ADASUVE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADASUVE (ADASUVE).
Loxapine (the active ingredient in ADASUVE) is a dibenzoxazepine antipsychotic agent that acts primarily as a dopamine D2 receptor antagonist. It also exhibits affinity for serotonin 5-HT2A, 5-HT2C, and histamine H1 receptors, and to a lesser extent, alpha-adrenergic and muscarinic receptors. The exact mechanism of its antipsychotic effect is thought to involve dopamine and serotonin receptor blockade.
| Metabolism | Loxapine is extensively metabolized in the liver primarily via cytochrome P450 (CYP) enzymes, including CYP1A2, CYP2D6, and CYP3A4. Major metabolites include hydroxyloxapine and N-methyloxapine (amoxapine), which possess pharmacological activity. |
| Excretion | Primarily renal (30-40% as unchanged drug and metabolites; ~50% as loxapine metabolites), with minor biliary/fecal elimination (<10%). |
| Half-life | Mean terminal half-life of loxapine is 6-8 hours; active metabolite 7-hydroxyloxapine (amoxapine) has half-life of ~30 hours. Clinically, steady state achieved within 3-5 days. |
| Protein binding | Approximately 96-97% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Vd ~2 L/kg (0.5-2 L/kg range); indicates extensive tissue distribution with high lipophilicity. |
| Bioavailability | Inhalation: ~70-80% (relative to IM injection). |
| Onset of Action | Inhalation: 10-30 minutes (max plasma concentration at 2-5 minutes). |
| Duration of Action | Variable; clinical effect on agitation typically wanes in 2-4 hours; monitoring for recurrence indicated. |
| Molecular Weight | 401.4 |
Inhalation: 10 mg as a single dose via oral inhalation up to a maximum of 2 doses within a 24-hour period, each dose separated by at least 2 hours. For agitation associated with schizophrenia or bipolar I disorder.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl 30-89 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Child-Pugh Class A or B: No dose adjustment. Child-Pugh Class C: Not recommended due to lack of data. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; off-label use is not recommended. |
| Geriatric use | No specific dose adjustment for age; however, elderly patients may have increased sensitivity, particularly to QT prolongation and orthostatic hypotension. Use with caution and monitor vital signs. |
| 1st trimester | Insufficient human data; animal studies show developmental toxicity at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Limited data; potential adverse effects (e.g., dystonia, extrapyramidal symptoms). Use with caution. |
| 3rd trimester | Risk of neonatal withdrawal or extrapyramidal symptoms; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for ADASUVE (ADASUVE).
| Placental transfer | Crosses placenta; concentration in cord blood similar to maternal plasma. |
| Breastfeeding | Present in breast milk in low amounts; monitor infant for sedation, poor feeding. Limited data. |
| Lactation Rating |
■ 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. ADASUVE is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
Known hypersensitivity to loxapine or any componentSevere CNS depressionComatose states
| Precautions | Increased mortality in elderly patients with dementia-related psychosis, Inhalation-related bronchospasm (ADASUVE is for oral inhalation only and can cause acute bronchospasm; contraindicated in patients with asthma, COPD, or other reactive airways disease), Cardiovascular effects (e.g., QT prolongation, orthostatic hypotension), Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Seizures, Leukopenia, neutropenia, and agranulocytosis, Suicidal ideation and behavior, Cerebrovascular adverse events in elderly patients with dementia, Hyperprolactinemia, Potential for overdose due to rapid systemic absorption, Risk of misuse/abuse |
| Food/Dietary |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. In animal studies, loxapine (active metabolite) induced fetal developmental toxicity including skeletal anomalies and reduced fetal weight at maternal toxic doses. No adequate human studies. First trimester: potential risk of major malformations unknown. Second/third trimester: risk of extrapyramidal symptoms and/or withdrawal in neonates after in utero exposure. |
| Fetal Monitoring | Monitor maternal vital signs, mental status, and extrapyramidal symptoms. For fetus, perform serial growth ultrasounds and fetal monitoring. Neonates should be monitored for extrapyramidal symptoms, sedation, and withdrawal after delivery. |
| Fertility Effects | Hyperprolactinemia may occur, potentially impairing fertility via suppression of hypothalamic-pituitary-gonadal axis. Effects are reversible upon discontinuation. |
| No known food interactions. Avoid alcohol and CNS depressants due to additive sedation. |
| Clinical Pearls | ADASUVE (loxapine) inhalation powder is a rapid-acting atypical antipsychotic for acute agitation in schizophrenia or bipolar I disorder. Administer only under supervision in a healthcare setting; monitor for bronchospasm, especially in patients with asthma or COPD. Use caution with CNS depressants; may cause orthostatic hypotension. Ensure patient can inhale deeply; do not use if patient has active respiratory infection or recent history of bronchospasm. Maximum dose: one 10 mg dose in 24 hours. |
| Patient Advice | ADASUVE is a single-use inhaler for agitation; do not try to use it yourself—only a healthcare professional will administer it. · You will be asked to take a deep breath from the inhaler; the medication is a powder that is inhaled. · After use, you may feel dizzy or sleepy; avoid driving or operating machinery for at least 24 hours. · Tell your doctor if you have asthma, COPD, or any breathing problems; ADASUVE can cause sudden breathing problems. · Notify your doctor if you have a cough, wheezing, or difficulty breathing after using ADASUVE. |