Indacaterol Research Articles

POTENTIOMETRIC DETERMINATION OF GLYCOPYRRONIUM BROMIDE IN BINARY MIXTURE WITH INDACATEROL MALEATE USING POLYVINYL CHLORIDE (PVC) MEMBRANE, COATED GRAPHITE AND CARBON PASTE SENSORS

A novel approach was conducted in this article for the determination of glycopyrronium bromide (GLY) in binary mixture with indacaterol maleate using ion selective electrodes for its selective determination in pure form and pharmaceutical formulation. Four ion selective electrode sensors were designed for determination of glycopyrronium bromide namely; glycopyrronium bromide-polyvinyl chloride (GLY-PVC) membrane, GLY-Coated graphite sensor and GLY-modified carbon paste sensors. The sensors are based on the ion association complexes of GLY cation with sodium tetra phenyl borate (GLY-TPB) and phosphomolybidic acid (GLY-PMA) counter anions as ion exchange sites using dioctylphthalate (DOP) as plasticizer. Validation of the method shows suitability of the proposed sensors for use in the quality control assessment of GLY and for its routine analysis. The results obtained were statistically compared to reported method and there was no significant difference between the proposed methods and the reported method regarding the accuracy and precision. The method was validated according to International Conference on Harmonization (ICH) guidelines and the results were satisfactory.

A validated capillary electrophoretic method for the determination of indacaterol and its application to a pharmaceutical preparation

Indacaterol is a new inhaled ultra-long acting β2-agonist. It has been recently approved in the European Union for the treatment of chronic obstructive pulmonary disease. This paper reports, for the first time, a method for the determination and validation of Indacaterol (IND) using an internal standard in capsules. Capillary electrophoretic separation was performed on an uncoated fused-silica capillary (50 cm effective length, 75 μm i.d.) and background electrolyte composed of 20 mmol L−1 of sodium tetraborate buffer, 15% (v/v) methanol (pH = 10.0) with the application of 20 kV of potential; 10 s at 5 × 103 N m−2 (50 mbar) of injection time; and wavelength of 200 nm and 25 °C of temperature. The linearity was evaluated in the range of 4.90 × 10−6 mol L−1 (2.50 μg mL−1) and 3.94 × 10−5 mol L−1 (20.00 μg mL−1), with R = 0.9993 for inter-day. LOD and LOQ values were 2.18 × 10−8 mol L−1 (0.011 μg mL−1) and 7.25 × 10−8 mol L−1 (0.037 μg mL−1) for inter-day, respectively. The precision values were 0.50–1.06% for intra-day and 2.12% for inter-day as RSD%. The accuracy was tested by the standard addition method with the recovery values being between 98.79 and 99.09 as percentages with RSD% interval of 0.01–0.80. The developed method was validated according to ICH guidelines. Indacaterol was successfully determined in Arcapta® capsule dosage form by the validated CE method with a relative error of 0.28%. The result was within the requirements of the USP 34-NF29. Therefore, the validated method may be used for the determination of Indacaterol in its capsules in quality control laboratories.

Bronchoprotective tolerance with indacaterol is not modified by concomitant tiotropium in persistent asthma.

Tiotropium is a long acting muscarinic antagonist (LAMA), licensed as triple therapy with inhaled corticosteroid and long-acting beta-agonist (ICS/LABA). There may be a synergistic benefit between LAMA and LABA as a consequence of receptor cross-talk, which in turn could modify beta-2 receptor downregulation and associated tolerance induced by LABA. We hypothesize this mechanism may result in a reduction of airway hyperresponsiveness (AHR) when using triple therapy. We evaluated 14 non-smoking asthmatics using an open-label, randomized crossover design. ICS with Indacaterol and Tiotropium (IND/TIO) vs ICS with Indacaterol (IND) over 4weeks with challenge performed after first and last doses at trough. We found no significant difference in mannitol sensitivity, expressed as the provocative dose of mannitol required to reach a 15% drop in FEV1 , or mannitol reactivity, expressed as the response dose ratio (RDR: max % fall in FEV1 /cumulative dose), when comparing ICS/IND/TIO to ICS/IND. Geometric mean fold differences for RDR comparing single and chronic dosing were 3.26-fold (95% CI 1.46-7.29) and 2.51-fold (95% CI 1.32-4.79) for IND and IND/TIO, respectively. Furthermore, salbutamol recovery post-challenge was significantly blunted after chronic compared to single dosing with either ICS/IND (P<.005) or ICS/IND/TIO (P<.05). Our data suggest that concomitant tiotropium does not modify the bronchoprotective tolerance induced by Indacaterol, in turn suggesting that cross-talk may not be clinically relevant when using triple therapy. This study was registered on clinicaltrials.gov as NCT02039011.

