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Recent OTC Developments in Asthma

W. Steven Pray, PhD, DPh
Bernhardt Professor, Nonprescription Products and Devices

College of Pharmacy

Southwestern Oklahoma State University

Weatherford, Oklahoma

Gabriel E. Pray, PharmD Candidate
College of Pharmacy
Southwestern Oklahoma State University

Weatherford, Oklahoma



7/17/2013

US Pharm
. 2013;38(7):24-31.

Pharmacists fill numerous prescriptions for asthma products in a typical week. Occasionally, patients also ask about nonprescription products. It is vital for the pharmacist to understand the role of OTC asthma products in order to render proper advice.

Smoke-Free Laws and Asthma Prevalence

At least 21% of U.S. adults have asthma and also smoke cigarettes.1 The link between smoking and asthma is compelling. The CDC identifies tobacco smoke as one of the most common triggers of an asthma attack, for smokers and those around them.1 Secondhand smoke is a noxious mix of gases and fine particles, composed of both the smoke issuing from the burning tobacco product and the smoke-filled exhalations from smokers. Secondhand smoke contains over 7,000 chemicals; hundreds are known to be toxic, and 70 or more are carcinogenic.1

All patients with asthma must strenuously avoid any contact with cigarette smoke. This may mean banishing smoking family members from the house and car and declining to visit homes where smokers are present. Patients with asthma should also be urged to avoid restaurants and hotels that still allow smoking. Restaurants with smoking sections may seem to be safe, but they provide inadequate protection for those sensitive to smoke, even if the owners promise that their filter or ventilation system is effective.

What is the effect of stringent nonsmoking laws on asthma? England was experiencing an asthma crisis several years ago; the number of children with severe asthma attacks was increasing by 2.2% each year.2 English law banned smoking in enclosed public places and workplaces in July 2007. The number of admissions to hospitals for childhood asthma dropped by 12.3% the first year public smoking was banned.2

One particularly dangerous habit for those with asthma is casino gambling. Casinos are fully aware of the high smoking rates among recreational and serious gamblers, so there is no incentive for them to limit or stop smoking by their patrons.3 When casinos do have nonsmoking areas, individuals usually must pass through smoking areas of the casino to reach them. Non-smoking casinos are extremely rare, but perhaps will become more common if those with asthma request them.

The Status of Combination Ephedrine Tablets

Patients may ask the pharmacist whether nonprescription ephedrine combination products are appropriate for their asthma. It is important to stress that the bronchodilators ephedrine, epinephrine, and racepinephrine are all FDA approved for self-treatment of asthma as of this writing.4 Despite the FDA approval of these products, there are issues with their use. First, federal law made ephedrine a Schedule V controlled substance to limit its availability and to help stop production of methamphetamine. Second, currently available products (e.g., Primatene Tablets, Bronkaid Caplets) include guaifenesin, which is not FDA approved for any use in asthma.4

On the Primatene Tablets Web site, under a “Frequently Asked Questions” page, the question “What is an expectorant?” appears.5 The answer fails to provide any asthma-related justification for its inclusion, only providing a narrow description of the use of expectorants in facilitating removal of sputum from the respiratory tract.

A further issue with ephedrine-guaifenesin combination tablets involves the widely accepted Guidelines for the Diagnosis and Management of Asthma developed by the National Heart, Lung, and Blood Institute (NHLBI), last updated in 2007.6,7 In its treatment section, there were no circumstances in which either ephedrine or guaifenesin is recommended for patients with asthma.

The Status of CFC-Containing Epinephrine Inhalers

Epinephrine inhalers with chlorofluorocarbon (CFC) propellants (e.g., Primatene Mist, Bronkaid Mist) had been available for many years. However, gathering concern over CFC-induced damage to the ozone layer caused the United States to play a leading role in developing an international, coordinated approach to control their use. On January 1, 1989, the U.S. was one of 192 signatories to the Montreal Protocol on Substances that Deplete the Ozone Layer, known informally as the Montreal Protocol.8 Many years were given to change the propellants in medical aerosols, and December 31, 2011, was the deadline for the changeover for nonprescription asthma inhalers.9-11 Sales of the primary remaining product, Primatene Mist, were prohibited after that date. On April 8, 2013, the manufacturer of Primatene Mist (Armstrong Pharmaceuticals, Inc.) announced that it had submitted a New Drug Appli-cation (NDA) to the FDA for Primatene HFA Inhalation Aerosol, using the environmentally friendly propellant known as hydrofluoroalkane (HFA) to deliver epinephrine to the patient.12


