Navigating New COPD Medications

SEPTEMBER 02, 2015
As the population ages, we are seeing an increase in the incidence of chronic obstructive pulmonary disease (COPD).

COPD is the third-leading cause of death in the United States and the second-leading cause of disability.1 Data on incidence are not exact due to the fact that COPD is often underreported, but estimated incidence is 12.7 million adults in the United States alone.2

The cost of care is estimated at approximately $49.9 billion as of 2010.2 In light of the disease’s high cost of care and irreversibility, it is extremely important to properly manage COPD.
 
Current guidelines recommend treatment based on multiple factors that include exacerbation number or hospitalizations, symptom scale, and airflow limitation severity.3 The main medication classes used to treat COPD are beta-agonists (short- and long-acting), antimuscarinics (short- and long-acting), and inhaled corticosteroids.

Over the past 5 years, several advancements have been made in these medication classes—not only through newly approved drugs, but also through new formulations of old drugs.4 Since very few of these medications have been evaluated against one another in clinical studies, it’s important to understand how their characteristics may influence drug selection and use in COPD management.
 
Here are the advantages of these new medications, as well as some basic information to help clinicians identify the best medication for individual patients.4
 
Short-acting beta-agonists (SABAs)
SABAs are traditionally reserved for acute COPD exacerbations. These medications have a quick onset and swiftly dilate the airways.
 
COPD exacerbations’ response to SABAs is often lower than what is seen in asthma exacerbations.1

Albuterol sulfate (Proair Respiclick)
This is a new formulation of the existing drug albuterol, the most commonly prescribed SABA.
 
The FDA approved the use of the Respiclick delivery system on March 31, 2015.4 In contrast to the traditional metered-dose inhaler (MDI), Proair Respiclick is the first dry powder rescue inhaler on the market.
 
One major advantage of this dry powder inhaler (DPI) is that patients do not need to have the hand-breath coordination required for traditional MDIs.5 Because DPIs are activated by breath, the patient can choose when to deliver the dose and does not have to coordinate breathing with the actuation.
 
The hand-breath coordination required by MDIs can be difficult for patients experiencing an acute COPD exacerbation, and nebulizers may be cost-prohibitive or functionally difficult, particularly for those without strong caregiver support. DPI use may help improve albuterol delivery and provide effective relief during acute situations.
 
Patients who have been using MDIs or nebulizers for long periods of time may require additional counseling on proper DPI technique.
 
Currently, Proair Respiclick is only approved in patients 12 and older. Those with declining lung function who are not able to inhale sharply and/or deeply should not use this medication.
 
Common side effects such as tachycardia and tremor resemble those seen with other delivery systems for albuterol. The cost without insurance is approximately $50 to $60 per inhaler, which is similar to the cost of Proair HFA inhaler and Ventolin HFA inhalers.6
 
Long-acting beta-agonists (LABAs) and long-acting antimuscarinics (LAMAs)
Both LABAs and LAMAs are used as long-term maintenance therapies in COPD management. They are useful in patients with moderate-to-severe disease who experience symptoms on a consistent basis and/or have not experienced relief from short-acting medications.
 
These long-acting agents have been shown to improvement lung function and reduce symptoms, but they have little to no impact on mortality.1

LABAs

Indacterol (Arcapta Neohaler)
Indacaterol is an ultra LABA approved by the FDA on July 1, 2011, and marketed under the proprietary name Arcapta Neohaler as a DPI.4 It requires a capsule to be physically placed in the inhaler before each use. This medication is unique in that it is only used in COPD and not in asthma.7
 
Arcapta Neohaler’s major advantage is its once-daily dosing.8 Current data show that this improves lung function greater than twice-daily salmeterol or formoterol.9  
 
It also appears to maintain efficacy in the geriatric population, which is an especially important consideration because COPD is more common in older adults, and there is a known age-related decrease in lung compliance that can decrease the effective delivery of inhaled medications.
 
The most common side effects are runny nose, cough, sore throat, headache, and nausea. The estimated cost for a 1-month supply of indacaterol is approximately $200 to $215, making it one of the more expensive inhalers.7

Olodaterol (Striverdi Respimat)
This is a new medication with a novel delivery system. It was approved by the FDA on July 31, 2014.4
 
Like indacaterol, olodaterol is dosed once a day.10 Both medications have shown similar efficacy in the treatment of COPD.11
 
The Respimat formulation is a slow-moving mist that does not contain a propellant like traditional MDIs. This helps the medication follow the natural curve of the throat more easily and travel deep into the lungs.
 
