One day in 2007, Susan Combs was prescribed a different rescue inhaler. She saw no need for a change, but she wasn’t given a choice.
Befuddled and angered, Combs capitulated after doing basic Internet research on the device. She took some puffs from the ProAir HFA inhaler to open her airways.
“It made me wheeze more. … Using the inhaler actually aggravated my symptoms,” said Combs, 48, who has severe asthma and chronic obstructive pulmonary disease. She had heard the usual medical responses – the new inhaler just feels different because the mist is finer, it tastes different, it needs to be cleaned more – but none explained her problem.
Combs said she had to go on four more medications to get her breathing “back to where it was” before being switched to the new inhaler, which is the most commonly prescribed of four HFA inhalers on the market.
Rescue inhalers pump medicine to open the airways during breathing emergencies such as asthma attacks. The episodes are usually short-lived, but if breathing trouble persists, it can land a person in the emergency room.
Combs, who lives in LaPorte, has had asthma for more than 40 years and goes through rescue inhalers quickly. She consumed the medication in her new inhaler even faster, going through it in eight days compared with two weeks for previous inhalers.
And her problems were just beginning.
On Dec. 31, the Food and Drug Administration’s ban on the sale of rescue inhalers that use chlorofluorocarbons, or CFCs, took effect. The U.S. followed many other countries, as part of an international pact, in banning CFC albuterol rescue inhalers because of the dangers to the ozone layer.
The CFC units were replaced by FDA-approved inhalers that use hydrofluoroalkane, or HFA, to propel the active ingredient – a reformulated albuterol.
Inhaler problems
An examination of various records and Journal Gazette interviews with patients and medical professionals found:
•Some of the tens of millions who have asthma and other conditions requiring a rescue inhaler have done fine with their switch. But others have struggled.
•Those who struggle say the problems with the new inhalers include trouble catching their breath, itching and burning in their lungs, dizziness, vomiting and heart problems. One couple attribute the death of their daughter to the inhaler switch.
•At least two of the four HFA albuterol inhaler makers report certain side effects occur more frequently than with the CFC inhaler alternatives. One company reports in a study that its HFA inhaler is, by certain measures, less effective than the CFC version.
•Most physicians and pharmacists interviewed for this story, including local health care professionals, said the inhalers seem comparable and the transition has been relatively smooth. But two doctors said HFA inhalers generally perform worse than CFC inhalers.
Combs, who lived in Arizona in 2007 when she was prescribed ProAir, which is made by Israel-based Teva Pharmaceutical Industries Ltd., tried other HFA inhalers.
After using one, Combs said her potassium levels dipped, her lungs felt slimy and heavy, she caught a serious upper-respiratory infection and suffered from vomiting, headaches and dizziness.
Another inhaler opened Combs’ airways, but she began having non-stop chest pain and heart palpitations. Her cardiologist, finding the left side of Combs’ heart enlarged, ordered her to immediately stop using the inhaler. Her last HFA inhaler option made her feel dizzy and gave her “really bad shakes.”
Today, Combs uses Ventorlin, a CFC albuterol rescue inhaler made by GlaxoSmithKline (not to be confused with the company’s Ventolin HFA). She buys her CFC inhalers from an online pharmacy in India.
She also uses a nebulizer – a medical device that delivers liquid medication in the form of mist – to stretch her supply of Ventorlin.
Not alone
Although it is illegal to sell or distribute CFC albuterol rescue inhalers in the U.S., federal law doesn’t penalize those who buy or use the inhalers, according to the Environmental Protection Agency, which is charged with enforcing the Clean Air Act.
An FDA official said patients should use caution when buying inhalers outside the U.S. as “the safety and efficacy of these products cannot be assured.”
Arthur Abramson is an insurance analyst in San Francisco with a bulldog’s tenacity and a researcher’s bent. The biology major, a self-described political junkie, has spent two years poring over meeting notes and scientific studies, calling doctors and pharmacists, swapping stories with fellow asthmatics and other inhaler users.
In March 2007, he met Combs in an online forum where participants were venting about HFA inhalers and the pending CFC inhaler ban. Abramson and Combs joined forces to co-found The National Campaign to Save CFC Asthma Inhalers, or SaveCFCinhalers.org.
“He has been a true crusader for all of us,” Combs said.
Abramson and Combs have collected more than 4,300 signatures on a petition calling for congressional and presidential action to overturn the CFC albuterol inhaler ban. The message is getting to some lawmakers.
“We have heard from a number of Hoosiers,” said Mark Hayes, Indiana press secretary for Sen. Richard Lugar. “The senator’s aware of the situation and studying it closely.”
But few expect wide-sweeping changes.
Smooth transition
Tyiesha Ginn, 17, switched from a CFC albuterol inhaler about three years ago and describes it as fairly uneventful. The Fort Wayne teenager said her Proventil HFA worked better than the old one.
“When (I would) use the CFC inhaler it wouldn’t work right away,” Ginn said. “I had to wait a couple minutes.” But the Proventil HFA inhaler worked immediately.
