Aripiprazole Oral Solution
- Generic Name: aripiprazole oral solution
- Brand Name: Aripiprazole Oral Solution
Aripiprazole Oral Solution (Aripiprazole Oral Solution) side effects drug center
Aripiprazole Oral Solution Side Effects Center
What Is Aripiprazole Oral Solution?
Aripiprazole oral solution is an atypical antipsychotic indicated for schizophrenia, and acute treatment of manic and mixed episodes associated with Bipolar I. Aripiprazole oral solution is available in generic form.
What Are Side Effects of Aripiprazole Oral Solution?
Common side effects of aripiprazole oral solution include:
- agitation,
- restlessness,
- extrapyramidal symptoms (abnormal movement, repetitive movements, muscle contractions involuntary movements),
- neuroleptic malignant syndrome (NMS) (a life-threatening reaction with symptoms including fever, altered mental status, muscle rigidity, and dizziness, and fainting),
- drowsiness,
- tremor,
- insomnia,
- fatigue,
- nausea,
- weight gain,
- difficulty regulating body temperature,
- difficulty swallowing (especially in the elderly),
- seizures (convulsions), and
- excess salivation.
Some patients have thoughts of suicide while taking aripiprazole oral solution. Tell your doctor if this occurs.
Dosage for Aripiprazole Oral Solution
The dose of aripiprazole oral solution is 1 mg/mL.
What Drugs, Substances, or Supplements Interact with Aripiprazole Oral Solution?
Aripiprazole oral solution may interact with itraconazole, clarithromycin, quinidine, fluoxetine, paroxetine, carbamazepine, rifampin, antihypertensive drugs, and benzodiazepines. Tell your doctor all medications and supplements you use.
Aripiprazole Oral Solution During Pregnancy or Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant before using aripiprazole oral solution. Aripiprazole oral solution may cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. Aripiprazole oral solution passes into breast milk. Breastfeeding while using aripiprazole oral solution is not recommended.
Additional Information
Our Aripiprazole Oral Solution Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Aripiprazole Oral Solution Consumer Information
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Tell your doctor right away if you have new or sudden changes in mood or behavior, including new or worse depression or anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, more active or talkative, or have thoughts about suicide or hurting yourself.
Call your doctor at once if you have:
- severe agitation, distress, or restless feeling;
- twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs;
- mask-like appearance of the face, trouble swallowing, problems with speech;
- seizure (convulsions);
- severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;
- low blood cell counts--fever, chills, sore throat, weakness, easy bruising, unusual bleeding, purple or red spots under your skin; or
- high blood sugar--increased thirst, increased urination, dry mouth, fruity breath odor.
You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medicine. Talk with your doctor if this occurs.
Common side effects may include:
- blurred vision;
- increased saliva or drooling;
- muscle stiffness;
- uncontrolled muscle movements, shaking, anxiety, feeling restless;
- weight gain;
- nausea, vomiting, constipation;
- increased or decreased appetite;
- headache, dizziness, drowsiness, feeling tired;
- sleep problems (insomnia); or
- cold symptoms such as stuffy nose, sneezing, sore throat;
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Aripiprazole Oral Solution (Aripiprazole Oral Solution)
Aripiprazole Oral Solution Professional Information
SIDE EFFECTS
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 [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
- Cerebrovascular Adverse Events, Including Stroke [see WARNINGS AND PRECAUTIONS]
- Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
- Neuroleptic Malignant Syndrome (NMS) [see WARNINGS AND PRECAUTIONS]
- Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS]
- Metabolic Changes [see WARNINGS AND PRECAUTIONS]
- Pathological Gambling and Other Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
- Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
- Falls [see WARNINGS AND PRECAUTIONS]
- Leukopenia, Neutropenia, and Agranulocytosis [see WARNINGS AND PRECAUTIONS]
- Seizures/Convulsions [see WARNINGS AND PRECAUTIONS]
- Potential for Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS]
- Body Temperature Regulation [see WARNINGS AND PRECAUTIONS]
- Suicide [see WARNINGS AND PRECAUTIONS]
- Dysphagia [see WARNINGS AND PRECAUTIONS]
The most common adverse reactions in adult patients in clinical trials (≥10%) were nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia, and restlessness.
