ABILIFY ASIMTUFII

Aripiprazole is an atypical antipsychotic which is present in ABILIFY ASIMTUFII as its monohydrate polymorphic form. Aripiprazole monohydrate is 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl] butoxy]-3,4 dihydrocarbostyril monohydrate. The empirical formula is C 23 H 27 Cl 2 N 3 O 2∙ H 2 O and its molecular weight is 466.40. The chemical structure is: ABILIFY ASIMTUFII (aripiprazole) is available as a white to off-white, sterile, aqueous extended-release suspension for intramuscular injection in 720 mg or 960 mg dose strength, pre-filled syringes. The labeled strengths are calculated based on the anhydrous form (aripiprazole). Inactive ingredients are carboxymethylcellulose sodium (5 mg/mL), polyethylene glycol 400 (1 mg/mL), povidone (4 mg/mL), sodium chloride (6.1 mg/mL), sodium phosphate monobasic monohydrate (0.74 mg/mL), sodium hydroxide (to adjust pH) and water for injection (q.s.). Chemical Structure

ABILIFY ASIMTUFII is indicated: for the treatment of schizophrenia in adults for maintenance monotherapy treatment of bipolar I disorder in adults ABILIFY ASIMTUFII is an atypical antipsychotic indicated: for the treatment of schizophrenia in adults ( 1 ) as maintenance monotherapy treatment of bipolar I disorder in adults ( 1 )

For patients naïve to aripiprazole, establish tolerability with oral aripiprazole prior to initiating treatment with ABILIFY ASIMTUFII ( 2.1 ) Administer by intramuscular injection in the gluteal muscle by a healthcare professional. Do not administer by any other route ( 2.1 ) Recommended dosage is 960 mg administered once every 2 months as a single injection. Dose can be reduced to 720 mg in patients with adverse reactions ( 2.2 ) For patients currently receiving an oral antipsychotic, there are two ways to initiate treatment with ABILIFY ASIMTUFII 1-day initiation: Administer one injection of ABILIFY ASIMTUFII 960 mg, one injection of Abilify Maintena 400 mg and a single oral dose of aripiprazole 20 mg ( 2.2 ) 14-day initiation: In conjunction with first ABILIFY ASIMTUFII 960 mg dose, take 14 consecutive days of concurrent oral aripiprazole (10 mg to 20 mg) or current oral antipsychotic ( 2.2 ) For patients currently receiving Abilify Maintena Administer ABILIFY ASIMTUFII 960 mg in place of the next scheduled injection of the Abilify Maintena. Missed doses: Dosage adjustment may be required ( 2.3 ) Known CYP2D6 poor metabolizers: Recommended dosage is 720 mg administered once every 2 months as a single injection ( 2.4 ) See Full Prescribing Information for important preparation and administration information ( 2.5 ) 2.1 Important Administration Information For patients who have never taken aripiprazole, establish tolerability with oral aripiprazole prior to initiating treatment with ABILIFY ASIMTUFII. Due to the half-life of oral aripiprazole (i.e., 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively), it may take up to 2 weeks to fully assess tolerability. ABILIFY ASIMTUFII must be administered as an intramuscular gluteal injection by a healthcare professional. Do not administer by any other route . For detailed preparation and administration instructions, [see Dosage and Administration (2.5) ] . 2.2 Recommended Dosage for ABILIFY ASIMTUFII The recommended dosage of ABILIFY ASIMTUFII is 960 mg, administered once every 2 months (56 days after previous injection). Patients Receiving Oral Antipsychotics There are two ways to initiate treatment with ABILIFY ASIMTUFII in patients receiving oral antipsychotics: 1-day initiation: Administer one intramuscular injection of ABILIFY ASIMTUFII 960 mg in the gluteal muscle, one injection of Abilify Maintena 400 mg in a separate gluteal or deltoid muscle, and one dose of oral aripiprazole 20 mg, on the first day of treatment with ABILIFY ASIMTUFII. Do not administer both injections into the same muscle. 14-day initiation: Administer one intramuscular injection of ABILIFY ASIMTUFII 960 mg in the gluteal muscle and continue treatment with oral aripiprazole (10 mg to 20 mg) for 14 consecutive days. For patients already stable on another oral antipsychotic (and known to tolerate aripiprazole), administer one intramuscular injection of ABILIFY ASIMTUFII 960 mg in the gluteal muscle and continue treatment with the oral antipsychotic for 14 consecutive days. Patients Receiving Abilify Maintena For patients receiving Abilify Maintena 400 mg (once monthly dosing), administer ABILIFY ASIMTUFII 960 mg (once every 2 month dosing) in place of the next scheduled injection of the Abilify Maintena. The first ABILIFY ASIMTUFII injection may be administered in place of the second, or later injection of Abilify Maintena. If there are adverse reactions with the ABILIFY ASIMTUFII 960 mg dosage, the dosage may be reduced to 720 mg once every 2 months. Patients may be given the ABILIFY ASIMTUFII injection up to 2 weeks before or 2 weeks after the 2-month scheduled timepoint. 