIFY, 0.30; placebo, 0.11). Changes in the Assessments of Involuntary Movement Scales were similar for adjunctive ABILIFY and adjunctive placebo. In the pediatric (10 to 17 years), short-term, bipolar mania trial, the Simpson Angus Rating Scale showed a significant difference between ABILIFY and placebo (ABILIFY, 0.90; placebo, −0.05). Changes in the Barnes Akathisia Scale and the Assessments of Involuntary Movement Scales were similar for the ABILIFY and placebo groups.
Major Depressive Disorder
In the short-term, placebo-controlled trials in major depressive disorder, the incidence of reported EPS-related events, excluding events related to akathisia, for adjunctive ABILIFY-treated patients was 8% vs. 5% for adjunctive placebo-treated patients; and the incidence of akathisia-related events for adjunctive ABILIFY-treated patients was 25% vs. 4% for adjunctive placebo-treated patients.
In the major depressive disorder trials, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between adjunctive ABILIFY and adjunctive placebo (ABILIFY, 0.31; placebo, 0.03 and ABILIFY, 0.22; placebo, 0.02). Changes in the Assessments of Involuntary Movement Scales were similar for the adjunctive ABILIFY and adjunctive placebo groups.
Autistic Disorder
In the short-term, placebo-controlled trials in autistic disorder in pediatric patients (6 to 17 years), the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 18% vs. 2% for placebo and the incidence of akathisia-related events for ABILIFY-treated patients was 3% vs. 9% for placebo.
In the pediatric (6 to 17 years) short-term autistic disorder trials, the Simpson Angus Rating Scale showed a significant difference between ABILIFY and placebo (ABILIFY, 0.1; placebo, –0.4). Changes in the Barnes Akathisia Scale and the Assessments of Involuntary Movement Scales were similar for the ABILIFY and placebo groups.
Tourette’s Disorder
In the short-term, placebo-controlled trials in Tourette’s disorder in pediatric patients (6 to 18 years), the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 7% vs. 6% for placebo and the incidence of akathisia-related events for ABILIFY-treated patients was 4% vs. 6% for placebo.
In the pediatric (6 to 18 years) short-term Tourette’s disorder trials, changes in the Simpson Angus Rating Scale, Barnes Akathisia Scale and Assessments of Involuntary Movement Scale were not clinically meaningfully different for ABILIFY and placebo.
Agitation Associated with Schizophrenia or Bipolar Mania
In the placebo-controlled trials in patients with agitation associated with schizophrenia or bipolar mania, the incidence of reported EPS-related events excluding events related to akathisia for ABILIFY-treated patients was 2% vs. 2% for placebo and the incidence of akathisia-related events for ABILIFY-treated patients was 2% vs. 0% for placebo. Objectively collected data on the Simpson Angus Rating Scale (for EPS) and the Barnes Akathisia Scale (for akathisia) for all treatment groups did not show a difference between ABILIFY and placebo.
Dystonia
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
Additional Findings Observed in Clinical Trials
Adverse Reactions in Long-Term, Double-Blind, Placebo-Controlled Trials
The adverse reactions reported in a 26 week, double-blind trial comparing oral 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 [8% (12/153) for ABILIFY vs. 2% (3/153) for placebo]. In this study, the majority of the cases of tremor were of mild intensity (8/12 mild and 4/12 moderate), occurred early in therapy (9/12 ≤49 days), and were of limited duration (7/12 ≤10 days). Tremor infrequently led to discontinuation (<1%) of ABILIFY. In addition, in a long-term (52 weeks), active-controlled study, the incidence of tremor was 5% (40/859) for ABILIFY. A similar profile was observed in a long-term monotherapy study and a long-term adjunctive study with lithium and valproate in bipolar disorder.
Other Adverse Reactions Observed During Clinical Trial Evaluation of ABILIFY
The following listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.
Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare reactions are those occurring in fewer than 1/1,000 patients:
Adults — Oral Administration
- Blood and Lymphatic System Disorders: rare – thrombocytopenia
- Cardiac Disorders: infrequent – bradycardia, palpitations, rare – atrial flutter, cardio-respiratory arrest, atrioventricular block, atrial fibrillation, angina pectoris, myocardial ischemia, myocardial infarction, cardiopulmonary failure
- Eye Disorders: infrequent – photophobia; rare – diplopia
- Gastrointestinal Disorders: infrequent – gastroesophageal reflux disease
- General Disorders and Administration Site Conditions: frequent – asthenia; infrequent – peripheral edema, chest pain; rare – face edema
- Hepatobiliary Disorders: rare – hepatitis, jaundice
- Immune System Disorders: rare – hypersensitivity
- Injury, Poisoning, and Procedural Complications: infrequent – fall; rare – heat stroke
- Investigations: frequent – blood prolactin decreased, weight decreased, infrequent – hepatic enzyme increased, blood glucose increased, blood lactate dehydrogenase increased, gamma glutamyl transferase increased; rare –blood prolactin increased, blood urea increased, blood creatinine increased, blood bilirubin increased, electrocardiogram QT prolonged, glycosylated hemoglobin increased
- Metabolism and Nutrition Disorders: frequent – anorexia; rare – hypokalemia, hyponatremia, hypoglycemia
- Musculoskeletal and Connective Tissue Disorders: infrequent – muscular weakness, muscle tightness; rare – rhabdomyolysis, mobility decreased
- Nervous System Disorders: infrequent – parkinsonism, memory impairment, cogwheel rigidity, hypokinesia, bradykinesia; rare – akinesia, myoclonus, coordination abnormal, speech disorder, Grand Mal convulsion; <1/10,000 patients – choreoathetosis
- Psychiatric Disorders: infrequent – aggression, loss of libido, delirium; rare – libido increased, anorgasmia, tic, homicidal ideation, catatonia, sleep walking
- Renal and Urinary Disorders: rare – urinary retention, nocturia
- Reproductive System and Breast Disorders: infrequent – erectile dysfunction; rare – gynaecomastia, menstruation irregular, amenorrhea, breast pain, priapism
- Respiratory, Thoracic, and Mediastinal Disorders: infrequent – nasal congestion, dyspnea
- Skin and Subcutaneous Tissue Disorders: infrequent – rash, hyperhidrosis, pruritus, photosensitivity reaction, alopecia; rare – urticaria
- Vascular Disorders: infrequent – hypotension, hypertension
Pediatric Patients — Oral Administration
Most adverse events observed in the pooled database of 1,686 pediatric patients, aged 6 to 18 years, were also observed in the adult population. Additional adverse reactions observed in the pediatric population are listed below.
- Eye Disorders: infrequent – oculogyric crisis
- Gastrointestinal Disorders: infrequent – tongue dry, tongue spasm
- Investigations: frequent – blood insulin increased
- Nervous System Disorders: infrequent – sleep talking
- Renal and Urinary Disorders frequent – enuresis
- Skin and Subcutaneous Tissue Disorders: infrequent – hirsutism
Adults — Intramuscular Injection
Most adverse reactions observed in the pooled database of 749 adult patients treated with ABILIFY injection, were also observed in the adult population treated with oral ABILIFY. Additional adverse reactions observed in the ABILIFY injection population are listed below.
General Disorders and Administration Site Conditions:
≥1/100 patients — injection site reaction; ≥1/1,000 patients and <1/100 patients — venipuncture site bruise
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