4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug interactions considered clinically relevant for inhaled corticosteroids with or without beta agonists are summarized in Table 7. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
| 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: moderate; fluticasone: major (CP) |
| steroids | quinolones | increased potential for serious tendonitis, tendon rupture with concurrent therapy | closely monitor patients requiring combination therapy; discontinue quinolone if tendon pain develops | 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 | moderate (CP) |
| 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 | 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 (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 (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 | moderate (CP) |
Legend:
- +CP = Clinical Pharmacology
- COPD = chronic obstructive pulmonary disease
- ECG = electrocardiogram
- MAOIs = monoamine oxidase inhibitors
- TCAs = tricyclic antidepressants