2.3 Missed Doses If more than 8 weeks and less than 14 weeks have elapsed since the last injection, administer the next dose of ABILIFY ASIMTUFII as soon as possible. The once every 2 month schedule should be resumed. If more than 14 weeks have elapsed since the last injection, restart treatment with either 1-day initiation or 14-day initiation with ABILIFY ASIMTUFII [see Dosage and Administration (2.2) ] . 2.4 Dosage Modifications for Cytochrome P450 Considerations Dosage adjustments for patients who are CYP2D6 poor metabolizers and/or in patients taking concomitant strong CYP3A4 inhibitors or CYP2D6 inhibitors for more than 14 days are described in Table 1. If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the dosage of ABILIFY ASIMTUFII may need to be increased to the previous dose. 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: Dosage Recommendations for ABILIFY ASIMTUFII in Patients Who are Known CYP2D6 Poor Metabolizers, Patients Taking Concomitant CYP2D6 Inhibitors, 3A4 Inhibitors, or CYP3A4 Inducers for Greater than 14 days Factors Dosage Recommendation CYP2D6 Poor Metabolizers Known CYP2D6 Poor Metabolizers 720 mg once every 2 months For the 1-day initiation regimen, administer a single 20 mg oral aripiprazole, 300 mg Abilify Maintena and 720 mg ABILIFY ASIMTUFII on Day 1. Known CYP2D6 Poor Metabolizers taking concomitant CYP3A4 inhibitors Avoid use Patients Taking 960 mg of ABILIFY ASIMTUFII Concomitant use of ABILIFY ASIMTUFII with Strong CYP2D6 inhibitors 720 mg once every 2 months Concomitant use of ABILIFY ASIMTUFII with Strong CYP3A4 inhibitors 720 mg once every 2 months Concomitant use of ABILIFY ASIMTUFII with Strong CYP2D6 and Strong CYP3A4 inhibitors Avoid use Concomitant use of ABILIFY ASIMTUFII with CYP3A4 inducers Avoid use 2.5 Preparation and Administration Instructions Read the complete instructions for preparation and administration below and consider referring to the separate Healthcare Provider "Instructions for Use" for additional preparation and administration considerations. To be prepared and administered by a healthcare professional only. For gluteal intramuscular injection only. Do not administer by any other route. Prior to administration, visually inspect ABILIFY ASIMTUFII pre-filled syringe for particulate matter and discoloration. The suspension should appear to be a uniform, homogeneous suspension that is opaque and milky-white in color. Do not use ABILIFY ASIMTUFII pre-filled syringe if the suspension is discolored, or particulate matter is present Each kit contains one sterile pre-filled syringe containing ABILIFY ASIMTUFII 720 mg or 960 mg and two safety needles: One sterile 1 ½ inch, 22 gauge needle (in black packaging) One sterile 2 inch, 21 gauge needle (in green packaging) Image Preparation Prior to Administration Remove the ABILIFY ASIMTUFII pre-filled syringe from the package. Tap the syringe on your hand at least 10 (ten) times (Figure 1). After tapping, shake the syringe vigorously for at least 10 (ten) seconds, until the medication is uniform (Figure 2). Figure 1 Figure 2 Figure 1 Figure 2 Select the appropriate needle Needle selection is determined by patient body type. For gluteal intramuscular administration only. For non-obese patients - 22-gauge, 1.5-inch (38 mm) safety needle with needle protection device (needle in black packaging) For obese patients - 21-gauge, 2-inch (51 mm) safety needle with needle protection device (needle in green packaging) Attach the needle Twist and pull off the pre-filled syringe tip-cap (Figure 3). While holding the base of the needle, ensure the needle is firmly seated on the safety device with a push. Gently twist clockwise until SECURELY fitted (Figure 3). Figure 3 Figure 3 Expel Air When you are ready to administer the injection of ABILIFY ASIMTUFII, hold the pre-filled syringe upright and remove the needle-cap straight up (Figure 4). Do not twist the needle-cap, as this may loosen the needle from the syringe. Figure 4 Slowly advance the plunger rod upward to expel the air and until the suspension fills needle base (Figure 5). Figure 5 Figure 4 Figure 5 Inject the dose Slowly inject the entire contents of the pre-filled syringe intramuscularly into the gluteal muscle of the patient (Figure 6) . Do not administer by any other route. Do not massage the injection site. Figure 6 Figure 6 Disposal Procedure After the injection, press the safety shield on a hard surface to cover and lock shield over the needle (Figures 7 and 8) Figure 7 Figure 8 Immediately discard used syringe and the unused needle in an approved sharps container. The unused needle should not be saved for future use. Figure 7 Figure 8

