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Friday, June 20, 2008

New FDA Policy Endangers Respiratory Patients

"...Your inhaler may be changing."

This is the quasi-advertising slug that has been making the medical community rounds for the past year or so. If you’re one of the 10 million Americans living with asthma, you may have seen it. But what you probably don’t know is that this change could actually kill you.

Earlier this year, the US Food and Drug Administration made the first major alteration in decades to all aerosol respiratory illness medications in this country by replacing the standard CFC aerosol propellants with a new propellant formulation known as “HFA". The change was made across the board -- CFCs were replaced by HFA without any alternative.

So what's wrong with switching CFCs to HFA? According to the growing preponderance of anecdotal evidence at The National Campaign to Save CFC Inhalers, HFA is making far too many people very, very ill. Reported problems with HFA inhalers run the gamut from ‘my medication doesn’t seem to be working as well’, to causing major upper respiratory and even system-wide infections requiring hospitalization and months of recuperation.

Rescued by an Inhaler

It goes without saying that the FDA is supposed to be tasked with ensuring the safety of all prescription medications. In the United States alone, more than 35 million chronic respiratory patients depend on FDA-approved prescription inhaled medications to achieve a reasonable quality of life. Diseases that make up the chronic respiratory category include asthma as well as COPD (chronic obstructive pulmonary disease), emphysema, tuberculosis, cystic fibrosis, lung cancer, pneumonia, and aspergillosis.

For the majority of the above patients, albuterol (also called salbutamol) has been the drug-of-choice in an emergency situation for decades. Most patients carry albuterol “rescue inhalers” with them at all times. Rescue inhalers mean a world of difference in a person’s day-to-day quality of life. Almost all respiratory patients will unfortunately have an emergency of the type rescue inhalers are designed to address. For some reason or another, their illness suddenly becomes extremely acute and immediate medication intervention is required no matter where the patient is at the time. With a simple rescue inhaler on hand that works, the acute condition of the moment is usually resolved before major medical care is required. Without a rescue inhaler that works as advertised at that moment, hospitalization and even death is a possibility.

Albuterol CFC rescue inhalers have provided this service consistently, and patients have been able to trust this medication to work for decades. The wholesale change to HFA by the FDA leads one believe that the FDA has rigorously determined that the new inhalers will do likewise. But in practice, are HFA rescue inhalers working when a patient really needs them -- in a major breathing emergency? The growing evidence is "no", but pinning down just how well HFA does perform has been difficult due to the broad range of patient complaints.

It isn't surprising there are so many nebulous complaints regarding the effectiveness of HFA inhalers. It’s hard to determine if someone is having adverse reactions to HFA because at the same time one is breathing in the propellant that might be an irritant, one is also breathing in the medication that counteracts the symptoms of the irritation. Just how well the medication masks an irritating effect from the propellant can vary wildly from person to person, and from moment to moment. If a person is pretty healthy, they might not notice the irritant much. However, if someone’s immune system gets run down by an illness or stress, normal "irritants" tend to get more irritating at an almost exponential rate.

Unless cause and effect is very clear, after using an HFA inhaler the patient doesn’t know what factors have combined in what amount to make them breathe as well as they are at that moment. Many patients’ complaints with HFA stem from a simple comparison of their old CFC inhalers with the new ones. Some complaints arise when a patient actually goes into anaphylaxis due to using an HFA inhaler. Often their life was saved by an old CFC inhaler that happened to be nearby.

There is very little hard scientific data on HFAs vs. CFCs in actual respiratory patients because the majority of the published clinical data was done on healthy people -- people for whom lung irritation is not an issue. However, in a UK field study done at the time albuterol/salbutamol HFA inhalers were released in the United Kingdom, MDs monitoring their use by actual respiratory patients found that four times the number of patients who had trouble tolerating CFC inhalers were made ill by HFA. (CFC intolerance is less than 1% of the patient population.) That makes at least one fact-based HFA intolerance estimate around 4%, or 1.4 million Americans. This number is probably low since understanding of just what problems are being caused by HFA verses normal external influences weren’t even under consideration at the time.

Midway through this year, most major pharmacies and mail order services have already switched to the FDA-approved HFA replacements exclusively, leaving patients who are having trouble with HFA inhalers to scramble for the remaining CFC inhalers on the market. According to FDA mandate, all CFC inhaler production must cease on December 31st, 2008 leaving HFA-sensitive patients without any legal options.

The War Over CFC Replacement

Albuterol inhalers have been available as generics in the in the US for decades. This medication alone was a $400 million dollar annual business even then. The CFC phase-out was an obvious opportunity for drug companies to return the medication's new formulation to a patented status. Which ever company(ies) got their hand of the FDA's approved replacement stood to find themselves with a huge cash cow in the making.