Interactions between glycopyrronium and indacaterol on cholinergic neurotransmission and contractile response in bovine trachealis

BackgroundMuscarinic-receptor antagonists and β-adrenoceptor agonists are used, alone or in combination, as first-line treatment for chronic obstructive pulmonary disease. Both drugs decrease airway smooth muscle tone by post-junctional mechanisms but they may have opposing effects on pre-junctional acetylcholine (ACh)-release.MethodsWe studied the effects of the muscarinic-receptor antagonist glycopyrronium (GLY), the β-adrenoceptor agonist indacaterol (IND) and their combination on electrically-induced ACh-release and contractile response in isolated bovine trachealis. Data were analyzed by paired t-test and analysis of variance for repeated or independent measures with Newmann-Keuls post-hoc test when appropriate.ResultsGLY 10−8 M decreased contractile response by 19 ± 6% (p = 0.010) without altering ACh-release. GLY 10−7 M and 10−6 M almost abolished contractile responses even if the ACh-release was increased by 27 ± 19% (p < 0.001) and 20 ± 8% (p = 0.004), respectively. IND 10−7 M had no significant effects on contractile response and ACh-release, whereas IND 10−6 M reduced contractile response by 24 ± 12% (p = 0.002) without altering ACh-release. IND 10−5 M decreased contractile response by 51 ± 17% (p < 0.001) and ACh-release by 22 ± 11% (p = 0.004). Co-incubation with GLY 10−8 M and IND 10−7 M did not alter ACh-release but inhibited contractile response by 41 ± 8% (p < 0.001). The latter effect was greater than with GLY 10−8 M, or IND 10−7 M, or IND 10−6 M given separately (p < 0.001 for all). The increment of ACh-release caused by GLY was attenuated by IND 10−5 M, though this did not affect contractile response.ConclusionsAt equimolar concentration, GLY alone attenuates airway smooth muscle contraction more than IND, despite an increased ACh-release. Combination of GLY with IND at submaximal concentrations has more than additive effect suggesting a synergistic post-junctional effect. Adding GLY to IND provides a greater inhibitory effect on airway smooth muscle contraction than increasing IND concentration.

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler\xae150 and 300\xa0\u03bcg

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

Rapid simultaneous determination of indacaterol maleate and glycopyrronium bromide in inhaler capsules using a validated stability-indicating monolithic LC method

BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. A combination of indacaterol maleate with glycopyrronium bromide has recently been approved as a once-daily maintenance therapy in patients with COPD. The very low dose (μg level/capsule) renders the analysis of such products challenges. This study reports for the first time about HPLC method for the quality control of such combination and it is a stability indicating at the same time.ResultsA rapid, simple, precise and reproducible HPLC method was developed and validated for simultaneous determination of indacaterol maleate and glycopyrronium bromide using tenoxicam as an internal standard. The chromatographic separation was achieved on an onyx monolithic C18 column (100 × 4.6 mm) using a mobile phase consisting of acetonitrile and 30 mM phosphate buffer (pH 3.5) (30:70, v/v), run at a flow rate of 2 mL/min with UV detection at 210 nm. The total analysis time was less than 3 min. The HPLC method was validated for linearity, limits of detection and quantitation, precision, accuracy, system suitability and robustness. Calibration curves were obtained in the concentration ranges of 1–44 µg/mL for indacaterol maleate and 0.5–20 µg/mL for glycopyrronium bromide. Stability tests were done through exposure of the analyte solution for different stress conditions and the results indicate no interference of degradants with HPLC method.ConclusionsThe method was successfully applied for the quantitative analysis of indacaterol maleate and glycopyrronium bromide both individually and in a combined pharmaceutical inhaler capsules to support the quality control and to assure the therapeutic efficacy of the two drugs. The simple procedure involved in sample preparation and the short run-time added the important property of high throughput to the method. Graphical abstractChemical structures and representative HPLC chromatogram of indacaterol maleate (IND; 22 μg/mL), glycopyrronium bromide (GLY; 10 μg/mL) and tenoxicam (IS, 15μg/mL) in commercial capsules.

