ABSTRACT
BACKGROUND: Medications are frequently combined in the nebulizer cup, so it is important to determine their chemical and physical compatibility. OBJECTIVE: To determine the chemical and physical compatibility of levalbuterol with ipratropium bromide, cromolyn sodium, acetylcysteine sodium, and budesonide. METHODS: We mixed one dose of levalbuterol inhalation solution concentrate (1.25 mg/0.5 mL) with one dose of ipratropium bromide (0.5 mg/2.5 mL), cromolyn sodium (20 mg/2 mL), acetylcysteine sodium (1,000 mg/5 mL), or budesonide (0.5 mg/2 mL). Immediately after mixing the 2 drugs (time zero [T(0)]), and again after 30 min at room temperature (T(30)), we visually inspected the admixtures, measured their pH, and conducted high-pressure liquid chromatography (HPLC). RESULTS: There was no evidence of physical incompatibility with these drugs combinations. With all the admixtures, both drugs were chemically stable for at least 30-min. Admixture pH had not changed significantly at T(30). Drug recovery was 93.2-102.6% of the initial or control values. CONCLUSIONS: The 2-drug admixtures we studied were compatible for at least 30 min at room temperature.
Subject(s)
Acetylcysteine/chemistry , Albuterol/chemistry , Budesonide/chemistry , Cromolyn Sodium/chemistry , Ipratropium/chemistry , Respiratory System Agents/chemistry , Acetylcysteine/administration & dosage , Administration, Inhalation , Albuterol/administration & dosage , Budesonide/administration & dosage , Cromolyn Sodium/administration & dosage , Drug Incompatibility , Drug Stability , Drug Therapy, Combination , Ipratropium/administration & dosage , Respiratory System Agents/administration & dosage , Time FactorsABSTRACT
BACKGROUND: The short-acting beta(2)-agonists levalbuterol and racemic albuterol are available for administration through a hydrofluoroalkane-134a (HFA) metered-dose inhaler (MDI). OBJECTIVE: This study compared the short-term safety and efficacy of cumulative doses of levalbuterol HFA MDI and racemic albuterol HFA MDI in asthmatic subjects. METHODS: This was a randomized, modified-blind, active-controlled, multicenter, 2-way crossover study. Subjects (n = 49) were randomized to 16 cumulative doses (1x, 2x, 4x, 8x, and 16x) of levalbuterol (45 microg per dose) or racemic albuterol (90 microg per dose) administered over a 2-hour period. After a 7-day washout period, subjects were crossed over to the other treatment. After each dose, safety outcomes and pulmonary function were assessed. RESULTS: Heart rate and (R)-albuterol exposure increased for both racemic albuterol HFA and levalbuterol HFA. For cumulative doses of 8x or greater, racemic albuterol HFA treatment had greater increases in mean heart rate than levalbuterol HFA (least-squares mean [+/- SD] difference at the 8x dose was 2.8 beats/min [95% CI, 0.3-5.3] and at the 16x dose was 3.5 beats/min [95% CI, 0.6-6.4]). (R)-albuterol plasma levels ranged from 10% to 18% higher after racemic albuterol HFA MDI dosing versus after levalbuterol HFA MDI. FEV(1) improvements were similar for both treatments. The relative potencies of the 2 therapies, based on FEV(1), were similar (ratio, 1.1 [90% CI, 0.9-1.2]; Finney method). CONCLUSION: In this study single-day cumulative dosing of asthmatic subjects with levalbuterol HFA MDI or racemic albuterol HFA MDI resulted in similar improvements in FEV(1) and tolerability. Plasma (R)-albuterol levels and mean heart rate were less with levalbuterol HFA MDI.
Subject(s)
Adrenergic beta-Agonists/administration & dosage , Albuterol/administration & dosage , Asthma/drug therapy , Bronchodilator Agents/administration & dosage , Heart Rate/drug effects , Administration, Inhalation , Adolescent , Adrenergic beta-Agonists/adverse effects , Adrenergic beta-Agonists/blood , Adrenergic beta-Agonists/therapeutic use , Adult , Albuterol/adverse effects , Albuterol/blood , Albuterol/therapeutic use , Bronchodilator Agents/blood , Bronchodilator Agents/therapeutic use , Cross-Over Studies , Double-Blind Method , Female , Forced Expiratory Volume , Humans , Hydrocarbons, Fluorinated/pharmacology , Male , Metered Dose Inhalers , SpirometryABSTRACT
BACKGROUND: Previous studies have raised concerns regarding the safety of regular use of beta2-agonists for treating asthma. Few studies have explored the safety of at least 1 year of use of racemic albuterol, and none have examined long-term dosing of levalbuterol. OBJECTIVE: To examine the long-term safety of levalbuterol hydrofluoroalkane (HFA) vs racemic albuterol HFA administered via metered-dose inhaler (MDI) in patients with stable asthma. METHODS: Patients with mild to moderate asthma (mean forced expiratory volume in 1 second [FEVI], 68.3% of predicted) 12 years or older participated in a multicenter, parallel-group, open-label study. Patients were randomized to levalbuterol HFA MDI (90 microg; 2 actuations of 45 microg; n = 496) or racemic albuterol HFA MDI (180 microg; 2 actuations of 90 microg; n = 250) for 52 weeks of 4 times daily dosing. The primary end point was the incidence of postrandomization adverse events. Asthma exacerbations and pulmonary parameters were also assessed. RESULTS: The overall incidence of adverse events was similar for levalbuterol (72.0%) and racemic albuterol (76.8%). Rates of beta-mediated adverse events, serious adverse events, and discontinuations because of adverse events were low (<15%) and were comparable between groups. Rates of asthma adverse events for levalbuterol and racemic albuterol were 18.3% and 19.6%, respectively. Mean percentage of predicted FEV1 improved after dosing and was stable for both groups. CONCLUSION: In this trial, up to 52 weeks of regular use of levalbuterol HFA MDI or racemic albuterol HFA MDI was well tolerated, and no deterioration of lung function was detected during the study period.
