INDICATION AND USES:
ABILIFY is an atypical antipsychotic. The oral formulations are indicated for:
- Schizophrenia (14.1)
- Acute Treatment of Manic and Mixed Episodes associated with Bipolar I (14.2)
- Adjunctive Treatment of Major Depressive Disorder (14.3)
- Irritability Associated with Autistic Disorder (14.4)
- Treatment of Tourette’s disorder (14.5)
- The injection is indicated for: Agitation associated with schizophrenia or bipolar mania (14.6)
DOSAGE AND ADMINISTRATION
| Initial Dose | Recommended Dose | Maximum Dose | ||
| Schizophrenia – adults (2.1) | 10 to 15 mg/day | 10 to 15 mg/day | 30 mg/day | |
| Schizophrenia – adolescents (2.1) | 2 mg/day | 10 mg/day | 30 mg/day | |
| Bipolar mania – adults: monotherapy (2.2) | 15 mg/day | 15 mg/day | 30 mg/day | |
| Bipolar mania – adults: adjunct to lithium or valproate (2.2) | 10 to 15 mg/day | 15 mg/day | 30 mg/day | |
| Bipolar mania – adults: pediatric patients: monotherapy or as an adjunct to lithium or valproate (2.2) | 2 mg/day | 10 mg/day | 30 mg/day | |
| Major Depressive Disorder – Adults adjunct to antidepressants (2.3) | 2 to 5 mg/day | 5 to 10 mg/day | 15 mg/day | |
| Irritability associated with autistic disorder – pediatric patients (2.4) | 2 mg/day | 5 to 10 mg/day | 15 mg/day | |
| Tourette’s disorder (2.5) | Patients < 50 kg | 2 mg/day | 5 mg/day | 10 mg/day |
| Patients >50 kg | 2 mg/day | 10 mg/day | 20 mg/day | |
| Agitation associated with schizophrenia or bipolar mania – adults (2.6) | 9.75 mg/1.3 mL injected IM | 30 mg/day injected IM | ||
- Oral formulations: Administer once daily without regard to meals (2)
- IM injection: Wait at least 2 hours between doses. Maximum daily dose 30 mg (2.6)
- Known CYP2D6 poor metabolizers: Half of the usual dose (2.7)
SIDE EFFECTS:
Commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo) were (6.1):
- Adult patients with schizophrenia: akathisia
- Pediatric patients (13 to 17 years) with schizophrenia: extrapyramidal disorder, somnolence, and tremor
- Adult patients (monotherapy) with bipolar mania: akathisia, sedation, restlessness, tremor, and extrapyramidal disorder
- Adult patients (adjunctive therapy with lithium or valproate) with bipolar mania: akathisia, insomnia, and extrapyramidal disorder
- Pediatric patients (10 to 17 years) with bipolar mania: somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, and dizziness
- Adult patients with major depressive disorder (adjunctive treatment to antidepressant therapy): akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision
- Pediatric patients (6 to 17 years) with autistic disorder: sedation, fatigue, vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, and lethargy
- Pediatric patients (6 to 18 years) with Tourette’s disorder: sedation, somnolence, nausea, headache, nasopharyngitis, fatigue, increased appetite
- Adult patients with agitation associated with schizophrenia or bipolar mania: nausea
CONTRAINDICATIONS:
Known hypersensitivity to ABILIFY (4)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities) (5.2)
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring (5.4) Tardive Dyskinesia: Discontinue if clinically appropriate (5.5)
- Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain (5.6)
- Hyperglycemia/Diabetes Mellitus: Monitor glucose regularly in patients with and at risk for diabetes (5.6)
- Dyslipidemia: Undesirable alterations in lipid levels have been observed in patients treated with atypical antipsychotics (5.6)
- Weight Gain: Weight gain has been observed with atypical antipsychotic use. Monitor weight (5.6)
- Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation (5.7)
- Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope (5.8)
- Leukopenia, Neutropenia, and Agranulocytosis: have been reported with antipsychotics including ABILIFY. Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of ABILIFY should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors (5.10)
- Seizures/Convulsions: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold (5.11)
- Potential for Cognitive and Motor Impairment: Use caution when operating machinery (5.12)
- Suicide: The possibility of a suicide attempt is inherent in schizophrenia and bipolar disorder. Closely supervise high-risk patients (5.14)
DRUG INTERACTIONS:
| Factors | Dosage Adjustments for ABILIFY |