Evidence has also shown a decrease in mouth and throat deposition that is seen with both MDIs and DPIs.12 It also does not require the force that a DPI does, which is useful for patients with declining lung function.
 
Olodaterol has greater selectivity for the β2 receptor over β1 than formoterol or salmeterol, thereby producing less tachycardia than the older LABAs. This may be especially helpful in patients who are unable to tolerate any notable impact on heart rate due to comorbidities.
 
However, olodaterol may still cause other adverse effects associated with LABAs, such as paradoxical bronchospasm, hypokalemia, dizziness, and hyperglycemia.10 The cost for this inhaler ranges from $87 to $18013.
 
LAMAs

Aclidinium bromide (Tudorza Pressair)
Aclidinium bromide was approved by the FDA on July 23, 2012.4 The DPI’s twice-daily dosing is more frequent than the other medications in its class, tiotropium and umeclidinium, which are dosed only once a day.
 
Like other DPIs, aclidinium does not require the mouth-breath coordination required for MDIs, giving it some advantage in patient populations that struggle with this. Data has shown that aclidinium will reach therapeutic levels within 2 days and is comparable in efficacy to tiotropium.15
Although aclidinium doesn’t have much of a clinical advantage over tiotropium, the inhaler does come preloaded, which may be desirable in patients with physical barriers to medication administration. Tiotropium w requires capsule insertion with each use.
 
Aclidinium is only approved in patients 18 and older.14 The most common side effects are headache, cough, and inflammation of nasal passages, though the drug may also cause serious side effects such as paradoxical bronchospasm, acute narrow angle glaucoma, and urinary retention. Therefore, it should be used with caution in patient populations prone to these effects.
 
The price for a single inhaler without insurance can exceed $300.6
 
Tiotropium (Spiriva Respimat)
Tiotropium was approved on September 24, 2014.4 It was originally approved in 2004 for use in COPD, but was formulated as a DPI that is currently still available.4
 
Like other DPIs, tiotroprium does not require hand-breath coordination, but it is known to cause hoarseness due to deposition of medication in the back of the mouth and throat. The once-daily Respimat formulation is far less likely to cause this reaction while still avoiding hand-breath coordination.
 
Tiotropium can cause many of the same side effects as other antimuscarinics, such as bronchospasm, glaucoma, and urinary retention.16 The most common side effects include dry mouth, sore throat, and runny nose.
 
The price for this inhaler is the same as its precursor, the Spiriva Handihaler. One inhaler may cost up to $380, making it the most expensive inhaler thus far.6
 
Umeclidium (Incruse Ellipta)
Umeclidium was approved in 2013 as a combination product with vilanterol (Anoro Ellipta). On April 30, 2014, it was approved as a DPI.4 It is the only inhaler that contains umeclidium alone.
 
It is dosed once a day, comes preloaded, and only requires 1 inhalation per dose, making it easier to use than tiotropium.17
 
The most common side effects of this medication include cough, arthralgia, upper respiratory tract infection, and nasopharyngitis.18 This inhaler can cost up to $270 without insurance.6
 
Combination products

In COPD management, combination products for inhalation have a unique advantage over monotherapies in that they provide superior efficacy with lower doses of each component drug, resulting in a lower incidence of dose-related side effects. 
 
Many of these products can also simplify a COPD patient’s drug regimen by reducing the number of inhalations per day.1,2
 
Ipratropium bromide/albuterol sulfate (Combivent Respimat)
This combination product was approved by the FDA in October 2011. It was released as a replacement for the Combivent inhalation aerosol, which was discontinued at the end of 2013 due to the use of chlorofluorocarbons in its formulation.
 
Combivent Respimat has the same benefits and limitations as the Respimat inhalation device discussed earlier, and it may be useful in patients with decreased lung function who cannot inhale deep enough on their own to use traditional inhalers effectively.
 
It is currently the only approved product for acute COPD exacerbation management that uses this technology. The average price for a single 20/100 mcg inhaler (120 metered doses) can exceed $300, which is considerably more expensive than other medications used in the acute management of COPD exacerbations.
 