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, bipolar disorder, major depressive disorder, Dementia of the Alzheimer's type, Parkinson's disease, and alcoholism, and who had approximately 7,619 patient-years of exposure to oral aripiprazole. A total of 3,390 patients were treated with oral aripiprazole for at least 180 days and 1,933 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, bipolar mania, autistic disorder, or Tourette's disorder 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 (monotherapy and adjunctive therapy with antidepressants or mood stabilizers) included (in overlapping categories) double-blind, comparative and noncomparative open-label studies, inpatient and outpatient studies, fixed- and flexible-dose studies, and short- and longerterm exposure.
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 aripiprazole was administered in doses ranging from 2 mg/day to 30 mg/day.
Commonly Observed Adverse Reactions
The only commonly observed adverse reaction associated with the use of aripiprazole in patients with schizophrenia (incidence of 5% or greater and aripiprazole incidence at least twice that for placebo) was akathisia (aripiprazole 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 aripiprazole was administered at doses of 15 mg/day or 30 mg/day.
Commonly Observed Adverse Reactions
Commonly observed adverse reactions associated with the use of aripiprazole in patients with bipolar mania (incidence of 5% or greater and aripiprazole incidence at least twice that for placebo) are shown in Table 16.
Table 16: Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials of Adult Patients with Bipolar Mania Treated with Oral Aripiprazole Monotherapy
| Preferred Term | Percentage of Patients Reporting Reaction | |
| Aripiprazole (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 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.
Table 17: Adverse Reactions in Short-Term, Placebo-Controlled Trials in Adult Patients Treated with Oral Aripiprazole
| System Organ Class Preferred Term |
Percentage of Patients Reporting Reaction* | |
| Aripiprazole (n=l,843) |
Placebo (n=l,166) |
|
| Eye Disorders | ||
| Blurred Vision | 3 | 1 |
| Gastrointestinal Disorders | ||
| Nausea | 15 | 11 |
| Constipation | 11 | 7 |
| Vomiting | 11 | S |
| 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 |
| *Adverse reactions reported by at least 2% of patients treated with oral aripiprazole, except adverse reactions which had an incidence equal to or less than placebo. | ||
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 aripiprazole was administered at doses of 15 mg/day 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 aripiprazole compared to 6% for patients treated with adjunctive placebo. The most common adverse drug reactions associated with discontinuation in the adjunctive aripiprazole-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 aripiprazole 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 aripiprazole (doses of 15 mg/day 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.
Table 18: Adverse Reactions in a Short-Term, Placebo-Controlled Trial of Adjunctive Therapy in Patients with Bipolar Disorder
| System Organ Class Preferred Term |
Percentage of Patients Reporting Reaction* | |
| Aripiprazole + 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 |
| *Adverse reactions reported by at least 2% of patients treated with oral aripiprazole, except adverse reactions which had an incidence equal to or less than placebo. †Lithium or Valproate |
||
Pediatric Patients (13 to 17 years) With Schizophrenia
The following findings are based on one 6-week, placebo-controlled trial in which oral aripiprazole was administered in doses ranging from 2 mg/day to 30 mg/day.
Adverse Reactions Associated With Discontinuation Of Treatment
The incidence of discontinuation due to adverse reactions between aripiprazole-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 aripiprazole in adolescent patients with schizophrenia (incidence of 5% or greater and aripiprazole 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 aripiprazole was administered in doses of 10 mg/day or 30 mg/day.
Adverse Reactions Associated With Discontinuation Of Treatment
The incidence of discontinuation due to adverse reactions between aripiprazole-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 aripiprazole in pediatric patients with bipolar mania (incidence of 5% or greater and aripiprazole incidence at least twice that for placebo) are shown in Table 19.
Table 19: Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials of Pediatric Patients (10 to 17 years) with Bipolar Mania Treated with Oral Aripiprazole
| Preferred Term | Percentage of Patients Reporting Reaction | |
| Aripiprazole (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 aripiprazole was administered in doses of 2 mg/day to 15 mg/day.
Adverse Reactions Associated With Discontinuation Of Treatment
The incidence of discontinuation due to adverse reactions between aripiprazole-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 aripiprazole in pediatric patients with autistic disorder (incidence of 5% or greater and aripiprazole incidence at least twice that for placebo) are shown in Table 20.
