Aripiprazole (Page 2 of 15)

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 1 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 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. [see Clinical Studies ( 14.5) ].

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

2.7 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 When the coadministered drug is withdrawn from the combination therapy, aripiprazole dosage should then be adjusted to its original level. When the coadministered CYP3A4 inducer is withdrawn, aripiprazole dosage should be reduced to the original level over 1 to 2 weeks.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 Aripiprazole in Patients who are known CYP2D6 Poor Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, 3A4 Inhibitors, and/or CYP3A4 Inducers

Factors	Dosage Adjustments for Aripiprazole
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 aripiprazole is administered to patients with major depressive disorder, aripiprazole should be administered without dosage adjustment as specified in Dosage and Administration ( 2.3).

2.8 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 [see Clinical Pharmacology ( 12.3) ].

2.9 Dosing of Orally Disintegrating Tablets

The dosing for Aripiprazole Orally Disintegrating Tablets is the same as for the oral tablets [see Dosage and Administration (2.1, 2.2, 2.3, and 2.4)].

3 DOSAGE FORMS AND STRENGTHS

Aripiprazole tablets, USP are available as described in Table 3.

Table 3: Aripiprazole Tablet, USP Presentations

Tablet Strength	Tablet Color/Shape	Tablet Markings
2 mg	yellow round	debossed with “2” on one side and “16” on other side
5 mg	white to off-white round	debossed with “5” on one side and “17” on other side
10 mg	white to off-white round	debossed with “10” on one side and “18” on other side
15 mg	white to off-white round	debossed with “15” on one side and “19” on other side
20 mg	white to off-white round	debossed with “20” on both sides
30 mg	white to off-white round	debossed with “30” on one side and “21” on other side