Aripiprazole (Page 10 of 12)

14.2 Bipolar Disorder

Maintenance Treatment of Bipolar I Disorder
Monotherapy Maintenance Therapy
A maintenance trial was conducted in adult patients meeting DSM-IV criteria for bipolar I disorder with a recent manic or mixed episode who had been stabilized on open-label aripiprazole and who had maintained a clinical response for at least 6 weeks. The first phase of this trial was an open-label stabilization period in which inpatients and outpatients were clinically stabilized and then maintained on open-label aripiprazole (15 or 30 mg/day, with a starting dose of 30 mg/day) for at least 6 consecutive weeks. One hundred sixty-one outpatients were then randomized in a double-blind fashion, to either the same dose of aripiprazole they were on at the end of the stabilization and maintenance period or placebo and were then monitored for manic or depressive relapse. During the randomization phase, aripiprazole was superior to placebo on time to the number of combined affective relapses (manic plus depressive), the primary outcome measure for this study (Study 7 in Figure 7). A total of 55 mood events were observed during the double-blind treatment phase. Nineteen were from the aripiprazole group and 36 were from the placebo group. The number of observed manic episodes in the aripiprazole group (6) were fewer than that in the placebo group (19), while the number of depressive episodes in the aripiprazole group (9) was similar to that in the placebo group (11).
An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender; however, there were insufficient numbers of patients in each of the ethnic groups to adequately assess inter-group differences.Figure 7: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse (Bipolar Study 7)

Figure 7
(click image for full-size original)

Adjunctive Maintenance Therapy
An adjunctive maintenance trial was conducted in adult patients meeting DSM-IV criteria for bipolar I disorder with a recent manic or mixed episode. Patients were initiated on open-label lithium (0.6 to 1.0 mEq/L) or valproate (50 to 125 μg/mL) at therapeutic serum levels, and remained on stable doses for 2 weeks. At the end of 2 weeks, patients demonstrating inadequate response (Y-MRS total score ≥16 and ≤35% improvement on the Y-MRS total score) to lithium or valproate received aripiprazole with a starting dose of 15 mg/day with the option to increase to 30 mg or reduce to 10 mg as early as day 4, as adjunctive therapy with open-label lithium or valproate. Prior to randomization, patients on the combination of single-blind aripiprazole and lithium or valproate were required to maintain stability (Y-MRS and MADRS total scores ≤12) for 12 consecutive weeks. Three hundred thirty-seven patients were then randomized in a double-blind fashion, to either the same dose of aripiprazole they were on at the end of the stabilization period or placebo plus lithium or valproate and were then monitored for manic, mixed, or depressive relapse for a maximum of 52 weeks. Aripiprazole was superior to placebo on the primary endpoint, time from randomization to relapse to any mood event (Study 8 in Figure 8). A mood event was defined as hospitalization for a manic, mixed, or depressive episode, study discontinuation due to lack of efficacy accompanied by Y-MRS score >16 and/or a MADRS >16, or an SAE of worsening disease accompanied by Y-MRS score >16 and/or a MADRS >16. A total of 68 mood events were observed during the double-blind treatment phase. Twenty-five were from the aripiprazole group and 43 were from the placebo group. The number of observed manic episodes in the aripiprazole group (7) were fewer than that in the placebo group (19), while the number of depressive episodes in the aripiprazole group (14) was similar to that in the placebo group (18). The Kaplan-Meier curves of the time from randomization to relapse to any mood event during the 52-week, double-blind treatment phase for aripiprazole and placebo groups are shown in Figure 8.Figure 8: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse to Any Mood Event (Bipolar Study 8)

Figure 8
(click image for full-size original)

An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender; however, there were insufficient numbers of patients in each of the ethnic groups to adequately assess inter-group differences.

Additional pediatric use information is approved for Otsuka America Pharmaceutical, Inc.’s ABILIFY® (aripiprazole) product. However, due to Otsuka America Pharmaceutical, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Aripiprazole tablets, USP 2 mg are light green to green, modified rectangular, bevel edged biconvex tablets debossed with ‘I’ on one side and ’94’ on other side.
Bottles of 30 Tablets NDC 16714-141-01
Aripiprazole tablets, USP 5 mg are light blue to blue, modified rectangular, bevel edged biconvex tablets debossed with ‘I’ on one side and ’95’ on other side.
Bottles of 30 Tablets NDC 16714-142-01
Aripiprazole tablets, USP 10 mg are light pink to pink, modified rectangular, bevel edged biconvex tablets debossed with ‘I’ on one side and ’96’ on other side.
Bottles of 30 Tablets NDC 16714-143-01
Aripiprazole tablets, USP 15 mg are light yellow to yellow, round, bevel edged biconvex tablets debossed with ‘I’ on one side and ’97’ on other side.
Bottles of 30 Tablets NDC 16714-144-01
Aripiprazole tablets, USP 20 mg are white to off-white, round, bevel edged biconvex tablets debossed with ‘I’ on one side and ’98’ on other side.
Bottles of 30 Tablets NDC 16714-145-01
Aripiprazole tablets, USP 30 mg are light pink to pink, round, bevel edged biconvex tablets debossed with ‘I’ on one side and ’99’ on other side.
Bottles of 30 Tablets NDC 16714-146-01

16.2 Storage

Store at 20º to 25º C (68º to 77ºF) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION


Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Discuss the following issues with patients prescribed aripiprazole tablets:
Clinical Worsening of Depression and Suicide Risk
Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication [see Warnings and Precautions (5.3)].

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with aripiprazole tablets and should counsel them in its appropriate use. A patient Medication Guide including information about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for aripiprazole tablets. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. It should be noted that aripiprazole tablets are not approved as a single agent for treatment of depression and has not been evaluated in pediatric major depressive disorder.

Pathological Gambling and Other Compulsive Behaviors
Advise patients and their caregivers of the possibility that they may experience compulsive urges to shop, intense urges to gamble, compulsive sexual urges, binge eating and/or other compulsive urges and the inability to control these urges while taking aripiprazole. In some cases, but not all, the urges were reported to have stopped when the dose was reduced or stopped [see Warnings and Precautions (5.7)].

Interference with Cognitive and Motor Performance
Because aripiprazole tablets may have the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that aripiprazole therapy does not affect them adversely [see Warnings and Precautions (5.12)].
Concomitant Medication
Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions [see Drug Interactions (7)].
Heat Exposure and Dehydration
Patients should be advised regarding appropriate care in avoiding overheating and dehydration [see Warnings and Precautions (5.13)].
Pregnancy
Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with aripiprazole. Advise patients that aripiprazole may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) in a neonate. Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to aripiprazole during pregnancy [see Use in Specific Populations (8.1)].

ABILIFY® is a trademark of Otsuka Pharmaceutical Company.

Medication Guide available at www.northstarrxllc.com/products or call 1-800-206-7821

Manufactured for:
Northstar Rx LLC

Memphis, TN 38141.

By: HETEROTM
Hetero Labs Limited, Unit V, Polepally, Jadcherla,

Mahabubnagar — 509 301, India.

Issued: 08/2020

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