Table 20: Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials of Pediatric Patients (6 to 17 years) with Autistic Disorder Treated with Oral Aripiprazole
| Percentage of Patients Reporting Reaction | ||
| Aripiprazole (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 | S | 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 aripiprazole was administered in doses of 2 mg/day to 20 mg/day.
Adverse Reactions Associated With Discontinuation Of Treatment
The incidence of discontinuation due to adverse reactions between aripiprazole-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 aripiprazole in pediatric patients with Tourette's disorder (incidence of 5% or greater and aripiprazole incidence at least twice that for placebo) are shown in Table 21.
Table 21: Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials of Pediatric Patients (6 to 18 years) with Tourette's Disorder Treated with Oral Aripiprazole
| Preferred Term | Percentage of Patients Reporting Reaction | |
| Aripiprazole (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 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.
Table 22: Adverse Reactions in Short-Term, Placebo-Controlled Trials of Pediatric Patients (6 to 18 years) Treated with Oral Aripiprazole
| System Organ ClassPreferred Term | Percentage of Patients Reporting Reaction* | |
| Aripiprazole (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 |
| *Adverse reactions reported by at least 2% of pediatric patients treated with oral aripiprazole, except adverse reactions which had an incidence equal to or less than placebo. | ||
Adult Patients Receiving Aripiprazole 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 aripiprazole was administered at doses of 2 mg 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 aripiprazole-treated patients and 2% for adjunctive placebo-treated patients.
Commonly Observed Adverse Reactions
The commonly observed adverse reactions associated with the use of adjunctive aripiprazole in patients with major depressive disorder (incidence of 5% or greater and aripiprazole 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 aripiprazole (doses ≥2 mg/day) and for which the incidence in patients treated with adjunctive aripiprazole was greater than the incidence in patients treated with adjunctive placebo in the combined dataset.
Table 23: Adverse Reactions in Short-Term, Placebo-Controlled Adjunctive Trials in Patients with Major Depressive Disorder
| System Organ Class Preferred Term |
Percentage of Patients Reporting Reaction* | |
| Aripiprazole + 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 | 2 | |
| Metabolism and Nutrition Disorders | ||
| Increased Appetite | 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 |
| *Adverse reactions reported by at least 2% of patients treated with adjunctive aripiprazole, except adverse reactions which had an incidence equal to or less than placebo. †Antidepressant Therapy |
||
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 mg/day, 5 mg/day, 10 mg/day, 15 mg/day, 20 mg/day, and 30 mg/day) of oral aripiprazole 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%; 10 mg, 13%; 30 mg, 21.6%); somnolence (incidences were placebo, 6%; 10 mg, 11%; 30 mg, 21.6%); and tremor (incidences were placebo, 2%; 10 mg, 2%; 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%; 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 aripiprazoletreated patients was 13% vs. 12% for placebo; and the incidence of akathisia-related events for aripiprazole-treated patients was 8% vs. 4% for placebo. In the shortterm, 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 aripiprazole-treated patients was 25% vs. 7% for placebo; and the incidence of akathisia-related events for aripiprazole-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 aripiprazole and placebo, with the exception of the Barnes Akathisia Scale (aripiprazole, 0.08; placebo, -0.05). In the pediatric (13 to 17 years) schizophrenia trial, the objectively collected data did not show a difference between aripiprazole and placebo, with the exception of the Simpson Angus Rating Scale (aripiprazole, 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 aripiprazole 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 aripiprazole-treated patients was 16% vs. 8% for placebo and the incidence of akathisia-related events for monotherapy aripiprazole-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 aripiprazole-treated patients was 15% vs. 8% for adjunctive placebo and the incidence of akathisia-related events for adjunctive aripiprazole-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 aripiprazole-treated patients was 26% vs. 5% for placebo and the incidence of akathisia-related events for aripiprazole-treated patients was 10% vs. 2% for placebo.
