LOS ANGELES - While the Food and Drug Administration (FDA) is working to phase out the use of chlorofluorocarbons (CFCs) in metered-dose inhalers (MDIs), one alternative is showing promise. In fact, HFA134A may provide better drug delivery than CFCs.
"The Montreal Agreement said that the production of CFCs would be banned by January 1996. MDIs received an exemption from this law until alternative delivery systems could be found. However, the exemptions are temporary, and we are undergoing a transition to make alternative delivery systems. The FDA is committed to this," said Gary S. Rachelefsky, MD, clinical professor and codirector of the allergy clinic at UCLA and associate director of the allergy and immunology training program.
According to Rachelefsky, the pharmaceutical industry is accelerating the development of dry powder devices and is changing the propellants in MDIs. "To substitute the propellant, we must have the same convenience we have now, the same route of delivery, the same indications, the same populations and the same degree of safety and efficacy," he said.
Chloride is the part of CFCs that is dangerous to the ozone layer. The major propellant that has been developed is HFA134A, which has fluorides but no chlorides.
However, unexpectedly, when the pharmaceutical industry used the propellant in an MDI, it changed the whole MDI. Fortunately, it appears as though it changed the MDI for the better. "It changed the delivery of the drug, and it changed how the drug worked in terms of size of particles. There were so many changes that, basically, a new drug was developed when they changed the propellant," he explained.
One change is that the valve was moved closer to the patient. Loss of prime occurs when the propellant evaporates after a period of not being used. The further the valve is away from the patient, the greater the chance that the medicine will evaporate.
"When HFA134A was used, it improved the technology of the delivery of drugs. When you use an MDI that has CFC in it, you get a jolt. Cold medicine hits the back of your throat and frequently causes coughing. When they changed the propellant, the spray became less forceful and less irritating to the upper airway," Rachelefsy said. "Then, it was noticed that if you leave a CFC MDI anything but uprightif it lies flat for four hoursmuch less medicine comes out in the first dose. With the HFA134A propellant, there is no loss of dose no matter how the MDI is positioned."
Additionally, the dose will be consistent until the medicine is gone. This was a problem with CFC inhalers. If there was not much medicine left in the MDI, patients would often not get an adequate dose.
HFA134A is also able to tolerate cold temperatures. "CFCs do not work in cold air. The propellant freezes and must be thawed out. HFA134A works in any temperature. Additionally, the temperature of the plume or the spray with the HFA134A is 56°F or 57°F; it is much lower with CFCs. This is one reason why patients often cough after using a CFC MDI," he said.
Although HFA134A appears promising, the phase out of CFCs is still a couple of years away. The FDA has said that three alternative products must be found before the phase out of CFCs will begin.
"The problem with inhaled corticosteroids is that, even though they are in the same therapeutic class, they are different compounds. So each individual product needs to be examined, rather than grouping them by therapeutic class," he said. "Also, before the phase out can begin, there must be an adequate supply available in the United States, and there must be one year of marketing to make sure that they're used and they're safe. These drugs really need to be studied as new drugs".
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