ARIPIPRAZOLE INJ,SUSP,SA
Clinical Criteria Summary
Document 518
Transitioning Veteran Criteria
- Veteran is transitioning care from the Department of Defense to VHA.
- A VA prescriber has assessed and consulted with the Veteran, determining that continuing the medication is safe and clinically appropriate.
- Exclusion Criteria (Patient should NOT receive a long-acting injectable antipsychotic if any apply)
- Patient has never taken the ordered long-acting injectable antipsychotic in any formulation (e.g., oral).
- Patient has a hypersensitivity to the ordered antipsychotic.
- For Aripiprazole: Patient is taking a CYP3A4 inducer.
- For Aripiprazole: Patient is taking a CYP2D6 AND CYP3A4 inhibitor.
- Inclusion Criteria – Mandatory Requirements (All must be met)
- Diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder.
- Prescriber is a VA Mental Health Provider.
- Patient has taken and tolerated the ordered antipsychotic prior to receiving it as a LAI for an adequate length of time.
- Patient will be transitioned from oral medication to the long-acting injectable per guidelines/manufacturer recommendations.
- Inclusion Criteria – Conditional Requirements (One must be met)
- Patient has relapsed or been hospitalized for the intended indication or complications due to nonadherence when treated with oral antipsychotics.
- Patient’s care environment makes a LAI a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely).
Document 519
Transitioning Veteran
- Veteran is transitioning care from the Department of Defense to VHA, and a VA prescriber has determined continuing the medication is safe and clinically appropriate. (If met, remainder of criteria does not apply)
- Exclusion Criteria (Patient should NOT receive a long-acting injectable antipsychotic if any are met)
- Patient has never taken the ordered long-acting injectable antipsychotic in any formulation (e.g., oral)
- Patient has hypersensitivity to the ordered antipsychotic
- For Aripiprazole (Aristada Initio only): Patient is a known CYP2D6 poor metabolizer, or is receiving a benzodiazepine, antihypertensive drugs, strong CYP3A4 inducers, a strong CYP3A4 inhibitor, or a strong CYP2D6 inhibitor
- Inclusion Criteria (Patient must meet ALL of the following)
- Diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder
- Prescriber is a VA Mental Health Provider
- Patient has taken and tolerated the ordered antipsychotic prior to receiving it as a long-acting injectable for an adequate length of time
- Patient will be transitioned from oral medication to the long-acting injectable per guidelines/manufacturer recommendations
- Inclusion Criteria (Patient must meet ONE of the following)
- Patient has relapsed or been hospitalized for the intended indication or complications due to nonadherence when treated with oral antipsychotics
- Patient’s care environment makes a long-acting injectable a more reliable route of administration (e.g., homeless, lack of medication supervision, or medication cannot be stored safely)
Document 520
Transitioning Veteran
- Veteran is transitioning care from the Department of Defense to VHA
- VA prescriber has assessed and consulted with the Veteran and determined that continuing the medication is safe and clinically appropriate
- (Note: If met, remainder of criteria for use is not applicable)
- Exclusion Criteria (Patient should NOT receive a long-acting injectable antipsychotic if ANY are met)
- Patient has never taken the long-acting injectable antipsychotic ordered in any formulation (e.g., oral)
- Patient has a hypersensitivity to the antipsychotic ordered
- For Aripiprazole (Abilify Maintena): patient is taking a CYP3A4 inducer
- Inclusion Criteria (ALL of the following must be met)
- Diagnosis of schizophrenia or schizoaffective disorder, or bipolar disorder
- Prescriber is a VA Mental Health Provider
- Patient has taken and tolerated the antipsychotic ordered prior to receiving it as a LAI for an adequate length of time
- Patient will be transitioned from oral medication to the long-acting injectable per guidelines/manufacturer recommendations
- Inclusion Criteria (ONE of the following must be met)
- Patient has relapsed or been hospitalized for the intended indication or complications of the intended indication because of nonadherence when treated with oral antipsychotics
- Patient’s care environment is such that a LAI is a more reliable route of administration (e.g., homeless, lack of medication supervision, or the medication cannot be stored safely)
Document 539
Indications
- • Treatment of schizophrenia in adults
- • Maintenance monotherapy treatment of bipolar I disorder in adults
Patient Selection & Clinical Context