INFLOW study: a prospective observational study for assessment of indacaterol and other bronchodilators in symptomatic chronic obstructive pulmonary disease patients from Egypt

BackgroundThe INdacaterol eFfectiveness and utiLizatiOn in COPD: real-World evaluation (INFLOW) study demonstrated significant improvements in health status with decreasing Clinical COPD Questionnaire (CCQ) scores in routine clinical practice with indacaterol (IND) and other bronchodilators from 12 countries in Asia, the Middle East and South Africa. Here, we report the data on real-life effectiveness of IND and other bronchodilators from Egypt.MethodsIn this 6-month, noninterventional, open-label study, patients were prescribed IND (150 or 300 μg) or other longacting β2-agonists (LABAs) or tiotropium (TIO) (monotherapy or in combination with IND or LABAs) as a part of routine medical care. Health status (CCQ scores), patient and physician satisfaction and safety were assessed.ResultsData were analysed from 152 patients (IND, n=88; IND+TIO, n=27; other-LABAs, n=6; TIO, n=10; and other- LABAs+TIO, n=21). At the end of the study, reduction from baseline CCQ total score was significant (P<0.0001) with IND and other treatments. Approximately 80% of patients were satisfied and physicians rated the current prescribed treatments as ‘good’ or ‘very good’ for over 70% of the patients. More than 80% of patients rated the indacaterol inhaler (Breezhaler) device as ‘easy’ and ‘very easy to use’, and physicians rated over 70% of patients as ‘clearly understood the use of the device’. No adverse events related to premature discontinuation were reported.ConclusionIn real-world settings, IND as monotherapy or in combination with TIO was effective in improving the health status in COPD patients and is well tolerated. The majority of patients reported that the Breezhaler device was easy to use.

Indacaterol and glycopyrronium versus indacaterol on body plethysmography measurements in COPD\u2014a randomised controlled study

BackgroundDual bronchodilator therapy is recommended for symptomatic patients with chronic obstructive pulmonary disease (COPD). There are limited data on effects of a combination of two long-acting bronchodilators on lung function including body plethysmography.MethodsThis multicentre, randomised, double-blind, single-dose, cross-over, placebo-controlled study evaluated efficacy and safety of the free combination of indacaterol maleate (IND) and glycopyrronium bromide (GLY) versus IND alone on spirometric and body plethysmography parameters, including inspiratory capacity (IC), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), total lung capacity (TLC) and airway resistance (Raw) in moderate-to-severe COPD patients.ResultsSeventy-eight patients with FEV1 % pred. (mean ± SD) 56 ± 13% were randomised. The combination of IND + GLY versus IND presented a numerically higher peak-IC (Δ = 0.076 L, 95% confidence interval [CI]: −0.010 – 0.161 L; p = 0.083), with a statistically significant difference in mean IC over 4 h (Δ = 0.054 L, 95%CI 0.022 – 0.086 L; p = 0.001). FEV1, FVC and Raw, but not TLC, were consistently significantly improved by IND + GLY compared to IND alone. Safety profiles of both treatments were comparable.ConclusionThe free combination of IND + GLY improved lung function parameters as evaluated by spirometry and body plethysmography, with a similar safety profile compared to IND alone.Trial registrationNCT01699685

Long-term safety of glycopyrrolate: A randomized study in patients with moderate-to-severe COPD (GEM3)

BackgroundChronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the United States. Long-acting muscarinic antagonists (LAMAs) are a class of medications used as maintenance therapy for COPD. The GEM3 (Glycopyrrolate Effect on syMptoms and lung function) study assessed the long-term safety and efficacy of a LAMA, glycopyrrolate (GLY) 15.6 μg twice daily (b.i.d.), compared with an approved long-acting β2-agonist (LABA), indacaterol (IND) 75 μg once daily (q.d.) in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation. MethodsThis 52-week, multicenter, double-blind, parallel-group study randomized patients (1:1) of the United States to receive GLY 15.6 μg b.i.d. or IND 75 μg q.d. both delivered via the Neohaler® device. The primary objective was to assess the safety and tolerability in terms of adverse event (AE) reporting rates over 52 weeks. Safety was also determined by evaluating multiple secondary endpoints, including vital signs, electrocardiograms (ECGs), and time to first moderate or severe exacerbation. Efficacy-related secondary endpoints included pre-dose forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). ResultsOf the 511 randomized patients (GLY, n = 254; IND, n = 257), 81.6% completed the study. The overall incidences of AEs (GLY, 77.3%; IND, 77.0%) and serious AEs (GLY, 13.1%; IND, 13.3%) were comparable between the groups. The incidence of major adverse cardiovascular events was low and comparable between the groups. No clinically relevant differences for vital signs or ECG parameters were observed between the treatment groups. The three sudden deaths reported within 30 days of the treatment (GLY, n = 2; IND, n = 1) were adjudicated as unrelated to the study medication. In terms of efficacy, GLY 15.6 μg b.i.d. showed improvements in pre-dose FEV1 and FVC from baseline, which was comparable to those with IND 75 μg q.d., with no statistically significant differences. No significant differences were observed between the treatment groups in the time to first moderate or severe COPD exacerbation. ConclusionGLY 15.6 μg b.i.d. showed a long-term safety profile comparable to that of IND 75 μg q.d. and provided rapid and sustained bronchodilation over 52 weeks in patients with COPD with moderate-to-severe airflow limitation. Clinical trial registration numberNCT01697696.