It is also more expensive than the other delivery options for ipratropium bromide/albuterol/sulfate. The generic nebulizer solution of ipratropium-albuterol generally costs less than $50 for 30 doses.19,20
 
Fluticasone furoate/vilanterol (Breo Ellipta)
Approved in April 2015, this product combines the new LABA vilanterol with an inhaled corticosteroid (ICS) already on the market, fluticasone.
 
Like indacaterol, vilanterol allows this ICS/LABA product to be dosed once a day, compared with similar combination products with salmeterol or formoterol that are dosed twice a day. Unlike indacaterol, however, vilanterol is not available as a monotherapy in the United States. 21
 
Since Breo Ellipta contains an ICS, long-term use is associated with an elevated risk of pneumonia. The Ellipta inhaler itself is a DPI.
 
Similar to Diskus inhalers, all doses are contained within the device, and a counter keeps track of how many doses are left. The inhalation technique for the Ellipta inhaler differs from other DPIs, however, due to a unique air vent feature near the mouthpiece. This design allows for drug delivery with long, steady inhalations, similar to MDIs without the hand-breath coordination.22
 
This stands is in stark contrast to the quick, forceful inhalation required by other DPIs, and this feature is beneficial for patients who may not be able to inhale forcefully enough to effectively use traditional DPIs.22 It is important to counsel patients to avoid covering the air vent with their fingers or mouth while inhaling, since it would interfere with the device.
 
The average cost of 1 inhaler (28 doses) ranges between $300 and $380. 21, 23

Umeclidinium/vilanterol (Anoro Ellipta)
Anoro Ellipta is a combination of 2 newer COPD medications, vilanterol and umeclidinium. It was the first LABA/LAMA product to receive FDA approval.
 
Aside from the benefits of the Ellipta inhaler, this product could be especially useful for patients who need dual therapy for COPD management but cannot tolerate an ICS.24, 25 Because it does not contain an ICS, patients do not have to rinse their mouth after use. 
 
It is also dosed once a day, which may be more convenient for patients who need to take both a LABA and LAMA, regardless of ICS use.26  
 
Like many other new COPD medications, the average monthly case cost can exceed $300.
 
Tiotropium bromide/olodaterol (Stiolto Respimat)
Stiolto Respimat combines the LAMA tiotropium with the new LABA olodaterol.  This product was approved by the FDA in May 2015, making it one of the newest products approved for the management of COPD to date.27 It is the only other LABA/LAMA product approved in the United States besides Anoro Ellipta.28
 
It is administered as a once-daily dose of 2 inhalations using the Respimat inhaler, compared with the 1 inhalation required for Anoro Ellipta.26,28  The only other notable difference between these products is the inhalation device used.12,22 
 
The average cost of the 2 inhalers is similar.
 
Conclusion
 
Proper COPD management is crucial to help reduce exacerbations and improve quality of life. The pharmacologic advancements made in recent years have added to the options patients and clinicians can use.  From medication combinations to inhalation devices, these new products offer patients effective, easier-to-use options for managing their COPD.
 
While current guidelines make no specific recommendations in favor of these newer products versus comparable ones previously on the market, these products do offer benefits for patients who have trouble with their current COPD medications or have problems with adherence. However, these products are generally more expensive than older products, and the higher cost must be weighed against potential benefits.
 
The introduction of these products in the market highlights an important shift in drug therapy where the delivery system may be the deciding factor in drug selection when clinical efficacy is comparable.
 
This article was co-authored by Morgan Posey, PharmD Candidate 2016, and Nicholas Childers, PharmD Candidate 2016, at Auburn University's Harrison School of Pharmacy.
 
 References:
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Marilyn Bulloch, PharmD, BCPS, FCCM
Marilyn Bulloch, PharmD, BCPS, FCCM
Marilyn Novell Bulloch, PharmD BCPS, is an Associate Clinical Professor of Pharmacy Practice at the Auburn University School of Pharmacy and an Adjunct Associate Professor at the University of Alabama-Birmingham School of Medicine and the University of Alabama College of Community Health Sciences . She completed a post-graduate pharmacy practice residency at the University of Alabama-Birmingham Hospital and a post-graduate specialty residency in critical care pharmacy at Charleston Area Medical Center in Charleston, West Virginia. Dr. Bulloch also completed a Faculty Scholars Program in geriatrics through the University of Alabama-Birmingham Geriatric Education Center in 2011. She serves on multiple committees and in leadership positions for many local, state, and national pharmacy and interdisciplinary medical organizations.
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