Clinical Cornerstone • SELECTED TOPICS IN RESPIRATORY AND ALLERGIC DISEASES • Vol. 9, No.3

Hydrofluoroalkane Mandate in Effect January 1, 2009: Switch From Chlorofluorocarbon- to Hydrofluoroalkane-Propelled Inhalers Requires Active Transition STEPHEN PETERS, MD, PhD

Professor of Medicine & Pediatrics Wake Forest University School of Medicine Winston-Salem, North Carolina

The manufacture, sale, and distribution of chlorofluorocarbon-propelled albuterol metered-dose inhalers ceased as of December 31,2008. Clinicians should actively transition patients to currently available hydrofluoroalkane­propelled devices, providing concise education and instruction for using the newer devices. (Clinical Corners/one. 2009;9[4]:50-53) © 2009 Elsevier. All rights reserved.

The switch is on: patients using traditional albuterol rescue inhalers must transition to a more environmen­tally friendly device now that chlorofluorocarbon (CFC)-propelled devices are no longer available. In concordance with the terms of the Montreal Protocol on Substances that Deplete the Ozone Layer, production of albuterol inhalers containing CFCs has ceased in the United States and CFC-propelled albuterol inhalers are no longer permitted to be manufactured or distributed as of December 31, 2008. Patients requiring albuterol rescue inhalers must transition to 1 of the 4 available hydrofluoroalkane (HFA)-propelled devices. HFA­propelled devices deliver the same medications as their CFC counterparts, but they do so without significant­ly harming the environment. 1 Important differences exist among the HFA devices, however, necessitating the need for effective patient education. Clinicians are challenged to actively make this transition a safe and successful one for their patients. A brief but focused intervention can often lead the way toward an optimal outcome.

The transition of patients to HFA-propelled inhalers is an important issue in asthma care today, even though the decision was made several years ago. In 2005, under the

terms of the Montreal Protocol on Substances that De­plete the Ozone Layer, the US Food and Drug Adminis­tration (FDA) removed the essential use designation for albuterol inhalers containing CFCs.1.2 The FDA came to this decision after it was determined that HFA-propelled inhalers represented safe and effective alternatives to CFC-propelled inhalers and do not pose a significant threat to the environment.2.3 Consequently, a multiyear phase-out of CFC-propelled albuterol inhalers was en­acted, culminating with the termination of the manufac­ture, sale, and distribution of CFC-propelled albuterol inhalers in the United States as of December 31, 2008.1.2 It should be noted that this ban does not impact the avail­ability of CFC-propelled pirbuterol, which is delivered via a breath-actuated inhalation device.

Nationwide, more than 50 million prescriptions are filled for albuterol each year, making it the seventh most commonly prescribed medication in the United States.1

Therefore, an imposing number of patients and clinicians are affected by the transition to HFA. It is vitally impor­tant for clinicians to ensure that all of their patients who need rescue albuterol inhalers are successfully transi­tioned to HFA-propelled devices and remain adherent to their asthma management plans.

This article was made possible through an educational grant from Teva Specialty Pharmaceuticals.

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Clinical Cornerstone • SELECTED TOPICS IN RESPIRATORY AND ALLERGIC DISEASES • Vol. 9, No.3

PATIENT RELUCTANCE: RESISTING THE TRANSITION Despite efforts to educate the public and ease the transi­tion to HFA-propelled devices, obstacles remain to mak­ing the transition to HFA-propelled devices a smooth one, not the least of which is patients' reluctance to change. Many patients have been using CFC-propelled albuterol inhalers for years-at times in life-threatening situations-and they are confident in and comfortable with the older formulation. These patients must now adapt to an albuterol formulation that tastes, smells, and feels different from what they are used to and costs sig­nificantly more because of the lack of HFA-propelled generic albuterol substitutes. Prior to the CFC phaseout, the majority of albuterol prescriptions filled in the United States were for CFC-propelled generic albuterol. 1

"Probably about 30 to 35 percent of my patients don't want to try anything new," notes Gary S. Rachelefsky, MD, Director of the Executive Center for Allergy, Asthma and Respiratory Disease in Los Angeles, California. "They're comfortable with the inhalers they use for rescue now, and they're concerned that something new may not be as effective." There have also been reports of patients "hoarding" CFC devices or, in extreme cases, abandon­ing their rescue therapy rather than transitioning to an HFA device.-I