| Known CYP2D6 Poor Metabolizers | Administer half of usual dose |
| Known CYP2D6 Poor Metabolizers and strong CYP3A4 inhibitors | Administer a quarter of usual dose |
| Strong CYP2D6 or CYP3A4 inhibitors | Administer half of usual dose |
| Strong CYP2D6 and CYP3A4 inhibitors | Administer a quarter of usual dose |
| Strong CYP2D6 inducers | Double usual dose over 1 to 2 weeks |
OVERDOSE:
In clinical trials and in postmarketing experience, adverse reactions of deliberate or accidental overdosage with oral ABILIFY have been reported worldwide. These include overdoses with oral ABILIFY alone and in combination with other substances. No fatality was reported with ABILIFY alone. The largest known dose with a known outcome involved acute ingestion of 1260 mg of oral ABILIFY (42 times the maximum recommended daily dose) by a patient who fully recovered. Deliberate or accidental overdosage was also reported in children (age 12 and younger) involving oral ABILIFY ingestions up to 195 mg with no fatalities. Common adverse reactions (reported in at least 5% of all overdose cases) reported with oral ABILIFY overdosage (alone or in combination with other substances) include vomiting, somnolence, and tremor. Other clinically important signs and symptoms observed in one or more patients with ABILIFY overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia.
Management of Overdosage: No specific information is available on the treatment of overdose with ABILIFY. An electrocardiogram should be obtained in case of overdosage and if QT interval prolongation is present, cardiac monitoring should be instituted. Otherwise, management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers. Charcoal: In the event of an overdose of ABILIFY, an early charcoal administration may be useful in partially preventing the absorption of aripiprazole. Administration of 50 g of activated charcoal, one hour after a single 15 mg oral dose of ABILIFY, decreased the mean AUC and Cmax of aripiprazole by 50%. Hemodialysis: Although there is no information on the effect of hemodialysis in treating an overdose with ABILIFY, hemodialysis is unlikely to be useful in overdose management since aripiprazole is highly bound to plasma proteins
- Uses
-
INDICATION AND USES:
ABILIFY is an atypical antipsychotic. The oral formulations are indicated for:
- Schizophrenia (14.1)
- Acute Treatment of Manic and Mixed Episodes associated with Bipolar I (14.2)
- Adjunctive Treatment of Major Depressive Disorder (14.3)
- Irritability Associated with Autistic Disorder (14.4)
- Treatment of Tourette’s disorder (14.5)
- The injection is indicated for: Agitation associated with schizophrenia or bipolar mania (14.6)
DOSAGE AND ADMINISTRATION
Initial Dose Recommended Dose Maximum Dose Schizophrenia – adults (2.1) 10 to 15 mg/day 10 to 15 mg/day 30 mg/day Schizophrenia – adolescents (2.1) 2 mg/day 10 mg/day 30 mg/day Bipolar mania – adults: monotherapy (2.2) 15 mg/day 15 mg/day 30 mg/day Bipolar mania – adults: adjunct to lithium or valproate (2.2) 10 to 15 mg/day 15 mg/day 30 mg/day Bipolar mania – adults: pediatric patients: monotherapy or as an adjunct to lithium or valproate (2.2) 2 mg/day 10 mg/day 30 mg/day Major Depressive Disorder – Adults adjunct to antidepressants (2.3) 2 to 5 mg/day 5 to 10 mg/day 15 mg/day Irritability associated with autistic disorder – pediatric patients (2.4) 2 mg/day 5 to 10 mg/day 15 mg/day Tourette’s disorder (2.5) Patients < 50 kg 2 mg/day 5 mg/day 10 mg/day Patients >50 kg 2 mg/day 10 mg/day 20 mg/day Agitation associated with schizophrenia or bipolar mania – adults (2.6) 9.75 mg/1.3 mL injected IM 30 mg/day injected IM - Oral formulations: Administer once daily without regard to meals (2)
- IM injection: Wait at least 2 hours between doses. Maximum daily dose 30 mg (2.6)
- Known CYP2D6 poor metabolizers: Half of the usual dose (2.7)
- Side Effects
-
SIDE EFFECTS:
Commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo) were (6.1):
- Adult patients with schizophrenia: akathisia
- Pediatric patients (13 to 17 years) with schizophrenia: extrapyramidal disorder, somnolence, and tremor
- Adult patients (monotherapy) with bipolar mania: akathisia, sedation, restlessness, tremor, and extrapyramidal disorder
- Adult patients (adjunctive therapy with lithium or valproate) with bipolar mania: akathisia, insomnia, and extrapyramidal disorder
