Abilify Maintena

Name: Abilify Maintena

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Abilify Maintena?

  • If you need to store Abilify Maintena at home, talk with your doctor, nurse, or pharmacist about how to store it.

Indications and Usage for Abilify Maintena

Abilify Maintena (aripiprazole) is indicated for:

• Treatment of schizophrenia in adults [see Clinical Studies (14.1)] • Maintenance monotherapy treatment of bipolar I disorder in adults [see Clinical Studies (14.2)]

Abilify Maintena Dosage and Administration

Dosage Overview for the Treatment of Schizophrenia and Maintenance Monotherapy of Bipolar I Disorder

Abilify Maintena is only to be administered by intramuscular injection by a healthcare professional. The recommended starting and maintenance dose of Abilify Maintena is 400 mg monthly (no sooner than 26 days after the previous injection).

For patients who have never taken aripiprazole, establish tolerability with oral aripiprazole prior to initiating treatment with Abilify Maintena. Due to the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.

After the first Abilify Maintena injection, administer oral aripiprazole (10 mg to 20 mg) for 14 consecutive days to achieve therapeutic aripiprazole concentrations during initiation of therapy. For patients already stable on another oral antipsychotic (and known to tolerate aripiprazole), after the first Abilify Maintena injection, continue treatment with the antipsychotic for 14 consecutive days to maintain therapeutic antipsychotic concentrations during initiation of therapy.

If there are adverse reactions with the 400 mg dosage, consider reducing the dosage to 300 mg once monthly.

Dosage Adjustments for Missed Doses

If the second or third doses are missed:

• If more than 4 weeks and less than 5 weeks have elapsed since the last injection, administer the injection as soon as possible. • If more than 5 weeks have elapsed since the last injection, restart concomitant oral aripiprazole for 14 days with the next administered injection.

If the fourth or subsequent doses are missed:

• If more than 4 weeks and less than 6 weeks have elapsed since the last injection, administer the injection as soon as possible. • If more than 6 weeks have elapsed since the last injection, restart concomitant oral aripiprazole for 14 days with the next administered injection.

Dosage Adjustments for Cytochrome P450 Considerations

Dosage adjustments are recommended in patients who are CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater than 14 days (see Table 1). Dosage adjustments for 200 mg and 160 mg are obtained only by using the 300 mg or 400 mg strength vials for intramuscular deltoid or gluteal injection.

If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the Abilify Maintena dosage may need to be increased [see DOSAGE AND ADMINISTRATION (2.1)].

Avoid the concomitant use of CYP3A4 inducers with Abilify Maintena for greater than 14 days because the blood levels of aripiprazole are decreased and may be below the effective levels.

Dosage adjustments are not recommended for patients with concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days.

Table 1: Dose Adjustments of Abilify Maintena in Patients who are known CYP2D6 Poor Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, 3A4 Inhibitors, and/or CYP3A4 Inducers for Greater than 14 days
Factors Adjusted Dose
* 200 mg and 160 mg dosage adjustments are obtained only by using the 300 mg or 400 mg strength vials.

CYP2D6 Poor Metabolizers

Known CYP2D6 Poor Metabolizers

300 mg

Known CYP2D6 Poor Metabolizers taking concomitant CYP3A4 inhibitors

200 mg*

Patients Taking 400 mg of Abilify Maintena

Strong CYP2D6 or CYP3A4 inhibitors

300 mg

CYP2D6 and CYP3A4 inhibitors

200 mg*

CYP3A4 inducers

Avoid use

Patients Taking 300 mg of Abilify Maintena

Strong CYP2D6 or CYP3A4 inhibitors

200 mg*

CYP2D6 and CYP3A4 inhibitors

160 mg*

CYP3A4 inducers

Avoid use

Abilify Maintena comes in two types of kits. See instructions for reconstitution/injection/disposal procedures for 1) Pre-filled Dual Chamber Syringe [see DOSAGE AND ADMINISTRATION (2.5)], and 2) Vials [see DOSAGE AND ADMINISTRATION (2.6)].

Different Aripiprazole Formulations and Kits

There are two aripiprazole formulations for intramuscular use with different dosages, dosing frequencies, and indications. Abilify Maintena is a long-acting aripiprazole formulation with 4 week dosing intervals indicated for the treatment of schizophrenia and maintenance monotherapy of bipolar I disorder in adults. In contrast, aripiprazole injection (9.75 mg per vial) is a short-acting formulation indicated for agitation in patients with schizophrenia or mania. Do not substitute these products. Refer to the prescribing information for aripiprazole injection for more information about aripiprazole injection. Abilify Maintena comes in two types of kits. See instructions for reconstitution/injection/disposal procedures for 1)

Pre-filled Dual Chamber Syringe available in 300 mg or 400 mg strength syringes [see DOSAGE AND ADMINISTRATION (2.5)], and 2) Single-use vials available in 300 mg or 400 mg strength vials [see DOSAGE AND ADMINISTRATION (2.6)].

The 200 mg and 160 mg dosage adjustments are obtained only by using the 300 mg or 400 mg strength vials.

Pre-filled Dual Chamber Syringe: Preparation and Administration Instructions

Preparation Prior to Reconstitution

For deep intramuscular deltoid or gluteal injection by healthcare professionals only. Do not administer by any other route. Inject full syringe contents immediately following reconstitution. Administer once monthly.

Lay out and confirm that components listed below are provided in the kit:

• One Abilify Maintena (aripiprazole) pre-filled dual chamber syringe (400 mg or 300 mg as appropriate) for extended release injectable suspension containing lyophilized powder and Sterile Water for Injection • One 23 gauge, 1 inch (25 mm) hypodermic safety needle with needle protection device for deltoid administration in non-obese patients • One 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection device for gluteal administration in non-obese patients or deltoid administration in obese patients • One 21 gauge, 2 inch (51 mm) hypodermic safety needle with needle protection device for gluteal administration in obese patients

Reconstitution of Lyophilized Powder in Pre-filled Dual Chamber Syringe

Reconstitute at room temperature.

a) Push plunger rod slightly to engage threads. And then, rotate plunger rod until the rod stops rotating to release diluent. After plunger rod is at complete stop, middle stopper will be at the indicator line (See Figure 1).