In the adult bipolar mania trials with monotherapy aripiprazole, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between aripiprazole and placebo (aripiprazole, 0.5; placebo, -0.01 and aripiprazole, 0.21; placebo, -0.05). Changes in the Assessments of Involuntary Movement Scales were similar for the aripiprazole and placebo groups. In the bipolar mania trials with aripiprazole as adjunctive therapy with either lithium or valproate, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between adjunctive aripiprazole and adjunctive placebo (aripiprazole, 0.73; placebo, 0.07 and aripiprazole, 0.3; placebo, 0.11). Changes in the Assessments of Involuntary Movement Scales were similar for adjunctive aripiprazole 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 aripiprazole and placebo (aripiprazole, 0.9; placebo, -0.05). Changes in the Barnes Akathisia Scale and the Assessments of Involuntary Movement Scales were similar for the aripiprazole 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 aripiprazole-treated patients was 8% vs. 5% for adjunctive placebo-treated patients; and the incidence of akathisia-related events for adjunctive aripiprazoletreated 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 aripiprazole and adjunctive placebo (aripiprazole, 0.31; placebo, 0.03 and aripiprazole, 0.22; placebo, 0.02). Changes in the Assessments of Involuntary Movement Scales were similar for the adjunctive aripiprazole 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 aripiprazole-treated patients was 18% vs. 2% for placebo and the incidence of akathisia-related events for aripiprazole-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 aripiprazole and placebo (aripiprazole, 0.1; placebo, -0.4). Changes in the Barnes Akathisia Scale and the Assessments of Involuntary Movement Scales were similar for the aripiprazole 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 aripiprazole-treated patients was 7% vs. 6% for placebo and the incidence of akathisia-related events for aripiprazole-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 aripiprazole 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 aripiprazole 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 aripiprazole 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 aripiprazole. In addition, in a long-term (52 week), active-controlled study, the incidence of tremor was 5% (40/859) for aripiprazole. 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 The Premarketing Evaluation Of Aripiprazole
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 - 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
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of aripiprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to establish a causal relationship to drug exposure: occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups, blood glucose fluctuation, oculogyric crisis, and drug reaction with eosinophilia and systemic symptoms (DRESS).
DRUG INTERACTIONS
Drugs Having Clinically Important Interactions With Aripiprazole
Table 25: Clinically Important Drug Interactions with Aripiprazole
| Concomitant Drug Name or Drug Class | Clinical Rationale | Clinical Recommendation |
| Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin) or strong CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) | The concomitant use of aripiprazole with strong CYP 3 A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of aripiprazole alone [see Clinical Pharmacology (12.3)]. | With concomitant use of aripiprazole with a strong CYP3 A4 inhibitor or CYP2D6 inhibitor, reduce the aripiprazole dosage [see DOSAGE AND ADMINISTRATION]. |
| Strong CYP3A4 Inducers (e.g., carbamazepine, rifampin) | The concomitant use of aripiprazole and carbamazepine decreased the exposure of aripiprazole compared to the use of aripiprazole alone [see CLINICAL PHARMACOLOGY]. | With concomitant use of aripiprazole with a strong CYP3 A4 inducer, consider increasing the aripiprazole dosage [see DOSAGE AND ADMINISTRATION]. |
| Antihypertensive Drugs | Due to its alpha adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents. | Monitor blood pressure and adjust dose accordingly [see WARNINGS AND PRECAUTIONS]. |
| Benzodiazepines (e.g., lorazepam) | The intensity of sedation was greater with the combination of oral aripiprazole and lorazepam as compared to that observed with aripiprazole alone. The orthostatic hypotension observed was greater with the combination as compared to that observed with lorazepam alone [see WARNINGS AND PRECAUTIONS]. | Monitor sedation and blood pressure. Adjust dose accordingly. |
Drugs Having No Clinically Important Interactions With Aripiprazole
Based on pharmacokinetic studies, no dosage adjustment of aripiprazole is required when administered concomitantly with famotidine, valproate, lithium, lorazepam.
In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin, escitalopram), or CYP3A4 (e.g., dextromethorphan) when co-administered with aripiprazole. Additionally, no dosage adjustment is necessary for valproate, lithium, lamotrigine, lorazepam, or sertraline when co-administered with aripiprazole [see CLINICAL PHARMACOLOGY].
Drug Abuse And Dependence
Controlled Substance
Aripiprazole is not a controlled substance.
Abuse
Aripiprazole has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of aripiprazole misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior).
Dependence
In physical dependence studies in monkeys, withdrawal symptoms were observed upon abrupt cessation of dosing. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNSactive drug will be misused, diverted, and/or abused once marketed.
Read the entire FDA prescribing information for Aripiprazole Oral Solution (Aripiprazole Oral Solution)
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