Intrinsic differences in the inhaler devices can further add to patients' reluctance. The spray from an HFA in­haler tastes different because of variations in the propel­lant and elastomers and excipients.1 It also may feel warmer than the spray from a CFC inhaler because it is propelled out of the metered-dose inhaler canister with less force and, therefore, at a warmer temperature. Pa­tients are concerned. "They don't think they are getting the medicine in," says Dr. Rachelefsky. "It is a softer spray, it is not as cold, and they don't feel it." Patients may take more puffs of their inhaler than prescribed be­cause of their mistaken belief that they aren't getting enough medication; this can lead to unwanted secondary effects because of albuterol overdosage.

Clearly, clinician intervention is warranted to ensure a safe and effective transition to HFA devices. Clinicians can help prepare patients for this transition by helping them to understand what to expect from their new rescue inhalers. As is often the case in clinical practice, effective patient education can lead the way toward optimal outcomes.

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KEY POINT

IIProbably about 30 to 3S percent of

my patients don't want to try any­

thing new. They're comfortable with

the inhalers they use for rescue now,

and they're concerned that some­

thing new may not be as effective."

-Gary s. Rachelefsky, MD, Director

of the Executive Center for Allergy,

Asthma and Respiratory Disease,

Los Angeles, California

FACILITATING AN ACTIVE HFA TRANSITION: AN INTERVENTION FOR OPTIMAL OUTCOMES At present, 3 FDA-approved HFA-propelled albuterol inhalers are available: ProAir® HFA Inhalation Aerosol (Teva Specialty Pharmaceuticals LLC, Horsham, Penn­sylvania), Proventil® HFA Inhalation Aerosol (Schering­Plough Corporation, Kenilworth, New Jersey), and Ventolin® HFA Inhalation Aerosol (GlaxoSmithKline, Research Triangle Park, North Carolina). Additionally, an HFA-propelled inhaler containing levalbuterol, a medica­tion similar to albuterol, is available as Xopenex® HFA Inhalation Aerosol (Sepracor, Inc., Marlborough, Massa­chusetts) (Figure). Each of these agents has been proven to possess similar safety profiles and efficacy, both to one another and to their CFC counterparts.2- 5

When a patient who has been using a CFC device is given an initial prescription for an HFA-propelled al­buterol inhaler, it is important to explain the reasons for this change. Patients should always be reassured of the efficacy of their new inhaler. Indeed, many patients may find it heartening to know that the smaller particle size of albuterol that is produced with an HFA-propelled de­vice actually leads to better bronchial distribution, which may ultimately make it more effective than its CFC counterpart.1 Differences between CFC and HFA de­vices in resulting serum levels of albuterol are not de­tectable after the standard 2-puff dose, but higher plas­ma levels of albuterol are found after 12 puffs with the new HFA devices. 1

Clinical Cornerstone • SELECTED TOPICS IN RESPIRATORY AND ALLERGIC DISEASES • Vol. 9, No.3

ProAif'ID HFA

Proventil® HFA

Ventolin® HFA

Xopenex® HFA

Figure. Hydrofluoroalkane (HFA)-propelled albuterol inhalers. Proair® HFA Inhalation Aerosol (Teva Specialty Pharmaceuticals LLC, Horsham, Pennsylvania), Proventil® HFA Inhala­tion Aerosol (Schering-Plough Corporation, Kenilworth, New Jersey), Ventolin® HFA Inhalation Aerosol (GlaxoSmithKline, Research Triangle Park, North Carolina), Xopen­ex® HFA Inhalation Aerosol (Sepracor, Inc., Marlborough, Massacusetts).

Patients need to be encouraged to promptly report any difficulties they are having with their new inhalers or any change in symptoms. This can lead to early intervention when faulty inhaler technique or a clogged inhaler is to blame, or, in rare cases, where there is an allergic reac­tion. Such early intervention can help prevent an asthma exacerbation or other factors associated with worsening asthma control.

HFA- AND CFC-PROPELLED INHALERS: UNDERSTANDING THE DIFFERENCES As previously noted, the inherent differences between HFA- and CFC-propelled inhalers can pose some chal­lenges to the clinician who is attempting to transition reluctant patients to HFA devices. Helping patients un­derstand these differences and reassuring them that they are still getting the same rescue medication may help patients overcome their fears and apprehensions.

