Aripiprazole lauroxil (long-acting injectable [Aristada]): Drug information

For additional information see "Aripiprazole lauroxil (long-acting injectable [Aristada]): Patient drug information"

For abbreviations, symbols, and age group definitions show table

ALERT: US Boxed Warning

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. Aripiprazole lauroxil is not approved for the treatment of patients with dementia-related psychosis.

Brand Names: US

Aristada;
Aristada Initio

Pharmacologic Category

Second Generation (Atypical) Antipsychotic

Dosing: Adult

Dosage guidance:

Dosage form information: Aripiprazole lauroxil is available as two different IM suspensions: Aristada Initio is used as an initial loading dose, and Aristada is used for maintenance dosing. Aristada Initio is not to be used for repeated dosing.

Clinical considerations: Consult a psychiatry specialist for all management decisions; select antipsychotic carefully based on patient preference, clinical characteristics, history, comorbidities, and medication adverse effects profile (Ref).

Schizophrenia

Schizophrenia:

Regimen with 1-day oral aripiprazole overlap (avoid in known CYP2D6 poor metabolizers):

Note: Establish tolerability with oral aripiprazole prior to initiating long-acting IM injection; due to the prolonged half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.

Loading dose (Aristada Initio): IM: 675 mg once, followed by initial dose of Aristada (see “Initial dose” below).

Oral overlap: Administer 30 mg oral aripiprazole on the same day as the Aristada Initio loading dose. No further oral overlap is needed.

Initial dose (Aristada): IM: On same day as Aristada Initio loading dose or within 10 days, administer the first dose of Aristada based on current oral aripiprazole dose (see “Dose Conversions That Attain Similar Steady-State Aripiprazole Exposure During Maintenance Treatment” table). Maximum single dose: 1,064 mg. Initiate maintenance dosing 1 to 2 months after initial Aristada dose.

Maintenance dose (Aristada): IM: Administer same dose as first Aristada dose; adjust dose and frequency based on response and tolerability. May administer each maintenance dose as early as two weeks after the previous Aristada dose. Maximum dose: 882 mg every month or 1,064 mg every 2 months (Ref).

Regimen with 21-day oral aripiprazole overlap:

Note: Establish tolerability with oral aripiprazole prior to initiating Aristada; due to the prolonged half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.

Initial dose (Aristada): IM: Administer the initial Aristada dose based on current oral aripiprazole dose (see “Dose Conversions That Attain Similar Steady-State Aripiprazole Exposure During Maintenance Treatment” table). Maximum single dose: 1,064 mg. Initiate maintenance dosing 1 to 2 months after this initial dose.

Oral overlap: Continue current oral aripiprazole dose for 21 days after first Aristada dose.

Dose Conversions That Attain Similar Steady-State Aripiprazole Exposure During Maintenance Treatment
Oral aripiprazole dose	Initial IM Aristada dose
10 mg/day	441 mg every month
15 mg/day	662 every month or 882 mg every 6 weeks or 1,064 mg every 2 months
≥20 mg/day	882 mg every month

Missed dose: Administer missed dose of Aristada as soon as possible. Supplemental dose(s) may be appropriate; see “Supplemental Dose Recommendations Following Missed Doses” table.

Supplemental Dose Recommendations Following Missed Doses
Dose of Last Aristada Injection	Length of Time Since Last Injection
^a In patients who require oral supplemental dose(s), administer the same dose of oral aripiprazole that the patient was receiving prior to initiation of Aristada, unless otherwise indicated.
441 mg	≤6 weeks	>6 and ≤7 weeks	>7 weeks
662 mg	≤8 weeks	>8 and ≤12 weeks	>12 weeks
882 mg	≤8 weeks	>8 and ≤12 weeks	>12 weeks
1,064 mg	≤10 weeks	>10 and ≤12 weeks	>12 weeks
Supplementation for Re-initiation of Aristada	No supplementation required.	Supplement with: Oral aripiprazole^a for 7 days, or 675 mg Aristada Initio IM once.	Supplement with: 675 mg Aristada Initio IM once plus 30 mg oral aripiprazole once or oral aripiprazole for 21 days.^a

Discontinuation of therapy: Switching to other treatments is generally advised if side effects are intolerable or treatment is not effective. However, if a patient insists on stopping treatment, gradual dose reduction to avoid withdrawal reactions is generally not needed with long-acting injectable antipsychotics. The risk of withdrawal symptoms from discontinuation of long-acting injectables is low because the rate of drug elimination is slow. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).

