aripiprazole

Abilify is a prescription medicine used to treat the symptoms of schizophrenia, bipolar I disorder (manic depression), major depressive disorder, irritability associated with autistic disorder, and Tourette's disorder. Abilify may be used alone or with other medications. Abilify is an antipsychotic, antimanic agent.

It is not known if Abilify is safe and effective in children younger than 6 years of age.

WARNING

INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Abilify is not approved for the treatment of patients with dementia-related psychosis.

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.

In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

Abilify may cause serious side effects including:

• severe agitation or distress,
• feeling restless,
• twitching or uncontrollable movements of your eyes, lips, tongue, face, arms or legs,
• mask-like appearance of the face,
• trouble swallowing,
• speech problems,
• seizure (convulsions),
• thoughts of suicide or self-harm,
• stiff or rigid muscles,
• high fever,
• sweating,
• confusion,
• fast or uneven heartbeats,
• tremors (shaking),
• feeling lightheaded,
• chills,
• sore throat,
• mouth sores,
• skin sores,
• cough,
• difficulty breathing,
• increased thirst,
• increased urination,
• dry mouth, and
• fruity breath odor

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Abilify include:

• uncontrolled muscle movements,
• anxiety,
• feeling restless,
• weight gain,
• nausea,
• vomiting,
• constipation,
• increased appetite,
• headache,
• dizziness,
• drowsiness,
• feeling tired,
• sleep problems (insomnia),
• stuffy nose, and
• sore throat

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Abilify. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Drug Abuse And Dependence

Controlled Substance

Abilify is not a controlled substance.

Abuse

• Abilify 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 Abilify 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 CNS-active drug will be misused, diverted, and/or abused once marketed.

Schizophrenia

Adults

• The recommended starting and target dose for Abilify is 10 or 15 mg/day administered on a once-a-day schedule without regard to meals. Abilify has been systematically evaluated and shown to be effective in a dose range of 10 to 30 mg/day, when administered as the tablet formulation; however, doses higher than 10 or 15 mg/day were not more effective than 10 or 15 mg/day. Dosage increases should generally not be made before 2 weeks, the time needed to achieve steady-state.
• Maintenance Treatment: Maintenance of efficacy in schizophrenia was demonstrated in a trial involving patients with schizophrenia who had been symptomatically stable on other antipsychotic medications for periods of 3 months or longer. These patients were discontinued from those medications and randomized to either Abilify 15 mg/day or placebo, and observed for relapse. Patients should be periodically reassessed to determine the continued need for maintenance treatment.

Adolescents

• The recommended target dose of Abilify is 10 mg/day. Aripiprazole was studied in adolescent patients 13 to 17 years of age with schizophrenia at daily doses of 10 mg and 30 mg. The starting daily dose of the tablet formulation in these patients was 2 mg, which was titrated to 5 mg after 2 days and to the target dose of 10 mg after 2 additional days. Subsequent dose increases should be administered in 5 mg increments. The 30 mg/day dose was not shown to be more efficacious than the 10 mg/day dose. Abilify can be administered without regard to meals. Patients should be periodically reassessed to determine the need for maintenance treatment.

Switching From Other Antipsychotics

• There are no systematically collected data to specifically address switching patients with schizophrenia from other antipsychotics to Abilify or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

Bipolar I Disorder

Acute Treatment Of Manic And Mixed Episodes

Adults

• The recommended starting dose in adults is 15 mg given once daily as monotherapy and 10 mg to 15 mg given once daily as adjunctive therapy with lithium or valproate. Abilify can be given without regard to meals. The recommended target dose of Abilify is 15 mg/day, as monotherapy or as adjunctive therapy with lithium or valproate. The dose may be increased to 30 mg/day based on clinical response. The safety of doses above 30 mg/day has not been evaluated in clinical trials.

Pediatrics

• The recommended starting dose in pediatric patients (10 to 17 years) as monotherapy is 2 mg/day, with titration to 5 mg/day after 2 days, and a target dose of 10 mg/day after 2 additional days. Recommended dosing as adjunctive therapy to lithium or valproate is the same. Subsequent dose increases, if needed, should be administered in 5 mg/day increments. Abilify can be given without regard to meals.

Adjunctive Treatment Of Major Depressive Disorder

Adults

• The recommended starting dose for Abilify as adjunctive treatment for patients already taking an antidepressant is 2 to 5 mg/day. The recommended dosage range is 2 to 15 mg/day. Dosage adjustments of up to 5 mg/day should occur gradually, at intervals of no less than 1 week. Patients should be periodically reassessed to determine the continued need for maintenance treatment.

Irritability Associated With Autistic Disorder

Pediatric Patients (6 To 17 Years)

• The recommended dosage range for the treatment of pediatric patients with irritability associated with autistic disorder is 5 to 15 mg/day.
• Dosing should be initiated at 2 mg/day. The dose should be increased to 5 mg/day, with subsequent increases to 10 or 15 mg/day if needed. Dose adjustments of up to 5 mg/day should occur gradually, at intervals of no less than 1 week. Patients should be periodically reassessed to determine the continued need for maintenance treatment.

