Offering Long-Acting Injectables to Patients Living with Bipolar I Disorder or Schizophrenia

As a psychiatrist, I recognize that bipolar I disorder and schizophrenia symptoms can pose challenges for patients, such as social stigma or lack of awareness of their condition. These challenges can lead to negative patient outcomes such as relapse and hospitalization, heightening the need to consider all treatment options that meet individual patient needs.¹ Considering that in the United States, approximately 4.8 million adults are diagnosed with bipolar I disorder, and about 2.8 million live with schizophrenia, individualized and practical treatment plans are important in promoting positive outcomes within these patient populations.^2,3

Long-acting injectables (LAIs) represent one option in the therapeutic landscape for these conditions. LAIs are intramuscular shots administered by healthcare professionals at intervals ranging from weeks to months that are designed to slowly release continuous antipsychotic medication.⁴

LAIs may help deliver stable medication levels and provide clinicians with a potential adherence indicator through scheduled injection visits. If a patient misses an injection appointment, it may be a clue that their patient may not be adherent with their medication for their bipolar I disorder or schizophrenia.⁵ Further, LAIs may reduce daily reminders of the condition, potentially allowing patients to focus on other meaningful aspects of their lives.

One example of a long-acting injectable is ABILIFY MAINTENA® (aripiprazole), an extended-release injectable suspension for the treatment of schizophrenia in adults and for the maintenance monotherapy treatment of bipolar I disorder in adults. In 2023, the FDA approved ABILIFY ASIMTUFII® (aripiprazole). This is the only FDA-approved two-month long-acting injectable for the maintenance treatment of bipolar I disorder in adults.The efficacy and safety of ABILIFY ASIMTUFII is based on the pivotal studies of ABILIFY MAINTENA. Please see IMPORTANT SAFETY INFORMATION, including BOXED WARNING for INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS, for ABILIFY ASIMTUFII and ABILIFY MAINTENA below.

A pivotal 52-week, placebo-controlled multiphase maintenance study investigated ABILIFY MAINTENA’s effectiveness in delaying the time to recurrence of mood episodes in adults living with bipolar I disorder with a history of one or more manic or mixed episodes with manic symptoms that required hospitalization or treatment with either a mood stabilizer or antipsychotic. Please see the full study design and results here.

Additionally, the effectiveness of ABILIFY MAINTENA in reducing the risk of psychotic relapses in schizophrenia was evaluated during a 52-week, placebo-controlled multiphase maintenance study of adult patients living with schizophrenia diagnosed for more than three years with a history of symptom exacerbation or relapse when not receiving antipsychotic treatment. Please find the full study design and results here.

A 12-week, randomized, double-blind, placebo-controlled study in which acutely relapsed adult patients with schizophrenia were randomized to either ABILIFY MAINTENA or intramuscular placebo was conducted to evaluate the efficacy for patients living with schizophrenia. Safety was also assessed throughout the duration of the study. Please see the full study design and results here.

The aripiprazole concentrations of ABILIFY ASIMTUFII were explored in a pharmacokinetic bridging study, which was a 32-week, open-label, multiple-dose, randomized, parallel-arm, multicenter study in patients living with schizophrenia or bipolar I disorder. Primary objectives included establishing the similarity of aripiprazole plasma concentrations and exposure following ABILIFY ASIMTUFII and ABILIFY MAINTENA® (aripiprazole) administration and establishing the safety and tolerability of multiple-dose administrations of ABILIFY ASIMTUFII. The full study design and results are shared here.

For patients stabilized on oral antipsychotics, transitioning to an LAI like ABILIFY MAINTENA or ABILIFY ASIMTUFII may reduce the daily burden of medication intake. Integrating LAIs such as ABILIFY MAINTENA or ABILIFY ASIMTUFII into treatment regimens for adults with bipolar I disorder and schizophrenia may provide patients with another treatment option that may help achieve their treatment goals. It’s important for mental healthcare providers to understand the benefits and risks of LAIs, and work with patients to create an individualized treatment plan that takes factors such as a patient’s lifestyle, schedule, and caregiver situation into consideration. To learn more, visit abilifymaintenahcp.com.

