ARISTADA INITIO KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARISTADA INITIO KIT (ARISTADA INITIO KIT).
Aripiprazole lauroxil is a prodrug of aripiprazole, a partial agonist at D2 and serotonin 5-HT1A receptors and antagonist at serotonin 5-HT2A receptors. The active metabolite, aripiprazole, exerts antipsychotic effects through modulation of dopaminergic and serotonergic neurotransmission.
| Metabolism | Aripiprazole lauroxil is hydrolyzed by esterases (e.g., carboxylesterases) to form N-hydroxymethyl aripiprazole, which is then converted to aripiprazole. Aripiprazole is primarily metabolized by CYP2D6 and CYP3A4 via dehydrogenation, hydroxylation, and N-dealkylation. |
| Excretion | Aripiprazole lauroxil is metabolized to aripiprazole. The primary route of elimination is hepatic metabolism via CYP3A4 and CYP2D6; approximately 25% of the dose is excreted renally as aripiprazole and metabolites, and about 55% is excreted in feces. The active metabolite dehydro-aripiprazole accounts for about 40% of exposure. |
| Half-life | The terminal elimination half-life of aripiprazole following a single intramuscular injection of aripiprazole lauroxil is approximately 15-18 days for the 662 mg dose, with a range of 9.4-28.9 days. Steady state is reached after approximately 4 months of monthly dosing. |
| Protein binding | Aripiprazole is 99% bound to serum proteins, primarily albumin. |
| Volume of Distribution | The volume of distribution of aripiprazole is approximately 4.9 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Following intramuscular injection of aripiprazole lauroxil, the bioavailability is approximately 100% relative to oral aripiprazole. The oral bioavailability of aripiprazole is 87%. |
| Onset of Action | Following intramuscular injection of ARISTADA INITIO (aripiprazole lauroxil), aripiprazole concentrations reach therapeutic levels within 4 days. The onset of clinical effect (antipsychotic response) is typically observed within 1-2 weeks. |
| Duration of Action | With the combination of a single 30 mg oral aripiprazole dose plus ARISTADA INITIO, therapeutic plasma concentrations are maintained for 4 weeks, allowing for initiation of ARISTADA (aripiprazole lauroxir) once-monthly at the next dose. |
| Molecular Weight | 448.388 |
675 mg intramuscularly once, administered as a single dose on day 1 of treatment, followed by oral aripiprazole or ARISTADA 441 mg, 662 mg, or 882 mg on day 8.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for patients with renal impairment (including end-stage renal disease). |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A and B). Not studied in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment recommended for elderly patients; consider age-related factors such as renal/hepatic function and concomitant medications. |
| 1st trimester | Aripiprazole lauroxil is not recommended during the first trimester due to lack of safety data; however, aripiprazole exposure has been associated with a low risk of neural tube defects and other malformations. Use only if potential benefit justifies risk. |
| 2nd trimester | Limited data; aripiprazole may cause abnormal muscle movements (extrapyramidal symptoms) and withdrawal symptoms in neonates after third trimester exposure. Consider lower doses and monitor fetal growth. |
| 3rd trimester | Use during third trimester may increase risk for neonatal extrapyramidal symptoms, sedation, and withdrawal. Monitor neonate for symptoms such as agitation, hypertonia, hypotonia, tremor, somnolence, and feeding difficulties. |
Clinical note
Comprehensive clinical and safety monograph for ARISTADA INITIO KIT (ARISTADA INITIO KIT).
| Placental transfer | Aripiprazole crosses the placenta; animal studies show transfer, and human data confirm measurable cord blood concentrations approximately 70-90% of maternal serum levels. |
| Breastfeeding |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ARISTADA INITIO KIT (aripiprazole lauroxil) is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
Hypersensitivity to aripiprazole or any component of the formulationConcurrent use with strong CYP3A4 inducers (e.g., rifampin) due to reduced efficacy
| Precautions | Increased mortality in elderly patients with dementia-related psychosis, Suicidal thoughts and behaviors, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Metabolic changes (hyperglycemia, dyslipidemia, weight gain), Orthostatic hypotension, Leukopenia, neutropenia, and agranulocytosis, Seizures, Body temperature dysregulation, Dysphagia, Concomitant use with opioids causing sedation, respiratory depression, coma, and death |
| Food/Dietary | Grapefruit and grapefruit juice may increase aripiprazole levels; avoid concomitant consumption. |
Loading safety data…
| Aripiprazole is excreted into human breast milk; infant serum levels are estimated to be 0.12-16% of maternal weight-adjusted dose. Limited data suggest low risk of adverse effects, but monitor infant for sedation, poor feeding, and extrapyramidal symptoms. Use caution and consider benefits of breastfeeding versus potential risks. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. Aripiprazole, the active component, has been associated with increased risk of neural tube defects and other malformations in animal studies. In humans, first-trimester exposure may increase risk of congenital malformations, particularly cardiovascular defects. Third-trimester exposure may cause extrapyramidal symptoms and/or withdrawal symptoms in neonates. Use only if potential benefit justifies risk to fetus. |
| Fetal Monitoring | Monitor maternal blood pressure, glucose, and weight gain. Assess for signs of extrapyramidal symptoms. Fetal monitoring: ultrasound for fetal growth and anatomy in second trimester; fetal heart rate monitoring in third trimester. Neonatal monitoring: observe for extrapyramidal symptoms and withdrawal post-delivery. |
| Fertility Effects | Aripiprazole may cause hyperprolactinemia, which can lead to menstrual irregularities, galactorrhea, and reduced fertility. The effect is generally mild and reversible upon discontinuation. No direct impairment of fertility has been established in animal studies. |
| Clinical Pearls | Administer only as a single dose to initiate ARISTADA therapy. Must be given by gluteal IM injection using the provided thin-wall needle. Do not massage injection site. Swirl vial gently, do not shake. Refrigerate but do not freeze. Protect from light. |
| Patient Advice | This injection is given once to start your treatment and must be followed by a dose of ARISTADA one month later. · Report any persistent pain, swelling, or redness at injection site. · Avoid alcohol while taking this medication. · Seek emergency care if you experience sudden drowsiness, confusion, or difficulty swallowing. |