Figure 1

b) Vertically shake the syringe vigorously for 20 seconds until drug is uniformly milky-white (See Figure 2).

Figure 2

c) Visually inspect the syringe for particulate matter and discoloration prior to administration. The reconstituted Abilify Maintena suspension should appear to be a uniform, homogeneous suspension that is opaque and milky-white in color.

Injection Procedure

Use appropriate aseptic techniques throughout injection procedure. For deep intramuscular injection only.

a) Twist and pull off Over-cap and Tip-cap (See Figure 3).

Figure 3

b) Select appropriate needle (See Figure 4).

Figure 4

For deltoid administration:

• 23 gauge, 1 inch (25 mm) hypodermic safety needle with needle protection device for non-obese patients • 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection device for obese patients

For gluteal administration:

• 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection device for non-obese patients • 21 gauge, 2 inch (51 mm) hypodermic safety needle with needle protection device for obese patients c) While holding the needle cap, ensure the needle is firmly seated on the safety device with a push. Twist clockwise until SNUGLY fitted (See Figure 5).

Figure 5

d) Then PULL needle-cap straight up (see Figure 6).

Figure 6

e) Hold syringe UPRIGHT and ADVANCE PLUNGER ROD SLOWLY TO EXPEL THE AIR. Expel air until suspension fills needle base. If it’s not possible to advance plunger rod to expel the air, check that plunger rod is rotated to a complete stop (See Figure 7).

Figure 7

f) Inject slowly into the deltoid or gluteal muscle. Do not massage the injection site.

Disposal Procedure

a) Engage the needle safety device and safely discard all kit components (See Figure 8). Abilify Maintena pre-filled dual chamber syringe is for single-use only.

Figure 8

b) Rotate sites of injections between the two deltoid or gluteal muscles.

Vial: Preparation and Administration Instructions

Preparation Prior to Reconstitution

For deep intramuscular injection by healthcare professionals only. Do not administer by any other route. Inject immediately after reconstitution. Administer once monthly.

a) Lay out and confirm that components listed below are provided in the kit: • Vial of Abilify Maintena (aripiprazole) for extended-release injectable suspension lyophilized powder • 5 mL vial of Sterile Water for Injection, USP • One 3 mL luer lock syringe with pre-attached 21 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection device • One 3 mL luer lock disposable syringe with luer lock tip • One vial adapter • One 23 gauge, 1 inch (25 mm) hypodermic safety needle with needle protection device for deltoid administration in non-obese patients • One 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection device for gluteal administration in non-obese patients or deltoid administration in obese patients • One 21 gauge, 2 inch (51 mm) hypodermic safety needle with needle protection device for gluteal administration in obese patients b) Abilify Maintena should be suspended using the Sterile Water for Injection as supplied in the kit. c) The Sterile Water for Injection and Abilify Maintena vials are for single-use only. d) Use appropriate aseptic techniques throughout reconstitution and reconstitute at room temperature. e) Select the amount of Sterile Water for Injection needed for reconstitution (see Table 2). Table 2: Amount of Sterile Water for Injection Needed for Reconstitution

400 mg Vial

300 mg Vial

Dose

Sterile Water for Injection

Dose

Sterile Water for Injection

400 mg

1.9 mL

300 mg

1.5 mL

Important: There is more Sterile Water for Injection in the vial than is needed to reconstitute Abilify Maintena (aripiprazole) for extended-release injectable suspension. The vial will have excess Sterile Water for Injection; discard any unused portion.

Reconstitution of Lyophilized Powder in Vial

a) Remove the cap of the vial of Sterile Water for Injection and remove the cap of the vial containing Abilify Maintena lyophilized powder and wipe the tops with a sterile alcohol swab. b) Using the syringe with pre-attached hypodermic safety needle, withdraw the pre-determined Sterile Water for Injection volume from the vial of Sterile Water for Injection into the syringe (see Figure 9). Residual Sterile Water for Injection will remain in the vial following withdrawal; discard any unused portion.

Figure 9

c) Slowly inject the Sterile Water for Injection into the vial containing the Abilify Maintena lyophilized powder (see Figure 10).

Figure 10

d) Withdraw air to equalize the pressure in the vial by pulling back slightly on the plunger. Subsequently, remove the needle from the vial. Engage the needle safety device by using the one-handed technique (see Figure 11). Gently press the sheath against a flat surface until the needle is firmly engaged in the needle protection sheath. Visually confirm that the needle is fully engaged into the needle protection sheath, and discard.

Figure 11

e) Shake the vial vigorously for 30 seconds until the reconstituted suspension appears uniform (see Figure 12).

Figure 12

f) Visually inspect the reconstituted suspension for particulate matter and discoloration prior to administration. The reconstituted Abilify Maintena is a uniform, homogeneous suspension that is opaque and milky-white in color. g) If the injection is not performed immediately after reconstitution keep the vial at room temperature and shake the vial vigorously for at least 60 seconds to re-suspend prior to injection. h) Do not store the reconstituted suspension in a syringe.

Preparation Prior to Injection

a) Use appropriate aseptic techniques throughout injection of the reconstituted Abilify Maintena suspension. b) Remove the cover from the vial adapter package (see Figure 13). Do not remove the vial adapter from the package.

Figure 13

c) Using the vial adapter package to handle the vial adapter, attach the prepackaged luer lock syringe to the vial adapter (see Figure 14).

Figure 14

d) Use the luer lock syringe to remove the vial adapter from the package and discard the vial adapter package (see Figure 15). Do not touch the spike tip of the adapter at any time.

Figure 15

e) Determine the recommended volume for injection (Table 3). Table 3: Abilify Maintena Reconstituted Suspension Volume to Inject
400 mg Vial 300 mg Vial

Dose

Volume to Inject

Dose

Volume to Inject

400 mg

2 mL

---

---

300 mg

1.5 mL

300 mg

1.5 mL

200 mg

1 mL

200 mg

1 mL

160 mg

0.8 mL

160 mg

0.8 mL

f) Wipe the top of the vial of the reconstituted Abilify Maintena suspension with a sterile alcohol swab. g) Place and hold the vial of the reconstituted Abilify Maintena suspension on a hard surface. Attach the adapter-syringe assembly to the vial by holding the outside of the adapter and pushing the adapter's spike firmly through the rubber stopper, until the adapter snaps in place (see Figure 16).