The political struggle over which large US pharmaceutical company would get the lucrative monopoly on CFC replacements started more than a decade ago. There are two types of inhaler technology currently in use worldwide: ‘metered dose inhalers’ [MDIs] that require a propellant, and ‘dry powder inhalers’ [DPIs] that use turbulent air flow caused by the patient breathing in to disperse the medication – this means no propellants are needed. Glaxo Smith-Kline was fast off the mark, introducing an albuterol DPI under the brand name Ventolin Rotacaps in 1989. Clinical studies found Ventolin Rotacaps as efficacious as their CFC counterparts.

So what happened to Glaxo’s Rotacaps system? It lost out in the ensuing political dog fight and Glaxo discontinued production everywhere in 2003. When the fur finished flying, the FDA approved four “branded” albuterol MDIs only. Schering-Plough has been the biggest winner so far. Their Proventil HFA has absolutely dominated rescue inhaler sales in the United States this year. Today, albuterol has not only been moved from generic back to proprietary and the financial cost to patients tripled or quadrupled, but there will be no legal alternatives to HFA in the United States come January 1, 2009.

HFAs vs. CFCs in the Environment

It's been fairly universal knowledge that chlorofluorocarbons are "bad" for decades, but the reasons why are a complex mix of chemistry and physics. There are a number of published theories involving the exact photochemical processes by which CFCs produce damage to the protective, UV-blocking ozone [O3] layer of the Earth’s atmosphere. It's safe to say that today in 2008, most of the scientific community believes that CFCs are still a major contributor to the infamous O3 “hole”. The public education campaign against CFCs dates back to 1987, when the Montreal Protocol on Substances that Deplete the Ozone Layer was enacted. At that time, worldwide CFC emissions were on the order of 1.2 million tons per year. However, the medical use of CFCs has been almost negligible since it began to be measured. At peak use, CFC inhalers have accounted for a maximum of just 0.83 % of the 1987 total. In the United States, CFC inhalers account for less than 0.3 % annually.

It’s political and career suicide to fight the “all CFCs bad” paradigm. Yet, there are scientists and learned folks out there who have quietly run their numerical models with the result that CFC MDI use has no appreciable degrading effect on the ozone layer. Getting them to speak up has been no easy matter.

When the Clean Air Act was updated in 1991 to address the Montreal Protocol, chlorofluorocarbons in aerosols were slated to be phased out world-wide by 2010, including when being used in medical necessities. The assumption was that technology would provide a new propellant as good as or better than CFCs before the drop-dead date was reached. It’s now 2008, and the new technology lung patients are forced to accept is HFA or the highway – there are no alternatives.

Making matters worse, ethanol -- a toxic, Class 3 residual solvent produced from corn and known to cause the actual constriction of airways in lung patients -- is added to three of the four most common HFA rescue inhalers in amounts varying from 10%-14% by weight. Yet the FDA has issued assurances that the ethanol in HFA inhalers is present in amounts too small to cause any danger. So just how much is too small? Ask the person who nearly dies from anaphylaxis because the snack they just ate doesn’t contain peanuts but may contain ingredients from a plant that processes peanuts.

And what about DPIs? With no propellants needed, it might seem like DPIs are the best solution to the problem of getting respiratory patients their medication. Unfortunately, there are millions of Americans whose normal day-to-day lung function is not strong enough to breathe deep enough to make a DPI effective for them. MDIs, and therefore propellants, are necessary.

Fighting the Government to Breathe in 2009

When all is said and done, the bottom line is that until the FDA acknowledges the HFA debacle and approves another form of albuterol MDI, the average respiratory patient cannot rely on HFA products for a rescue inhaler. To be truly safe, patients should always carry a nebulizer -- a mechanical air pump that disperses liquids for aspiration -- with liquid albuterol or epinephrine ampules for emergencies. Comparatively, nebulizers are big, bulky, and inconvenient.... and if toting a nebulizer around everywhere won't be making a serious a dent in your quality of life, who knows what does.

Meanwhile, albuterol DPI rescue inhalers are available by other manufacturers throughout the rest of the civilized world except North America for literally pennies on the dollar that Schering Plough is making with Proventil HFA.

Respiratory patients who want to fight back find themselves facing the some of the biggest, ugliest and nastiest bureaucracies, monopolies and politicos out there: the FDA, the EPA, the US pharmaceutical money-making monster, and even the Corn lobby-from-hell. The battle may look impossible, but this is about the quality of life, and possibly even death for 35 million Americans.

If you or someone you know wants to fight back, The National Campaign to Save CFC Inhalers is a great place to start.

Just Transition ‘Em

Finally, according to this slick and likely expensive Patient HFA Transition Guide for MDs, there are just four simple steps to transitioning all respiratory patients to HFA inhalers:

1. IDENTIFY patients that currently use CFC bronchodilators.
2. INITIATE discussion and inform patients of their HFA treatment options.
3. INSTRUCT patients about new use and care directions.
4. TRANSITION your patients.

Amazingly simple, isn't it?

Posted by PetraFried in the City 6/20/2008 09:36:00 AM