Drug Interactions between budesonide / formoterol / glycopyrrolate and smallpox vaccine

GENERALLY AVOID: The administration of live virus smallpox vaccine during corticosteroid therapy may be associated with a risk of localized or disseminated infection due to enhanced replication of vaccine virus in the presence of diminished immune competence. Patients receiving high dosages of systemic corticosteroids (e.g., greater than 20 mg/day or 2 mg/kg/day of prednisone or equivalent for more than 2 weeks) and those who are systemically immunosuppressed due to long-term topical or aerosol use of corticosteroids may also have an increased risk of neurologic reactions to vaccines and decreased or suboptimal immunologic response due to antibody inhibition. The risk of ocular complications may be increased in patients who are using ophthalmic corticosteroids.

MANAGEMENT: Routine nonemergency smallpox vaccination is considered a relative contraindication in patients receiving immunosuppressive corticosteroid therapy or ophthalmic corticosteroids. Vaccination should be deferred until after such therapy is discontinued and immune function has been restored. The interval depends on the dosage, duration, and route of corticosteroid therapy administered, but may be at least 3 months in most cases of systemic corticosteroid use. In patients who have recently been vaccinated, high-dose corticosteroid therapy should not be initiated for at least 2 weeks. Household contacts of immunosuppressed patients should also not be vaccinated. However, there are no absolute contraindications to vaccination if a high-risk exposure has occurred. In an outbreak emergency, smallpox vaccine is generally recommended for all persons, regardless of medical conditions. The risk for experiencing serious complications from the vaccine should be weighed against the risk of acquiring a potentially fatal smallpox infection. Vaccines may generally be administered to patients receiving corticosteroids as replacement therapy (e.g., for Addison's disease).

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.