Figure 16

h) Slowly withdraw the recommended volume from the vial into the luer lock syringe to allow for injection (see Figure 17). A small amount of excess product will remain in the vial.

Figure 17

Injection Procedure a) Detach the luer lock syringe containing the recommended volume of reconstituted Abilify Maintena suspension from the vial. b) Select the appropriate hypodermic safety needle and attach the needle to the luer lock syringe containing the suspension for injection. While holding the needle cap, ensure the needle is firmly seated on the safety device with a push. Twist clockwise until snugly fitted and then pull the needle cap straight away from the needle (see Figure 18).

For deltoid administration:

• 23 gauge, 1 inch (25 mm) hypodermic safety needle with needle protection device for non-obese patients • 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection device for obese patients

For gluteal administration:

• 22 gauge, 1.5 inch (38 mm) hypodermic safety needle with needle protection device for non-obese patients • 21 gauge, 2 inch (51 mm) hypodermic safety needle with needle protection device for obese patients

Figure 18

c) Slowly inject the recommended volume as a single intramuscular injection into the deltoid or gluteal muscle. Do not massage the injection site. Disposal Procedure a) Engage the needle safety device as described in Section 2.6, Step (d) of Reconstitution of Lyophilized Powder in Vial and safely discard all kit components (see Figure 8). Dispose of the vials, adapter, needles, and syringe appropriately after injection. The Sterile Water for Injection and Abilify Maintena vials are for single-use only. b) Rotate sites of injections between the two deltoid or gluteal muscles.

Adverse Reactions

The following adverse reactions are discussed in more detail in other sections of the labeling:

• Increased Mortality in Elderly Patients with Dementia - Related Psychosis Use [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)] • Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with Dementia-Related Psychosis [see BOXED WARNINGand WARNINGS AND PRECAUTIONS (5.2)] • Neuroleptic Malignant Syndrome [see WARNINGS AND PRECAUTIONS (5.3)] • Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS (5.4)] • Metabolic Changes [see WARNINGS AND PRECAUTIONS (5.5)] • Pathological Gambling and Other Compulsive Behaviors [see WARNINGS AND PRECAUTIONS (5.6)] • Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS (5.7)] • Falls [see WARNINGS AND PRECAUTIONS (5.8)] • Leukopenia, Neutropenia, and Agranulocytosis [see WARNINGS AND PRECAUTIONS (5.9)] • Seizures [see WARNINGS AND PRECAUTIONS (5.10)] • Potential for Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS (5.11)] • Body Temperature Regulation [see WARNINGS AND PRECAUTIONS (5.12)] • Dysphagia [see WARNINGS AND PRECAUTIONS (5.13)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Safety Database of Abilify Maintena and Oral Aripiprazole

Oral aripiprazole has been evaluated for safety in 16,114 adult patients who participated in multiple-dose, clinical trials in schizophrenia and other indications, and who had approximately 8,578 patient-years of exposure to oral aripiprazole. A total of 3,901 patients were treated with oral aripiprazole for at least 180 days, 2,259 patients were treated with oral aripiprazole for at least 360 days, and 933 patients continuing aripiprazole treatment for at least 720 days.

Abilify Maintena has been evaluated for safety in 2,128 adult patients in clinical trials in schizophrenia, with approximately 2,633 patient-years of exposure to Abilify Maintena. A total of 1,229 patients were treated with Abilify Maintena for at least 180 days (at least 7 consecutive injections) and 935 patients treated with Abilify Maintena had at least 1 year of exposure (at least 13 consecutive injections).

Abilify Maintena has been evaluated for safety in 804 adult patients in clinical trials in bipolar I disorder, with approximately 530 patient-years of exposure to Abilify Maintena. A total of 419 patients were treated with Abilify Maintena for at least 180 days (at least 7 consecutive injections) and 287 patients treated with Abilify Maintena had at least 1 year of exposure (at least 13 consecutive injections).

The conditions and duration of treatment with Abilify Maintena included double-blind and open-label studies. The safety data presented below are derived from the 12-week double-blind placebo-controlled study of Abilify Maintena in adult patients with schizophrenia.

Adverse Reactions with Abilify Maintena

Most Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials in Schizophrenia

Based on the placebo-controlled trial of Abilify Maintena in schizophrenia, the most commonly observed adverse reactions associated with the use of Abilify Maintena in patients (incidence of 5% or greater and aripiprazole incidence at least twice that for placebo) were increased weight (16.8% vs 7.0%), akathisia (11.4% vs 3.5%), injection site pain (5.4% vs 0.6%) and sedation (5.4% vs 1.2%).

Commonly Reported Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials in Schizophrenia

The following findings are based on the double-blind, placebo-controlled trial that compared Abilify Maintena 400 mg or 300 mg to placebo in patients with schizophrenia. Table 7 lists the adverse reactions reported in 2% or more of Abilify Maintena-treated subjects and at a greater proportion than in the placebo group.


Table 7: Adverse Reactions in ≥ 2% of Abilify Maintena-Treated Adult Patients with Schizophrenia in a 12-Week Double-Blind, Placebo-Controlled Trial a
Percentage of Patients Reporting Reactiona
System Organ Class Abilify Maintena Placebo
Preferred Term (n=167) (n=172)

Gastrointestinal Disorders

  Constipation

10

7

  Dry Mouth

4

2

  Diarrhea

3

2

  Vomiting

3

1

  Abdominal Discomfort

2

1

General Disorders and Administration Site Conditions

  Injection Site Pain

5

1

Infections and Infestations

  Upper Respiratory Tract Infection

4

2

Investigations

  Increased Weight

17

7

  Decreased Weight

4

2

Musculoskeletal and Connective Tissue Disorders

  Arthralgia

4

1

  Back Pain

4

2

  Myalgia

4

2

  Musculoskeletal Pain

3

1

Nervous System Disorders

  Akathisia

11

4

  Sedation

5

1

  Dizziness

4

2

  Tremor

3

1

Respiratory, Thoracic and Mediastinal

  Nasal Congestion

2

1

  a This table does not include adverse reactions which had an incidence equal to or less than placebo.