Simultaneous spectrophotometric determination of indacaterol and glycopyrronium in a newly approved pharmaceutical formulation using different signal processing techniques of ratio spectra

Three spectrophotometric methods have been developed and validated for determination of indacaterol (IND) and glycopyrronium (GLY) in their binary mixtures and novel pharmaceutical dosage form. The proposed methods are considered to be the first methods to determine the investigated drugs simultaneously. The developed methods are based on different signal processing techniques of ratio spectra namely; Numerical Differentiation (ND), Savitsky–Golay (SG) and Fourier Transform (FT). The developed methods showed linearity over concentration range 1–30 and 10–35 (μg/mL) for IND and GLY, respectively. The accuracy calculated as percentage recoveries were in the range of 99.00%–100.49% with low value of RSD% (<1.5%) demonstrating an excellent accuracy of the proposed methods. The developed methods were proved to be specific, sensitive and precise for quality control of the investigated drugs in their pharmaceutical dosage form without the need for any separation process.

Effect of once-daily indacaterol maleate/mometasone furoate on exacerbation risk in adolescent and adult asthma: a double-blind randomised controlled trial

ObjectiveTo investigate the safety and efficacy of QMF149, a once-daily, fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol maleate and inhaled corticosteroid (ICS) mometasone furoate (MF) for the treatment of...

Spectrophotometric and spectrofluorimetric determination of indacaterol maleate in pure form and pharmaceutical preparations: application to content uniformity.

Two simple, rapid, sensitive and precise spectrophotometric and spectrofluorimetric methods were developed for the determination of indacaterol maleate in bulk powder and capsules. Both methods were based on the direct measurement of the drug in methanol. In the spectrophotometric method (Method I) the absorbance was measured at 259 nm. The absorbance-concentration plot was rectilinear over the range 1.0-10.0 µg mL(-1) with a lower detection limit (LOD) of 0.078 µg mL(-1) and lower quantification limit (LOQ) of 0.238 µg mL(-1). Meanwhile in the spectrofluorimetric method (Method II) the native fluorescence was measured at 358 nm after excitation at 258 nm. The fluorescence-concentration plot was rectilinear over the range of 1.0-40.0 ng mL(-1) with an LOD of 0.075 ng mL(-1) and an LOQ of 0.226 ng mL(-1). The proposed methods were successfully applied to the determination of indacaterol maleate in capsules with average percent recoveries ± RSD% of 99.94 ± 0.96 for Method I and 99.97 ± 0.81 for Method II. In addition, the proposed methods were extended to a content uniformity test according to the United States Pharmacopoeia (USP) guidelines and were accurate, precise for the capsules studied with acceptance value 3.98 for Method I and 2.616 for Method II.

Profile of inhaled glycopyrronium bromide as monotherapy and in fixed-dose combination with indacaterol maleate for the treatment of COPD.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. The cornerstone of pharmacological treatment for COPD is bronchodilation. Inhaled glycopyrronium bromide is a long-acting muscarinic antagonist developed as a maintenance treatment for patients with COPD. Phase III trials have shown that glycopyrronium produces rapid and sustained bronchodilation with an efficacy similar to tiotropium and is well tolerated, with a low incidence of muscarinic side effects in patients with moderate to severe COPD. A combination of glycopyrronium bromide with indacaterol maleate (QVA149) has recently been approved as a once-daily maintenance therapy in adult patients with COPD. Phase III trials (the IGNITE program) with QVA149 have demonstrated significant improvements in lung function versus placebo, glycopyrronium, and tiotropium in patients with moderate to severe COPD, with no safety concerns of note. Hence QVA149 is a safe treatment option for moderate to severe COPD patients in whom long-acting muscarinic antagonist monotherapy is inadequate.

