ARISTADA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ARISTADA (ARISTADA).
Aripiprazole lauroxil is a prodrug of aripiprazole, a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at 5-HT2A receptors. The mechanism of action in schizophrenia and bipolar I disorder is thought to be mediated through these receptor interactions.
| Metabolism | Aripiprazole lauroxil is hydrolyzed by esterases to N-hydroxymethyl aripiprazole, which is then converted to aripiprazole. Aripiprazole is primarily metabolized by CYP2D6 and CYP3A4. |
| Excretion | Primarily renally excreted (approximately 60% as metabolites, <1% unchanged). Fecal elimination accounts for about 20%. |
| Half-life | Terminal elimination half-life of aripiprazole lauroxil (the prodrug in ARISTADA) is approximately 54 days (range 29-74 days) after IM injection, allowing monthly dosing. |
| Protein binding | >99% bound, primarily to albumin. |
| Volume of Distribution | Approximately 4.9 L/kg (based on aripiprazole), indicating extensive tissue distribution. |
| Bioavailability | Intramuscular: 100% (complete release from injection site). Oral aripiprazole: 87%. |
| Onset of Action | Intramuscular: therapeutic effects observed within 4-7 days; full efficacy may take several weeks. |
| Duration of Action | Sustained for 4-6 weeks after a single IM injection due to slow dissolution and conversion to aripiprazole. |
Initial dose: 675 mg intramuscularly every 4 weeks for the first 2 doses, then maintenance dose of 882 mg intramuscularly every 4 weeks. Alternatively, 1064 mg intramuscularly every 6 weeks after appropriate initiation.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (CrCl >=30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | No dosage adjustment required for mild hepatic impairment (Child-Pugh class A). Not recommended for moderate to severe hepatic impairment (Child-Pugh class B or C) due to lack of studies. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years of age. |
| Geriatric use | No specific dosage adjustment recommended, but caution due to potential increased sensitivity and renal function decline. Monitor for adverse effects and consider lower initial doses if clinically appropriate. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ARISTADA (ARISTADA).
| Breastfeeding | Aripiprazole is excreted in human breast milk; the milk-to-plasma ratio (M/P) is approximately 0.5 to 3.0 based on limited data. In lactating women, the relative infant dose (RID) is estimated to be about 1.4% to 8.3% of the weight-adjusted maternal dose. Caution is advised; consider the developmental and health benefits of breastfeeding along with the mother's clinical need for Aristada and any potential adverse effects on the breastfed child. Monitor the infant for signs of sedation, extrapyramidal symptoms, or inadequate weight gain. |
| Teratogenic Risk | Aristada (aripiprazole lauroxil) is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, aripiprazole caused developmental toxicity, including teratogenic effects, at doses similar to or less than the maximum recommended human dose (MRHD). During the first trimester, there is a potential risk of major congenital malformations, although data are limited. During the second and third trimesters, exposure may increase the risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ARISTADA is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to aripiprazole or any component of the formulation"]
| Precautions | ["Increased mortality in elderly patients with dementia-related psychosis","Cerebrovascular adverse events in elderly patients with dementia","Neuroleptic malignant syndrome","Tardive dyskinesia","Metabolic changes (hyperglycemia, dyslipidemia, weight gain)","Orthostatic hypotension","Leukopenia, neutropenia, and agranulocytosis","Seizures","Body temperature dysregulation","Dysphagia","Potential for cognitive and motor impairment"] |
| Food/Dietary | Avoid grapefruit juice due to CYP3A4 inhibition. No specific food restrictions beyond that. |
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| Fetal Monitoring | Monitor pregnant women for exacerbation of psychiatric symptoms, gestational weight gain, glucose intolerance, and blood pressure. Fetal monitoring should include ultrasound for fetal growth and development if concerns arise. Neonates exposed during late pregnancy should be observed for extrapyramidal symptoms and withdrawal signs. |
| Fertility Effects | In animal studies, aripiprazole impaired fertility and reproductive performance in female rats at doses equivalent to the MRHD. In humans, the effect on fertility is unknown; however, hyperprolactinemia, which may cause menstrual irregularities and impaired fertility, is a potential adverse effect of antipsychotics due to dopamine D2 receptor blockade. Consider evaluating prolactin levels if fertility issues arise. |
| Clinical Pearls | Initiate with a single 672 mg test dose to confirm tolerability. Administer only via gluteal IM injection; do not administer IV. The drug forms a liquid crystal depot upon injection. Ensure proper needle selection: 2-inch needle for gluteal injection. Do not massage injection site. Monitor for post-injection syndrome (rare but serious). |
| Patient Advice | Do not stop taking this medication abruptly; continue regular visits for injections. · Report any severe muscle stiffness, fever, confusion, or irregular heartbeat immediately. · Avoid alcohol and grapefruit juice while on this medication. · You may experience injection site reactions; notify your doctor if they worsen. · Use effective contraception if of childbearing potential; discuss risks with your doctor. |