Three key differences should be discussed with pa­tients: the difference in the plume, when and how to clean an HFA device, and when and how to prime it.

Although the dosage of albuterol in HFA inhalers is the same, the spray from them may taste different and feel warmer than that from CFC-propelled albuterol in­halers. Perhaps most significantly, the force of the spray from an HFA-propelled inhaler may feel softer than that of a CFC-propelled inhaler. As Dr. Rachelefsky has not-

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ed, patients often mistake this softer spray as an indica­tion that they are not receiving or benefiting from their medication. Clinicians should reassure their patients oth­erwise and counsel them against taking more puffs of their inhaler than has been prescribed for them, as this can lead to an overdose of albuterol.

HFA-propelled inhalers need to be primed and cleaned differently and more often than their CFC counterparts. This is a particularly important point as HFA inhalers tend to clog easier than their CFC counterparts because the HFA makes the albuterol in them sticky. Cleaning the device properly helps avoid this. Patients should be in­structed to rinse the actuator under warm running water at least once a week to avoid clogging.

Each of the HFA-propelled inhalers has its own in­structions for priming, cleaning, and usage; clinicians should advise patients to follow the instructions that are unique to the particular device prescribed for them.

CLINICIAN RECOMMENDATIONS In summary, clinicians can help ensure a smooth transition to HFA-propelled albuterol inhalers for their patients by fol­lowing 4 simple but effective interventional action steps: • Reassure patients they are receiving the same medi­

cine and dose with their HFA-propelled inhalers as they received with older CFC devices; the new HFA devices just have a more gentle delivery

Clinical Cornerstone • SELECTED TOPICS IN RESPIRATORY AND ALLERGIC DISEASES • Vol. 9, No.3

- Help build patient confidence in the new HFA­propelled inhalers

• Teach patients about differences they may feel when using an HFA device - Softer spray - Different taste - Warmer mist

• Demonstrate and teach how to properly use the HFA inhaler. Do this often: - Ask patients to demonstrate inhaler technique when

first transitioning them to HFA-propelled devices and periodically thereafter to ensure proper tech­nique has not eroded

- Provide patients with placebo inhalers to practice their technique

- Reassure patients that a softer plume does not indi­cate they are not getting their medicine

• Explain the importance of inhaler maintenance, in­cluding weekly cleaning for HFA inhalers and when the device should be primed - Rinse actuator under warm running water at least

once a week - Never float or submerge the inhaler in water - Follow unique instructions for specific device A fact sheet for patients entitled Important Tips for

Transitioning to an HFA Inhaler is included in this pub­lication. It is intended to aid clinicians in their interven-

tions with patients and to be a useful tool for patients making the switch. Clinicians are encouraged to copy it and distribute it freely to their patients and colleagues.

RESOURCES More information on the Montreal Protocol and the tran­sition to HFA-propelled inhalers can be found at: • http://www.fda.govlcder/mdi/albuterol.htm • www.epa.gov/ozone/title6/phaseout/mdi

REFERENCES 1. Hendeles L Colice GL Meyer RJ. Withdrawal of albuterol

inhalers containing chlorofluorocarbon propellants. N Engl .T Med. 2007356:1344-1351.

2. US Food and Drug Administration. Questions and Answers on Final Rule of Albuterol MDIs. http://www.fda.gov/cder/ mdi/mdifaqs.htm. Accessed December L 2008.

3. Craig-McFeely PM. Wilton LV. Soriano JE. et al. Prospective observational cohort safety study to monitor the introduction of a non-CFC formulation of salbutamol with HFA134a in England. Int .T Clin Pharmacal Ther. 2003:41:67-76.

4. Tarkan L Rough transition to a new asthma inhaler. http:// www.nytimes.comI200 8/051 13/healthl 13 asth. html. Accessed December 16. 2008.

5. Lumry W. Noveck R. Weinstein S. et al. Switching from Ventolin CFC to Ventolin HFA is well tolerated and effec­tive in patients with asthma. Ann Allergy Asthma Immllnol. 2001:86:297-303.

Address correspondence to: Stephen Peters, MD, PhD, Section on Pulmonary and Critical Care Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157. E-mail: sppeters@wfubmc.edu

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