ABILIFY ASIMTUFII is contraindicated in patients with a known hypersensitivity to aripiprazole, or any of the excipients. Hypersensitivity reactions ranging from pruritus/urticaria to anaphylaxis have been reported in patients receiving aripiprazole [see Adverse Reactions (6.1) ] . Known hypersensitivity to aripiprazole, or to any excipients of ABILIFY ASIMTUFII ( 4 )

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 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 and Syncope [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) ] Most commonly observed adverse reactions (incidence ≥5% and at least twice the rate of placebo) were increased weight, akathisia, injection site pain, and sedation ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. The safety of ABILIFY ASIMTUFII for the treatment of schizophrenia in adults and maintenance monotherapy treatment of bipolar I disorder in adults is based on adequate and well-controlled studies of Abilify Maintena. The safety data from those studies is presented below. Safety Database of Abilify Maintena (once monthly dosing) 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 (once monthly dosing) 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). Safety Database of ABILIFY ASIMTUFII (once every 2 month dosing) In a 32 week open-label study of ABILIFY ASIMTUFII in adult patients with schizophrenia or bipolar I disorder, 266 patients were randomized to receive either ABILIFY ASIMTUFII 960 mg (132 patients) or Abilify Maintena 400 mg (134 patients). A total of the 132 patients received at least one injection of ABILIFY ASIMTUFII, a total of 114 patients received at least two consecutive injections (4 months treatment) of ABILIFY ASIMTUFII, and a total of 104 patients received at least four consecutive injections (8 months treatment) of ABILIFY ASIMTUFII. Of the total 266 patients receiving ABILIFY ASIMTUFII 960 mg or Abilify Maintena 400 mg, 185 had schizophrenia and 81 had bipolar I disorder. Injection site reactions for ABILIFY ASIMTUFII (once every 2 month dosing) presented in this section is based on this open-label study (see section titled " Injection Site Reactions with Abilify ASIMTUFII "). Adverse Reactions in Studies with Abilify Maintena (once monthly dosing) 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. Most Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials in Schizophrenia with Abilify Maintena 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 with Abilify Maintena 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 6 lists the adverse reactions reported in 2% or more of Abilify Maintena-treated patients and at a greater proportion than in the placebo group. Table 6: Adverse Reactions in ≥2% of Adult Patients with Schizophrenia Treated with Abilify Maintena in a 12-Week Double-Blind, Placebo-Controlled Study This table does not include adverse reactions which had an incidence equal to or less than placebo. Preferred Term Abilify Maintena (n=167) Placebo (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 Demographic Differences An examination of population subgroups was performed across demographic subgroup categories for adverse reactions experienced by at least 5% of Abilify Maintena patients at least twice the rate of 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 patients ≥65 years of age. Injection Site Reactions with ABILIFY ASIMTUFII ABILIFY ASIMTUFII was evaluated in 266 patients with schizophrenia or bipolar I disorder in an open-label, multiple-dose, randomized, parallel-arm multi-center study. The percentage of patients in the open-label study reporting any injection site-related adverse reactions (all reported as injection site pain) was 19% for patients treated with ABILIFY ASIMTUFII 960 mg and 9% for patients treated with Abilify Maintena 400 mg. In both treatment groups, the majority of the injection site pain events coincided with the first injection of ABILIFY ASIMTUFII 960 mg (21/24 patients) or Abilify Maintena 400 mg (7/12 patients), was reported with decreasing frequency upon subsequent injections. The overall mean visual analog scale scores (0=no pain to 100=unbearably painful) for patient reported rating of pain were similar in both treatment groups at the last injection: 0.8 pre-dose and 1.4 post-dose for the ABILIFY ASIMTUFII 960 mg group compared to 1.3 post-dose for the Abilify Maintena 400 mg group. 