Other Adverse Reactions Observed During the Clinical Trial Evaluation of Abilify Maintena

The following listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.

Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients:

Blood and Lymphatic System Disorders: rare - thrombocytopenia

Cardiac Disorders: infrequent – tachycardia; rare - bradycardia, sinus tachycardia

Endocrine Disorders: rare - hypoprolactinemia

Eye Disorders: infrequent - vision blurred, oculogyric crisis

Gastrointestinal Disorders: infrequent - abdominal pain upper, dyspepsia, nausea; rare -swollen tongue

General Disorders and Administration Site Conditions: frequent - fatigue, injection site reactions (including erythema, induration, pruritus, injection site reaction, swelling, rash, inflammation, hemorrhage); infrequent - chest discomfort, gait disturbance; rare-irritability, pyrexia

Hepatobiliary Disorders: rare - drug induced liver injury

Immune System Disorders: rare - drug hypersensitivity

Infections and Infestations: rare - nasopharyngitis

Investigations: infrequent - blood creatine phosphokinase increased, blood pressure decreased, hepatic enzyme increased, liver function test abnormal, electrocardiogram QT-prolonged; rare - blood triglycerides decreased, blood cholesterol decreased, electrocardiogram T-wave abnormal

Metabolism and Nutrition Disorders: infrequent - decreased appetite, obesity, hyperinsulinemia

Musculoskeletal and Connective Tissue Disorders: infrequent - joint stiffness, muscle twitching, trismus; rare - rhabdomyolysis

Nervous System Disorders: infrequent - extrapyramidal disorder, hypersomnia, lethargy; rare- bradykinesia, convulsion, dysgeusia, memory impairment, oromandibular dystonia

Psychiatric Disorders: frequent - anxiety, insomnia restlessness; infrequent- agitation, bruxism, psychotic disorder, suicidal ideation; rare - aggression, hypersexuality, panic attack

Renal and Urinary Disorders: rare - glycosuria, pollakiuria, urinary incontinence

Reproductive System and Breast Disorders: infrequent - ejaculation delayed

Vascular Disorders: infrequent - hypertension

Demographic Differences

An examination of population subgroups was performed across demographic subgroup categories for adverse reactions experienced by at least 5% of Abilify Maintena subjects at least twice rate of the placebo (i.e., increased weight, akathisia, injection site pain, and sedation) in the double-blind placebo-controlled trial. This analysis did not reveal evidence of differences in safety differential adverse reaction incidence on the basis of age, gender, or race alone; however, there were few subjects ≥ 65 years of age.

Injection Site Reactions of Abilify Maintena

In the data from the short-term, double-blind, placebo-controlled trial with Abilify Maintena in patients with schizophrenia, the percent of patients reporting any injection site-related adverse reaction (all reported as injection site pain) was 5.4% for patients treated with gluteal administered Abilify Maintena and 0.6% for placebo. The mean intensity of injection pain reported by subjects using a visual analog scale (0=no pain to 100=unbearably painful) approximately one hour after injection was 7.1 (SD 14.5) for the first injection and 4.8 (SD 12.4) at the last visit in the double-blind, placebo-controlled phase.

In an open-label study comparing bioavailability of Abilify Maintena administered in the deltoid or gluteal muscle, injection site pain was observed in both groups at approximately equal rates.

Extrapyramidal Symptoms (EPS)

In the short-term, placebo-controlled trial of Abilify Maintena in adults with schizophrenia, the incidence of reported EPS-related events, excluding events related to akathisia, for Abilify Maintena-treated patients was 9.6% vs. 5.2% for placebo. The incidence of akathisia-related events for Abilify Maintena-treated patients was 11.5% vs. 3.5% for placebo.

Dystonia

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups. In the short-term, placebo-controlled trial of Abilify Maintena in adults with schizophrenia, the incidence of dystonia was 1.8% for Abilify Maintena vs. 0.6% for placebo.

Neutropenia

In the short-term, placebo-controlled trial of Abilify Maintena in adults with schizophrenia, the incidence of neutropenia (absolute neutrophil count ≤1.5 thous/µL) for Abilify Maintena-treated patients was 5.7% vs. 2.1% for placebo. An absolute neutrophil count of <1 thous/µL (i.e. 0.95 thous/µL) was observed in only one patient on Abilify Maintena and resolved spontaneously without any associated adverse events [see WARNINGS AND PRECAUTIONS (5.9)].

Adverse Reactions Reported in Clinical Trials with Oral Aripiprazole

The following is a list of additional adverse reactions that have been reported in clinical trials with oral aripiprazole and not reported above for Abilify Maintena:

Cardiac Disorders: palpitations, cardiopulmonary failure, myocardial infarction, cardio-respiratory arrest, atrioventricular block, extrasystoles, angina pectoris, myocardial ischemia, atrial flutter, supraventricular tachycardia, ventricular tachycardia

Eye Disorders: photophobia, diplopia, eyelid edema, photopsia

Gastrointestinal Disorders: gastroesophageal reflux disease, swollen tongue, esophagitis, pancreatitis, stomach discomfort, toothache

General Disorders and Administration Site Conditions: asthenia, peripheral edema, chest pain, face edema, angioedema, hypothermia, pain

Hepatobiliary Disorders: hepatitis, jaundice

Immune System Disorders: hypersensitivity

Injury, Poisoning, and Procedural Complications: heat stroke

Investigations: blood prolactin increased, blood urea increased, blood creatinine increased, blood bilirubin increased, blood lactate dehydrogenase increased, glycosylated hemoglobin increased

Metabolism and Nutrition Disorders: anorexia, hyponatremia, hypoglycemia, polydipsia, diabetic ketoacidosis

