Loxapine for schizophrenia

Chakrabarti, Abhijit; Bagnall, Anne‐Marie; Chue, Pierre; Fenton, Mark; Palanisamy, Vikram; Wong, Winson; Xia, Jun

doi:10.1002/14651858.cd001943.pub2

Cited by 50 publications

(37 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4 Acute agitation associated with psychiatric diseases often results in severe distress to patients and their caregivers and is a major contributor to the ongoing stigmatization of mental illness. 5 Oral loxapine, introduced more than 35 years ago in the United States, Canada, and Europe, has a well-established efficacy and safety profile in the treatment ofschizophrenia, 6,7 and an intramuscular formulation was previously approved for the treatment of agitation. [8][9][10][11] Its antipsychotic effects are similar to those of other antipsychotics such as haloperidol and are likely attributable to its actionat dopamine D2 receptors.…”

mentioning

confidence: 99%

Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens

Spyker

Riesenberg²,

Cassella

2015

The Journal of Clinical Pharma

View full text Add to dashboard Cite

This randomized, double-blind, placebo-controlled, parallel-group study was to determine the pharmacokinetic characteristics, safety, and tolerability of multiple doses of inhaled loxapine aerosol in subjects on a stable, oral, chronic antipsychotic regimen. Loxapine was delivered by means of a unique thermally generated aerosol comprising drug particles of a size designed for deep lung delivery and absorption. Thirty-two subjects were randomized 1:1:1:1 to receive inhaled loxapine (total doses of 15, 20, or 30 mg) or inhaled placebo administered in 3 divided doses, given 4 hours apart. Following inhalation, the median T max was 2 minutes, and concentrations declined to about half C max approximately 5 minutes later across the 3 dose levels. The dose proportionality across data from this study combined with data from the single-dose study showed a slope (90%CI) of log AUC inf versus log dose of 0.818 (0.762-0.875) across the 8 doses (n ¼ 60 subjects) studied, indicating reasonable dose proportionality. The most common adverse events were cough (3 of 32, 9%), sedation (3 of 32, 9%), and dysgeusia (2 of 32, 6%). The inhalation of multiple doses of inhaled loxapine were well tolerated in study subjects and provided a safe, well-tolerated means for rapidly and reliably achieving therapeutic plasma concentrations of loxapine. ClinicalTrials. gov identifier: NCT00555412

show abstract

mentioning

confidence: 99%

Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens

Spyker

Riesenberg²,

Cassella

2015

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Loxapine is a well-known, midpotency, typical antipsychotic. Loxapine has had a number of head-to-head trials for schizophrenia and a Cochrane study found that loxapine is an option for schizophrenic patients who require rapid tranquilization [24]. Alexza Pharmaceuticals has completed Phase I-III studies on a combination medication-delivery system; Staccato loxapine.…”

Section: Resultsmentioning

confidence: 99%

“…The review included 41 studies, comparing loxapine to haloperidol, thiothixene, risperidone, clozapine and quetiapine. Another finding was that loxapine exhibited a similar degree of adverse events compared with the typical and atypical agents [24].…”

Section: Review Nordstrommentioning

confidence: 92%

“…It has been shown to have a positive affect on schizophrenia and has also been considered in the treatment of psychotic depression [22] and bipolar disorder [23]. A 2007 Cochrane study concluded that loxapine is an option for schizophrenic patients who require rapid tranquilization [24]. The review included 41 studies, comparing loxapine to haloperidol, thiothixene, risperidone, clozapine and quetiapine.…”

Section: Review Nordstrommentioning

confidence: 99%

See 1 more Smart Citation

Inhaled loxapine for rapid treatment of agitation in schizophrenia and bipolar disorder: an update

Nordstrom¹

2012

Neuropsychiatry

View full text Add to dashboard Cite

Agitation is a common presenting problem in emergency departments and treatments currently range from de-escalation techniques to medications, in either oral or intramuscular forms. Oral medications can be diverted and have a relatively long delay of onset. This delay is problematic for agitated patients in that the agitation may escalate prior to onset of action of the medication. This can lead to the need for intramuscular medications or even physical restraints. Regarding intramuscular medications, they tend to work more quickly but are highly invasive. A new delivery system using loxapine is currently being

show abstract

“…O ral loxapine, introduced more than 35 years ago in the United States, Canada, and Europe, has a wellestablished efficacy and safety profile in the treatment of schizophrenia, (1,2) and an intramuscular formulation was previously approved for the treatment of agitation. (3)(4)(5)(6) Its antipsychotic effects are similar to those of other antipsychotics such as haloperidol, and are likely attributable to its action at dopamine D2 receptors.…”

Section: Introductionmentioning

confidence: 99%

Safety and Tolerability of Inhaled Loxapine in Subjects with Asthma and Chronic Obstructive Pulmonary Disease—Two Randomized Controlled Trials

Gross

Greos²,

Meltzer

et al. 2014

Journal of Aerosol Medicine and Pulmonary Drug Delivery

View full text Add to dashboard Cite

Background: Loxapine, a first-generation antipsychotic, delivered with a novel inhalation delivery device developed for the acute treatment of agitation in patients with schizophrenia or bipolar disorder was evaluated in subjects with asthma or chronic obstructive pulmonary disease (COPD). Methods: Separate randomized, double-blind, parallel-arm, placebo-controlled trials compared two administrations of inhaled loxapine (10 mg) 10 hr apart with placebo in 52 subjects with asthma and in 53 subjects with COPD. A thermally-generated drug aerosol of loxapine was delivered to the deep lung for rapid systemic absorption. Controller medications were continued throughout the study, but quick-relief bronchodilators were withheld from 6-8 hr before through 34 hr after dose 1, unless indicated as rescue. Results: All airway adverse events (AEs) were of mild or moderate severity. Symptomatic bronchospasm occurred in 53.8% of subjects with asthma after inhaled loxapine and 11.5% after placebo; and in 19.2% of COPD subjects after inhaled loxapine and 11.1% after placebo. Subjects required inhaled albuterol as follows: asthma: 53.8% after inhaled loxapine and 11.5% after placebo; and COPD: 23.1% after inhaled loxapine and 14.8% after placebo. Respiratory signs/symptoms requiring treatment responded to rescue bronchodilator [forced expiratory volume in 1 sec (FEV 1 ) return to within 10% of baseline] within 1 hr in 11 of 15 events in asthma subjects and four of seven events in COPD subjects, the remainder by the last spirometry. Conclusions: In subjects with either asthma or COPD, FEV 1 decline and bronchospasm can occur following inhaled loxapine, but more frequently in asthmatic subjects. Most subjects with bronchospasm responded to rescue bronchodilator within 1 hr. No treatment-related serious AE occurred. Although inhaled loxapine is contraindicated in patients with active airways disease per the current approved US labeling, these studies demonstrated that rescue bronchodilator mitigated the symptomatic bronchospasms that may occur in case of inadvertent use.

show abstract

Loxapine for schizophrenia

Abstract: Analysis 2.10. Comparison 2 LOXAPINE versus TYPICAL ANTIPSYCHOTICS, Outcome 10 Mental state: 1d. General-average change score (BPRS, high score=worse

Cited by 50 publications

References 45 publications

Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens

Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens

Inhaled loxapine for rapid treatment of agitation in schizophrenia and bipolar disorder: an update

Safety and Tolerability of Inhaled Loxapine in Subjects with Asthma and Chronic Obstructive Pulmonary Disease—Two Randomized Controlled Trials

Contact Info

Product

Resources

About