- Pediatric patients (10 to 17 years) with bipolar mania: somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, and dizziness
- Adult patients with major depressive disorder (adjunctive treatment to antidepressant therapy): akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision
- Pediatric patients (6 to 17 years) with autistic disorder: sedation, fatigue, vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, and lethargy
- Pediatric patients (6 to 18 years) with Tourette’s disorder: sedation, somnolence, nausea, headache, nasopharyngitis, fatigue, increased appetite
- Adult patients with agitation associated with schizophrenia or bipolar mania: nausea
- Precautions
-
CONTRAINDICATIONS:
Known hypersensitivity to ABILIFY (4)
WARNINGS AND PRECAUTIONS:
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities) (5.2)
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring (5.4) Tardive Dyskinesia: Discontinue if clinically appropriate (5.5)
- Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain (5.6)
- Hyperglycemia/Diabetes Mellitus: Monitor glucose regularly in patients with and at risk for diabetes (5.6)
- Dyslipidemia: Undesirable alterations in lipid levels have been observed in patients treated with atypical antipsychotics (5.6)
- Weight Gain: Weight gain has been observed with atypical antipsychotic use. Monitor weight (5.6)
- Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation (5.7)
- Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope (5.8)
- Leukopenia, Neutropenia, and Agranulocytosis: have been reported with antipsychotics including ABILIFY. Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of ABILIFY should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors (5.10)
- Seizures/Convulsions: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold (5.11)
- Potential for Cognitive and Motor Impairment: Use caution when operating machinery (5.12)
- Suicide: The possibility of a suicide attempt is inherent in schizophrenia and bipolar disorder. Closely supervise high-risk patients (5.14)
- Interactions
-
DRUG INTERACTIONS:
Factors Dosage Adjustments for ABILIFY Known CYP2D6 Poor Metabolizers Administer half of usual dose Known CYP2D6 Poor Metabolizers and strong CYP3A4 inhibitors Administer a quarter of usual dose Strong CYP2D6 or CYP3A4 inhibitors Administer half of usual dose Strong CYP2D6 and CYP3A4 inhibitors Administer a quarter of usual dose Strong CYP2D6 inducers Double usual dose over 1 to 2 weeks - Overdose
-
OVERDOSE:
In clinical trials and in postmarketing experience, adverse reactions of deliberate or accidental overdosage with oral ABILIFY have been reported worldwide. These include overdoses with oral ABILIFY alone and in combination with other substances. No fatality was reported with ABILIFY alone. The largest known dose with a known outcome involved acute ingestion of 1260 mg of oral ABILIFY (42 times the maximum recommended daily dose) by a patient who fully recovered. Deliberate or accidental overdosage was also reported in children (age 12 and younger) involving oral ABILIFY ingestions up to 195 mg with no fatalities. Common adverse reactions (reported in at least 5% of all overdose cases) reported with oral ABILIFY overdosage (alone or in combination with other substances) include vomiting, somnolence, and tremor. Other clinically important signs and symptoms observed in one or more patients with ABILIFY overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia.
Management of Overdosage: No specific information is available on the treatment of overdose with ABILIFY. An electrocardiogram should be obtained in case of overdosage and if QT interval prolongation is present, cardiac monitoring should be instituted. Otherwise, management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers. Charcoal: In the event of an overdose of ABILIFY, an early charcoal administration may be useful in partially preventing the absorption of aripiprazole. Administration of 50 g of activated charcoal, one hour after a single 15 mg oral dose of ABILIFY, decreased the mean AUC and Cmax of aripiprazole by 50%. Hemodialysis: Although there is no information on the effect of hemodialysis in treating an overdose with ABILIFY, hemodialysis is unlikely to be useful in overdose management since aripiprazole is highly bound to plasma proteins