Switching antipsychotics: An optimal, universal strategy for switching antipsychotic drugs has not been established. Strategies include: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Liver Impairment: Adult

No dosage adjustment necessary.

Dosing: Older Adult

Note: Avoid for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. If used, consider deprescribing attempts to assess continued need and/or lowest effective dose. Of note, use in certain indications may be appropriate (eg, schizophrenia) (Ref). Consult a psychiatry specialist for all management decisions (Ref).

Schizophrenia: Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Nervous system: Akathisia (11%)

1% to 10%:

Endocrine & metabolic: Weight gain (2%; ≥7% increase: 9% to 10%)

Local: Injection-site reaction (4% to 5%), pain at injection site (3% to 4%)

Nervous system: Extrapyramidal reaction (5% to 7%), headache (5%), insomnia (3% to 4%), parkinsonism (4%), restlessness (3%)

Neuromuscular & skeletal: Dystonia (2%), increased creatine phosphokinase in blood specimen (1% to 2%)

<1%:

Cardiovascular: Orthostatic hypotension

Local: Erythema at injection site, induration at injection site, swelling at injection site

Frequency not defined:

Cardiovascular: Angina pectoris, palpitations, tachycardia

Gastrointestinal: Constipation, xerostomia

Nervous system: Anxiety, asthenia, dizziness, myasthenia

Postmarketing: Nervous system: Impulse control disorder (including binge eating, compulsive shopping, hypersexuality, intense gambling urges) (FDA Safety Alert 2016)

Contraindications

Hypersensitivity (eg, anaphylaxis, pruritus, urticaria) to aripiprazole or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics.

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC/ANC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm³.

• Cerebrovascular effects: An increased incidence of cerebrovascular effects (eg, transient ischemic attack, stroke), including fatalities, has been reported in placebo-controlled trials of antipsychotics for the unapproved use in elderly patients with dementia-related psychosis.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Dyslipidemia: Lipid changes, including increases in total cholesterol, LDL cholesterol, and triglycerides and decreases in HDL cholesterol, have been reported; risk profile may differ between antipsychotic agents. Compared to other antipsychotics, the risk of dyslipidemia with aripiprazole lauroxil is minimal-to-low (Solmi 2017).

• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (eg, Alzheimer disease), particularly in patients >75 years (Herzig 2017; Maddalena 2004).

• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Keepers 2020]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.

• Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. All patients should be monitored for symptoms of hyperglycemia (eg, polydipsia, polyuria, polyphagia, weakness). Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control. Patients with risk factors for diabetes (eg, obesity or family history) should have a baseline fasting blood sugar and periodic assessment of glucose regulation. Hyperglycemia may resolve with discontinuation of therapy; however, some patients may require treatment of diabetes after discontinuation of therapy. Compared to other antipsychotics, the risk of hyperglycemia with aripiprazole lauroxil is minimal-to-low (Solmi 2017).

• Impulse control disorders: Has been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, uncontrolled sexual urges, uncontrolled spending, binge or compulsive eating, and/or other intense urges. Patients with prior history of impulse control issues may be at increased risk. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in most, but not all, cases (Gaboriau 2014; Moore 2014; Smith 2011).

• Neuroleptic malignant syndrome: Use may be associated with neuroleptic malignant syndrome; monitor for mental status changes, fever, muscle rigidity and/or autonomic instability.

• Orthostatic hypotension: May cause orthostatic hypotension; increased risk at initiation of therapy or during dose escalation. Use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Consider using lower starting dosages and slower titrations in these patients.

• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

• Weight gain: Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Monitoring of weight is recommended. Compared to other antipsychotics, the risk of weight gain with aripiprazole lauroxil is minimal (Solmi 2017).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiac disease, cerebrovascular disease, prior myocardial infarction, ischemic heart disease, or conditions which predispose to hypotension.

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death (APA [Reus 2016]). Aripiprazole lauroxil is not approved for the treatment of dementia-related psychosis.

• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.

Special populations:

• CYP2D6 poor metabolizers: Known CYP2D6 poor metabolizers may be at risk for elevated aripiprazole concentrations. Avoid use of the 675 mg strength aripiprazole lauroxil nanocrystal dispersion (Aristada Initio) in this population; dose adjustment is required with other strengths of aripiprazole lauroxil (Aristada).

