Abilify Maintena
aripiprazole · Kit
Uses
(aripiprazole) is indicated: for the treatment of schizophrenia in adults for maintenance monotherapy treatment of bipolar I disorder in adults ABILIFY MAINTENA is an atypical antipsychotic indicated: for treatment of schizophrenia in adults ( 1 ) for maintenance monotherapy treatment of bipolar I disorder in adults ( 1 )
Dosage and administration
Only to be administered by intramuscular injection in the deltoid or gluteal muscle by a healthcare professional ( 2.1 ) For patients naïve to aripiprazole, establish tolerability with oral aripiprazole prior to initiating ABILIFY MAINTENA ( 2.1 ) Recommended dosage is 400 mg administered monthly as a single injection. Dose can be reduced to 300 mg in patients with adverse reactions ( 2.2 ) There are two ways to initiate treatment with ABILIFY MAINTENA 1-day initiation: Administer two separate intramuscular injections of ABILIFY MAINTENA 400 mg and a single oral dose of aripiprazole 20 mg ( 2.2 ) 14-day initiation: In conjunction with first ABILIFY MAINTENA 400 mg dose, take 14 consecutive days of concurrent oral aripiprazole (10 mg to 20 mg) or current oral antipsychotic ( 2.2 ) Dosage adjustments are required for missed doses ( 2.3 ) Known CYP2D6 poor metabolizers: Recommended starting and maintenance dose is 300 mg administered monthly as a single injection ( 2.4 ) See full prescribing information for ABILIFY MAINTENA dosage modifications due to drug interactions ( 2.4 ). ABILIFY MAINTENA comes in two types of kits. See instructions for reconstitution/injection/disposal procedures for 1) Pre-filled Dual Chamber Syringe ( 2.6 ), and 2) Vials ( 2.7 ). 2.1 Important Administration Information 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 (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 MAINTENA must be administered by intramuscular injection by a healthcare professional. Do not administer by any other route. For detailed preparation and administration instructions, [see Dosage and Administration (2.6 , 2.7) ] . 2.2 Recommended Dosage for ABILIFY MAINTENA The recommended dose of ABILIFY MAINTENA is 400 mg monthly (no sooner than 26 days after the previous injection). There are two ways to initiate treatment with ABILIFY MAINTENA in patients receiving oral antipsychotics: 1-day initiation: Administer two intramuscular injections of ABILIFY MAINTENA 400 mg in two different injection sites (in either the deltoid or gluteal muscle), and one dose of oral aripiprazole 20 mg on the first day of treatment with ABILIFY MAINTENA. Do not administer both injections into the same muscle. 14-day initiation: When ABILIFY MAINTENA injection is initiated in patients receiving oral aripiprazole administer one intramuscular injection of ABILIFY MAINTENA 400 mg in either the deltoid or gluteal muscle and continue treatment with 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), administer one intramuscular injection of ABILIFY MAINTENA 400 mg in either the deltoid or gluteal muscle and continue treatment with the oral antipsychotic for 14 consecutive days to maintain therapeutic antipsychotic concentrations during initiation of therapy. If there are adverse reactions with the 400 mg dosage, the dosage may be reduced to 300 mg once monthly. 2.3 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 treatment with either 1-day initiation or 14-day initiation with ABILIFY MAINTENA [see Dosage and Administration (2.2) ] . 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 treatment with either 1-day initiation or 14-day initiation with ABILIFY MAINTENA [see Dosage and Administration (2.2) ] . 2.4 Dosage Modifications for Cytochrome P450 Considerations Refer to Table 1 and Table 2 for dosage modifications for patients who are CYP2D6 poor metabolizers and/or in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater than 14 days. If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the ABILIFY MAINTENA dosage may need to be increased to the previous dose [see Dosage and Administration (2.2) ] . 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 modifications are not recommended for patients with concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days. Table 1: Dosage Modifications for ABILIFY MAINTENA (1-Day Initiation) 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 No change for oral dosage required during initiation. CYP2D6 Poor Metabolizers Known CYP2D6 Poor Metabolizers 300 mg Known CYP2D6 Poor Metabolizers taking concomitant CYP3A4 inhibitors Avoid use Concomitant use with CYP Inhibitors and/or Inducers Strong CYP2D6 or CYP3A4 inhibitors 300 mg CYP2D6 and CYP3A4 inhibitors Avoid use CYP3A4 inducers Avoid use Table 2: Dosage Modifications for ABILIFY MAINTENA (14-Day Initiation) 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 No change for oral dosage required during initiation. CYP2D6 Poor Metabolizers Known CYP2D6 Poor Metabolizers 300 mg Known CYP2D6 Poor Metabolizers taking concomitant CYP3A4 inhibitors 200 mg 200 mg and 160 mg dosage adjustment is obtained only by using the 300 mg or 400 mg strength vials.
