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 LABAs and combination products 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 + |
|---|---|---|---|---|
| beta2-agonists | atomoxetine | concurrent administration may increase risk of cardiovascular adverse effects (e.g., tachycardia, hypertension); interaction may be less likely with inhaled beta2-agonists | monitor patients for increased cardiovascular adverse effects | 3-moderate (CP) |
| 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) | 2-major (CP) |
| beta2-agonists | diuretics, xanthine derivatives (e.g., theophylline), corticosteroids | potential for worsening of hypokalemia and/or ECG changes with beta2-agonist concurrent administration, especially with high beta2-agonist doses | administer combination cautiously, although common for xanthines and steroids to be administered adjunctively with beta2-agonists; monitor potassium levels as necessary | 3-moderate (CP) |
| beta2-agonists | MAOIs (including linezolid) | concurrent administration 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 | 2-major (CP) |
| beta2-agonists | QTc interval-prolonging medications (e.g., class I, III anti-arrhythmic, ziprasidone, dolasetron) | concurrent administration may increase risk of cardiotoxicity (e.g., life-threatening arrhythmias, cardiac arrest) due to potential for additive QTc interval prolongation and, rarely, torsades de pointes | administer combination cautiously | 3-moderate (CP) |
| beta2-agonists | TCAs | concurrent administration may potentiate effects on cardiovascular system and increase risk of adverse events | cautiously administer together, including within 2 weeks of TCA discontinuation; monitor patients and observe for changes in blood pressure, heart rate and ECG | 3-moderate (CP) |
| salmeterol, ICS | strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin) | salmeterol, ICS extensively CYP3A4 metabolized; conjunctive administration may increase salmeterol, ICS serum levels and potential for increased adverse cardiovascular effects (salmeterol), steroid adverse effects (ICS) | avoid combination, if possible; if combination necessary, monitor for salmeterol, ICS adverse effects and adjust therapy as necessary | 2-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 | 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 | moderate (CP) |
Legend:
- +CP = Clinical Pharmacology
- COPD = chronic obstructive pulmonary disease
- ECG = electrocardiogram
- MAOIs = monoamine oxidase inhibitors
- TCAs = tricyclic antidepressants