Other warnings/precautions:

• Appropriate use: Medication errors, including substitution and dispensing errors, could occur between the 675 mg strength aripiprazole lauroxil nanocrystal dispersion (Aristada Initio) and other aripiprazole lauroxil strengths (Aristada). The 675 mg strength nanocrystal dispersion (Aristada Initio) is not intended for repeat dosing, and is only used as a single dose in combination with oral aripiprazole for initiation of long-term treatment with intramuscular aripiprazole lauroxil (Aristada) or as a single dose to reinitiate treatment after a missed dose of intramuscular aripiprazole lauroxil (Aristada). The 675 mg strength aripiprazole lauroxil nanocrystal dispersion (Aristada Initio) is not interchangeable with other aripiprazole lauroxil strengths (Aristada).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Prefilled Syringe, Intramuscular:

Aristada: 1064 mg/3.9 mL (3.9 mL); 441 mg/1.6 mL (1.6 mL); 662 mg/2.4 mL (2.4 mL); 882 mg/3.2 mL (3.2 mL)

Prefilled Syringe, Intramuscular [preservative free]:

Aristada Initio: 675 mg/2.4 mL (2.4 mL)

Generic Equivalent Available: US

Pricing: US

Prefilled Syringe (Aristada Initio Intramuscular)

675MG/2.4ML (per mL): $1,217.60

Prefilled Syringe (Aristada Intramuscular)

441 mg/1.6 mL (per mL): $1,193.25

662MG/2.4ML (per mL): $1,194.15

882MG/3.2ML (per mL): $1,193.25

1064MG/3.9ML (per mL): $1,181.11

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

IM: For IM administration only. Administer the 441 mg dose (Aristada) and the 675 mg nanocrystal dispersion dose (Aristada Initio) in the deltoid or gluteal muscle, and other dose strengths (Aristada) in the gluteal muscle. Inject in a rapid and continuous manner. Avoid administering aripiprazole lauroxil nanocrystal dispersion (Aristada Initio) and aripiprazole lauroxil (Aristada) concurrently in the same muscle. Prior to administration, tap the syringe at least 10 times and then shake the syringe vigorously ≥30 seconds to ensure a uniform suspension. If the syringe is not used within 15 minutes, shake again for 30 seconds. Use the appropriate sized needle for the injection site; a 21-gauge, 1 inch or 20-gauge, 1.5-inch needle for deltoid injection and a 20-gauge, 1.5- or 2-inch needle for gluteal injection. Use the longer needles for patients with a larger amount of subcutaneous tissue overlaying the injection site muscle.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Aristada: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/207533s031lbl.pdf#page=36

Aristada Initio: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209830s020lbl.pdf#page=31

Use: Labeled Indications

Schizophrenia: Treatment of schizophrenia in adults.

Limitations of use: Aripiprazole lauroxil is available as two different IM suspensions: Aristada Initio is used as an initial loading dose, and Aristada is used for maintenance dosing. Aristada Initio is not to be used for repeated dosing.

Medication Safety Issues

Sound-alike/look-alike issues:

ARIPiprazole may be confused with proton pump inhibitors (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, RABEprazole)

Aristada may be confused with Arista AH (hemostatic device), Arixtra

Older Adult: High-Risk Medication:

Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of stroke and a greater rate of cognitive decline and mortality in patients with dementia. Evidence also suggests there may be an increased risk of mortality with use independent of dementia. Avoid antipsychotics for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. Use may be appropriate for labeled indications including schizophrenia, bipolar disorder, Parkinson disease psychosis, major depressive disorder, or for short-term use as an antiemetic (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Substrate of CYP2D6 (Major), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Agents With Seizure Threshold Lowering Potential: May increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor

Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor

Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor

Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor

Amisulpride (Oral): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor

Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider Therapy Modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor

Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Benzgalantamine-Galantamine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor

Benzodiazepines: ARIPiprazole Lauroxil may increase CNS depressant effects of Benzodiazepines. ARIPiprazole Lauroxil may increase hypotensive effects of Benzodiazepines. Specifically, the risk of orthostatic hypotension may be increased. Risk C: Monitor

Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor

Blood Pressure Lowering Agents: May increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor

Bornaprine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, tardive dyskinesia symptoms may be potentiated. Risk C: Monitor

Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Bromopride: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid

Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Cabergoline: May decrease therapeutic effects of Antipsychotic Agents. Risk X: Avoid

Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor

Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor

CYP2D6 Inhibitors (Moderate): May increase active metabolite exposure of ARIPiprazole Lauroxil. Risk C: Monitor

CYP2D6 Inhibitors (Strong): May increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification

CYP3A4 Inducers (Moderate): May decrease serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease active metabolite exposure of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Risk D: Consider Therapy Modification

CYP3A4 Inhibitors (Moderate): May increase serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor

CYP3A4 Inhibitors (Strong): May increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP3A4 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg). Max dose is 441 mg in CYP2D6 PMs or if also taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification

Deutetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor

Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may increase adverse/toxic effects of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor

Donepezil: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor

DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

Guanethidine: Antipsychotic Agents may decrease therapeutic effects of Guanethidine. Risk C: Monitor

Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Huperzine A: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor

Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Lithium: May increase neurotoxic effects of Antipsychotic Agents. Lithium may decrease serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor

Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid

Metergoline: Antipsychotic Agents may decrease therapeutic effects of Metergoline. Metergoline may decrease therapeutic effects of Antipsychotic Agents. Risk C: Monitor

Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Metoclopramide: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid

MetyroSINE: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor

Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor

OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor

Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid

Piribedil: Antipsychotic Agents may decrease therapeutic effects of Piribedil. Piribedil may decrease therapeutic effects of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid

Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor

Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Quinagolide: Antipsychotic Agents may decrease therapeutic effects of Quinagolide. Risk C: Monitor

RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Rivastigmine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor

Serotonergic Agents (High Risk): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor

Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor

Sulpiride: Antipsychotic Agents may increase adverse/toxic effects of Sulpiride. Risk X: Avoid

Tetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor

Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor

Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Reproductive Considerations

Evaluate pregnancy status and provide preconception counseling prior to initiating treatment in patients who could become pregnant (APA [Keepers 2020]; BAP [McAllister-Williams 2017]). Patients effectively treated may continue their current antipsychotic medication when planning a pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]); the lowest effective dose and avoidance of polytherapy is recommended (BAP [Barnes 2020]; BAP [McAllister-Williams 2017]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment and the risks of discontinuing antipsychotic therapy (ACOG 2023; BAP [McAllister-Williams 2017]).

Antipsychotic agents may be associated with sexual dysfunction. Some second generation (atypical) antipsychotics may cause hyperprolactinemia, resulting in menstrual disorders or impaired spermatogenesis. Consider changing to a medication that is prolactin-sparing in patients with clinical symptoms. Contraception should be provided if pregnancy is not desired, as unintended pregnancies may occur when changing to a prolactin-sparing medication (APA [Keepers 2020]; BAP [McAllister-Williams 2017]).

Pregnancy Considerations

Aripiprazole crosses the placenta; aripiprazole and the active metabolite dehydro-aripiprazole can be detected in the cord blood at delivery (Nguyen 2011; Watanabe 2011).

Refer to the aripiprazole monograph for additional information.

Data collection to monitor pregnancy and infant outcomes following exposure to aripiprazole lauroxil is ongoing. Encourage pregnant patients 45 years and younger with a history of psychiatric illness to enroll in the National Pregnancy Registry for Psychiatric Mediations (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/).

Breastfeeding Considerations

Aripiprazole is present in breast milk.

Aripiprazole may decrease breast milk supply. Monitor infants exposed to aripiprazole via breast milk for dehydration and appropriate weight gain.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Refer to the Aripiprazole monograph for additional information.

Monitoring Parameters

Frequency of Antipsychotic Monitoring for Aripiprazole Lauroxil^a,b
Monitoring parameter	Frequency of monitoring	Comments
Adherence	Every visit
Blood chemistries (electrolytes, renal function, liver function, TSH)	Annually
CBC	As clinically indicated	Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia
Extrapyramidal symptoms	Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high risk^c
Fall risk	Every visit
Fasting plasma glucose/HbA_1c	4 months after initiation; annually	Check more frequently than annually if abnormal. Follow diabetes guidelines.
Lipid panel	4 months after initiation; annually	Check more frequently than annually if abnormal. Follow lipid guidelines.
Mental status and alertness	Every visit
Metabolic syndrome history	Annually	Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease
Prolactin	Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported.	Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function
Tardive dyskinesia	Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high risk^d
Vital signs (BP, orthostatics, temperature, pulse, signs of infection)	Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change.
Weight/Height/BMI	8 and 12 weeks after initiation and dose change; quarterly	Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome. Consider changing antipsychotic if BMI increases by ≥1 unit. Some experts recommend checking weight and height at every visit.
^aFor all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected ADRs) in addition to the timeline. ^b ADA 2004; APA [Keepers 2020]; de Hert 2011; Gugger 2011; manufacturer’s labeling. ^c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic. ^dRisk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or CNS injury; and past or current EPS.