The Asthma Inhalers Relief Act of 2012

Apparently, the manufacturer of Primatene Mist overestimated the demand for its product and produced excess inventory, so that considerable product with the CFC-propellant remained after the deadline for legal sales had passed.13 As a result, a bill known in successive Congresses as the Asthma Inhalers Relief Act of 2012 (and later, 2013) was introduced.14,15 If the bill had become law, it would have allowed the company to sell its remaining stockpile past the FDA-mandated legal deadline. This would have put the U.S. in the peculiar position of legally permitting sales of ozone-depleting products in contradiction of an existing law.13,16 The manufacturer also initiated an online campaign aimed at soliciting consumers to sign a petition to bring Primatene Mist CFC Inhalers back to the market, a clear violation of the Montreal Protocol.17 The expira-tion date for the overstocked inhalers is August 2013, so the issue will shortly become moot.

A New Nonprescription Asthma Product

Asthmanefrin Inhalation Solution is a new asthma product that contains the FDA-approved ingredient racepinephrine 2.25%.18,19 The product consists of a bottle of liquid medication and a separate battery-powered atomizer (EZ Breathe Atomizer). Until HFA-pressurized inhalers containing epinephrine return to the market, this is the only nonprescription inhalation option for asthma treatment.

Racepinephrine acts in the same manner as other nonprescription bronchodilators, through relaxation of airway muscle spasm, relieving shortness of breath. Nonprescription bronchodilators may cause increased rate and force of the heart beat, hypertension, nervousness, sleepless-ness, and nausea or vomiting.20

Labels of Nonprescription Asthma Products

The labels of Primatene Tablets, Bronkaid Caplets, and Asthmanefrin Inhalation Solution carry important instructions that the pharmacist should be thoroughly familiar with when patients attempt to purchase these products.19,21,22

The indications for nonpre-scription asthma products are for temporary relief of mild symptoms of intermittent asthma, such as wheezing, tightness of the chest, and shortness of breath. Since the tablets/caplets contain guaifenesin as well, the products also carry labeling that they help loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive.21,22 Bronkaid labels add that guaifenesin acts to drain the bronchial tubes.21

Patients are warned to see a physician in several situations: if they are not improved in 20 minutes (inhalation solution), or in 60 minutes (tablets) if the problem worsens; or if they have more than two asthma attacks in a week. Patients must also see a physician if they exceed the recommended usage. For Primatene Tablets (containing 12.5 mg of ephedrine and 200 mg of guaifenesin per tablet), the maximum use is more than 12 tablets in 24 hours or more than 8 tablets in 24 hours for 3 or more days a week.22 Greater usage indicates that the asthma is worsening. Bronkaid Caplets contain 25 mg of ephedrine and 400 mg of guaifenesin per caplet, so the usage danger point is different: more than 6 caplets in 24 hours or more than 4 caplets in 24 hours for 3 or more days per week.21 Both products warn patients that they will not give relief as quickly as an inhaled bronchodilator.21,22

The maximum-use point for Asthmanefrin Inhalation Solution beyond which a physician should be consulted is more than 12 inhalations in 24 hours or more than 9 inhalations in 24 hours for 3 or more days a week.19

Patients are cautioned not to use OTC bronchodilators unless a physician has diagnosed asthma. There is also a notification not to use them if the patient is currently taking a monoamine oxidase (MAO) inhibitor or has stopped taking it within the past 2 weeks. The Asthmanefrin labels warn against use if the solution is brown or cloudy. Bronkaid Tablets warn against use if the patient is allergic to any of the ingredients. All labels request that female patients ask a health professional before use if they are pregnant or breastfeeding.19,21,22

