Abstract
ABSTRACT
International guidelines recommend inhaled therapy over oral therapy for asthma because of greater efficacy and safety. Metered-dose inhalers (MDIs) are the delivery system of choice for the majority of patients with asthma. They have been well tried and tested and proven to be safe, reliably delivering a reproducible and precise dose, and account for 85% of the 400 million inhalers currently sold worldwide.
Current products using chlorofluorocarbon (CFC) 11/12 as the propellant are being reformulated. Under the Montreal Protocol, CFCs are to be phased out worldwide, though MDIs have been granted temporary exemption, thus far until 1997.
Two propellants, hydrofluoroalkane (HFA) 134a and 227, have been identified by the pharmaceutical industry to replace CFCs. However, they have different properties and reformulation has been difficult in relation to surfactants, valves and elastomeric seals. The manufacturing process has been re-engineered to take place at high pressure, because at normal pressure HFA 134a is a gas, in contrast with CFC 11 which is a liquid at room temperature.
Glaxo has carried out an extensive toxicological assessment of HFA 134a and thorough clinical testing has shown it to be well tolerated. To date they have carried out safety and efficacy testing on reformulations of salbutamol, salmeterol and fluticasone propionate (FP).
Single-dose studies of salbutamol, 200μg, with HFA134a have been shown to provide equivalent protection against bronchial provocation by histamine in both adults and children with asthma when compared with the currently available CFC preparations. In a subsequent 4-week study, both formulations had similar effects on morning peak flow and the patients believed that the two preparations were equivalent. Single doses of salmeterol, 50μg and 100μg, provide equal protection against bronchial provocation by methacholine compared with the respective dose of the current CFC formulation. A 4-week study comparing both preparations showed equivalent effect with similar improvements in morning peak flow for both preparations.
A double-blind study has compared FP, 250μg twice daily, with HFA 134a and the current CFC formulation in moderate asthmatics previously taking up to 800μg a day of inhaled corticosteroid. Morning peak flow improved by approximately 20 L/min in both treatment groups.
Monitoring of adverse events and clinical and laboratory test data has shown a very similar profile for safety and tolerability of HFA 134a formulations when compared with current CFC formulations, with no new or unexpected adverse events in over 2000 patients.
Both propellants will be available during the transition period. Doctors and patients will continue to see the need for MDIs and they will remain the most widely used delivery system for asthma therapy into the next millennium.
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