Mechanism of Action

Aripiprazole lauroxil is a prodrug of aripiprazole. Following intramuscular injection, aripiprazole lauroxil is likely converted by enzyme-mediated hydrolysis to N-hydroxymethyl aripiprazole, which is then hydrolyzed to aripiprazole. Aripiprazole is a quinolinone antipsychotic that exhibits high affinity for D₂, D₃, 5-HT_1A, and 5-HT_2A receptors; moderate affinity for D₄, 5-HT_2C, 5-HT₇, alpha₁ adrenergic, and H₁ receptors. It also possesses moderate affinity for the serotonin reuptake transporter; has no affinity for muscarinic (cholinergic) receptors. Aripiprazole functions as a partial agonist at the D₂ and 5-HT_1A receptors, and as an antagonist at the 5-HT_2A receptor (de Bartolomeis 2015).

Pharmacokinetics (Adult Data Unless Noted)

Onset of action:

Aristada: 5 to 6 days following injection; within 4 days following injection when administered concomitantly with oral aripiprazole.

Aristada Initio (675 mg strength nanocrystal dispersion): Reaches systemic circulation on day of injection; reaches clinically relevant serum concentrations 4 days following injection when administered concomitantly with oral aripiprazole 30 mg.

Duration of action: Aristada: 36 days following appearance in the systemic circulation.

Distribution: V_d: 268 L.

Protein binding: >99%, primarily to albumin.

Metabolism: Prodrug; undergoes enzyme-mediated hydrolysis to N-hydroxymethyl aripiprazole followed by enzyme-mediated hydrolysis to aripiprazole. Aripiprazole undergoes hepatic metabolism via CYP2D6, CYP3A4 (dehydro-aripiprazole metabolite has affinity for D₂ receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma) (Sheehan 2010).

Half-life elimination:

Aristada: 53.9 to 57.2 days.

Aristada Initio (675 mg strength nanocrystal dispersion): 15 to 18 days.

Time to peak, serum: Aristada Initio (675 mg strength nanocrystal dispersion): 16 to 35 days (median 27 days).

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(PR) Puerto Rico: Aristada | Aristada initio

