Improving Lung Function (FEV1) in COPD Through Appropriate Counseling on Use of Inhaled Medications

Pharmacy TimesMarch 2018 Central Nervous System
Volume 84
Issue 3

Chronic obstructive pulmonary disease (COPD) is a progressive, but treatable, disease characterized by airflow limitation and inflammation.

This article was sponsored by Boehringer Ingelheim Pharmaceuticals, Inc.

Please see the Prescribing Information for STIOLTO® RESPIMAT® (tiotropium bromide and olodaterol) Inhalation Spray, including boxed WARNING and the Medication Guide and Instructions for Use.


STIOLTO RESPIMAT is a combination of tiotropium, an anticholingeric, and olodaterol, a long-acting beta2-adrenergic agonist (LABA), indicated for long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.3


STIOLTO RESPIMAT is not indicated to treat acute deteriorations of COPD. STIOLTO RESPIMAT is not indicated to treat asthma.3


As STIOLTO RESPIMAT contains the LABA olodaterol, the medication carries a boxed warning for an increased risk of asthma-related death.3

WARNING: ASTHMA-RELATED DEATH Long-acting beta2-adrenergic agonists (LABA) such as olodaterol, one of the active ingredients in STlOLTO RESPIMAT, increase the risk of asthma-related death. Data from a large, placebo-controlled US study that compared the safety of another long acting beta2-adrenergic agonist (salmeterol) with placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of all LABA, including olodaterol, one of the active ingredients in STlOLTO RESPIMAT. The safety and efficacy of STlOLTO RESPIMAT in patients with asthma have not been established. STlOLTO RESPIMAT is not indicated for the treatment of asthma.

Chronic obstructive pulmonary disease (COPD) is a progressive, but treatable, disease characterized by airflow limitation and inflammation.1 Although COPD affects people of all ages, it is primarily a disease of older adults, with approximately three-fourths (74.2%) of all patients with COPD older than 55 years.2 Pharmacists have a pivotal role to help ensure that treatments for COPD deliver on patients’ expectations to help them manage their disease effectively. Part of this is accomplished through understanding the role of guideline-recommended pharmacotherapy, such as the use of multiple bronchodilator classes and long-acting drug options.1 Additionally, instruction on the proper use of drug products and delivery devices is key to efficacy and experience with prescribed medications. This article reviews this information, as well as a treatment option for management of COPD.


One chronic management treatment is the combination of 2 bronchodilatory medications: muscarinic antagonists and long-acting beta2-agonists (LABAs).1 STIOLTO® RESPIMAT® (tiotropium bromide and olodaterol) inhalation spray is one such combination product. Both medications in STIOLTO RESPIMAT exert bronchodilatory effects. The muscarinic antagonist tiotropium inhibits M3 receptors of the smooth muscle in the lung, resulting in bronchodilation, while olodaterol binds to and activates beta2-adrenoceptors in the airways, resulting in cyclic adenosine monophosphate-mediated bronchodilation.3


In two 52-week randomized, double-blind, parallel group studies, patients received STIOLTO RESPIMAT, tiotropium alone, or olodaterol alone through the RESPIMAT inhaler. Enrolled patients were 40 years or older with a clinical diagnosis of COPD, a smoking history longer than 10 pack-years, severe pulmonary impairment, and a forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio after receiving a bronchodilator of less than 70%. Treatments were administered at the same time of day every morning.3

