Allergy and Asthma Source

ROUGH TRANSITION TO A NEW ASTHMA INHALER
By Laurie Tarkan
Published: May 13, 2008
The New York Times
Millions of people with asthma and other lung diseases will have to switch inhalers by the end of the year. And for many, the transition will not be smooth.
The change — mandated by the federal government in 2005, to go into effect next Jan. 1 — is to comply with the 1987 treaty to protect the earth’s ozone layer. It bans most uses of chlorofluorocarbons, or CFCs, which are used as propellants in many inhalers.

CFC-free inhalers have been available for more than a decade. But four million to five million users have yet to switch, according to the consumer advocacy group Allergy and Asthma Network Mothers of Asthmatics.

For one thing, the old inhalers cost much less — an average of $13.50, or one-third the price of a CFC-free inhaler, which uses propellants called HFAs, for hydrofluoroalkanes. (CFC inhalers are generic; HFA inhalers are brand-name.) People with asthma use an average of three or four inhalers a year, but some patients use one a month.

Moreover, the new and old inhalers differ in feel, force and taste, and how they are primed and cleaned. Advocates for people with asthma say doctors and patients have not been educated about the changes.

“What the government failed to do is to mandate anyone to tell patients and physicians this transition was happening,” said Nancy Sander, president of the asthma group. “There is no education, no monitoring of patients, no financial assistance to patients who have to pay higher prices for the new drugs.”

As a result, she and others say, there have been unnecessary fears about the newer inhalers, preventable trips to the emergency room and even some hoarding of CFC inhalers.

Callers to a hot line run by Ms. Sander’s group have complained that when they were switched to the new inhalers, the differences between the two types were never explained. Many thought that their device was broken or that their symptoms were not being relieved by the new inhalers.

The Food and Drug Administration says that since January 2007 it has received 415 complaints about HFA inhalers’ costing too much or not working properly. After a public meeting last month in which doctors and patients said most people were unaware of the transition, the agency has been stepping up educational efforts, with several public service announcements expected by the end of this month, said Deborah Henderson, an official at the Center for Drug Evaluation and Research.

Both types of inhalers use albuterol, a short-acting medication that can prevent an asthma attack when used preventively — before exercising, for example — or at the first sign of breathing trouble.

But the cost difference has meant huge gains for drug companies. As people switched to HFA inhalers in 2006 and 2007, sales of all albuterol inhalers jumped from about $500 million to $1.1 billion, according to I.M.S. Health, a health care information company. Of the 40.5 million prescriptions written for albuterol inhalers last year, it said, about half were CFC and half were HFA inhalers.

And even though there are important differences between the four brands of HFA inhalers, some insurers cover only one of the four. Advocates say the higher cost may keep patients from buying inhalers or force them to cut back on other medications or switch to a less effective over-the-counter inhaler that uses epinephrine.

Several members of Congress are asking the Bush administration to require insurers, including the Medicare and Medicaid programs, to cover the new inhalers equally. Representative Steve Kagen, a Wisconsin Democrat who is also an allergy and asthma physician, said it was important “to make sure there’s as little co-pay as possible.”

The four HFA inhalers are Ventolin by GlaxoSmithKline, ProAir by Teva, Proventil by Schering-Plough and Xopenex by Sepracor. (Xopenex uses a different chemical, levalbuterol.) All companies have give-away programs for those in need and are providing free samples that doctors give to their patients. There is also financial assistance available through the Partnership for Prescription Assistance (1-888-477-2669).

Studies show that HFA inhalers are as effective as CFC inhalers and have the same rate of side effects. But if they are not used properly, patients will not get adequate doses. There are three critical differences.

HFA inhalers must be pumped four times to prime them — a number that was not so critical with the more forgiving CFC inhalers, said Dr. Leslie Hendeles, professor of pharmacy and pediatrics at the University of Florida. And each brand of the newer inhaler requires a different frequency of priming.

HFA inhalers have a weaker spray. “It’s very soft so people think it’s not working,” Dr. Stoloff said. Where CFC inhalers deliver a powerful force that feels as if the airway is being pushed open, the newer ones provide a warm, soft mist that also has a distinct taste.

They also require a slower inhale. “You have to take a nice slow, deep breath and hold it,” Ms. Sander said. If people worry that it’s not working, they may not take the second puff, may fail to wait the necessary 30 seconds between puffs or may take too many puffs. ,And their anxiety may rise, further constricting their airways.

HFA inhalers need to be washed with warm water and air dried once a week. The medication is stickier and will clog the hole, reducing the amount of medication the spray delivers.

There are also important differences among the brands, though some doctors simply write Albuterol HFA on the prescription, leaving the pharmacist to choose the brand. Only one, Ventalin, has a dose counter, which helps users keep track of how much medication is left. ProAir appears to be on many insurance companies’ lists of approved medications, but it has the softest spray, Dr. Stoloff said.

To read the full article, go to NY Times.com

Acknowledgement: thanks to Dr. Munitz for calling our attention to this article

from the FDA

This information reflects FDA’s current analysis of available data concerning these drugs. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue. Nor does it mean that FDA is advising health care professionals to discontinue prescribing this product. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.