Patients are instructed to ask a physician before use if they have ever been hospitalized for asthma or if they have heart disease, hyper-tension, diabetes, thyroid disease, seizures, narrow-angle glaucoma, a psychiatric or emotional condition, or trouble urinating due to an enlarged prostate gland. Because of the guaifenesin, the tablets/caplets add prohibitions against use if the patient has cough that occurs with too much phlegm (mucus) or cough that lasts or is chronic, as occurs with smoking, asthma, chronic bronchitis, or emphysema. Patients are instructed to speak to a physician or pharmacist if they are taking prescription medications for asthma, obesity, weight control, depression, or psychiatric or emotional disorders, or if they are taking any drug containing phenylephrine, pseudo-ephedrine, ephedrine, or caffeine (i.e., for allergies, a cough or cold, or pain).19,21,22

Patients should stop use and speak to a physician if their asthma worsens or if they have difficulty sleeping, rapid heart beat, tremors, nervousness, or seizures. These products can induce hypertension or tachycardia, increasing the risk of heart attack or stroke that could cause death. The risk is increased with preexisting hypertension or heart disease or if the patient exceeds the recommended dose or regimen. Patients should avoid using caffeine and supplements that claim to have a stimulant effect. Persons under the age of 12 years should not use the tablets/caplets, and those under the age of 4 years should not use the inhalation solution.19,21,22

PATIENT INFORMATION

Do You Have Asthma?

The first question to answer is whether you really have asthma. The symptoms of asthma are wheezing, coughing that is worse in the morning or at night, tightness of the chest, and shortness of breath. However, it is more complicated than this. Some people with asthma will not have all of these symptoms. Further, there are other medical conditions that cause symptoms that mimic asthma’s, such as a sinus infection or chronic obstructive pulmonary disease (COPD). You cannot decide whether you have asthma and treat it yourself. Rather, you must make an appointment with a physician. Your physician will perform an examination, order the appropriate tests, and determine whether you have asthma or not.

Can You Treat Asthma on Your Own?

Suppose your physician has diagnosed asthma. Can you control asthma on your own without heeding the input from your physician? Absolutely not. Proper control of asthma is extremely complicated. Your physician can help you meet the following goals to maximize your health:

1. Prevent the symptoms of asthma before they occur, including shortness of breath and chronic cough.

2. Make sure you do not need to use inhalers for quick relief from symptoms very often.

3. Keep your lungs functioning as well as they can.

4. Allow you to carry out your normal daily activities and also to sleep all night without problems.

5. Prevent asthma attacks of such severity that you are forced to go to the emergency room and/or be hospitalized for care.

What About Nonprescription Products?

From the above discussion, it should be apparent that the best medical advice for asthma treatment is to use only those drugs that are prescribed by your physician. However, you have probably seen advertisements for nonprescription asthma medications such as Primatene, Bronkaid, and Asthmanefrin. What is their role?

Those caring for asthma patients can consult a well-accepted set of guidelines for asthma treatment written by the National Heart, Lung, and Blood Institute (NHLBI). The expert panel that created these guidelines recommends safer and more effective prescription products for asthma and does not believe that nonprescription products have any role in asthma treatment.

If you are using your prescription asthma medications as recommended, you should never add OTC products to the regimen without checking with your physician first. This will prevent unwanted side effects and will also ensure that the more effective prescription medications work as directed.

If you decline to get your prescriptions filled and elect to use the nonprescription products instead, you have made a risky decision. They do not work as well, so your asthma may not be controlled. They are less safe to use, and may cause unwanted side effects. Overall, it is far better to follow your physician’s advice and use your prescribed medications as directed.

Remember, if you have questions, Consult Your Pharmacist.