Researchers evaluated the primary end points of a change in baseline FEV1 area under the curve (AUC)0-3h and trough FEV1 levels after 24 weeks of treatment. Patients receiving STIOLTO RESPIMAT experienced a 256-mL improvement in FEV1 AUC0-3h, which was significantly greater (P <.0001) than improvements on the same measure with tiotropium alone (139 mL) or olodaterol alone (133 mL). Increases in trough FEV1 after 24 weeks with STIOLTO RESPIMAT averaged 136 mL, significantly greater (P <.0001) than the mean 65-mL improvement with tiotropium or the mean 54-mL increase with olodaterol.3 Similar results were seen in a replicate study. Patients receiving STIOLTO RESPIMAT experienced a 268-mL improvement in FEV1 AUC0-3h, which was significantly greater than tiotropium alone (165 mL) or olodaterol alone (136 mL). Increases in trough FEV1 after 24 weeks with STIOLTO RESPIMAT averaged 145 mL, significantly greater the mean 96-mL improvement with tiotropium or the mean 57-mL increase with olodaterol.3


STIOLTO RESPIMAT has been used by 1988 patients across two 52-week active-controlled trials, a 12-week placebo-controlled trial, three 6-week placebo-controlled crossover trials, and several other smaller studies. Common adverse events were nasopharyngitis, cough, and back pain, each of which occurred with STIOLTO RESPIMAT more often than with active control medications, at an incidence greater than 3%.3


STIOLTO RESPIMAT is administered using the RESPIMAT inhaler, which is designed to deliver medication in a slow-moving mist independent of inspiratory effort.4 As with all inhaled drugs, the actual amount of medication delivered to the lungs may depend on patient factors such as the coordination between the actuation of the inhaler and inspiration through the delivery system. The duration of inspiration should be at least as long as the spray duration (1.5 seconds).3 Upon actuation, a specially engineered nozzle propels 2 fine jets of liquid at a precise angle to form a slow moving mist of approximately 1.5 seconds.4

STIOLTO RESPIMAT is administered as 2 inhalations once daily at the same time each day. No more than 2 inhalations should be used in a given 24-hour period. Before the first use or after 21 days of nonuse, patients should actuate the inhaler toward the ground until an aerosol cloud is visible and should then repeat the actuation 3 times. Additionally, if the medication is not used for 3 days, the inhaler must be actuated once before use.3


Patients should be instructed on proper inhaler preparation methods for STIOLTO RESPIMAT before the first use. To start, with the cap closed, instruct patients to press the safety catch, pull to remove the clear base, and write the “discard by” date on the label (3 months from the date the cartridge is inserted). Then, instruct patients to place the narrow end of the cartridge into the inhaler (leaving about an eighth of an inch of the cartridge visible when the cartridge is fully inserted) and, finally, to replace the clear base.3

To prime the inhaler, instruct patients to hold it upright with the cap closed and turn the clear base one-half turn in the direction of the black arrows on the label until the inhaler clicks. Then, patients should flip the green cap, point the inhaler toward the ground, and press the dose-release button. This action of closing and opening the green cap and pressing the dose-release button while aiming the inhaler at the ground should be repeated until a fine mist is visible, and then 3 additional times after the first visible mist forms. At this point, the inhaler is ready to deliver the labeled number of doses (30).3

To administer the inhaler on a daily basis, patients should remember the acronym TOP: (1) Turn the clear base in the direction of the black arrows one-half turn until it clicks; (2) Open the green cap, exhale completely, and close your lips around the mouthpiece, being careful not to cover the inhaler air vents; and (3) Press the dose-release button to inhale medication. Each daily dose consists of 2 inhalations, with both inhalations administered on a daily basis at the same time of day (see FIGURE).3


Understanding the role of pharmacologic management in COPD and being familiar with current guidelines, such as combination therapy and long-acting medications, is important. This knowledge can be used as pharmacists work with prescribers in identifying appropriate options for patients, including product selection that aligns with treatment guidelines.

Patients with COPD can be informed of the value of pharmacologic treatment and instructed on how to use inhaled medications, such as STIOLTO RESPIMAT. Counseling patients on the inhaler is a key point; with the patient’s permission, pharmacists can prime the inhaler before dispensing the medication. Expressing the importance of the TOP acronym is important because it will remind patients of the proper daily use of the STIOLTO RESPIMAT inhaler.



