Drug Interactions between budesonide / formoterol and sargramostim

MONITOR: Glucocorticoids may potentiate the myeloproliferative effects of colony stimulating factors. The proposed mechanism has not been established. Glucocorticoids are known to mediate their immunosuppressive effects on target cells via binding to cytosolic glucocorticoid receptors, which leads to decreased expression of proinflammatory molecules and increased expression of anti-inflammatory molecules. However, in cases of neutrophil-dominated asthma, treatment with corticosteroids have been shown to promote neutrophil survival, leading to increases in airway tissue neutrophils and hence neutrophilic inflammation. Glucocorticoids have shown anti-apoptotic effects on different cell types in vitro, including human neutrophils, with dexamethasone inhibiting spontaneous neutrophil apoptosis in a concentration-dependent manner. Various mechanisms proposed for this observed inhibition of neutrophil apoptosis have included up-regulation of anti-apoptotic Bcl-2 family members, stabilization and induction of inhibitor of apoptosis proteins (IAPs), activation of nuclear factor kappa B (NK-kB), suppression of components of the extrinsic pathway of apoptosis, and induction of signaling molecules such as mitogen activated protein kinase (MAPK) phosphatase-1 and serum and glucocorticoid activated kinase-1 (SGK-1). However, the interaction has not been reported in the product labeling for the granulocyte colony stimulating factors (G-CSFs). In addition, it is unclear whether the interaction extends to inhaled corticosteroids. The clinical significance of this interaction for the granulocyte macrophage colony stimulating factor (GM-CSF) sargramostim has also not been established.

MANAGEMENT: According to the product labeling for sargramostim, patients receiving concomitant treatment with sargramostim and glucocorticoids may require more frequent clinical and laboratory monitoring for signs of excess myeloproliferative effects.

Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater risk of developing hypokalemia.