Musculoskeletal and Connective Tissue Disorders: muscle rigidity, muscular weakness, muscle tightness, decreased mobility, rhabdomyolysis, musculoskeletal stiffness, pain in extremity, muscle spasms

Nervous System Disorders: coordination abnormal, speech disorder, hypokinesia, hypotonia, myoclonus, akinesia, bradykinesia, choreoathetosis

Psychiatric Disorders: loss of libido, suicide attempt, hostility, libido increased, anger, anorgasmia, delirium, intentional self-injury, completed suicide, tic, homicidal ideation, catatonia, sleep walking

Renal and Urinary Disorders: urinary retention, polyuria, nocturia

Reproductive System and Breast Disorders: menstruation irregular, erectile dysfunction, amenorrhea, breast pain, gynecomastia, priapism

Respiratory, Thoracic, and Mediastinal Disorders: nasal congestion, dyspnea, pharyngolaryngeal pain, cough

Skin and Subcutaneous Tissue Disorders: rash (including erythematous, exfoliative, generalized, macular, maculopapular, papular rash; acneiform, allergic, contact, exfoliative, seborrheic dermatitis, neurodermatitis, and drug eruption), hyperhidrosis, pruritus, photosensitivity reaction, alopecia, urticaria

Post-marketing Experience

The following adverse reactions have been identified during post-approval use of oral aripiprazole or Abilify Maintena. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups and blood glucose fluctuation.

Use in specific populations

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ABILIFY during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.

Risk Summary

Neonates exposed to antipsychotic drugs, including Abilify Maintena, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. There are insufficient data with Abilify Maintena use in pregnant women to inform a drug-associated risk. In animal reproduction studies, oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses 10 and 11 times, respectively, the maximum recommended human dose (MRHD) produced fetal death, decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal abnormalities, and diaphragmatic hernia. Oral and intravenous aripiprazole administration during the pre- and post-natal period in rats at doses 10 times the maximum recommended human dose (MRHD) produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival. Consider the benefits and risks of Abilify Maintena and possible risks to the fetus when prescribing Abilify Maintena to a pregnant woman. Advise pregnant women of potential fetal risk.

The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs (including oral aripiprazole) during the third trimester of pregnancy. These symptoms have varied in severity. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates exhibiting extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.

Animal Data

In animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits.

Pregnant rats were treated with oral doses of 3, 10, and 30 mg/kg/day which are approximately 1 to 10 times the maximum recommended human dose [MRHD] of 30 mg/day on mg/m2 basis of aripiprazole during the period of organogenesis. Treatment at the highest dose caused a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight and undescended testes. Delayed skeletal ossification was observed at 3 and 10 times the oral MRHD on mg/m2 basis.

At 3 and 10 times the oral MRHD on mg/m2 basis, delivered offspring had decreased body weights. Increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed in offspring from the highest dose group (the other dose groups were not examined for these findings). Postnatally, delayed vaginal opening was seen at 3 and 10 times the oral MRHD on mg/m2 basis and impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) along with some maternal toxicity were seen at the highest dose; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity.

In pregnant rats treated with aripiprazole intravenously at doses of 3, 9, and 27 mg/kg/day, which are 1 to 9 times the oral MRHD on mg/m2 basis, during the period of organogenesis, decreased fetal weight and delayed skeletal ossification were seen at the highest dose which also caused maternal toxicity.

In pregnant rabbits treated with oral doses of 10, 30, and 100 mg/kg/day which are 2 to 11 times human exposure at the oral MRHD based on AUC and 6 to 65 times the oral MRHD of aripiprazole on mg/m2 basis during the period of organogenesis, decreased maternal food consumption and increased abortions were seen at the highest dose as well as increased fetal mortality. Decreased fetal weight and increased incidence of fused sternebrae were observed at 3 and 11 times the MRHD based on AUC.

In pregnant rabbits receiving aripiprazole injection intravenously at doses of 3 , 10 , and 30 mg/kg/day, which are 2 to 19 times the oral MRHD on mg/m2 basis during the period of organogenesis, the highest dose caused pronounced maternal toxicity that resulted in decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased fetal skeletal ossification. The fetal no-effect dose was 5 times the human exposure at the oral MRHD based on AUC and is 6 times the oral MRHD on mg/m2 basis.

In rats treated with oral doses of 3, 10, and 30 mg/kg/day, which are 1 to 10 times the oral MRHD of aripiprazole on a mg/m2 basis, peri- and post-natally (from day 17 of gestation through day 21 postpartum), slight maternal toxicity and slightly prolonged gestation were seen at the highest dose. An increase in stillbirths and decreases in pup weight (persisting into adulthood) and survival were also seen at this dose.

In rats treated with aripiprazole intravenously at doses of 3, 8, and 20 mg/kg/day which are 1 to 6 times the oral MRHD on mg/m2 basis from day 6 of gestation through day 20 postpartum, increased stillbirths were seen at 3 and 6 times the MRHD on mg/m2 basis, and decreases in early postnatal pup weight and survival were seen at the highest dose; these doses produced some maternal toxicity. There were no effects on postnatal behavioral and reproductive development.

Lactation

Risk Summary

Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, the effects on the breastfed infant, or the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for Abilify Maintena and any potential adverse effects on the breastfed infant from Abilify Maintena or from the underlying maternal condition.

Pediatric Use

Abilify Maintena has not been studied in children 18 years of age or younger. However, juvenile animal studies have been conducted in rats and dogs.

Juvenile Animal Studies

Aripiprazole in juvenile rats caused mortality, CNS clinical signs, impaired memory and learning, and delayed sexual maturation when administered at oral doses of 10, 20, 40 mg/kg/day from weaning (21 days old) through maturity (80 days old). At 40 mg/kg/day, mortality, decreased activity, splayed hind limbs, hunched posture, ataxia, tremors and other CNS signs were observed in both genders. In addition, delayed sexual maturation was observed in males. At all doses and in a dose-dependent manner, impaired memory and learning, increased motor activity, and histopathology changes in the pituitary (atrophy), adrenals (adrenocortical hypertrophy), mammary glands (hyperplasia and increased secretion), and female reproductive organs (vaginal mucification, endometrial atrophy, decrease in ovarian corpora lutea) were observed. The changes in female reproductive organs were considered secondary to the increase in prolactin serum levels. A No Observed Adverse Effect Level (NOAEL) could not be determined and, at the lowest tested dose of 10 mg/kg/day, there is no safety margin relative to the systemic exposures (AUC0-24) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. All drug-related effects were reversible after a 2-month recovery period, and most of the drug effects in juvenile rats were also observed in adult rats from previously conducted studies.

