Drug Interaction Report

ADJUST DOSING INTERVAL: Anticholinergics, beta-agonists, and theophylline may inhibit the bronchial airway response to methacholine. Methacholine is a cholinergic agonist that binds muscarinic receptors in bronchial smooth muscle, which leads to bronchoconstriction. Since patients with asthma exhibit greater sensitivity to induced bronchoconstriction than healthy subjects, methacholine is used to diagnose bronchial airway hyperreactivity in the absence of clinically apparent asthma. Bronchodilation caused by anticholinergics, beta-agonists, and theophylline may counteract methacholine-induced bronchoconstriction, possibly leading to diagnostic failure.

MANAGEMENT: Treatment with anticholinergics, beta-agonists, and theophylline should be interrupted before methacholine administration for the following durations:
--Short-acting anticholinergics (e.g., ipratropium): 12 hours
--Long-acting anticholinergics (e.g., tiotropium): At least 168 hours
--Short-acting beta-agonists (e.g., albuterol): 6 hours
--Long-acting beta-agonists (e.g., salmeterol): 36 hours (some authorities recommend 48 hours for ultra-long-acting beta-agonists [e.g., indacaterol, olodaterol, vilanterol])
--Oral theophylline: 12 to 48 hours

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.