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.
RCT Entities:
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.
Authors: Joshua D Rabinowitz; Martin Wensley; Peter Lloyd; Daniel Myers; William Shen; Amy Lu; Craig Hodges; Ron Hale; Daniel Mufson; Alejandro Zaffaroni Journal: J Pharmacol Exp Ther Date: 2004-01-29 Impact factor: 4.030
Authors: M R Miller; J Hankinson; V Brusasco; F Burgos; R Casaburi; A Coates; R Crapo; P Enright; C P M van der Grinten; P Gustafsson; R Jensen; D C Johnson; N MacIntyre; R McKay; D Navajas; O F Pedersen; R Pellegrino; G Viegi; J Wanger Journal: Eur Respir J Date: 2005-08 Impact factor: 16.671
Authors: Joshua D Rabinowitz; Peter M Lloyd; Patrik Munzar; Daniel J Myers; Steve Cross; Ramesh Damani; Reynaldo Quintana; Daniel A Spyker; Pravin Soni; James V Cassella Journal: J Pharm Sci Date: 2006-11 Impact factor: 3.534
Authors: Daniela I Staquicini; E Magda Barbu; Rachel L Zemans; Beth K Dray; Fernanda I Staquicini; Prashant Dogra; Marina Cardó-Vila; Cindy K Miranti; Wallace B Baze; Luisa L Villa; Jorge Kalil; Geetanjali Sharma; Eric R Prossnitz; Zhihui Wang; Vittorio Cristini; Richard L Sidman; Andrew R Berman; Reynold A Panettieri; Rubin M Tuder; Renata Pasqualini; Wadih Arap Journal: Med (N Y) Date: 2020-12-10
Authors: Maurizio Pompili; Giuseppe Ducci; Alessandro Galluzzo; Gianluca Rosso; Claudia Palumbo; Domenico De Berardis Journal: Int J Environ Res Public Health Date: 2021-04-20 Impact factor: 3.390