ABILIFY ASIMTUFII
Clinical safety rating: caution
ABILIFY ASIMTUFII (aripiprazole) is a long-acting injectable atypical antipsychotic used for the treatment of schizophrenia and maintenance monotherapy of bipolar I disorder. It provides sustained therapeutic plasma levels with monthly intramuscular administration.
Aripiprazole is a partial agonist at D2 and 5-HT1A receptors and an antagonist at 5-HT2A receptors. The active metabolite, dehydro-aripiprazole, contributes to the pharmacological activity. Abilify Asimtufii is a long-acting injectable formulation for intramuscular use.
| Metabolism | Primarily hepatic via CYP2D6 and CYP3A4; active metabolite dehydro-aripiprazole is formed primarily by CYP3A4 and CYP2D6; exhibits significant interindividual variability due to CYP2D6 polymorphism. |
| Excretion | Renal (approximately 25% unchanged and 55% as metabolites), fecal (approximately 20%). |
| Half-life | Terminal elimination half-life: 29-40 days (aripiprazole) and 48-63 days (dehydraripiprazole), allowing monthly dosing. |
| Protein binding | >99% bound to serum albumin. |
| Volume of Distribution | 4.9 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Intramuscular: 100% (as a depot suspension). |
| Onset of Action | Extended-release intramuscular injection: therapeutic effect typically observed within 2-4 weeks after first injection. |
| Duration of Action | Approximately 1 month (4 weeks) due to depot formulation; steady-state achieved after 4 monthly doses. |
| Molecular Weight | 448.38 |
| Action Class | Atypical antipsychotic |
Recommended starting dose: 400 mg intramuscularly once monthly, with a single oral dose of 10-20 mg aripiprazole or continued oral therapy for 14 days to ensure tolerability. Maintenance dose: 300-400 mg monthly.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dosage adjustment required for patients with renal impairment (CrCl ≥15 mL/min). Insufficient data for patients with end-stage renal disease (CrCl <15 mL/min). |
| Liver impairment | No dosage adjustment recommended for mild to moderate hepatic impairment (Child-Pugh class A or B). Use with caution in severe hepatic impairment (Child-Pugh class C) as experience is limited. |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy have not been established. |
| Geriatric use | Use with caution due to increased sensitivity to orthostatic hypotension and sedative effects. Consider lower starting doses (300 mg orally equivalent) but no specific dose adjustment for the injectable form is recommended. |
| 1st trimester | Aripiprazole exposure in the first trimester is associated with a potential increased risk of congenital malformations, particularly neural tube defects. Use only if benefit outweighs risk. |
| 2nd trimester | Monitor for preterm birth and intrauterine growth restriction. Consider dose adjustment due to physiological changes. |
| 3rd trimester | Risk of extrapyramidal symptoms and withdrawal in neonates. Use lowest effective dose and monitor neonate closely. |
Clinical note
Pregnancy Category C: Aripiprazole crosses the placenta and may cause extrapyramidal symptoms or withdrawal in neonates. Use only if potential benefit justifies risk to the fetus.
| Placental transfer | Aripiprazole crosses the placenta as demonstrated in cord blood samples showing concentrations approximately 50-100% of maternal serum levels. |
| Breastfeeding | Aripiprazole is excreted into breast milk in low to moderate amounts. Infant serum concentrations are typically subtherapeutic but cases of somnolence and irritability have been reported. Weigh benefits of breastfeeding against potential risks to the infant. |
■ FDA Black Box Warning
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. Abilify Asimtufii is not approved for the treatment of patients with dementia-related psychosis.
| Common Effects | Weight gain, Akathisia, Insomnia, Headache, Nausea, Vomiting, Constipation, Sedation |
| Serious Effects | Neuroleptic malignant syndrome, tardive dyskinesia, stroke in elderly dementia patients, agranulocytosis, severe orthostatic hypotension, seizures, allergic reactions (angioedema, anaphylaxis). |
Hypersensitivity to aripiprazole or any excipients
| Precautions | Increased mortality in elderly patients with dementia-related psychosis; cerebrovascular adverse events (e.g., stroke, transient ischemic attack) in elderly patients with dementia-related psychosis; neuroleptic malignant syndrome (NMS); tardive dyskinesia; metabolic changes (hyperglycemia/diabetes mellitus, dyslipidemia, weight gain); pathological gambling and other compulsive behaviors; orthostatic hypotension; leukopenia/neutropenia/agranulocytosis; seizures; body temperature dysregulation; dysphagia; potential for additive effects with alcohol or CNS depressants; injection site reactions; risk of extrapyramidal symptoms; suicidal thoughts/behaviors. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C: First trimester risk of congenital malformations unknown; second/third trimester exposure may cause extrapyramidal and/or withdrawal symptoms in neonates. Advise use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor for extrapyramidal symptoms, sedation, hyperprolactinemia in mother; fetal growth and neonatal withdrawal symptoms post-delivery. |
| Fertility Effects | May cause hyperprolactinemia, possibly impairing fertility; reversible upon discontinuation. |
| Food/Dietary | Avoid grapefruit juice and grapefruit products as they may increase aripiprazole levels. Alcohol should be limited or avoided due to additive CNS depression and increased risk of sedation. |
| Clinical Pearls | ABILIFY ASIMTUFII (aripiprazole) is a long-acting injectable suspension for intramuscular use. Administer only by a healthcare professional. Observe patient for 2 hours post-injection due to risk of post-injection delirium/sedation syndrome. Requires 3 consecutive daily doses of oral aripiprazole (10-20 mg) before initiation to confirm tolerability. Dosing: 441 mg IM monthly (equates to 400 mg aripiprazole). Do not substitute with other aripiprazole formulations on a mg-per-mg basis. Contraindicated in patients with known hypersensitivity to aripiprazole. |
| Patient Advice | This medication is given as an injection once a month by your healthcare provider. · Do not try to inject yourself; it must be given by a healthcare professional. · After each injection, you will need to stay at the doctor's office or clinic for at least 2 hours to be monitored for any serious side effects. · You will need to take oral aripiprazole for 3 days before your first injection to see if you can tolerate the medication. · Common side effects include headache, insomnia, nausea, and injection site pain. · Seek emergency care if you have allergic reaction (hives, difficulty breathing, swelling), uncontrolled muscle movements, or thoughts of suicide. · Avoid alcohol and grapefruit juice while on this medication. · Tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. · Do not stop treatment without consulting your doctor. |