FDA is investigating a possible association between the use of Singulair and behavior/mood changes, suicidality (suicidal thinking and behavior) and suicide. Singulair is a medicine in the drug class known as leukotriene receptor antagonists. Singulair is used to treat asthma and the symptoms of allergic rhinitis (sneezing, stuffy nose, runny nose, itching of the nose) and to prevent exercise-induced asthma.

Over the past year, the maker of Singulair, Merck & Co, Inc., has updated the prescribing information and patient information for Singulair to include the following post-marketing adverse events: tremor (March 2007), depression (April 2007), suicidality (suicidal thinking and behavior) (October 2007), and anxiousness (February 2008).

In February 2008, FDA and Merck discussed how best to communicate these labeling changes to prescribers and patients. Merck plans to highlight the recent changes in the prescribing information in face-to-face interactions with prescribers and provide prescribers with patient information leaflets about Singulair. The Singulair website includes the most current prescribing information and patient information for Singulair (www.singulair.com).

FDA is working with Merck to further evaluate a possible link between the use of Singulair and behavior/mood changes, suicidality and suicide in response to inquiries received by FDA. FDA has requested that Merck evaluate Singulair study data for more information about suicidality and suicide. FDA is reviewing the postmarketing reports it has received of behavior/mood changes, suicidality and suicide in patients who took Singulair.

Due to the complexity of the analyses, FDA anticipates that it may take up to 9 months to complete the ongoing evaluations. As soon as this review is complete, FDA will communicate the conclusions and recommendations to the public.

Singulair is an effective medicine that is indicated for the treatment of asthma and symptoms of allergic rhinitis. Patients should not stop taking Singulair before talking to their doctor if they have questions about this new information. Until further information is available, healthcare professionals and caregivers should monitor patients taking Singulair for suicidality (suicidal thinking and behavior) and changes in behavior and mood.

Other leukotriene modifying medications include zafirlukast (Accolate), which is also a leukotriene receptor antagonist and zileuton (Zyflo and Zyflo CR), which is a leukotriene synthesis inhibitor. FDA is reviewing postmarketing reports it has received of behavior/mood changes, suicidality and suicide in patients who took Accolate, Zyflo, and Zyflo CR and will assess whether further investigation is warranted.

This early communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs.

The FDA urges both healthcare professionals and patients to report side effects from the use of Singulair, Accolate, Zyflo, and Zyflo CR to the FDA’s MedWatch Adverse Event Reporting program

on-line at [www.fda.gov/medwatch/report.htm];
by returning the postage-paid FDA form 3500 [available in PDF format at [www.fda.gov/medwatch/getforms.htm] to 5600 Fishers Lane, Rockville, MD 20852-9787;
faxing the form to 1-800-FDA-0178; or
by phone at 1-800-332-1088

from Medscape:

Immunotherapy Prevents Asthma Over Long Term in Children With Allergic Rhinitis
News Author: Will Boggs, MD

August 10, 2007 ― Specific immunotherapy for allergic rhinitis in children prevents the development of asthma for up to 7 years after treatment ends, according to results of a follow-up of the Preventive Allergy Treatment (PAT) study.

The PAT study investigated whether the clinical effects of 3 years of subcutaneous specific immunotherapy persist in children with seasonal allergic rhinoconjunctivitis caused by birch and/or grass pollen allergy as they grow up. The results at 10 years after the start of treatment appear in the August issue of Allergy.

Dr. L. Jacobsen from ALK-Abello, Horsholm, Denmark and colleagues evaluated the primary clinical effect and secondary preventive effect on the development of asthma in 147 participants in the PAT study 7 years after termination of specific immunotherapy.

Among 117 children who were free of asthma at baseline, those treated with SIT were 4.6 times more likely than those treated with placebo to remain free of asthma during the 10 years of follow-up, the authors report.

Specifically, 24 of 53 control patients developed asthma, compared with 16 of 64 patients in the specific immunotherapy group.

The beneficial clinical effect on conjunctivitis and rhinitis following specific immunotherapy also persisted 7 years after completion of 3 years of treatment.

Neither group showed significant bronchial hyperresponsiveness after 5 or 10 years, the investigators say, and there were no differences between the treatment and placebo groups in bronchial responsiveness to methacholine (as measured by change from baseline).

“This 10-year follow-up study demonstrates that specific immunotherapy for 3 years with high-dose standardized allergen extracts shows persistent long-term effect on clinical symptoms after termination of treatment and long term, preventive effect on later development of asthma in children with seasonal rhinoconjunctivitis,” Dr. Jacobsen and colleagues conclude.

“In this light,” they write, “specific immunotherapy should be recognized not only as first line therapeutic treatment for allergic rhinoconjunctivitis but also as secondary preventive treatment for respiratory allergic disease.”

Allergy. 2007;62:943-948.

Reuters Health Information 2007. © 2007 Reuters Ltd.

