Has weight gain been reported as an adverse reaction to fluticasone/salmeterol-inhalation therapy?/

Fråga: Has weight gain been reported as an adverse reaction to fluticasone/salmeterol-inhalation therapy? Background: An asthmatic female patient has been treated with Seretide inhalations (fluticasone 250 ug and salmeterol 50 ug, twice daily) for five months. Five weeks ago, it became evident that the patient had gained 5 kg in weight. At a follow-up appointment about two weeks later, her total weight gain had increased to 16 kg. The patient has experienced problems with excessive weight gain previously (during pregnancy).

Sammanfattning: Inhalation steroids have indeed been associated with weight gain, which is reported to be reversible upon drug withdrawal or dose adjustment in some cases. However, to date, there is no data on fluticasone and weight gain.

Svar: Weight gain is a known dose-dependent side effect of oral corticosteroid therapy (1). Questions about weight gain and inhaled corticosteroids have been previously answered in Drugline (2, 3). In summary, an association between budesonide and weight gain was found, which can sometimes be excessive (> 20 kg), but appeared to be reversible upon drug withdrawal or lowering of the dose in some cases (see below).

To date, 11 cases of weight gain (eight men and three women) associated with budesonide (Pulmicort) are listed in Swedis (the Swedish Drug Information System) (reference 4). Five of these improved (ie weight loss) after cessation of the steroid and continued medication with beta2-agonist only. In another case, weight gain was observed as both salmeterol and budesonide were withdrawn. This is the only case in Swedis where salmeterol has been associated with weight gain, and in light of the other reports, it seems more likely that budesonide was the causative agent here.

There are no reports in Swedis, or in the scientific literature, concerning fluticasone and effects on body weight. However, the risk of systemic effects is evident with this drug, where growth- and adrenal suppression by inhaled fluticasone has been described (5, 6).

There have been speculations about a potential role of adrenergic agonists in weight-reduction therapy, in particular appetite reduction by ephedrine (7, 8). Anabolic actions have also been proposed, where especially long-action beta2-agonists such as salmeterol were suggested to cause skeletal muscle growth in rat (9, 10). In summary, the possible impact of adrenergic agents on body weight in humans, is not clear.

Finally, we recommend this case be reported to SADRAC (The Swedish Adverse Drug Research Advisory Committee).