2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372 [PubMed 37139824]
American College of Obstetricians and Gynecologists (ACOG). Treatment and management of mental health conditions during pregnancy and postpartum: ACOG clinical practice guideline No. 5. Obstet Gynecol. 2023;141(6):1262-1288. doi:10.1097/AOG.0000000000005202 [PubMed 37486661]
American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity, Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601. [PubMed 14747245]
Aristada (aripiprazole lauroxil) [prescribing information]. Waltham, MA: Alkermes, Inc; February 2020.
Aristada (aripiprazole lauroxil) [prescribing information]. Waltham, MA: Alkermes Inc; January 2025.
Aristada Initio (aripiprazole lauroxil) [prescribing information]. Waltham, MA: Alkermes Inc; January 2025.
Barnes TR, Drake R, Paton C, et al. Evidence-based guidelines for the pharmacological treatment of schizophrenia: updated recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2020;34(1):3-78. doi:10.1177/0269881119889296 [PubMed 31829775]
Cerovecki A, Musil R, Klimke A, et al. Withdrawal symptoms and rebound syndromes associated with switching and discontinuing atypical antipsychotics: theoretical background and practical recommendations. CNS Drugs. 2013;27(7):545-572. doi: 10.1007/s40263-013-0079-5. [PubMed 23821039]
de Bartolomeis A, Tomasetti C, Iasevoli F. Update on the mechanism of action of aripiprazole: translational insights into antipsychotic strategies beyond dopamine receptor antagonism. CNS Drugs. 2015;29(9):773-799. [PubMed 26346901]
De Hert M, Detraux J, van Winkel R, Yu W, Correll CU. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8(2):114-126. doi:10.1038/nrendo.2011.156 [PubMed 22009159]
Ehret MJ, Davis E, Luttrell SE, Clark C. Aripiprazole Lauroxil NanoCrystal® Dispersion Technology (Aristada Initio®). Clin Schizophr Relat Psychoses. 2018;12(2):92-96. doi: 10.3371/CSRP.EHDA071918. [PubMed 30040476]
FDA Safety Alert. MedWatch. FDA drug safety communication: FDA warns about new impulse control problems associated with mental health drug aripiprazole (Abilify, Abilify Maintena, Aristada). Available at http://www.fda.gov/Drugs/DrugSafety/ucm498662.htm. Accessed May 5, 2016.
Gaboriau L, Victorri-Vigneau C, Gérardin M, Allain-Veyrac G, Jolliet-Evin P, Grall-Bronnec M. Aripiprazole: a new risk factor for pathological gambling? A report of 8 case reports. Addict Behav. 2014;39(3):562-565. [PubMed 24315783]
Gugger JJ. Antipsychotic pharmacotherapy and orthostatic hypotension: identification and management. CNS Drugs. 2011;25(8):659-671. doi:10.2165/11591710-000000000-00000 [PubMed 21790209]
Herzig SJ, LaSalvia MT, Naidus E, et al. Antipsychotics and the risk of aspiration pneumonia in individuals hospitalized for nonpsychiatric conditions: a cohort study. J Am Geriatr Soc. 2017;65(12):2580-2586. doi:10.1111/jgs.15066 [PubMed 29095482]
Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868-872. doi:10.1176/appi.ajp.2020.177901 [PubMed 32867516]
Maddalena AS, Fox M, Hofmann M, Hock C. Esophageal dysfunction on psychotropic medication. A case report and literature review. Pharmacopsychiatry. 2004;37(3):134-138. [PubMed 15138897]
McAllister-Williams RH, Baldwin DS, Cantwell R, et al. British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017. J Psychopharmacol. 2017;31(5):519-552. doi:10.1177/0269881117699361 [PubMed 28440103]
Moore TJ, Glenmullen J, Mattison DR. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern Med. 2014;174(12):1930-1933. [PubMed 25329919]
Nguyen T, Teoh S, Hackett LP, Ilett K. Placental transfer of aripiprazole. Aust N Z J Psychiatry. 2011;45(6):500-501. [PubMed 21413838]
Refer to manufacturer’s labeling.
Remington G, Chue P, Stip E, Kopala L, Girard T, Christensen B. The crossover approach to switching antipsychotics: what is the evidence? Schizophr Res. 2005;76(2-3):267-272. [PubMed 15949658]
Reus VI, Fochtmann LJ, Eyler AE, et al The American Psychiatric Association Practice Guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543-546. doi: 10.1176/appi.ajp.2015.173501. [PubMed 27133416]
Sheehan JJ, Sliwa JK, Amatniek JC, Grinspan A, Canuso CM, et al. Atypical antipsychotic metabolism and excretion. Curr Drug Metab. 2010;11(6):516-525. [PubMed 20540690]
Smith N, Kitchenham N, Bowden-Jones H. Pathological gambling and the treatment of psychosis with aripiprazole: case reports. Br J Psychiatry. 2011;199(2):158-159. [PubMed 21804151]
Soares-Weiser K, Fernandez HH. Tardive dyskinesia. Semin Neurol. 2007;27(2):159-169. [PubMed 17390261]
Solmi M, Murru A, Pacchiarotti I, Undurraga J, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757-777. doi: 10.2147/TCRM.S117321. [PubMed 28721057]
Spanarello S, La Ferla T. The pharmacokinetics of long-acting antipsychotic medications. Curr Clin Pharmacol. 2014;9(3):310-317. doi:10.2174/15748847113089990051 [PubMed 23343447]
Steinman M, Reeve E. Deprescribing. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 30, 2021.
Takeuchi H, Kantor N, Uchida H, Suzuki T, Remington G. Immediate vs gradual discontinuation in antipsychotic switching: a systematic review and meta-analysis. Schizophr Bull. 2017;43(4):862-871. doi: 10.1093/schbul/sbw171. [PubMed 28044008]
Watanabe N, Kasahara M, Sugibayashi R, et al. Perinatal use of aripiprazole: a case report. J Clin Psychopharmacol. 2011;31(3):377-379 [PubMed 21532364]

Topic 104548 Version 248.0

خرید پکیج

Aripiprazole lauroxil (long-acting injectable [Aristada]): Drug information