Drug interactions between Combivent and theophylline

theophylline ↔ albuterol

Applies to:theophylline and Combivent (albuterol/ipratropium)

MONITOR: Concomitant use of a beta-2 adrenergic agonist with theophylline may result in additive risk and/or severity of hypokalemia and adverse cardiovascular effects such as palpitations, tachycardia, and blood pressure elevations. The interaction may be more likely when a systemic or nebulized formulation of the beta-2 agonist or a high dosage of theophylline is used. The resultant hypokalemia is often transient and not clinically significant; however, serious events including rare cases of cardiorespiratory arrest and intestinal pseudo-obstruction have been reported. In addition, since beta-2 agonists may sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. Pharmacokinetically, some beta-2 agonists given systemically may decrease the plasma concentrations of theophylline. Albuterol, isoproterenol, and terbutaline have been specifically implicated, usually increasing theophylline clearance by approximately 10% to 30%, although some studies with albuterol and terbutaline failed to demonstrate a significant effect on theophylline pharmacokinetics. The interaction also did not occur in studies with fenoterol, formoterol, and metaproterenol. A case report described a significant increase in theophylline clearance during intravenous administration of albuterol in a 19-month-old child with severe asthma. The patient required a threefold increase in theophylline dosage to maintain therapeutic serum concentrations. Theophylline clearance decreased by 50% upon discontinuation of albuterol.

MANAGEMENT: Although theophylline and beta-2 agonists are commonly used together to produce bronchodilation, it may be appropriate to monitor patient response as well as serum potassium level, blood pressure and heart rate during coadministration, especially if the beta-2 agonist is administered systemically. Close monitoring is particularly important in patients with severe asthma, since the potential increases in blood pressure and heart rate during coadministration of these agents may have more serious consequences in the presence of hypoxemia or hypercapnia due to increased myocardial oxygen consumption. Patients should be advised to notify their physician if they experience worsening of their respiratory condition or potential signs and symptoms of hypokalemia such as fatigue, weakness, myalgia, muscle cramps, numbness, tingling, abdominal pain, constipation, palpitations, and irregular heartbeat.