All LABA are contraindicated in patients with asthma without use of a long-term asthma control medication. STIOLTO is contraindicated in patients with hypersensitivity to tiotropium, ipratropium (atropine derivatives), olodaterol, or any component of this product.

In clinical trials and postmarketing experience with tiotropium, immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash have been reported. Hypersensitivity reactions were also reported in clinical trials with STIOLTO.


STIOLTO should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition, or used as rescue therapy for acute symptoms. Acute symptoms should be treated with an inhaled short-acting beta2-agonist. Patients who have been taking inhaled, short-acting beta2-agonists on a regular basis should discontinue the regular use of these drugs and use them only for acute respiratory symptoms.

STIOLTO should not be used more often or at higher doses than recommended, or in conjunction with other LABA as an overdose may result.

Immediate hypersensitivity reactions, including urticaria, angioedema, rash, bronchospasm, anaphylaxis, or itching may occur after administration of STIOLTO. If such a reaction occurs, discontinue therapy with STIOLTO and consider alternative treatments. Patients with a history of hypersensitivity reactions to atropine or its derivatives should be closely monitored for similar hypersensitivity reactions to STIOLTO.

If paradoxical bronchospasm occurs, STIOLTO should be discontinued immediately.

STIOLTO can produce a clinically significant cardiovascular effect in some patients, as measured by increases in pulse rate, systolic or diastolic blood pressure, and/or symptoms. If such effects occur, STIOLTO may need to be discontinued.

Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, in patients with known or suspected prolongation of the QT interval, and in patients who are unusually responsive to sympathomimetic amines.

Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a physician immediately if signs or symptoms of acute narrow-angle glaucoma develop (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema).

Use with caution in patients with urinary retention, which can be associated with symptoms like difficulty passing urine and painful urination in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Patients with moderate to severe renal impairment (creatinine clearance of <60 mL/min) treated with STIOLTO should be monitored closely for anticholinergic side effects.

Be alert to hypokalemia, which has the potential to produce adverse cardiovascular effects. Be alert to hyperglycemia.


The most common adverse reactions with STIOLTO (>3% incidence and higher incidence than any of the comparators—tiotropium and/or olodaterol) were: nasopharyngitis, 12.4% (11.7%/12.6%), cough, 3.9% (4.4%/3.0%), and back pain, 3.6% (1.8%/3.4%).


  • Use caution if administering adrenergic drugs because sympathetic effects of olodaterol may be potentiated.
  • Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of olodaterol.
  • Beta agonists, such as olodaterol, can acutely worsen the ECG changes and/or hypokalemia that may result from administration of non-potassium sparing diuretics. The action of adrenergic agents on the cardiovascular system may be potentiated by monoamine oxidase inhibitors or tricyclic antidepressants or other drugs known to prolong the QTc interval. Therefore beta-agonists should be used with extreme caution in patients being treated with these drugs. Drugs that prolong the QTc interval may be associated with an increased risk of ventricular arrhythmias.
  • Beta-blockers should be used with caution as they can inhibit the therapeutic effect of beta agonists which may produce severe bronchospasms in patients with COPD. However, under certain circumstances, e.g. as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD. In this setting, cardio selective beta-blockers could be considered, although they should be administered with caution.
  • Avoid co-administration of STIOLTO with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

STIOLTO is for oral inhalation only. The STIOLTO cartridge is only intended for use with the STIOLTO RESPIMAT inhaler.

Inform patients not to spray STIOLTO into the eyes.


  • Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2017 Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD website. Published January 2017. Accessed December 3, 2017.
  • Centers for Disease Control and Prevention. Chronic obstructive pulmonary disease among adults—United States, 2011. MMWR Morb Mortal Wkly Rep. 2012;61(46):938-943.
  • Stiolto Respimat [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2016.
  • Dalby R, Spallek M, Voshaar T. A review of the development of Respimat Soft Mist Inhaler. Int J Pharmaceutics. 2004;283(1-2):1-9.


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