Dosage forms and strengths
For extended-release injectable suspension : 300 mg and 400 mg of lyophilized powder for reconstitution in: single-dose, pre-filled, dual chamber syringe single-dose vial The reconstituted extended-release injectable suspension is a uniform, homogeneous suspension that is opaque and milky-white in color. For extended-release injectable suspension: 300 mg and 400 mg strength lyophilized powder for reconstitution in ( 3 ): single-dose, pre-filled, dual chamber syringe single-dose vial
Contraindications
4 CONTRAINDICATIONS ABILIFY MAINTENA is contraindicated in patients with a known hypersensitivity to aripiprazole. Hypersensitivity reactions ranging from pruritus/urticaria to anaphylaxis have been reported in patients receiving aripiprazole [see Adverse Reactions (6.1 and 6.2) ] . Known hypersensitivity to aripiprazole ( 4 )
Warnings and precautions
Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities) ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring ( 5.3 ) Tardive Dyskinesia: Discontinue if clinically appropriate ( 5.4 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain ( 5.5 ) – Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with and at risk for diabetes ( 5.5 ) – Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics ( 5.5 ) – Weight Gain: Gain in body weight has been observed; clinical monitoring of weight is recommended ( 5.5 ) Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation ( 5.6 ) Orthostatic Hypotension: Use with caution in patients with known cardiovascular or cerebrovascular disease ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts in patients with a history of a clinically significant low white blood cell count (WBC)/absolute neutrophil count (ANC). Consider discontinuation if clinically significant decline in WBC/ANC in the absence of other causative factors ( 5.9 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold ( 5.10 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery ( 5.11 ) 5.1 Increased Mortality in Elderly Patients with Dementia- Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. ABILIFY MAINTENA is not approved for the treatment of patients with dementia-related psychosis. 5.2 Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with Dementia-Related Psychosis In placebo-controlled clinical studies (two flexible-dose and one fixed-dose study) of dementia-related psychosis, there was an increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, in oral aripiprazole-treated patients (mean age: 84 years; range: 78 to 88 years). In the fixed-dose study, there was a statistically significant dose response relationship for cerebrovascular adverse reactions in patients treated with oral aripiprazole. ABILIFY MAINTENA is not approved for the treatment of patients with dementia-related psychosis . 5.3 Neuroleptic Malignant Syndrome A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) may occur with administration of antipsychotic drugs, including ABILIFY MAINTENA. Rare cases of NMS occurred during aripiprazole treatment in the worldwide clinical database. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported. 5.4 Tardive Dyskinesia A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome.
Side effects
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 Warning and 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 with ABILIFY MAINTENA in patients with schizophrenia (incidence ≥5% and at least twice that for 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. 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 8 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 8: Adverse Reactions in ≥2% of ABILIFY MAINTENA-Treated Adult Patients with Schizophrenia in a 12-Week Double-Blind, Placebo-Controlled Trial This table does not include adverse reactions which had an incidence equal to or less than placebo. Percentage of Patients Reporting Reaction 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 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.
Drug interactions
7 DRUG INTERACTIONS CYP2D6 inhibitors and CYP3A4 Inhibitors : See full prescribing information for ABILIFY MAINTENA dosage modifications when used concomitantly with CYP2D6 inhibitors and/or CYP3A4 inhibitors for greater than 14 days ( 7.1 ) CYP3A4 Inducers : Avoid concomitant use for greater than 14 days ( 7.1 ) See full prescribing information for additional clinically significant drug interactions ( 7.1 ) 7.1 Drugs Having Clinically Important Interactions with ABILIFY MAINTENA Table 9: Clinically Important Drug Interactions with ABILIFY MAINTENA: Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Strong CYP3A4 Inhibitors (e.g., ketoconazole) or strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) The concomitant use of oral aripiprazole with strong CYP3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole [see Clinical Pharmacology (12.3) ]. With concomitant use of ABILIFY MAINTENA with a strong CYP3A4 inhibitor or CYP2D6 inhibitor for more than 14 days, reduce the ABILIFY MAINTENA dosage [see Dosage and Administration (2.4) ]. Strong CYP3A4 Inducers (e.g., carbamazepine) The concomitant use of oral aripiprazole and carbamazepine decreased the exposure of aripiprazole [see Clinical Pharmacology (12.3) ]. Avoid use of ABILIFY MAINTENA in combination with carbamazepine and other inducers of CYP3A4 for greater than 14 days [see Dosage and Administration (2.4) ] . Antihypertensive Drugs Due to its alpha-adrenergic antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents. Monitor blood pressure and adjust dose accordingly [see Warnings and Precautions (5.7) ]. Benzodiazepines (e.g., lorazepam) 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) ]. Monitor sedation and blood pressure. Adjust dose accordingly. 7.2 Drugs Having No Clinically Important Interactions with ABILIFY MAINTENA Based on pharmacokinetic studies with oral aripiprazole, no dosage adjustment of ABILIFY MAINTENA 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 (e.g., dextromethorphan, fluoxetine, paroxetine, or venlafaxine), CYP2C9 (e.g., warfarin), CYP2C19 (e.g., omeprazole, warfarin), or CYP3A4 (e.g., dextromethorphan) when coadministered with ABILIFY MAINTENA. Additionally, no dosage adjustment is necessary for valproate, lithium, lamotrigine, lorazepam, or sertraline when coadministered with ABILIFY MAINTENA. [See Clinical Pharmacology (12.3) ] .