A severe asthmatic, Ginn said she was using her CFC inhaler at least once a day. Her physician, Pushpom James, put her on two maintenance medications about the same time so she wouldn’t have to use her rescue inhaler as much. Ginn now uses her HFA inhaler about once a week.
James is a pulmonologist and medical director of the Pediatric Pulmonary and Cystic Fibrosis Clinic at Lutheran Children’s Hospital. She has helped more than 2,000 patients switch to HFA rescue inhalers.
At first, James said she heard some complaints from patients who said the inhaler didn’t feel as if it was working, but those concerns didn’t persist.
James said patients shouldn’t rely heavily on inhalers; those who need more than two doses a week should be on maintenance medication. James didn’t dismiss other’s concerns about HFA inhalers but said numerous factors could contribute.
“I just don’t think that they’re in good condition if they’re needing so much HFA product.”
Doctors differ
Steven Myers, a family practitioner in Raleigh, N.C., thinks CFC inhalers are more effective. Myers, an asthmatic for 35 years, said HFA inhalers provide a slower response and shorter relief than older inhalers.
Myers, who works in urgent care, thinks the forced switch to HFA inhalers has led to more emergency room visits.
Even cleaned regularly, HFA inhalers are not as efficient as CFC inhalers, echoed another physician.
Many of the patients who see Michael Light, a pulmonologist and professor of medicine at the University of Miami in Florida, have cystic fibrosis. Light prefers to prescribe the rescue medication Maxair Autohaler, which uses pirbuterol instead of albuterol as its active ingredient.
Produced by Pennsylvania-based Graceway Pharmaceuticals LLC, it’s the only CFC rescue inhaler still on the market. A proposal by the FDA and EPA could ban it as early as Dec. 31.
Michael O’Connor, attorney for Graceway, said he didn’t know whether it would be pulled from the market. Graceway is developing an alternative CFC-free inhaler with a goal of making it available by 2015.
O’Connor said he knows of no published studies comparing albuterol inhalers and Maxair’s pirbuterol. But, he said, there is anecdotal evidence that not everyone responds the same to both.
An issue of studies
Abramson, of SaveCFCInhalers.org, says the HFA rescue inhalers were never tested on severe asthmatics and other pulmonary patients, such as those with chronic obstructive pulmonary disease, cystic fibrosis or lung cancer.
“Large U.S. postmarketing studies of HFA inhalers should have been done to ensure patient safety,” he said, “but they were never done.”
The FDA, however, maintains that HFA inhalers are a suitable alternative to the CFC inhalers.
An article two years ago in the New England Journal of Medicine said patients who switched to the newer HFA inhalers had “similar patterns of reported adverse events” as they did with the CFC inhalers. The article also said postmarketing studies have shown no increase in hospitalization rates associated with use of HFA inhalers.
Though they cost more, the article said, the inhalers, when used correctly, are similar in effectiveness and safety to CFC inhalers. The HFA inhalers are brand names and generally cost about $30 to $60 without a coupon. They replaced generic CFC inhalers, which cost $5 to $10.
But other evidence indicates HFA inhalers are less effective and have side effects that occur more frequently.
Side effects with Proventil HFA – the second-most commonly prescribed HFA rescue inhaler – and albuterol CFC inhalers are similar, according to a clinical study detailed on Schering-Plough Corp.’s Web site.
But, “rapid heart beat, vomiting, chest pain, and palpitation occurred more frequently with Proventil HFA,” the site says.
Julie Lux, a company spokeswoman, said Schering-Plough reports complaints of adverse events to the FDA. Lux said the company has worked to educate patients and smooth the transition to the new inhalers. She urged people to consult with their doctors.
But opponents of the CFC inhaler ban say smoothing the transition includes glossing over disparities among the different inhalers.
Light said salespeople promoting the ProAir HFA inhaler aggressively downplay potential patient complaints. Light said he tends “to believe the patient before the drug company.”
Denise Bradley, a spokeswoman for Teva Pharmaceutical, which makes ProAir, said the company’s representatives try to educate physicians, patients and pharmacists. The company also takes “all patient feedback seriously,” she said.
“Much patient feedback has gone into our education materials so we can best answer all patient questions on the transition,” Bradley said.
In a new-drug application in 2000 for another HFA inhaler, GlaxoSmithKline detailed differences between its Ventolin HFA inhaler and the CFC albuterol inhaler.
The application said the HFA inhaler “raised no safety concerns in pediatric, adolescent, and adult patients.” But, it continued, “Throat irritation and cough were seen in slightly greater numbers of albuterol HFA patients than either placebo or CFC albuterol controls.”
A clinical comment a few pages later said “unfavorable changes in physical examinations were observed in the ears, nose and throat” for 13 percent of those studied in the albuterol HFA group. That was more than 2.5 times the rate of unfavorable changes observed in the albuterol CFC group.
In its conclusion, the application says effectiveness is comparable between the two inhalers but notes less improvement for some patients using the HFA inhaler, a longer time before the HFA inhaler takes effect, a shorter duration of effect and an increased rate of clogging.