Cost-effectiveness of the LABA/LAMA dual bronchodilator indacaterol/glycopyrronium in a Swedish healthcare setting

Indacaterol/glycopyrronium (IND/GLY) is a once-daily inhaled fixed-dose combination of indacaterol (IND), a long-acting β2-adrenergic agonist (LABA), and glycopyrronium (GLY), a long-acting muscarinic antagonist (LAMA) for use as maintenance treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD) in adults. To determine the economic benefits of IND/GLY compared with the free combination of indacaterol and glycopyrronium (IND+GLY), and with the fixed-dose combination of salmeterol/fluticasone (SFC), in a moderate-to-severe COPD population with low-exacerbation risk. The model-based analysis extrapolated results up to lifetime time horizon and calculated costs per quality-adjusted life year. Assuming equal efficacy, a cost-minimisation analysis compared IND/GLY vs IND+GLY using model inputs from the double-blind, randomised SHINE trial. The double-blind, randomised ILLUMINATE and TORCH trials were used to analyse cost-effectiveness versus SFC. To consider ICS-related pneumonia events, published odds ratio comparing an ICS-exposed group to a control group of COPD patients was used. Direct and indirect drug costs as well as drug acquisition costs (in Swedish Krona [SEK]) were derived from published Swedish sources. Cost and effects were discounted with 3%. Uncertainty was assessed by one-way and probabilistic sensitivity analyses (PSA). IND/GLY was cost-saving vs IND+GLY with incremental savings of SEK (EUR) 768 (85), and 3309 (368) per patient over one and five years. IND/GLY was found to be less costly and more effective compared to SFC with cost savings of SEK (EUR) 2744 (303), 8854 (976), 13,938 (1536), 27,495 (3031) and 43,033 (4744) over one, three, five, ten years and lifetime. The PSA indicated that all iterations produced dominant results for IND/GLY. IND/GLY is cost-minimising vs IND+GLY and dominates SFC in the maintenance treatment of COPD patients in Sweden. Encouraging dual bronchodilator therapy over an ICS-containing combination results in lower total costs and better outcomes compared to combination therapy including fluticasone in moderate-to-severe COPD patients with low exacerbation risk.

Efficacy and safety of coadministration of once-daily indacaterol and glycopyrronium versus indacaterol alone in COPD patients: the GLOW6 study

BackgroundAddition of a second bronchodilator from a different pharmacological class may benefit patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by bronchodilator monotherapy. GLOW6 evaluated the efficacy and safety of once-daily coadministration of the long-acting β2-agonist indacaterol (IND) and the long-acting muscarinic antagonist glycopyrronium (GLY) versus IND alone in patients with moderate-to-severe COPD.Materials and methodsIn this randomized, double-blind, parallel group, placebo-controlled, 12-week study, patients were randomized 1:1 to IND 150 μg and GLY 50 μg daily (IND + GLY) or IND 150 μg daily and placebo (IND + PBO) (all delivered via separate Breezhaler® devices). The primary objective was to demonstrate the superiority of IND + GLY versus IND + PBO for trough forced expiratory volume in 1 second (FEV1) at week 12. Other end points included trough FEV1 at day 1, FEV1 area under the curve from 30 minutes to 4 hours (AUC30min–4h), peak FEV1, inspiratory capacity and trough forced vital capacity (FVC) at day 1 and week 12, and transition dyspnea index (TDI) focal score, COPD symptoms, and rescue medication use over 12 weeks.ResultsA total of 449 patients were randomized (IND + GLY, 226; IND + PBO, 223); 94% completed the study. On day 1 and at week 12, IND + GLY significantly improved trough FEV1 versus IND + PBO, with treatment differences of 74 mL (95% CI 46–101 mL) and 64 mL (95% CI 28–99 mL), respectively (both P<0.001). IND + GLY significantly improved postdose peak FEV1, FEV1 AUC30min–4h, and trough FVC at day 1 and week 12 versus IND + PBO (all P<0.01). TDI focal score and COPD symptoms (percentage of days able to perform usual daily activities and change from baseline in mean daytime respiratory score) were significantly improved with IND + GLY versus IND + PBO (P<0.05). The incidence of adverse events was similar for the two treatment groups.ConclusionIn patients with moderate-to-severe COPD, once-daily coadministration of IND and GLY provides significant and sustained improvement in bronchodilation versus IND alone from day 1, with significant improvements in patient-centered outcomes.