Use in specific populations
Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure ( 8.1 ) Lactation: Monitor the breastfed infant for dehydration and lack of appropriate weight gain ( 8.2 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ABILIFY MAINTENA 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 following delivery (see Clinical Considerations ). Overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including ABILIFY MAINTENA, during pregnancy (see Clinical Considerations ) . Aripiprazole exposure during pregnancy may decrease milk supply in the post-partum period [see Use in Specific Populations (8.2) ] . 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 MRHD produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival (see Data ) . The background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. 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. Data 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 MRHD of 30 mg/day on a mg/m 2 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/m 2 basis. At 3 and 10 times the oral MRHD on a mg/m 2 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 a mg/m 2 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/m 2 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/m 2 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/m 2 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.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ABILIFY MAINTENA 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 following delivery (see Clinical Considerations ). Overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including ABILIFY MAINTENA, during pregnancy (see Clinical Considerations ) . Aripiprazole exposure during pregnancy may decrease milk supply in the post-partum period [see Use in Specific Populations (8.2) ] . 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 MRHD produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival (see Data ) . The background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. 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. Data 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 MRHD of 30 mg/day on a mg/m 2 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/m 2 basis. At 3 and 10 times the oral MRHD on a mg/m 2 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 a mg/m 2 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/m 2 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/m 2 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/m 2 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/m 2 basis.
Pediatric use
8.4 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 (AUC 0-24 ) 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 (AUC 0-24 ) 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
8.5 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 have not identified differences in responses between the elderly and younger patients [see Clinical Pharmacology (12.3) ] . 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) ].
Overdosage
Human Experience The largest known case of acute ingestion with a known outcome involved 1260 mg of oral aripiprazole (42 times the maximum recommended daily dose) in a patient who fully recovered. Common adverse reactions (reported in at least 5% of all overdose cases) reported with oral aripiprazole overdosage (alone or in combination with other substances) include vomiting, somnolence, and tremor. Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia. Management of Overdosage In case of overdosage, call the Poison Control Center immediately at 1-800-222-1222.
Description
Aripiprazole is an atypical antipsychotic which is present in ABILIFY MAINTENA 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 MAINTENA (aripiprazole) is an extended-release injectable suspension available in 400 mg or 300 mg strength pre-filled dual chamber syringes and 400 mg or 300 mg strength vials. The labeled strengths are calculated based on the anhydrous form (aripiprazole). Inactive ingredients (per administered dose) for 400 mg and 300 mg strength products, respectively, include carboxymethyl cellulose sodium (16.64 mg and 12.48 mg), mannitol (83.2 mg and 62.4 mg), sodium phosphate monobasic monohydrate (1.48 mg and 1.11 mg) and sodium hydroxide (pH adjuster). Chemical Structure
Mechanism of action
12.1 Mechanism of Action The mechanism of action of aripiprazole in the treatment of schizophrenia and bipolar I disorder is unknown. The efficacy of aripiprazole could be mediated through a combination of partial agonist activity at dopamine D 2 and serotonin 5-HT 1A receptors and antagonist activity at 5-HT 2A receptors.
