4. Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for nebulized bronchodilators are summarized in Table 3. Only those drug-drug interactions classified as contraindicated or those considered life-threatening which have not yet been classified will be reviewed:

Table 3. Nebulized Bronchodilator Drug-Drug Interactions^1-11,14

Target Drug	Interacting Drug	Interaction	Recommendation	Clinical Significance Level
beta2-agonists	MAOIs+ (including linezolid)	concurrent administration of MAOIs with beta2-agonists may increase risk of  tachycardia, hypomania, or agitation due to potentiation of effects on vascular system	administer combination cautiously or within 2 weeks of MAOI discontinuation; observe patients for adverse effects	moderate
beta2-agonists	beta blockers	concurrent administration may decrease effectiveness of beta-adrenergic blocker or beta-2 agonists	combination not recommended in asthma/COPD patients; if adjunctive therapy necessary, utilize cardioselective beta blocker (e.g., atenolol, bisoprolol)	moderate
beta2-agonists	diuretics	potential for worsening of diuretic- associated  hypokalemia and/or ECG changes with beta2-agonist concurrent administration, especially with high beta2-agonist doses	administer combination cautiously; monitor potassium levels as necessary	moderate
beta2-agonists	QTc interval-prolonging medications (e.g., class I, III anti-arrhythmics, tricyclic antidepressants, dolasetron)	concurrent administration may increase risk of cardiotoxicity (e.g., life-threatening arrhythmias, cardiac arrest) as arformoterol and formoterol may cause QTc interval prolongation and, rarely, torsades de pointes	administer combination cautiously	major
glycopyrrolate	anticholinergics	concurrent administration may produce additive anticholinergic effects and potential for increased adverse effects	cautiously administer glycopyrrolate with other anticholinergics; monitor for increased adverse effects	moderate
ipratropium, ipratropium/racemic albuterol	antimuscarinics	concurrent administration may produce additive anticholinergic effects and potential for increased adverse effects	cautiously administer ipratropium with other antimuscarinics; monitor for increased adverse effects	major

Legend

• *CP = Clinical Pharmacology
• MAOIs = monoamine oxidase inhibitors
• ECG = electrocardiogram