- • Typically reserved for patients who are nonadherent with or do not prefer oral medications
- • May be an appropriate choice for patients who have responded to oral aripiprazole and require a long-acting injectable (LAI) antipsychotic for adherence
Administration & Dosing Requirements
- • Intramuscular (IM) gluteal injection every 2 months
- • Available as 720 mg/2.4 mL or 960 mg/3.2 mL injections
- • Requires oral supplementation for 14 days after the initial injection
- • Early maintenance dose is allowed up to 2 weeks before the next scheduled dose due
Safety, Warnings & Precautions
- • Not approved for elderly patients with dementia-related psychosis (increased risk of death)
- • Monitor for: Cerebrovascular adverse reactions in elderly patients with dementia-related psychosis, Neuroleptic Malignant Syndrome, Tardive Dyskinesia, Metabolic Changes, Pathological Gambling and Other Compulsive Behaviors, Orthostatic Hypotension and Syncope, Leukopenia/Neutropenia/Agranulocytosis, Seizures, Potential for Cognitive and Motor Impairment
- • Adverse reactions observed in ≥2% of adult patients with schizophrenia (vs. placebo): Constipation, Dry Mouth, Diarrhea, Vomiting, Abdominal Discomfort, Injection Site Pain, Upper Respiratory Tract Infection, Increased Weight, Decreased Weight, Arthralgia, Back Pain, Myalgia, Musculoskeletal pain, Akathisia, Sedation, Dizziness, Tremor, Nasal Congestion
Specific Populations
- • Pregnancy: Insufficient data to inform drug-associated risk. Neonates exposed during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, feeding disorder). Monitor neonates exhibiting these symptoms and manage appropriately. Consider benefits/risks to fetus when prescribing.
- • Lactation: Present in human breast milk; insufficient data on amount, effects on breastfed infant, or effects on milk production. Weigh development/health benefits of breastfeeding against the mother's clinical need and potential adverse effects on the infant.
Place in Therapy & Use Considerations
- • Chief advantage: Lower risk for metabolic effects (e.g., weight gain) compared to other atypical antipsychotics; convenient every-2-month dosing may aid patients with scheduling difficulties
- • Disadvantages/Barriers: May be unsuitable for patients unable or unwilling to receive a gluteal injection; requirement for 2-week oral overlap may lead to non-adherence, mistaken continuation past the 2-week period (increasing side effect risk), or decreased treatment efficacy/relapse risk; no manufacturer-recommended conversions when switching from oral to this formulation
Document 547
Indications
- Schizophrenia in adults
- Maintenance monotherapy treatment of bipolar I disorder in adults
Administration & Preparation
- Route: Intramuscular (IM) injection into deltoid or gluteal muscle
- Refrigeration: Not required
- Reconstitution/Shaking Requirements:
- Aripiprazole Maintena: Room temperature; shake 20 seconds (pre-filled syringe) or 30 seconds (vial)
- Aripiprazole Aristada: Tap 10x + shake 30 seconds (syringe)
- Aripiprazole Asimtufii: Tap 10x + shake 10 seconds (syringe)
Dosing & Scheduling
- Aripiprazole Maintena: Monthly dosing; conversions include 15mg oral to 300mg IM monthly, and 20mg oral to 400mg IM monthly
- Aripiprazole Aristada: Monthly, q6 weeks, or q2 months dosing; conversions include 10mg oral to 441mg IM monthly, 15mg oral to 662mg IM monthly/882mg q6wks/1064mg q2months IM, and 20mg oral to 882mg IM monthly
- Aripiprazole Asimtufii: Q2 months dosing; conversion includes 400mg IM qmonth to 960mg q2months
Oral Overlap Requirements
- Maintena and Asimtufii: Require 14-day oral overlap
- Aristada: Requires 21-day oral overlap unless administered with Initio (675mg) plus a 30 mg oral dose, which eliminates the need for oral overlap
Formulary & Logistical Considerations
- Formulary status: PA-F with CFU for all three dosage forms
- Medication selection should be based on patient-specific characteristics, patient preferences, and medication side effect profiles per the 2023 VA/DoD CPG for Schizophrenia
- Aristada represents 41% market share among aripiprazole LAIs, has a high PADR approval rate, and is the least expensive LAI among the aripiprazole products
- To avoid oral overlap, Aristada should be administered with Initio for maximum benefit and may be administered monthly or q2months (1064mg only)
- Reported adverse drug events (ADEs) are low, pharmacologically expected, and similar across all aripiprazole LAI dosage forms
- Logistical considerations include route of administration, oral overlap requirements, staff education for administration (duration product must be shaken, injection speed, injection location), refrigeration requirements, and cost