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 anticholinergics with beta agonists are summarized in Table 6. 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 |
|---|---|---|---|---|
| fluticasone/umeclidinium/vilanterol | 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 advised; if combined administration necessary, give cautiously; monitor patients for signs/ symptoms of corticosteroid excess | major (CP) |
| ipratropium/albuterol, umeclidinium/vilanterol, glycopyrrolate/formoterol, tiotropium/olodaterol | MAOIs* (including linezolid) | concurrent administration of MAOIs with beta2-agonists may increase risk of development 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) |
| ipratropium/albuterol, umeclidinium/vilanterol, glycopyrrolate/formoterol, tiotropium/olodaterol | beta blockers | concurrent administration may decrease effectiveness of beta-adrenergic blocker or beta2- agonists like albuterol | combination not recommended in asthma/COPD patients; if adjunctive therapy necessary, utilize cardioselective beta blocker (e.g., atenolol, bisoprolol) | major (CP) |
| ipratropium/albuterol, umeclidinium/vilanterol, glycopyrrolate/formoterol, tiotropium/olodaterol | 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) |
| 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) |
| umeclidinium/vilanterol | strong CYP3A4 inhibitors (e.g., fluconazole, ketoconazole, ritonavir, nefazodone) | adjunctive administration may result in elevated vilanterol serum levels and enhanced pharmacologic and adverse effects, including QT interval prolongation, as vilanterol is a CYP3A4 substrate | administer combination cautiously, and closely monitor patients for adverse cardiovascular/QT interval outcomes | moderate (CP) |
Legend:
- + CP = Clinical Pharmacology
- *MAOIs = monoamine oxidase inhibitors
- ^TCAs = tricyclic antidepressant