Aripiprazole in juvenile dogs (2 months old) caused CNS clinical signs of tremors, hypoactivity, ataxia, recumbency and limited use of hind limbs when administered orally for 6 months at 3, 10, 30 mg/kg/day. Mean body weight and weight gain were decreased up to 18% in females in all drug groups relative to control values. A NOAEL could not be determined and, at the lowest tested dose of 3 mg/kg/day, there is no safety margin relative to the systemic exposures (AUC0-24) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. All drug-related effects were reversible after a 2-month recovery period.

Geriatric Use

Clinical studies of oral aripiprazole did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience and pharmacokinetic data [see CLINICAL PHARMACOLOGY (12.3)] have not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

In single-dose and multiple-dose pharmacokinetic studies, there was no detectable age effect in the population pharmacokinetic analysis of oral aripiprazole in schizophrenia patients [see CLINICAL PHARMACOLOGY (12.3)]. No dosage adjustments are recommended based on age alone. Abilify Maintena is not approved for the treatment of patients with dementia-related psychosis [see also BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)].

CYP2D6 Poor Metabolizers

Dosage adjustment is recommended in known CYP2D6 poor metabolizers due to high aripiprazole concentrations. Approximately 8% of Caucasians and 3–8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM) [see DOSAGE AND ADMINISTRATION (2.3) and CLINICAL PHARMACOLOGY (12.3)].

Hepatic and Renal Impairment

No dosage adjustment for Abilify Maintena is required on the basis of a patient’s hepatic function (mild to severe hepatic impairment, Child-Pugh score between 5 and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 mL/minute) [see CLINICAL PHARMACOLOGY (12.3)].

Other Specific Populations

No dosage adjustment for Abilify Maintena is required on the basis of a patient’s sex, race, or smoking status [see CLINICAL PHARMACOLOGY (12.3)].

Clinical Studies

Schizophrenia

The efficacy of Abilify Maintena for treatment of schizophrenia was established in:

• One short-term (12-week), randomized, double-blind, placebo-controlled trial in acutely relapsed adults, Protocol 31-12-291 (Study 1) • One longer-term, double-blind, placebo-controlled, randomized-withdrawal (maintenance) trial in adults, Protocol 31-07-246 (Study 2).

Short-Term Efficacy

In the short-term (12-week), randomized, double-blind, placebo-controlled trial in acutely relapsed adults (Study 1), the primary measure used for assessing psychiatric signs and symptoms was the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30 item scale that measures positive symptoms of schizophrenia (7 items), negative symptoms of schizophrenia (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); total PANSS scores range from 30 to 210. The primary endpoint was the change from baseline in PANSS total score to week 10.

The inclusion criteria for this short-term trial included adult inpatients who met DSM‑IV‑TR criteria for schizophrenia. In addition, all patients entering the trial must have experienced an acute psychotic episode as defined by both PANSS Total Score ≥80 and a PANSS score of >4 on each of four specific psychotic symptoms (conceptual disorganization, hallucinatory behavior, suspiciousness/persecution, unusual thought content) at screening and baseline. The key secondary endpoint was the change from baseline in Clinical Global Impression-Severity (CGI-S) assessment scale to week 10. The CGI-S rates the severity of mental illness on a scale of 1 (normal) to 7 (among the most extremely ill) based on the total clinical experience of the rater in treating patients with schizophrenia. Patients had a mean PANSS total score of 103 (range 82 to 144) and a CGI-S score of 5.2 (markedly ill) at entry.

In this 12-week study (n=339) comparing Abilify Maintena (n=167) to placebo (n=172), patients were administered 400 mg Abilify Maintena or placebo on days 0, 28, and 56. The dose could be adjusted down and up within the range of 400 to 300 mg on a one-time basis. Abilify Maintena was superior to placebo in improving the PANSS total score at the end of week 10 (see Table 9).

Table 9: Schizophrenia Short-term Study

Study Number

Treatment Group

Primary Efficacy Measure: PANSS Total Score

Mean Baseline Score (SD)

LS Mean Change from Baseline (SE)

Placebo-subtracted Differencea (95% CI)

Study 1

Abilify Maintena (400 to 300 mg)

Placebo

102.4 (11.4)

103.4 (11.1)

-26.8 (1.6)

-11.7 (1.6)

-15.1 (-19.4, -10.8)

--

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.

The change in PANSS total score by week is shown in Figure 24. Abilify Maintena also showed improvement in symptoms represented by CGI-S score mean change from baseline to week 10. The results of exploratory subgroup analyses by gender, race, age, ethnicity, and BMI were similar to the results of the overall population.

  Figure 24: Weekly PANSS Total Score-Change in the 12-Week, Placebo-Controlled Study with Abilify Maintena

n = the number of patients remaining in the respective study arm at each time point

Longer-Term Efficacy

The efficacy of Abilify Maintena in maintaining symptomatic control in schizophrenia was established in a double-blind, placebo-controlled, randomized-withdrawal trial in adult patients (Study 2) who met DSM-IV-TR criteria for schizophrenia and who were being treated with at least one antipsychotic medication. Patients had at least a 3-year history of illness and a history of relapse or symptom exacerbation when not receiving antipsychotic treatment.

In addition to the PANSS and CGI-S, clinical ratings during this trial included the:

• Clinical Global Impression-Improvement (CGI-I) scale, a scale of 1 (very much improved) to 7 (very much worse) based on the change from baseline in clinical condition and • Clinical Global Impression-Severity of Suicide (CGI-SS) scale, which is comprised of 2 parts: Part 1 rates the severity of suicidal thoughts and behavior on a scale of 1 (not at all suicidal) to 5 (attempted suicide) based on the most severe level in the last 7 days from all information available to the rater and Part 2 rates the change from baseline in suicidal thoughts and behavior on a scale of 1 (very much improved) to 7 (very much worse).