P235 Dual-bronchodilation with once-daily QVA149 in patients with moderate-to-severe COPD: overview of the IGNITE program

IntroductionIn patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) whose symptoms are insufficiently controlled by monotherapy, current treatment strategies recommend the addition of a second bronchodilator with a different mechanism...

COPD 2013: An update on treatment and newly approved medications for pharmacists

To educate pharmacists about the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) guidelines for treatment of chronic obstructive pulmonary disease (COPD), newly approved medications, and recent developments since the guidelines were published. The evidence-based GOLD guidelines provide recommendations for clinicians managing patients with COPD. These guidelines were revised most recently in 2013. Three new medications (indacaterol maleate, aclidinium bromide, and fluticasone furoate/vilanterol) have been approved in the previous 2 years. Adding to the armamentarium of medications for treating COPD is useful. Studies also have been conducted to determine which inhaled agents are preferred for use when long-acting bronchodilators are needed as mono- and combination therapy. In addition, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors and macrolides are being studied for use in COPD. An extensive COPD pipeline consists of many oral and inhaled medications, including olodaterol and glycopyrronium maleate, which are in Phase III clinical trials. Medication adherence is a very important piece of COPD management. Pharmacists play an integral role in drug selection and patient education to ensure the best possible outcomes. The GOLD guidelines represent the standard of care for COPD management. New drug approvals and recent research may affect practitioner choices in managing the disease. Pharmacists can improve medication adherence and selection in order to maximize therapeutic effectiveness and ensure that patients are using inhalation delivery devices optimally.

The effect of indacaterol during an acute exacerbation of COPD

Some clinical trials have suggested that the inhaled long-acting β2-agonists (LABAs) may be effective in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since indacaterol, the first once-daily LABA to be developed for the regular treatment of COPD, exhibits fast onset of action and 24-h duration of bronchodilation, we have investigated its effects in patients with AECOPD managed in the emergency department.In a randomised controlled pilot trial, we have enrolled 29 consecutive patients with a recent (i.e., within ≤4 d) history of AECOPD and requiring hospitalization. All patients received a standard protocol consisting of ipratropium bromide aerosol 500 μg three times a day, intravenous methylprednisolone 20 mg twice-daily and, if indicated, oral levofloxacin 500 mg once-daily. Moreover, they were randomly allocated to one of the two 5-day treatment groups (indacaterol maleate 300 μg once-daily or salbutamol nebulizer 1250 μg three times a day).The administration of indacaterol 300 μg to patients admitted to emergency department for an AECOPD resulted in a greater improvement of pulmonary function compared with traditional therapy, without cardiovascular side effects.Our results suggest that indacaterol could be a useful option in the treatment of AECOPD. However, further larger double-blinded randomized clinical trials are needed to validate the intriguing results obtained in this setting.

Indacaterol/glycopyrronium bromide fixed-dose combination for the treatment of COPD

Chronic obstructive pulmonary disease (COPD) is a worldwide problem causing prolonged and progressive morbidity as well as premature mortality. Pharmacologic treatment consists primarily in the relief of symptoms and preventing or minimizing the consequences of exacerbations. Central to the pharmacologic management of COPD is the use of bronchodilator therapy. Two major classes of agents are frequently used: β-adrenoceptor agonists and antimuscarinic agents. These drugs are used mainly in the inhalational form, primarily as rescue medication, but occasionally for maintenance in combination therapy. The availability of "ultra-long"-acting β-adrenoceptor agonists and long-acting antimuscarinic agents opens the way for combinations of these agents to be used in maintenance therapy. Such a combination offers the potential of enhanced efficacy due to additive effects and better compliance as the result of once-daily treatment. This article reviews the rationale for current bronchodilator therapy of COPD as well as the current status of a fixed-dose combined inhaler using two novel long-acting agents: glycopyrronium bromide and indacaterol maleate.

長時間作用性吸入&beta;2刺激薬，インダカテロールマレイン酸塩（オンブレス&reg;）の薬理学的特性および臨床効果

長時間作用性吸入&beta;₂刺激薬，インダカテロールマレイン酸塩（オンブレス^&reg;）の薬理学的特性および臨床効果