What are the dosing, administration, contraindications, side effects, and monitoring recommendations for Abilify Maintena (aripiprazole) in adults for maintenance treatment of schizophrenia and bipolar I disorder?

Abilify Maintena (Aripiprazole Long-Acting Injectable)

Dosing and Administration

Abilify Maintena is administered as a 400 mg intramuscular injection once monthly (or 300 mg for patients requiring dose reduction), with a newer 2-month formulation (960 mg or 720 mg) now available for extended dosing intervals. 1, 2

Monthly Formulation (Abilify Maintena)

• Standard dose: 400 mg intramuscularly once monthly 3
• Reduced dose: 300 mg once monthly for patients requiring lower exposure 1
• Injection site: Deltoid or gluteal muscle 3
• Initiation: Requires 14 days of concurrent oral aripiprazole (10-20 mg daily) to achieve therapeutic levels 3

2-Month Formulation (Abilify Asimtufii/Ari 2MRTU)

• Standard dose: 960 mg intramuscularly every 2 months 1, 2
• Reduced dose: 720 mg every 2 months 1, 4
• Injection site: Gluteal muscle only (not deltoid) 1
• Flexibility: Can be administered within ±2 weeks of scheduled date 1
• Reinitiation: Only necessary if ≥14 weeks have passed since prior injection 1
• Switching from monthly: 960 mg Q2M substitutes for 400 mg Q1M; 720 mg Q2M substitutes for 300 mg Q1M 1, 4

Indications

Schizophrenia

• Maintenance treatment of schizophrenia in adults stabilized on oral aripiprazole 1, 3
• Particularly valuable for patients stable on oral aripiprazole who prefer or would benefit from long-acting formulation 3

Bipolar I Disorder

• Maintenance monotherapy of bipolar I disorder in adults 1, 2
• Approved for acute mania in adults at 5-15 mg/day oral equivalent 5
• Combination with lithium or valproate provides superior efficacy for severe presentations 5

Acute Agitation

• Intramuscular aripiprazole (immediate-release formulation, not Maintena) is approved for agitation associated with schizophrenia or bipolar I disorder 6

Contraindications and Precautions

Absolute Contraindications

• Known hypersensitivity to aripiprazole 3

Special Populations Requiring Caution

• Elderly patients with dementia-related psychosis: Increased mortality risk; aripiprazole is not approved for this indication 5
• CYP2D6 poor metabolizers: Require dose reduction due to increased exposure 4
• Concomitant CYP2D6 or CYP3A4 inhibitors: Require dose adjustment 4

Side Effects and Tolerability Profile

Favorable Metabolic Profile

• Aripiprazole is associated with fewer metabolic disturbances compared to other atypical antipsychotics, including lower risk of weight gain, diabetes, and dyslipidemia 3, 6
• Low risk for hyperprolactinemia 6
• Favorable cardiovascular tolerability profile 3

Common Adverse Effects

• Injection-site reactions (specific to LAI formulations) 2
• Low risk for extrapyramidal symptoms (EPS) 6
• Akathisia may occur but is less common than with typical antipsychotics 6

Serious but Rare Adverse Effects

• Neuroleptic malignant syndrome (rare with all antipsychotics) 3
• Tardive dyskinesia (lower risk than typical antipsychotics) 3

Monitoring Requirements

Baseline Assessment

• Body mass index (BMI), waist circumference, blood pressure 5
• Fasting glucose and fasting lipid panel 5
• Pregnancy test in females of childbearing potential 5

Ongoing Monitoring

• BMI monthly for 3 months, then quarterly 5
• Blood pressure, fasting glucose, and lipids at 3 months, then annually 5
• Assess for extrapyramidal symptoms, particularly akathisia, at each visit 7
• Monitor for injection-site reactions 2

Clinical Advantages and Special Considerations

Benefits of Long-Acting Injectable Formulation

• Ensures medication adherence, critical given that >90% of noncompliant patients with bipolar disorder relapse versus 37.5% of compliant patients 5
• Eliminates daily pill burden 3
• Provides steady plasma concentrations without daily fluctuations 3, 4

2-Month Formulation Advantages

• Extended dosing interval reduces injection frequency by 50% 1, 2
• Ready-to-use prefilled syringe simplifies administration 1
• Comparable pharmacokinetic exposure to monthly formulation 4

Combination Therapy Considerations

• When combined with mood stabilizers (lithium or valproate) for bipolar disorder, aripiprazole provides superior efficacy for severe mania and treatment-resistant cases 5
• Aripiprazole augmentation of clozapine is the most evidence-supported strategy for treatment-resistant schizophrenia, potentially reducing residual symptoms and metabolic side effects 7
• Combining aripiprazole with another antipsychotic may reduce negative symptoms in schizophrenia 8

Common Pitfalls to Avoid

• Failing to provide 14 days of oral aripiprazole overlap when initiating monthly Maintena, which delays achievement of therapeutic levels 3
• Administering 2-month formulation in deltoid muscle instead of gluteal, which is not approved 1
• Premature discontinuation before adequate trial duration (4-6 weeks at therapeutic dose) 5
• Neglecting baseline and ongoing metabolic monitoring, despite aripiprazole's favorable profile 5
• Using aripiprazole monotherapy for bipolar depression without mood stabilizer, which risks mood destabilization 5