ABILIFY (Page 22 of 24)

14.6 Agitation Associated with Schizophrenia or Bipolar Mania

The efficacy of intramuscular ABILIFY for injection for the treatment of agitation was established in three short-term (24-hour), placebo-controlled trials in agitated inpatients from two diagnostic groups: schizophrenia and bipolar I disorder (manic or mixed episodes, with or without psychotic features). Each of the trials included a single active comparator treatment arm of either haloperidol injection (schizophrenia studies) or lorazepam injection (bipolar mania study). Patients could receive up to three injections during the 24-hour treatment periods; however, patients could not receive the second injection until after the initial 2-hour period when the primary efficacy measure was assessed. Patients enrolled in the trials needed to be: (1) judged by the clinical investigators as clinically agitated and clinically appropriate candidates for treatment with intramuscular medication, and (2) exhibiting a level of agitation that met or exceeded a threshold score of ≥15 on the five items comprising the Positive and Negative Syndrome Scale (PANSS) Excited Component (i.e., poor impulse control, tension, hostility, uncooperativeness, and excitement items) with at least two individual item scores ≥4 using a 1-7 scoring system (1 = absent, 4 = moderate, 7 = extreme). In the studies, the mean baseline PANSS Excited Component score was 19, with scores ranging from 15 to 34 (out of a maximum score of 35), thus suggesting predominantly moderate levels of agitation with some patients experiencing mild or severe levels of agitation. The primary efficacy measure used for assessing agitation signs and symptoms in these trials was the change from baseline in the PANSS Excited Component at 2 hours post-injection. A key secondary measure was the Clinical Global Impression of Improvement (CGI-I) Scale. The results of the trials follow:

In a placebo-controlled trial in agitated inpatients predominantly meeting DSM-IV criteria for schizophrenia (n=350), four fixed ABILIFY injection doses of 1 mg, 5.25 mg, 9.75 mg, and 15 mg were evaluated. At 2 hours post-injection, the 5.25 mg, 9.75 mg, and 15 mg doses were statistically superior to placebo in the PANSS Excited Component (Study 1 in Table 31) and on the CGI-I Scale.

In a second placebo-controlled trial in agitated inpatients predominantly meeting DSM-IV criteria for schizophrenia (n=445), one fixed ABILIFY injection dose of 9.75 mg was evaluated. At 2 hours post-injection, ABILIFY for injection was statistically superior to placebo in the PANSS Excited Component (Study 2 in Table 31) and on the CGI-I Scale.

In a placebo-controlled trial in agitated inpatients meeting DSM-IV criteria for bipolar I disorder (manic or mixed) (n=291), two fixed ABILIFY injection doses of 9.75 mg and 15 mg were evaluated. At 2 hours post-injection, both doses were statistically superior to placebo in the PANSS Excited Component (Study 3 in Table 31).

Examination of population subsets (age, race, and gender) did not reveal any differential responsiveness on the basis of these subgroupings.

Table 31: Agitation Associated with Schizophrenia or Bipolar Mania Studies

Study Number

Treatment Group

Primary Efficacy Measure: PANSS Excited Component

Mean Baseline Score (SD)

LS Mean Change from Baseline (SE)

Placebo-subtracted Differencea (95% CI)

Agitation Associated with Schizophrenia

Study 1

ABILIFY (1 mg)

19.16 (3.26)

-4.47 (0.72)

-1.19 (-2.96 , 0.59)

ABILIFY (5.25 mg)*

19.41 (3.31)

-5.65 (0.68)

-2.37 (-4.10 , -0.63)

ABILIFY (9.75 mg)*

19.42 (2.80)

-6.69 (0.72)

-3.40 (-5.18 , -1.62)

ABILIFY (15 mg)*

19.34 (2.38)

-5.72 (0.72)

-2.44 (-4.21 , -0.68)

Placebo

19.18 (2.95)

-3.28 (0.70)

Study 2

ABILIFY (9.75 mg)*

18.82 (2.67)

-7.27 (0.59)

-2.48 (-3.77, -1.19)

Placebo

18.74 (2.71)

-4.78 (0.69)

Agitation Associated with Bipolar Mania

Study 3

ABILIFY (9.75 mg)*

18.77 (2.45)

-8.74 (0.57)

-2.99 (-4.53, -1.44)

ABILIFY (15 mg)*

18.29 (2.49)

-8.67 (0.57)

-2.91 (-4.44, -1.38)

Placebo

17.95 (2.63)

-5.76 (0.58)

SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.

a Difference (drug minus placebo) in least-squares mean change from baseline.

* Doses statistically significantly superior to placebo.

HOW SUPPLIED

Product: 68151-5121

NDC: 68151-5121-1 1 TABLET in a PACKAGE

17 PATIENT COUNSELING INFORMATION

See Medication Guide

Discuss the following issues with patients prescribed ABILIFY:

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 ABILIFY 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 ABILIFY. 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 ABILIFY is not approved as a single agent for treatment of depression and has not been evaluated in pediatric major depressive disorder.

Use of Orally Disintegrating Tablet

Do not open the blister until ready to administer. For single tablet removal, open the package and peel back the foil on the blister to expose the tablet. Do not push the tablet through the foil because this could damage the tablet. Immediately upon opening the blister, using dry hands, remove the tablet and place the entire ABILIFY DISCMELT Orally Disintegrating Tablet on the tongue. Tablet disintegration occurs rapidly in saliva. It is recommended that ABILIFY DISCMELT be taken without liquid. However, if needed, it can be taken with liquid. Do not attempt to split the tablet.

Interference with Cognitive and Motor Performance

Because ABILIFY 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 ABILIFY therapy does not affect them adversely [see WARNINGS AND PRECAUTIONS (5.10)].

Nursing

Advise patients that breastfeeding is not recommended with ABILIFY treatment because of the potential for serious adverse reactions in a nursing infant [see USE IN SPECIFIC POPULATIONS (8.3)].

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 (5.11)].

Sugar Content

Patients should be advised that each mL of ABILIFY Oral Solution contains 400 mg of sucrose and 200 mg of fructose.

Phenylketonurics

Phenylalanine is a component of aspartame. Each ABILIFY DISCMELT Orally Disintegrating Tablet contains the following amounts: 10 mg, 1.12 mg phenylalanine and 15 mg, 1.68 mg phenylalanine.

Tablets manufactured by Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan

Orally Disintegrating Tablets, Oral Solution, and Injection manufactured by Bristol-Myers Squibb Company, Princeton, NJ 08543 USA

Distributed and marketed by Otsuka America Pharmaceutical, Inc., Rockville, MD 20850 USA

ABILIFY is a trademark of Otsuka Pharmaceutical Company.

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Rev January 2016

© 2016, Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan

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