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/mcL) for Abilify Maintena-treated patients was 5.7% vs. 2.1% for placebo. An absolute neutrophil count of <1 thous/mcL (i.e., 0.95 thous/mcL) was observed in only one patient on Abilify Maintena and resolved spontaneously without any associated adverse reactions [see Warnings and Precautions (5.9) ]. Other Adverse Reactions 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. Blood and Lymphatic System Disorders: thrombocytopenia Cardiac Disorders: bradycardia, sinus tachycardia, tachycardia Endocrine Disorders: hypoprolactinemia Eye Disorders: vision blurred, oculogyric crisis Gastrointestinal Disorders: abdominal pain upper, dyspepsia, nausea, swollen tongue General Disorders and Administration Site Conditions: chest discomfort, fatigue, gait disturbance, injection site reaction (erythema, induration, pruritus, swelling, rash, inflammation, hemorrhage), irritability, pyrexia Hepatobiliary Disorders: drug-induced liver injury Immune System Disorders: drug hypersensitivity Infections and Infestations: nasopharyngitis Investigations: blood creatine phosphokinase increased, blood cholesterol decreased, blood pressure decreased, blood triglycerides decreased, electrocardiogram T wave abnormal, electrocardiogram QT-prolonged, hepatic enzyme increased, liver function test abnormal Metabolism and Nutrition Disorders: decreased appetite, hyperinsulinemia, obesity Musculoskeletal and Connective Tissue Disorders: joint stiffness, muscle twitching, rhabdomyolysis, trismus Nervous System Disorders: bradykinesia, convulsion, dysgeusia, extrapyramidal disorder, hypersomnia, lethargy, memory impairment, oromandibular dystonia, Psychiatric Disorders: anxiety, insomnia, restlessness, agitation, bruxism, psychotic disorder, suicidal ideation, aggression, hypersexuality, panic attack Renal and Urinary Disorders : glycosuria, pollakiuria, urinary incontinence Reproductive System and Breast Disorders: ejaculation delayed Vascular Disorders: hypertension 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: angina pectoris, atrial flutter, atrioventricular block, cardiopulmonary failure, cardio-respiratory arrest, extrasystoles, myocardial infarction, myocardial ischemia, palpitations, supraventricular tachycardia, ventricular tachycardia Eye Disorders: diplopia, photophobia, eyelid edema, photopsia Gastrointestinal Disorders: gastroesophageal reflux disease, swollen tongue, esophagitis, pancreatitis, stomach discomfort, toothache General Disorders and Administration Site Conditions: asthenia, chest pain, face edema, hypothermia, peripheral edema, pain Hepatobiliary Disorders: hepatitis, jaundice Immune System Disorders: hypersensitivity Injury, Poisoning, and Procedural Complications: heat stroke Investigations: blood prolactin decreased, blood bilirubin increased, blood creatinine increased, blood glucose increased, blood lactate dehydrogenase increased, blood prolactin increased, blood urea increased, glycosylated hemoglobin increased Metabolism and Nutrition Disorders: anorexia, diabetic ketoacidosis, hyponatremia, hypoglycemia, polydipsia Musculoskeletal and Connective Tissue Disorders: mobility decreased, muscle rigidity, muscle tightness, muscular weakness, musculoskeletal stiffness, pain in extremity, muscle spasms Nervous System Disorders: akinesia, choreoathetosis, coordination abnormal, hypokinesia, hypotonia, myoclonus, speech disorder Psychiatric Disorders: anger, anorgasmia, catatonia, completed suicide, delirium, loss of libido, homicidal ideation, intentional self-injury, hostility, libido increased, sleepwalking, suicide attempt, tic Renal and Urinary Disorders: nocturia, polyuria, urinary retention Reproductive System and Breast Disorders: amenorrhea, breast pain, erectile dysfunction, gynecomastia, menstruation irregular, priapism Respiratory, Thoracic, and Mediastinal Disorders: dyspnea, nasal congestion, pharyngolaryngeal pain, cough Skin and Subcutaneous Tissue Disorders: alopecia, hyperhidrosis, photosensitivity reaction, pruritus, rash (including erythematous, exfoliative, generalized, macular, maculopapular, papular rash; acneiform, allergic, contact, exfoliative, seborrheic dermatitis, neurodermatitis, and drug eruption), urticaria 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of aripiprazole. 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), blood glucose fluctuation, drug reaction with eosinophilia and systemic symptoms (DRESS), hiccups, pathological gambling, and fecal incontinence.