How supplied
How Supplied Pre-filled Dual Chamber Syringe: ABILIFY MAINTENA (aripiprazole) pre-filled dual chamber syringe for extended-release injectable suspension in single-dose syringes is available in 300 mg or 400 mg strength syringes. The pre-filled dual chamber syringe consists of a front chamber that contains the lyophilized powder of aripiprazole monohydrate and a rear chamber that contains sterile water for injection. 300 mg kit (NDC 59148-045-80) 300 mg, single-dose, pre-filled, dual chamber syringe containing ABILIFY MAINTENA (aripiprazole) for extended-release injectable suspension 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 400 mg kit (NDC 59148-072-80) 400 mg, single-dose, pre-filled, dual chamber syringe containing ABILIFY MAINTENA (aripiprazole) for extended-release injectable suspension 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 Single-Dose Vial: ABILIFY MAINTENA (aripiprazole) extended-release injectable suspension in single-dose vials is available in 300 mg or 400 mg strength vials. 300 mg kit (NDC 59148-232-12) 300 mg, single-dose vial of ABILIFY MAINTENA (aripiprazole) extended-release injectable suspension lyophilized powder 2.5 mL, single-dose vial of Sterile Water for Injection, USP One 3 mL, luer lock syringe with pre-attached 21-gauge, 1.5-inch 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 400 mg kit (NDC 59148-245-12) 400 mg, single-dose vial of ABILIFY MAINTENA (aripiprazole) extended-release injectable suspension lyophilized powder 2.5 mL, single-dose vial of Sterile Water for Injection, USP One 3 mL, luer lock syringe with pre-attached 21-gauge, 1.5-inch 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 Storage Pre-filled dual chamber syringe: Store below 30°C [86°F]. Do not freeze. Protect the syringe from light by storing in the original package until time of use. Vial: Store at 25°C (77°F), excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Storage
Storage Pre-filled dual chamber syringe: Store below 30°C [86°F]. Do not freeze. Protect the syringe from light by storing in the original package until time of use. Vial: Store at 25°C (77°F), excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide ) Neuroleptic Malignant Syndrome Counsel patients about a potentially fatal adverse reaction, Neuroleptic Malignant Syndrome (NMS) that has been reported in association with administration of antipsychotic drugs. Advise patients, family members, or caregivers to contact a health care provider or report to the emergency room if they experience signs and symptoms of NMS [see Warnings and Precautions (5.3) ] . Tardive Dyskinesia Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their health care provider if these abnormal movements occur [see Warnings and Precautions (5.4) ] . Metabolic Changes Educate patients about the risk of metabolic changes, how to recognize symptoms of hyperglycemia and diabetes mellitus, and the need for specific monitoring, including blood glucose, lipids, and weight [see Warnings and Precautions (5.5) ]. Pathological Gambling and Other Compulsive Behaviors Advise patients and their caregivers of the possibility that they may experience compulsive urges to shop, increased urges to gamble, compulsive sexual urges, binge eating and/or other compulsive urges and the inability to control these urges while taking aripiprazole. In some cases, but not all, the urges were reported to have stopped when the dose was reduced or stopped [see Warnings and Precautions (5.6) ] . Orthostatic Hypotension and Syncope Educate patients about the risk of orthostatic hypotension and syncope especially early in treatment, and also at times of re-initiating treatment or increases in dosage [see Warnings and Precautions (5.7) ]. Leukopenia/Neutropenia Advise patients with a pre-existing low WBC count or a history of drug-induced leucopenia/neutropenia that they should have their CBC monitored while receiving ABILIFY MAINTENA [see Warnings and Precautions (5.9) ]. Potential for Cognitive and Motor Impairment Inform patients that ABILIFY MAINTENA has the potential to impair judgment, thinking, or motor skills. Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery, or operating a motor vehicle, until they are reasonably certain that ABILIFY MAINTENA therapy does not affect them adversely [see Warnings and Precautions (5.11) ] . Heat Exposure and Dehydration Educate patients regarding appropriate care in avoiding overheating and dehydration [see Warnings and Precautions (5.12) ]. Concomitant Medication Advise patients to inform their health care providers of any changes to their current prescription or over-the-counter medications since there is a potential for clinically significant interactions [see Drug Interactions (7) ] . Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with ABILIFY MAINTENA. Advise patients that ABILIFY MAINTENA may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) in a neonate. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ABILIFY MAINTENA during pregnancy [see Use in Specific Populations (8.1) ]. Lactation ABILIFY MAINTENA use during pregnancy may affect milk supply. Advise the lactating patient to discuss any plans for breastfeeding with their healthcare provider, and to monitor the breastfed infant for dehydration and lack of appropriate weight gain [see Use in Specific Populations (8.2) ].
Label text from the FDA structured product label by Otsuka America Pharmaceutical, Inc. (revised Mar 24, 2026). Long sections are shortened; the complete label is on DailyMed.
Abilify Maintena NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 59148-045 | Kit | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-072 | Kit | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-232 | Kit | Otsuka America Pharmaceutical, Inc. | NDA |
| 59148-245 | Kit | Otsuka America Pharmaceutical, Inc. | NDA |
Frequently asked questions
What is Abilify Maintena used for?
(aripiprazole) is indicated: for the treatment of schizophrenia in adults for maintenance monotherapy treatment of bipolar I disorder in adults ABILIFY MAINTENA is an atypical antipsychotic indicated: for treatment of schizophrenia in adults ( 1 ) for maintenance monotherapy treatment of bipolar I disorder in adults ( 1 )
What are the side effects of Abilify Maintena?
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 Warning and Warnings and Precautions (5.2) ]… See the full label for the complete list.
Who makes Abilify Maintena?
Abilify Maintena is listed by 1 labeler in the FDA NDC directory, including Otsuka America Pharmaceutical, Inc..