Abilify

• Schizophrenia
• Acute Treatment of Manic and Mixed Episodes associated with Bipolar I Disorder
• Adjunctive Treatment of Major Depressive Disorder
• Irritability Associated with Autistic Disorder
• Treatment of Tourette's Disorder

• Administer once daily without regard to meals (
  2 DOSAGE AND ADMINISTRATION

  • Administer once daily without regard to meals

  		Initial Dose	Recommended Dose	Maximum Dose
  Schizophrenia – adults		10 to 15 mg/day	10 to 15 mg/day	30 mg/day
  Schizophrenia – adolescents		2 mg/day	10 mg/day	30 mg/day
  Bipolar mania – adults: monotherapy		15 mg/day	15 mg/day	30 mg/day
  Bipolar mania – adults: adjunct to lithium or valproate		10 to 15 mg/day	15 mg/day	30 mg/day
  Bipolar mania – pediatric patients: monotherapy or as an adjunct to lithium or valproate		2 mg/day	10 mg/day	30 mg/day
  Major Depressive Disorder – adults: adjunct to antidepressants		2 to 5 mg/day	5 to 10 mg/day	15 mg/day
  Irritability associated with autistic disorder – pediatric patients		2 mg/day	5 to 10 mg/day	15 mg/day
  Tourette's Disorder –	Patients <50 kg	2 mg/day	5 mg/day	10 mg/day
  	Patients ≥50 kg	2 mg/day	10 mg/day	20 mg/day

  • Known CYP2D6 poor metabolizers: Half of the usual dose

  2.1 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

  [see Clinical Studies (14.1)]

  .

  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

  [see Clinical Studies (14.1)]

  . 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 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

  [see Clinical Studies (14.1)]

  . 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.

  2.2 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

  [see Clinical Studies (14.2)]

  .

  2.3 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 one week

  [see Clinical Studies (14.3)]

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

  2.4 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 one week

  [see Clinical Studies (14.4)]

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

  2.5 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 one 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 one week

  [see Clinical Studies (14.5)].

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

  2.6 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 1). 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 1: Dose Adjustments for ABILIFY in Patients who are known CYP2D6 Poor Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, CYP3A4 Inhibitors, and/or CYP3A4 Inducers

  Factors	Dosage Adjustments for ABILIFY
  Known CYP2D6 Poor Metabolizers	Administer half of usual dose
  Known CYP2D6 Poor Metabolizers taking concomitant strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin)	Administer a quarter of usual dose
  Strong CYP2D6 (e.g., quinidine, fluoxetine, paroxetine) or CYP3A4 inhibitors (e.g., itraconazole, clarithromycin)	Administer half of usual dose
  Strong CYP2D6 and CYP3A4 inhibitors	Administer a quarter of usual dose
  Strong CYP3A4 inducers (e.g., carbamazepine, rifampin)	Double usual dose over 1 to 2 weeks

  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)

  .
  )

• Known CYP2D6 poor metabolizers: Half of the usual dose (
  2.6 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 1). 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 1: Dose Adjustments for ABILIFY in Patients who are known CYP2D6 Poor Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, CYP3A4 Inhibitors, and/or CYP3A4 Inducers

  Factors	Dosage Adjustments for ABILIFY
  Known CYP2D6 Poor Metabolizers	Administer half of usual dose
  Known CYP2D6 Poor Metabolizers taking concomitant strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin)	Administer a quarter of usual dose
  Strong CYP2D6 (e.g., quinidine, fluoxetine, paroxetine) or CYP3A4 inhibitors (e.g., itraconazole, clarithromycin)	Administer half of usual dose
  Strong CYP2D6 and CYP3A4 inhibitors	Administer a quarter of usual dose
  Strong CYP3A4 inducers (e.g., carbamazepine, rifampin)	Double usual dose over 1 to 2 weeks

  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)

  .
  )

ABILIFY^® (aripiprazole) Tablets are available as described in Table 2.