Table 7: ICS Drug-Drug Interactions

Target Drug Interacting Drug Interaction Recommendation Clinical Significance Level+
budesonide, budesonide/salmeterol, fluticasone, fluticasone/salmeterol,fluticasone/vilanterol, mometasone, mometasone/ formoterol strong CYP3A4 inhibitors (e.g., azole antifungals, erythromycin, clarithromycin, protease inhibitors) potential for increased steroid concentrations with risk for excessive adrenal suppression and Cushing syndrome development concurrent administration not recommended by Advair HFA®/Advair Diskus®, Flovent® Diskus by manufacturers; Flovent® HFA not recommended with ritonavir; for all others, adjunctively administer combination cautiously; monitor patients for signs/symptoms of corticosteroid excess budesonide, mometasone: 3-moderate; fluticasone: 2-major (CP) budesonide: major, moderate; fluticasone: major (DrugReax)
steroids quinolones increased potential for serious tendonitis, tendon rupture with concurrent therapy closely monitor patients requiring combination therapy; discontinue quinolone if tendon pain develops 3-moderate (CP)
systemic steroids bupropion potential increased seizure risk due to systemic steroid-induced lowering of seizure threshold utilize only recommended bupropion dosages; initiate bupropion therapy with low doses and titrate slowly when combination therapy warranted; closely monitor patients for seizure development major (DrugReax)
budesonide/ formoterol, fluticasone/salmeterol, fluticasone/vilanterol,  mometasone/formoterol MAOIs* (including linezolid) concurrent administration of MAOIs with beta 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 major (DrugReax) 1-severe (CP)
budesonide/ formoterol, fluticasone/salmeterol, fluticasone/vilanterol, mometasone/formoterol TCAs^ concurrent administration of TCAs with beta agonists may potentiate effects on cardiovascular system and increase risk of adverse events cautiously administer TCAs and beta agonists together, including within 2 weeks of TCA discontinuation; monitor patients and observe for changes in blood pressure, heart rate and ECG moderate (DrugReax) moderate (CP)
budesonide/formoterol, fluticasone/salmeterol, fluticasone/vilanterol, mometasone/formoterol beta blockers concurrent administration may decrease effectiveness of beta-adrenergic blocker or beta-2 agonists like formoterol, salmeterol combination not recommended in asthma/COPD patients; if adjunctive therapy necessary, utilize cardioselective beta blocker (e.g., atenolol, bisoprolol) major (DrugReax) 2-major (CP)
budesonide/formoterol, fluticasone/salmeterol, fluticasone/vilanterol, mometasone/formoterol diuretics potential for worsening of diuretic-associated hypokalemia and/or ECG changes with beta-agonist concurrent administration, especially with high beta-agonist doses administer combination cautiously; monitoring potassium levels may be necessary 3-moderate (CP)

Legend:

  • +CP = Clinical Pharmacology
  • COPD = chronic obstructive pulmonary disease
  • ECG = electrocardiogram
  • MAOIs = monoamine oxidase inhibitors
  • TCAs = tricyclic antidepressants