I was recently embroiled in an online discussion with several pulmonary and primary care colleagues regarding the efficacy of Allergen Immunotherapy in the treatment of asthma and the future of sublingual immunotherapy, which I think is worth sharing. Let’s start off with some Frequently Asked Questions:
Whare are “Allergy Shots”?
Allergen immunotherapy or “allergy shots” is a form of treatment aimed at decreasing sensitivity to substances called allergens which were identified by allergy testing. Allergen immunotherapy involves injecting increasing amounts of these allergens to a patient over a period of time to decrease the patient’s sensitivity to the allergens, prevent development of new allergies, and in children, prevent progression from allergic rhinitis to asthma. Allergen immunotherapy can lead to long-lasting relief of allergy symptoms after treatment is discontinued.

How does Allergen Immunotherapy work?
Allergen immunotherapy works like a vaccine. Your body responds to injected amounts of a specific allergen by developing immunity or tolerance. There are two phases to immunotherapy: a build-up phase and a maintenance phase.

When will the allergy shots start working and when can I stop my meds?
The benefits of allergen immunotherapy, in terms of reduced allergy symptoms, can begin during the build-up phase but may take as long as 12 months on the maintenance doses. It is important to continue taking allergy medications as prescribed together with the allergy shots during the build-up phase. Later, when your symptoms improve, you may discuss with your doctor whether you can discontinue some of your allergy medications.
If you do not get your allergy shots on schedule, it will take longer to reach the maintenance dose and longer for the allergy shots to work effectively.

How long do I have to take the Allergy shots?
With currently available allergen extracts, maintenance treatment is generally continued for 3 to 5 years after the build-up phase, which can take up to 6 to 9 months. The majority of inidividuals experience lasting remission but a minority may relapse after discontinuing immunotherapy, therefore the decision to stop must be individualized.

How effective is allergen immunotherapy?
Immunotherapy is successful in up to 90-95% of patients with seasonal allergies and up to 85% of patients with year-round allergies.

Asthma is a multifactorial disease. Allergic rhinitis/ sinusitis has definitively been shown to contribute to the severity of asthma in patients. One of the modalities used to treat allergic rhinitis/ sinusitis and asthma is allergen immunotherapy (IT). By no means is anyone suggesting that allergen immunotherapy be used INSTEAD OF inhaled steroids, however allergen IT does have solid data to show its efficacy when used in conjunction with other modalities.

This is topic has been addressed by the American College of Allergy, Asthma, and Immunology in its position paper on the Cost Effectiveness of Immunotherapy for Asthma.

Regarding sublingual immunotherapy, there is considerable evidence that sublingual immunotherapy for allergic rhino-conjunctivitis has been effective using high doses of grass extract. This is commercially available and used in Europe, but has yet to have FDA approval in the USA. Some studies showing efficacy are cited below:
1. Calderon M, Essendrop M. Specific immunotherapy with high dose SO standardized grass allergen tablets was safe and well tolerated. J Investig Allergol Clin Immunol. 2006;16(6):338-44. 2. Nelson HS. Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol. 2007 Feb 8; [Epub ahead of print]
That being said, appropriate dosing and efficacy with multiple SL allergen combinations are still an issue.

The “sublingual immunotherapy” that is pure quackery has been used to treat “idiopathic environmental intolerance” (IEI) by means of “neutralizing” extracts administered as sublingual drops usually at such a miniscule dose that it is really only placebo. See the AAAAI position statement on this.

For a tragic example of the use of these “neutralizing sublingual drops” for treatment of IEI or “multiple chemical sensitivity syndrome” see the “Tragic Example” post on this blog.

Link: Allergen Immunotherapy Practice Parameters
AAAI Tips to Remember: What are Allergy Shots?
Table: Clinical Indications for Allergen Immunotherapy

HAPPY MOTHER’S DAY!
Classic Mr. T video: “Treat Your Mother Right”

from the AAAAI 60th Annual Meeting: NAEPP Expert Panel Report:

Asthma reportedly affects about 7% of pregnant women, and some research has suggested that these women are at an increased risk of preeclampsia or having a child suffer perinatal mortality, preterm birth, or low birth weight.

However, by controlling asthma, those risks are thought to be decreased, noted Michael Schatz, MD, chief of the Allergy Department at Kaiser-Permanente Medical Center in San Diego, California, and coleader of the panel committee. “We can do something about what medicines we use,” Dr. Schatz said during his presentation. “How you control the asthma makes a difference.”

The new guidelines discuss the need to intensely monitor women with asthma once a month during pregnancy, reduce any triggers such as allergens and smoke, and educate patients on the importance of asthma control.

Caution must also be taken in step-down therapy, Dr. Nelson said, with more care taken than usual in preventing flare-ups, or even postponing step-down therapy until the pregnancy is completed.

The new recommendations primarily focus on the pharmacologic treatment of asthma. Researchers reviewed a total of 6,113 articles in the medical literature published between 1990 and May 2003, analyzing 44 in depth.

The new recommendations are as follows:

For mild intermittent asthma, pregnant women should be prescribed short-acting inhaled beta2-agonists, preferably albuterol.; Previously, the recommended drug was terbutaline.