Dosage adjustments for patients taking CYP2D6 inhibitors, CYP3A4 inhibitors, or CYP3A4 inducers for greater than 14 days ( 2.4 , 7.1 ): Factors Dosage Recommendation CYP2D6 Poor Metabolizers taking concomitant CYP3A4 inhibitors Avoid use Patients taking strong CYP2D6 or CYP3A4 inhibitors 720 mg For the 1-day initiation regimen, administer a single 20 mg oral aripiprazole, 300 mg Abilify Maintena and 720 mg ABILIFY ASIMTUFII on Day 1. Patients taking CYP2D6 and CYP3A4 inhibitors Avoid use Patients taking CYP3A4 inducers Avoid use 7.1 Drugs Having Clinically Important Interactions with ABILIFY ASIMTUFII Table 7 presents clinically significant drug interactions with ABILIFY ASIMTUFII. Table 7: Clinically Important Drug Interactions with ABILIFY ASIMTUFII Strong CYP3A4 Inhibitors AND/OR strong CYP2D6 inhibitors Clinical Rationale Concomitant use of oral aripiprazole with strong CYP3A4 AND/OR CYP2D6 inhibitors increased the exposure of aripiprazole [see Clinical Pharmacology (12.3) ]. Clinical Recommendation Concomitant use of a strong CYP3A4 inhibitor OR a strong CYP2D6 inhibitor Reduce the dosage of ABILIFY ASIMTUFII when administered concomitantly with a strong CYP3A4 inhibitor OR a strong CYP2D6 inhibitor for more than 14 days [see Dosage and Administration (2.4) ]. Concomitant Use of a strong CYP3A4 inhibitor AND a strong CYP2D6 inhibitor Avoid use of ABILIFY ASIMTUFII when administered concomitantly with a strong CYP3A4 inhibitor AND a strong CYP2D6 inhibitor for more than 14 days [see Dosage and Administration (2.4) ]. Strong CYP3A4 Inducers Clinical Rationale Concomitant use of oral aripiprazole and carbamazepine decreased the exposure of aripiprazole [see Clinical Pharmacology (12.3) ]. Clinical Recommendation Avoid use of ABILIFY ASIMTUFII in combination with a strong CYP3A4 inducer (e.g., carbamazepine) for greater than 14 days [see Dosage and Administration (2.4) ] . Antihypertensive Drugs Clinical Rationale Due to its alpha-adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents. Clinical Recommendation Monitor blood pressure and adjust dose accordingly [see Warnings and Precautions (5.7) ]. Benzodiazepines Clinical Rationale The intensity of sedation was greater with the combination of oral aripiprazole and lorazepam as compared to that observed with aripiprazole alone. The orthostatic hypotension observed was greater with the combination as compared to that observed with lorazepam alone [see Warnings and Precautions (5.7) ]. Clinical Recommendation Monitor sedation and blood pressure. Adjust dose accordingly. 7.2 Drugs Having No Clinically Important Interactions with ABILIFY ASIMTUFII Based on pharmacokinetic studies with oral aripiprazole, no dosage adjustment of ABILIFY ASIMTUFII is required when administered concomitantly with famotidine, valproate, lithium, lorazepam [see Clinical Pharmacology (12.3) ] . In addition, no dosage adjustment is necessary for substrates of CYP2D6, CYP2C9, CYP2C19, or CYP3A4 when coadministered with ABILIFY ASIMTUFII. Additionally, no dosage adjustment is necessary for valproate, lithium, lamotrigine, lorazepam, or sertraline when coadministered with ABILIFY ASIMTUFII [see Clinical Pharmacology (12.3) ] .

Storage Store at 25°C (77°F), excursions permitted between 15° and 30°C (59° to 86°F) [see USP Controlled Room Temperature].