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death (1.6 to 1.7 times) compared to placebo-treated patients. ABILIFY ASIMTUFII and ABILIFY MAINTENA are not approved for the treatment of patients with dementia-related psychosis.

Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in clinical trials of elderly patients with dementia-related psychosis treated with oral aripiprazole.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs including aripiprazole. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of aripiprazole, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation of treatment. Prescribing should be consistent with the need to minimize TD. If antipsychotic treatment is withdrawn, TD may remit, partially or completely.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

• Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with atypical antipsychotics including aripiprazole. Patients with diabetes mellitus should be regularly monitored for worsening of glucose control; those with risk factors for diabetes (e.g., obesity, family history of diabetes), should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
• Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
• Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

Pathological Gambling and Other Compulsive Behaviors: Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking aripiprazole. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping aripiprazole if such urges develop.

Orthostatic Hypotension or Syncope: ABILIFY ASIMTUFII and ABILIFY MAINTENA may cause orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension. Monitoring of orthostatic vital signs should be considered in patients who are vulnerable to hypotension.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue ABILIFY ASIMTUFII or ABILIFY MAINTENA at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.

Seizures: ABILIFY ASIMTUFII and ABILIFY MAINTENA should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: ABILIFY ASIMTUFII and ABILIFY MAINTENA may impair judgment, thinking, or motor skills. Patients should be cautioned about performing activities that require mental alertness such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that therapy with ABILIFY ASIMTUFII or ABILIFY MAINTENA does not affect them adversely.

Body Temperature Regulation: Use ABILIFY ASIMTUFII or ABILIFY MAINTENA with caution in patients who may experience conditions that increase body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with aripiprazole. Use caution in patients at risk for aspiration.

Alcohol: Advise patients to avoid alcohol while taking ABILIFY ASIMTUFII or ABILIFY MAINTENA.

Concomitant Medications: Dosage reductions are recommended in patients who are CYP2D6 poor metabolizers and/or in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater than 14 days. Avoid concomitant use of CYP3A4 inducers with ABILIFY ASIMTUFII and ABILIFY MAINTENA for greater than 14 days. Dosage adjustments are not recommended for patients with concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days.

Most Commonly Observed Adverse Reactions: The most commonly observed adverse reactions with ABILIFY MAINTENA in patients with schizophrenia (incidence of ≥5% and at least twice that for placebo) were increased weight, akathisia, injection site pain, and sedation.

Injection Site Reactions:

• ABILIFY MAINTENA: In a short-term, clinical trial with ABILIFY MAINTENA in patients with schizophrenia treated with gluteal administered ABILIFY MAINTENA, the percent of patients reporting any injection site-related adverse reaction was 5.4% and 0.6% for placebo. In an open label study of ABILIFY MAINTENA administered in the deltoid or gluteal muscle, injection site pain was observed at approximately equal rates.
• ABILIFY ASIMTUFII: In an open-label study in patients with schizophrenia or bipolar I disorder, the percent of patients reporting any injection site-related adverse reactions was 19% for ABILIFY ASIMTUFII and 9.0% for ABILIFY MAINTENA. In both treatment groups, the majority of the injection site pain events coincided with the first injection and were reported with decreasing frequency upon subsequent injections. Patient-reported rating of pain was similar in both treatment groups at the last injection.

Dystonia: Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy: Neonates exposed to antipsychotic drugs, including aripiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. Consider the benefits and risks of aripiprazole and possible risks to the fetus when prescribing aripiprazole to a pregnant woman. Advise pregnant women of potential fetal risk.

Lactation: Aripiprazole is present in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother and any potential risks to the infant.

INDICATIONS

ABILIFY ASIMTUFII® (aripiprazole) is an atypical antipsychotic indicated for:

• Treatment of schizophrenia in adults
• Maintenance monotherapy treatment of bipolar I disorder in adults

ABILIFY MAINTENA® (aripiprazole) is an atypical antipsychotic indicated for:

• Treatment of schizophrenia in adults
• Maintenance monotherapy treatment of bipolar I disorder in adults

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1‑800‑438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING, for ABILIFY ASIMTUFII and ABILIFY MAINTENA.

© 2024 Otsuka America Pharmaceutical, Inc. August 2024 23US24EXP0086