Dosing and uses of Adasuve (loxapine inhaled)
Adult dosage forms and strengths
powder for oral inhalation
- 10mg/single-use inhaler
Schizophrenia & Bipolar I Agitation
Indicated for acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults
10 mg inhaled PO once within a 24-hr period
Must be administered only by a healthcare professionaL
Dosing Considerations
Because of the risk of bronchospasm, is only available through a restricted program under a risk evaluation and mitigation strategy (REMS) and must be administered only in an enrolled healthcare facility
Prior to administering, screen all patients for a history of asthma, COPD, or other pulmonary disease, and examine patients (including chest auscultation) for respiratory signs (eg, wheezing)
Administration
Step 1. Open pouch and remove inhaler from package (indicator light on inhaler is off)
Step 2. Firmly pull the plastic tab from the rear of the inhaler; check that the green light turns on to indicate that the inhaler is ready for use
Use the inhaler within 15 minutes after removing the tab to prevent automatic deactivation of the inhaler; the green light will turn off, indicating that the inhaler is not usable
Discard the inhaler after one use
Step 3. Explain procedure to patient; inform the patient that the inhaler may produce a flash of light and a clicking sound, and it may become warm during use
Step 4. Instruct the patient to hold the inhalator away from the mouth and breathe out fully to empty the lungs
Step 5. Instruct the patient to put the mouthpiece of the inhaler between the lips, close the lips, and inhale through the mouthpiece with a steady deep breath; check that the green light turns off indicating that the dose has been delivered
Step 6. Instruct the patient to remove the mouthpiece from the mouth and hold the breath for as long as possible, up to 10 seconds
NOTE: If the green light remains on after the patient inhales, the dose has NOT been delivered; instruct the patient to repeat Steps 4-6 up to 2 additional times; if the green light still does not turn off, discard the inhaler and use a new one
Pediatric dosage forms and strengths
Safety and efficacy not established
Adasuve (loxapine inhaled) adverse (side) effects
>10%
Respiratory adverse effects in patients with COPD (19%)
Dysgeusia (14%)
Sedation (12%)
1-10%
Throat irritation (3%)
<1%
Bronchospasm (0.8%)
Akathisia (0.4%)
Neck dystonia and oculogyration (0.4%)
Warnings
Black box warnings
Bronchospasm
- Can cause bronchospasm that has the potential to lead to respiratory distress and respiratory arrest
- Administer only in an enrolled healthcare facility that has immediate access on-site to supplies and personnel and ready access to emergency response services; facilities must have a short-acting bronchodilator, including a nebulizer and inhalation solution, for immediate treatment of bronchospasm
- Prior to administering, screen patients regarding a current diagnosis, history, or symptoms of asthma, COPD and other lung diseases, and examine (including chest auscultation) patients for respiratory signs
- Monitor for signs and symptoms of bronchospasm following treatment
Dementia-related psychosis
- Patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials
- The deaths appeared to be either cardiovascular (eg, heart failure, stroke, sudden death) or infectious (eg, pneumonia) in nature
- This drug is not approved for the treatment of patients with dementia-related psychosis
Contraindications
Current diagnosis or history of asthma, COPD, or other lung disease associated with bronchospasm
Acute respiratory symptoms or signs (eg, wheezing)
Current use of medications to treat airways disease, such as asthma or COPd
History of bronchospasm following treatment
Known hypersensitivity (including serious skin reactions) to loxapine or amoxapine
Cautions
Can cause bronchospasm (see Black box warnings)
Monitor for signs and symptoms of bronchospasm following administration; perform a physical exam, including chest auscultation at least q15min for at least 1 hr after the dose
Increased mortality in elderly patients with demential-related psychosis (see Black box warnings)
Antipsychotic drugs can cause neuroleptic malignant syndrome; symptoms include hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability; associated findings include increased CPK, rhabdomyolysis, increased urine and serum myoglobin, and renal failure
May cause hypotension, orthostatic hypotension, and syncope
Lowers seizure threshold; use caution in patients with history of seizures
May cause cognitive and motor impairment
May cause sedation and somnolence; use caution when driving or operating machinery and when coadministered with other drugs known to cause CNS depression
May cause anticholinergic adverse reactions, including exacerbation of glaucoma and urinary retention; caution when coadministered with other drugs that elicit anticholinergic effects
Increased incidence of stroke and transient ischemic attack in elderly patients with dementia-related psychosis treated with antipsychotic drugs
Pregnancy and lactation
Pregnancy category: C
Neonates exposed to antipsychotic drugs during the 3rd trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery
These complications vary in severity; in some cases, symptoms have been self-limited, while in other cases neonates have required intensive care unit support and prolonged hospitalization
Lactation: Unknown whether distributed in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Adasuve (loxapine inhaled)
Mechanism of action
Typical antipsychotic (dibenzoxazepine subclass of tricyclic antipsychotic agents); mechanism of action is unknown, but is theorized to antagonize central dopamine D2 and serotonin 5-HT2a receptors
Absorption
Peak Plasma Time: 2 minutes
Peak Plasma Concentration: 257 ng/mL
AUC: 66 ng•h/mL (0-2 hr); 188 ng•h/mL (infinity)
Distribution
Protein Bound: 96.6%
Metabolism
Metabolized extensively in the liver by hydroxylation; forms 8-OH-loxapine by CYP1A2 and forms 7-OH-loxapine by CYP3A4 and CYP2D6
Metabolized by N-oxidation to form loxapine N-oxide by flavanoid monoamine oxidases
Demethylated to form amoxapine Because there are multiple metabolic pathways, the risk of metabolic interactions caused by an effect on an individual isoform is minimaL
Because there are multiple metabolic pathways, the risk of metabolic interactions caused by an effect on an individual isoform is minimaL
Elimination
Half-life: 7.16 hr (range 6-8 hr)
Excretion: feces (unconjugated metabolites); urine (conjugated metabolites)