Tourette's Disorder

Pediatric Patients (6 To 18 Years)

• The recommended dosage range for Tourette's Disorder is 5 to 20 mg/day.
• For patients weighing less than 50 kg, dosing should be initiated at 2 mg/day with a target dose of 5 mg/day after 2 days. The dose can be increased to 10 mg/day in patients who do not achieve optimal control of tics. Dosage adjustments should occur gradually at intervals of no less than 1 week.
• For patients weighing 50 kg or more, dosing should be initiated at 2 mg/day for 2 days, and then increased to 5 mg/day for 5 days, with a target dose of 10 mg/day on day 8. The dose can be increased up to 20 mg/day for patients who do not achieve optimal control of tics. Dosage adjustments should occur gradually in increments of 5 mg/day at intervals of no less than 1 week.

Patients should be periodically reassessed to determine the continued need for maintenance treatment.

Agitation Associated With Schizophrenia Or Bipolar Mania (Intramuscular Injection)

Adults

• The recommended dose in these patients is 9.75 mg. The recommended dosage range is 5.25 to 15 mg. No additional benefit was demonstrated for 15 mg compared to 9.75 mg. A lower dose of 5.25 mg may be considered when clinical factors warrant. If agitation warranting a second dose persists following the initial dose, cumulative doses up to a total of 30 mg/day may be given. However, the efficacy of repeated doses of Abilify injection in agitated patients has not been systematically evaluated in controlled clinical trials. The safety of total daily doses greater than 30 mg or injections given more frequently than every 2 hours have not been adequately evaluated in clinical trials.
• If ongoing Abilify therapy is clinically indicated, oral Abilify in a range of 10 to 30 mg/day should replace Abilify injection as soon as possible.

Administration Of Abilify Injection

• To administer Abilify Injection, draw up the required volume of solution into the syringe as shown in Table 1. Discard any unused portion.

Table 1: Abilify Injection Dosing Recommendations

• Abilify Injection is intended for intramuscular use only. Do not administer intravenously or subcutaneously. Inject slowly, deep into the muscle mass.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Dosage Adjustments For Cytochrome P450 Considerations

• Dosage adjustments are recommended in patients who are known CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers (see Table 2). When the coadministered drug is withdrawn from the combination therapy, Abilify dosage should then be adjusted to its original level.
• When the coadministered CYP3A4 inducer is withdrawn, Abilify dosage should be reduced to the original level over 1 to 2 weeks. Patients who may be receiving a combination of strong, moderate, and weak inhibitors of CYP3A4 and CYP2D6 (e.g., a strong CYP3A4 inhibitor and a moderate CYP2D6 inhibitor or a moderate CYP3A4 inhibitor with a moderate CYP2D6 inhibitor), the dosing may be reduced to one-quarter (25%) of the usual dose initially and then adjusted to achieve a favorable clinical response.

Table 2: Dose Adjustments for Abilify in Patients who are known CYP2D6 Poor Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, 3A4 Inhibitors, and/or CYP3A4 Inducers

• When adjunctive Abilify is administered to patients with major depressive disorder, Abilify should be administered without dosage adjustment as specified in Dosage and Administration (2.3).

Dosing Of Oral Solution

• The oral solution can be substituted for tablets on a mg-per-mg basis up to the 25 mg dose level. Patients receiving 30 mg tablets should receive 25 mg of the solution.

Dosing Of Orally Disintegrating Tablets

• The dosing for Abilify Orally Disintegrating Tablets is the same as for the oral tablets [see above Sections].

Drugs Having Clinically Important Interactions With Abilify

Table 25: Clinically Important Drug Interactions with Abilify

Drugs Having No Clinically Important Interactions With Abilify

• Based on pharmacokinetic studies, no dosage adjustment of Abilify 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 Abilify. Additionally, no dosage adjustment is necessary for valproate, lithium, lamotrigine, lorazepam, or sertraline when co-administered with Abilify.

Dementia

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Abilify (aripiprazole) is not approved for the treatment of patients with dementia-related psychosis.

Pregnancy

• Neonates exposed to antipsychotic drugs, including Abilify, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
• There are risks to the mother associated with untreated schizophrenia, bipolar I disorder, or major depressive disorder, and with exposure to antipsychotics, including Abilify, during pregnancy.

Breastfeeding

• Limited data from published literature report the presence of aripiprazole in human breast milk, at relative infant doses ranging between 0.7% to 8.3% of the maternal weight-adjusted dosage. There are reports of poor weight gain in breastfed infants exposed to aripiprazole and reports of inadequate milk supply in lactating women taking aripiprazole.
• The development and health benefits of breastfeeding should be considered along with the mother's clinical need for Abilify and any potential adverse effects on the breastfed infant from Abilify or from the underlying maternal condition.