This trial included:

• A 4 to 6 week open-label, oral conversion phase for patients on antipsychotic medications other than aripiprazole. A total of 633 patients entered this phase. • An open-label, oral aripiprazole stabilization phase (target dose of 10 mg to 30 mg once daily). A total of 710 patients entered this phase. Patients were 18 to 60 years old (mean 40 years) and 60% were male. The mean PANSS total score was 66 (range 33 to 124). The mean CGI-S score was 3.5 (mildly to moderately ill). Prior to the next phase, stabilization was required. Stabilization was defined as having all of the following for four consecutive weeks: an outpatient status, PANSS total score ≤80, CGI-S ≤4 (moderately ill), and CGI-SS score ≤2 (mildly suicidal) on Part 1 and ≤5 (minimally worsened) on Part 2; and a score of ≤4 on each of the following PANSS items: conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content. • A minimum 12-week uncontrolled, single-blind Abilify Maintena stabilization phase (treatment with 400 mg of Abilify Maintena given every 4 weeks in conjunction with oral aripiprazole [10 mg to 20 mg/day] for the first 2 weeks). The dose of Abilify Maintena may have been decreased to 300 mg due to adverse reactions. A total of 576 patients entered this phase. The mean PANSS total score was 59 (range 30 to 80) and the mean CGI-S score was 3.2 (mildly ill). Prior to the next phase, stabilization was required (see above for the definition of stabilization) for 12 consecutive weeks. • A double-blind, placebo-controlled randomized-withdrawal phase to observe for relapse (defined below). A total of 403 patients were randomized 2:1 to the same dose of Abilify Maintena they were receiving at the end of the stabilization phase, (400 mg or 300 mg administered once every 4 weeks) or placebo. Patients had a mean PANSS total score of 55 (range 31 to 80) and a CGI-S score of 2.9 (mildly ill) at entry. The dose could be adjusted up and down or down and up within the range of 300 to 400 mg on a one-time basis.

The primary efficacy endpoint was time from randomization to relapse. Relapse was defined as the first occurrence of one or more of the following criteria:

• CGI-I of ≥5 (minimally worse) and 1. an increase on any of the following individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) to a score >4 with an absolute increase of ≥2 on that specific item since randomization or 2. an increase on any of the following individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) to a score >4 and an absolute increase ≥4 on the combined four PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) since randomization • Hospitalization due to worsening of psychotic symptoms (including partial hospitalization), but excluding hospitalization for psychosocial reasons • CGI-SS of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2, or • Violent behavior resulting in clinically significant self-injury, injury to another person, or property damage.

A pre-planned interim analysis demonstrated a statistically significantly longer time to relapse in patients randomized to the Abilify Maintena group compared to placebo-treated patients and the trial was subsequently terminated early because maintenance of efficacy was demonstrated. The final analysis demonstrated a statistically significantly longer time to relapse in patients randomized to the Abilify Maintena group than compared to placebo-treated patients. The Kaplan-Meier curves of the cumulative proportion of patients with relapse during the double-blind treatment phase for Abilify Maintena and placebo groups are shown in Figure 25.

  Figure 25: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse1

1This figure is based on a total of 80 relapse events.

The key secondary efficacy endpoint, percentage of subjects meeting the relapse criteria, was statistically significantly lower in patients randomized to the Abilify Maintena group (10%) than in the placebo group (40%).

Bipolar I Disorder – Maintenance Monotherapy

The efficacy of Abilify Maintena for the maintenance treatment of bipolar I disorder was established in a 52-week double-blind, placebo-controlled, randomized withdrawal trial in adult patients who were experiencing a manic episode at trial entry, met DSM-IV-TR criteria for bipolar I disorder, and had a history of at least one previous manic or mixed episode with manic symptoms of sufficient severity to require one of the following interventions: hospitalization and/or treatment with a mood stabilizer, and/or treatment with an antipsychotic agent.

Clinical ratings during this trial included:

• Young Mania Rating Scale (YMRS)-an 11-item, clinician-rated scale used to assess the degree of manic symptomatology, in a range with 0 representing no symptoms, and 60 representing worst symptoms. • Montgomery-Asberg Depression Rating Scale (MADRS) – a 10-item clinician-related scale used to assess the degree of depressive symptomatology, with 1 representing no symptoms, and 60 representing worst symptoms. • Clinical Global Impression Bipolar Version Severity of Illness (CGI-BP-S) a scale of 1 (normal, not at all ill) to 7 (very severely ill patient) based on the patient’s severity of illness mania, depression, and overall bipolar illness.

This trial included:

• A 4 to 6 week, open-label, oral conversion phase for patients on treatments for bipolar I disorder other than aripiprazole. A total of 466 patients entered this phase. • A 2 to 8 week, open-label, oral aripiprazole stabilization phase (target dose of 15 mg to 30 mg once daily). A total of 632 patients entered this phase. Patients were 18 to 65 years old (mean 40.7 years) and 60% were female. The mean (range) baseline scores were: YMRS total, 16.9 MADRS total, 5.7, and CGI-BP-S overall, 3.4 (mildly to moderately ill). Prior to the next phase, stabilization was required. Stabilization was defined as having all of the following at one bi-weekly visit: Outpatient status, YMRS total score <12, MADRS total score <12, no active suicidality; with active suicidality defined as a score of 4 or more on the MADRS item 10 OR an answer of “yes” on question 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS). • A minimum 12-week, uncontrolled, single-blind Abilify Maintena stabilization phase (treatment with 400 mg of Abilify Maintena given every 4 weeks in conjunction with oral aripiprazole [10 mg to 20 mg/day] for the first 2 weeks). The dose of Abilify Maintena was allowed to be decreased to 300 mg due to adverse reactions. A total of 425 patients entered this phase. The mean (range) baseline scores were: YMRS total, 5.8, MADRS total 3.7, and CGI‑BP‑S overall, 2.1 (minimally ill). Prior to the next phase, stabilization was required (see above for the definition of stabilization) for 8 consecutive weeks starting at week 6. • A double-blind, placebo-controlled, randomized-withdrawal phase to observe for recurrence to a mood episode (defined below) for up to 52 weeks. A total of 266 patients were randomized 1:1 to the same dose of Abilify Maintena they were receiving at the end of the stabilization phase, (400 mg or 300 mg administered once every 4 weeks) or placebo. The mean (range) baseline scores were: YMRS total, 2.8 (0 to 12), MADRS total, 2.7 (0 to 12), and CGI-S overall, 1.7 (minimally ill). The dose could be decreased to 300 mg for tolerability and returned once to 400 mg.

