Patients using the CFC-free fluticasone inhaler developed by Glaxo Wellcome may receive an inadequate drug dose if they are transferred from the CFC-containing inhaler on a "dose for dose" basis, researchers in Scotland have suggested.
Professor Brian Lipworth and colleagues, from the asthma and allergy research group, Ninewells hospital and medical school, Dundee, believe that direct switching with no dose change, as recommended by the manufacturer, may be inadvisable.
Glaxo Wellcome's fluticasone propionate CFC-free inhaler uses hydrofluoroalkane-134a (HFA) as propellant. It is not yet available in the UK but it is licensed in several European countries. In the Lancet this week (1999;354:1357), the Dundee researchers report a study they carried out in 16 healthy volunteers to compare the CFC and HFA formulations, given in doses of 500, 1,000 and 2,000mg daily, from inhalers delivering a 250mg nominal dose. Lung bioavailability of the CFC product was about two-fold greater than that of the HFA product in terms of markers of adrenal suppression.
The researchers say: "We were unable to directly extrapolate our data on relative lung bioavailability in healthy individuals to the anti-inflammatory activity in asthmatic patients, although intuitively a lower degree of therapeutic efficacy would be predicted for a given labelled dose of the HFA formulation."
Speaking to The Journal on October 19, Professor Lipworth said that he felt there was a real danger that patients could have a relapse of their asthma if the swap was made on a one to one basis.
In response, Glaxo Wellcome said that Professor Lipworth's data were not consistent with those of the trials it had carried out, all of which had shown that a dose for dose switch was appropriate. This trial data had been submitted to the Medicines Control Agency.
Professor Lipworth is also concerned over dose equivalence of CFC and HFA beclomethasone inhalers. The issue here is the reverse of that with fluticasone in that he believes that the HFA product delivers more steroid than the CFC product.
Only one beclomethasone CFC-free inhaler is marketed so far in the UK. This is 3M's Qvar, which, because of bioavailability differences, is licensed for use at half the dose of CFC-containing beclomethasone inhalers. Baker Norton and Glaxo Wellcome are developing beclomethasone inhalers that are intended for direct "dose for dose" switch. Professor Lipworth said that his group had compared the Baker Norton HFA inhaler with a standard CFC-containing beclomethasone inhaler and found that the new inhaler provided twice the lung dose. Systemic bioavailability would thus be higher. The study was to be published next month.
He thought that, on safety grounds, a halving of steroid dose on transfer, as for Qvar, was probably indicated.
Professor Lipworth suggested that pharmaceutical companies were not carrying out proper dose response studies when assessing dose equivalence.
A spokeswoman for Baker Norton said that the company had trial data showing equivalence of its beclomethasone CFC and HFA inhalers and new gamma scintigraphy data, not yet published, backing the claim. She also pointed out that the HFA inhaler had been available in Eire for over a year with no reported problems.