The following information addresses potential interactions with salmeterol. When used in fixed combination with fluticasone, consider interactions associated with fluticasone.   No formal drug interaction studies have been performed to date with the fixed combinations.  
Salmeterol and fluticasone are substrates for CYP3A4.   
Drugs Affecting Hepatic Microsomal Enzymes
Potential pharmacokinetic (increased peak plasma concentrations and AUC of salmeterol) and pharmacologic interactions (increased risk of adverse cardiovascular effects [e.g., QTc prolongation, palpitations, sinus tachycardia]) with concomitant use of potent CYP3A4 inhibitors.    Concomitant use of potent CYP3A4 inhibitors with salmeterol alone or in fixed combination with fluticasone not recommended.   
Specific Drugs
Drug
Interaction
Comments
Atazanavir
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects   
Concomitant use not recommended   
β2-Adrenergic agonists, short-acting
Potential for increased adverse cardiovascular effects, but such effects less likely with a selective β2-adrenergic agonist like salmeterol     
Safety of concomitant use of >8 inhalations of supplemental, short-acting β2-agonist therapy with salmeterol inhalation therapy not established 
β-Adrenergic blocking agents
Potential for antagonism of pulmonary effects and production of severe bronchospasm in patients with asthma or COPD     
If concomitant therapy required, consider cautious use of cardioselective β-adrenergic blocking agents   
Clarithromycin
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects   
Concomitant use not recommended   
Cromolyn sodium
No apparent alteration in safety profile of salmeterol oral inhalation when administered concurrently      
Diuretics, non-potassium-sparing
Potential for additive hypokalemia and/or ECG changes, especially when recommended β-agonist dose is exceeded    
Clinical importance unknown; however, use concomitantly with caution    
Indinavir
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects   
Concomitant use not recommended   
Itraconazole
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects   
Concomitant use not recommended   
Ketoconazole
Increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects    
Concomitant use not recommended   
MAO inhibitors
Potential for increased effect of salmeterol on the vascular system    
Extreme caution recommended with concomitant therapy or within 2 weeks following discontinuance of an MAO inhibitor    
Nefazodone
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects   
Concomitant use not recommended   
Nelfinavir
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects   
Concomitant use not recommended   
Ritonavir
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects   
Concomitant use not recommended   
Saquinavir
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects   
Concomitant use not recommended   
Telithromycin
Possible increased peak concentrations and AUC of salmeterol; possible increased risk of adverse cardiovascular effects    
Concomitant use not recommended   
Tricyclic antidepressants
Potential for increased effect of salmeterol on the vascular system    
Extreme caution recommended with concomitant therapy or in patients receiving salmeterol within 2 weeks of discontinuance of these agents    
Xanthine derivatives
Potential for increased cardiotoxic effects with concomitant administration of sympathomimetic agents and aminophylline but not theophylline   
No apparent alteration in safety profile of salmeterol oral inhalation observed when administered concurrently with theophylline in patients with asthma or COPD in clinical studies
 Salmeterol drug interactions (more detail)
