HOSPITAL PRACTICE

Are generic albuterol inhalers an endangered species?

An official with the Food & Drug Administration gave an update on the phaseout of CFCs (chlorofluorocarbons) at the recent American Thoracic Society (ATA) conference in Seattle. Robert Meyer, M.D., director of the Office of Drug Evaluation II, division of pulmonary and allergy products, said the CFC phaseout is continuing as planned.

For the most part, the FDA has let the marketplace handle the phaseout. Many products have already been discontinued, such as certain vaginal, rectal, and cardiac spray formulations containing CFCs. Nasal corticosteroid inhalers also have been discontinued and replaced by nonaerosol sprays.

Regarding oral metered-dose inhalers (MDIs), manufacturers have been developing replacement products that use alternative propellants, Meyer said. So far, three CFC-free inhalers have been FDA-approved: Proventil HFA (albuterol, Schering), Ventolin HFA (albuterol, GlaxoSmithKline), and QVAR (beclomethasone, 3M Pharmaceuticals). Hydrofluoroalkane (HFA) is considered an acceptable alternative to CFC.

Other alternatives have been developed as well. Dry-powder inhalers (DPIs) are relatively new to the market. Some examples are fluticasone (Flovent Rotadisk, Glaxo), salmeterol (Serevent Diskus, Glaxo), and formoterol (Foradil, Novartis). Meyer said other MDIs, DPIs, and novel delivery systems are under evaluation.

While CFC-free versions of albuterol inhalers are now available, Meyer admitted albuterol presents a unique problem for the FDA. The main concern is that albuterol inhalers are so widely used. About half of all CFCs obtained in the United States go to make these inhalers. Another concern is albuterol is the only inhaled drug available generically. The FDA is not blind to the cost difference between the branded albuterol inhalers and the generics.

The agency is allowing albuterol inhalers to remain on the market despite their CFC content. For decades, albuterol has been on the essential product list, a list of CFC-containing medical products deemed medically necessary. However, the time may come when albuterol MDIs lose their exemption. Meyer said the FDA may deem some products nonessential even if no replacement is available. In fact, a group of organizations led by the American Lung Association (ALA) is lobbying to get albuterol removed from the essential list. Their argument is that CFC-containing inhalers are contributing to the depletion of the ozone layer, which can increase smog and aggravate asthma.

If ALA and others succeed, currently available generic albuterol inhalers could be removed from the essential list, giving patients no alternative but to buy the new HFA-containing brands. It will be several years before generics are available for these inhalers. Even if albuterol is not removed from the essential list, there is another problem. A Dutch company is the primary producer of pharmaceutical grade CFCs and will discontinue production in 2005. After that, a source is uncertain. The FDA is evaluating whether another supplier can and should be found to fill the void.

During the ATA conference, another FDA official discussed concerns about contamination of multi-dose vials (MDVs) and single-dose vials (SDVs) of inhaled drugs. Eugene Sullivan, M.D., division of pulmonary and allergy products, reported that several cases of bacterial contamination have occurred, resulting in serious infections. In one hospital, improper use of MDVs led to contamination of ventilators with Burkholderia cepacia. Twenty-eight people became ill due to this contamination, and seven of them died.

Upon investigation, the FDA found that at least one respiratory therapist was carrying an MDV in his pocket and using it for multiple patients. Similar outbreaks occurred in several other hospitals. In response, the FDA issued a Public Health Advisory recommending the use of one MDV per patient. The advisory suggested the albuterol should be diluted with saline in a disposable container before putting it into the nebulizer. The FDA is pursuing new labeling to reflect the recommendations and is suggesting manufacturers decrease the container size of MDVs.

Bacterial contamination is not the only concern about inhaled solutions. "All drug products may contain trace amounts of chemical impurities," said Sullivan. He explained that the plastic vials are permeable to some volatile chemicals, such as adhesives and solvents. Tests have, in fact, detected such chemicals in albuterol solutions, he added. The side effects that could result from inhaling the contaminated solutions are of concern to the FDA. People with atopic asthma are especially sensitive to irritants, and the impurities in albuterol solutions could trigger asthma attacks.

Just how many people could be affected by chemical contamination is impossible to say at this point. For now, the FDA has issued a draft guidance suggesting that vials be embossed rather than labeled and that some sort of nonaluminum foil overwrap be added around the vials. But removing the paper label raises another problem: an increased risk for drug errors because the embossed drug names are difficult to read.

Jillene Magill-Lewis, R.Ph.

The AUTHOR is a clinical writer based in Seattle.