ADVAIR DISKUS ADVAIR - GlaxoSmithKline

man. The change was characterized by degeneration, mononuclear cell infiltration and a
predilection for localisation within the left atrium. This change was not observed in
earlier studies when the drugs were administered alone.
The lesion was present 48 hours after a single exposure, but had resolved completely and
was absent after 14 days. There were no associated rises in plasma enzyme activities
(aspartate aminotransferase, lactate dehydrogenase or creatine phosphokinase) 48 hours
after exposure. There were no large differences in heart rate or rhythm between rats
given salmeterol alone or in combination with fluticasone propionate, although animals
exposed to the combination showed slightly larger and more prolonged falls in blood
pressure. No atrial lesions occurred in repeat dose studies in rats.
This is considered unlikely to be of relevance to man because it has been reported in rats
after co-administration of other commonly used and clinically well-tolerated beta 2 -
agonists and corticosteroids.
Long-Term Toxicity
Findings from repeat dose inhalation toxicity studies of up to 13 weeks duration in rats
and dogs were generally as expected for the doses of salmeterol xinafoate and fluticasone
propionate administered, most being typical of beta 2 -agonist or corticosteroid excess.
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