REFERENCES

1. Secondhand smoke and asthma. CDC. www.cdc.gov/tobacco/campaign/tips/diseases/secondhand-smoke-asthma.html. Accessed May 25, 2013.
2. Millett C, Lee JT, Laverty AA, et al. Hospital admissions for childhood asthma after smoke-free legislation in England. Pediatrics. 2013;131:e495-e501.
3. Cunningham-Williams RM, Cottler LB, Compton WM III, Spitznagel EL. Taking chances: problem gamblers and mental health disorders—results from the St. Louis Epidemiologic Catchment Area Study. Am J Public Health. 1998;88:1093-1096.
4. Pray WS. Nonprescription Product Therapeutics. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006.
5. Primatene Tablets. Frequently asked questions. Pfizer Consumer Healthcare. www.primatenetablets.com/faq. Accessed May 25, 2013.
6. How is asthma treated and controlled? National Heart, Lung, and Blood Institute. www.nhlbi.nih.gov/health/health-topics/topics/asthma/treatment.html. Accessed May 25, 2013.
7. Guidelines for the diagnosis and management of asthma (EPR-3). National Heart, Lung, and Blood Institute. www.nhlbi.nih.gov/guidelines/asthma/index.htm. Accessed May 25, 2013.
8. Use of ozone-depleting substances; removal of essential-use designations (epinephrine). FDA. Fed Regist. 2008;73:69532-69552.
9. Over-the-counter asthma inhalers containing chlorofluorocarbons (CFCs) will no longer be made or sold after Dec. 31, 2011. FDA News Release. September 22, 2011. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm272872.htm. Accessed May 25, 2013.
10. Primatene Mist with chlorofluorocarbons no longer available after Dec. 21, 2011. FDA. For Consumers. September 22, 2011. www.fda.gov/ForConsumers/ConsumerUpdates/ucm247196.htm. Accessed May 25, 2013.
11. Phase-out of epinephrine CFC metered-dose inhalers. FDA Drugs. December 29, 2011. www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm193304.htm. Accessed May 25, 2013.
12. Primatene HFA update. Armstrong Pharmaceuticals, Inc. April 8, 2013. www.primatene-mist.us.com/doc/Primatene-HFA-Statement-4-8-13.pdf. Accessed May 25, 2013.
13. Oldfield E. Manufacturer pushes to return Primatene Mist to shelves. Pharmacy Times. August 7, 2012. www.pharmacytimes.com/news/Manufacturer-Pushes-to-Return-Primatene-Mist-to-Shelves. Accessed May 25, 2013.
14. HR 6190 (112th): Asthma Inhalers Relief Act of 2012. Govtrack.us. July 25, 2012. www.govtrack.us/congress/bills/112/hr6190. Accessed May 25, 2013.
15. HR 1220: Asthma Inhalers Relief Act of 2013. Govtrack. March 15, 2013. www.govtrack.us/congress/bills/113/hr1220. Accessed May 25, 2013.
16. Makers of over-the-counter inhaler leading fight to have product back on market after removal due to environmental treaty. PR Newswire. July 18, 2012. www.prnewswire.com/news-releases/makers-of-over-the-counter-inhaler-leading-fight-to-have-product-back-on-market-after-removal-due-to-environmental-treaty-162846596.html. Accessed May 25, 2013.
17. Tell EPA: Bring back my Primatene Mist! Armstrong Pharmaceuticals, Inc. www.primatene-mist.us.com/bringback.asp. Accessed May 25, 2013.
18. EZ Breathe Atomizer. Instruction manual. Nephron Pharmaceutics Corp. www.asthmanefrin.com/wp-content/uploads/2013/02/323102254-S2EnglishRev-3.pdf. Accessed May 25, 2013.
19. Asthmanefrin Inhalation Solution, 2.25%. Nephron Pharmaceuticals Corp. www.asthmanefrin.com/wp-content/uploads/2013/04/Asthmanefrin_Sales_Sheet_2013-4-low-resolution.pdf. Accessed May 25, 2013.
20. Establishment of a monograph for OTC cough, cold, allergy, bronchodilator and antiasthmatic products. Fed Regist. 1976;38312-38424.
21. Bronkaid Caplets package insert. Morristown, NJ: Bayer Healthcare LLC; December 2012. http://labeling.bayercare.com/omr/online/bronkaid-caplets-009.pdf. Accessed May 25, 2013.
22. Primatene Tablets. Pfizer Consumer Healthcare. www.primatenetablets.com/primatene-tablets-label. Accessed May 25, 2013.
23. Consumer notification for Primatene Mist users. Armstrong Pharmaceuticals, Inc. June 13, 2012. www.primatene-mist.us.com/doc/Consumer_Notification_For_Primatene_Mist_6-13-12.pdf. Accessed May 25, 2013.

To comment on this article, contact rdavidson@uspharmacist.com.

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