The primary efficacy endpoint was time from randomization to recurrence of any mood episode. Recurrence was defined as the first occurrence of one or more of the following criteria:

1) Hospitalization for any mood episode OR 2) Any of the following: a. YMRS total score ≥15 OR b. MADRS total score ≥15 OR c. Clinical Global Impression - Bipolar Version-Severity (CGI-BP-S) score >4 (overall score) OR 3) Serious adverse event (SAE) of worsening disease (bipolar I disorder) OR 4) Discontinuation due to lack of efficacy or discontinuation due to an adverse event (AE) of worsening disease OR 5) Clinical worsening with the need for addition of a mood stabilizer, antidepressant treatment, antipsychotic medication, and/or increase greater than the allowed benzodiazepine doses for treatment of symptoms of an underlying mood disorder OR 6) Active suicidality, which is defined as a score of 4 or more on the MADRS item 10 OR an answer an answer of “yes” on question 4 or 5 on the C-SSRS

Analysis demonstrated a statistically significantly longer time to recurrence of any mood episode in subjects randomized to the Abilify Maintena group than compared to placebo-treated subjects. The Kaplan-Meier curves of the time of recurrence to any mood episode during the double-blind treatment phase for Abilify Maintena and placebo groups are shown in Figure 26.

  Figure 26: Kaplan-Meier Estimation of Cumulative Recurrence Rate for Any Mood Episode1

1This figure is based on a total of 103 recurrence events.

Analysis by type of mood recurrence demonstrated a statistically significantly longer time to recurrence for both manic and mixed mood episodes in subjects treated with Abilify Maintena compared to those treated with placebo. There was no substantial difference between treatment groups in delaying time to recurrence of depressive mood episodes.

An examination of subgroups did not reveal any clear evidence of differential responsiveness on the basis of age, sex, or race.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

  • confusion
  • disorientation
  • vomiting
  • slowed or uncontrollable movements
  • drowsiness
  • seizures
  • aggressive behavior
  • coma (loss of consciousness for a period of time)

Abilify Maintena Precautions

Serious side effects have been reported with Abilify Maintena including the following

  • Neuroleptic malignant syndrome (NMS). Tell your healthcare provider right away if you have some or all of the following symptoms of this life-threatening nervous system disorder:
    • high fever
    • stiff muscles
    • confusion
    • sweating
    • changes in pulse, heart rate, and blood pressure
  • High blood sugar. Increases in blood sugar can happen in some people who take Abilify Maintena.
    Call your healthcare provider if you have any of these symptoms of high blood sugar while taking Abilify Maintena:
    • feel very thirsty
    • need to urinate more than usual
    • feel very hungry
    • feel weak or tired
    • feel sick to your stomach
    • feel confused, or your breath smells fruity
  • Increase in weight. Weight gain has been reported in patients taking medicines like Abilify Maintena, so you and your healthcare provider should check your weight regularly. For children and adolescent patients (6 to 17 years of age) weight gain should be compared against that expected with normal growth.
  • Difficulty swallowing. This may lead to aspiration and choking.
  • Tardive dyskinesia. Call your healthcare provider about any movements you cannot control in your face, tongue, or other body parts. These may be signs of a serious condition. Tardive dyskinesia may not go away, even if you stop taking Abilify Maintena. Tardive dyskinesia may also start after you stop taking Abilify Maintena.
  • Orthostatic hypotension (decreased blood pressure). Lightheadedness or fainting can occur when rising too quickly from a sitting or lying position.
  • Low white blood cell count
  • Seizures (convulsions)
  • Problems controlling your body temperature so that you feel too warm. Avoid getting over-heated or dehydrated. Do not over-exercise. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much or heavy clothing. Drink plenty of water while taking Abilify Maintena.
  • Increased risk of death in elderly people with dementia-related psychosis. Abilify Maintena is not for the treatment of people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia).
  • Increase fat levels (cholesterol and triglycerides in your blood)

Important information about antidepressant medicines:

  • Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
  • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
  • Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
  • Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
  • Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child’s healthcare provider for more information.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how Abilify Maintena affects you. Abilify Maintena may make you drowsy. Do not drink alcohol while taking Abilify Maintena.

Abilify Maintena Usage

  • Abilify Maintena is given by injection in the buttock by a healthcare provider once a month.
  • After your first injection you should continue your current antipsychotic medicine for 2 weeks.
  • You should not miss a dose. If you miss a dose, call your healthcare provider right away to discuss what you should do next.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of aripiprazole injection in the pediatric population. Safety and efficacy have not been established.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Blood vessel disease or
  • Dehydration or
  • Heart attack or stroke, history of or
  • Heart disease or
  • Heart failure, history of or
  • Heart rhythm problems or
  • Hypotension (low blood pressure) or
  • Hypovolemia (decrease in the volume of blood) or
  • Ischemic heart disease, history of or
  • Trouble with swallowing—Use with caution. May cause side effects to become worse.
  • Depression or
  • Diabetes, or family history of or
  • Dyslipidemia (high cholesterol or fats in the blood) or
  • Hyperglycemia (high blood sugar) or
  • Neuroleptic malignant syndrome (NMS), history of or
  • Neutropenia (low white blood cells) or
  • Reduced white blood cell count, history of or
  • Seizures, history of—Use with caution. May make these conditions worse.
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