Drug interactions between Advair Diskus and hydrochlorothiazide/metoprolol

metoprolol ↔ salmeterol

Applies to:hydrochlorothiazide/metoprolol and Advair Diskus (fluticasone/salmeterol)

GENERALLY AVOID: Although cardioselective beta-blockers do not generally inhibit the bronchodilating effect of beta-2 adrenergic agonists, they may worsen pulmonary function in patients with asthma or other obstructive airway diseases. Cardioselective beta-blockers can occasionally precipitate acute bronchospasm in these patients, despite relative selectivity for beta-1 receptors in cardiac tissues. Presumably, beta-1 selectivity is dose-dependent and may be lost given a sufficient dose of the beta-blocker in susceptible patients. Other mechanisms may also be involved in bronchoconstriction that are unrelated to beta-2 blockade--for example, their effects on cholinergic M2 receptors and alpha-1 adrenoreceptors. Numerous single- and multiple-dose studies have been conducted in asthmatic and COPD patients with various cardioselective beta-blockers, including acebutolol, atenolol, bisoprolol, celiprolol, metoprolol, and nebivolol. Some reported no significant effects on pulmonary function or bronchodilator response to beta-2 adrenergic agonists, while others reported some negative effects on pulmonary function and/or airway hyperresponsiveness. Overall, a meta-analysis of more than two dozen studies found that use of cardioselective beta-blockers in patients with mild to moderate reversible airway disease produced no adverse respiratory effects or decreased responsiveness to beta-2 agonists in the short term. A meta-analysis of 19 studies conducted in patients with COPD by the same group of investigators reported similar results. However, little data exist regarding their safety during chronic use or use in patients with severe respiratory disease. There have been reports of worsening asthma and bronchospasm in patients receiving cardioselective beta-blockers including betaxolol (both systemic and ophthalmic) and esmolol. Several studies have suggested enhanced bronchosparing effects of celiprolol over other cardioselective beta-blockers due to its partial beta-2 agonistic and alpha-2 blocking activities. However, one study found no difference between celiprolol and nebivolol. A few studies also suggested a lower degree of beta-1 selectivity for acebutolol compared to other cardioselective beta-blockers. The clinical significance is unknown.

MANAGEMENT: Beta-blockers, including those with relative cardioselectivity, should generally be avoided in patients with bronchospastic diseases. However, given their demonstrated benefit in such conditions as heart failure, myocardial infarction, cardiac arrhythmias and hypertension, cardioselective beta-blockers may be administered with caution to those who do not respond to or tolerate alternative treatment. The benefits generally outweigh the risks in patients with mild or moderate reactive airway disease that is well controlled on inhaled corticosteroids and beta-2 adrenergic agonists, provided they have no prior history suggesting a predisposition to severe exacerbations. The dosage should start low, preferably in divided doses to avoid the higher plasma levels associated with longer dosing intervals, and titrated slowly according to therapeutic response and pulmonary function. Patients should be advised to contact their physician if they experience worsening of respiratory symptoms, which would warrant a reevaluation of the appropriateness of beta-blocker therapy. Cardioselective beta-blockers should be used with extreme caution, if at all, in patients prone to frequent exacerbations of their respiratory disease.

hydrochlorothiazide ↔ salmeterol

Applies to:hydrochlorothiazide/metoprolol and Advair Diskus (fluticasone/salmeterol)

MONITOR: The concomitant use of beta-2 adrenergic agonists and potassium-wasting diuretics 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. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or concomitant theophylline or corticosteroid therapy may be at a greater risk of developing hypokalemia.

MANAGEMENT: Caution is advised when beta-2 agonists are prescribed in combination with potassium-wasting diuretics. Serum potassium level and cardiovascular status should be monitored, especially if the beta-2 agonist is administered systemically or by nebulizer. Patients should be advised to notify their physician if they experience potential signs and symptoms of hypokalemia such as fatigue, weakness, myalgia, muscle cramps, numbness, tingling, abdominal pain, constipation, palpitations, and irregular heartbeat.