Drug Interactions between motixafortide and nebivolol / valsartan

GENERALLY AVOID: Concomitant use of beta blockers may increase the risk or severity of hypotension and other serious reactions (e.g., angioedema, bronchospasm, bradycardia) in patients who experience hypersensitivity to motixafortide. The mechanism has not been clearly delineated, but it has been proposed that beta blockade may lead to an increase in intracellular synthesis and release of histamine and other anaphylactic mediators by disturbing the homeostatic balance between alpha- and beta-adrenergic and cholinergic neurohumoral mechanisms. Additionally, beta blockade may enhance the responsiveness of the pulmonary, cardiovascular, skin, and other systems to anaphylactic mediators. In clinical studies, anaphylactic shock and hypersensitivity reactions occurred in 0.7% and 7.6% of motixafortide-treated patients, respectively.

MANAGEMENT: Because anaphylaxis in patients treated with beta blockers may be more severe and protracted, the prescribing information for motixafortide recommends that alternative, non-chronotropic agents be used in place of beta blockers when possible. If coadministration cannot be avoided and anaphylaxis occurs, clinicians should be aware of potential resistance to conventional treatments such as epinephrine due to beta-adrenergic blockade. Aggressive treatment and prolonged supportive therapy may be required in refractory cases. The same precautions should be observed in patients treated with beta blocker ophthalmic solutions, as they are systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels. All patients should be premedicated with a H1-antihistamine (e.g., diphenhydramine), a H2 antagonist (e.g., famotidine), and a leukotriene inhibitor (e.g., montelukast) 30 to 60 minutes prior to motixafortide administration to reduce the risk of anaphylactic shock and hypersensitivity reactions. Patients should be monitored for signs and symptoms of hypersensitivity for one hour following administration and managed accordingly.