Table S2.

Drug–drug interactions in Case #2

	Impact	Action	Mechanism
Drug–gene interactions
Carvedilol and CYP2D6	Major	Monitor therapy	CYPD6 rapid metabolizer status may increase metabolism of carvedilol
Warfarin and CYP2C9/VKORC1	Minor	Monitor therapy	Lower starting warfarin doses may be required due to reduced VKORC1 functionality
Drug–drug interactions based on CYP450 metabolism
Carvedilol and losartan potassium	Moderate	Monitor therapy	CYP2C9 inhibitors (losartan) may increase the serum concentration of carvedilol
Diltiazem HCl and fluticasone and vilanterol	Moderate	Monitor therapy	CYP3A4 inhibitors (diltiazem) may decrease the metabolism of CYP3A4 substrates
Losartan potassium and warfarin sodium	Moderate	Monitor therapy	CYP2C9 inhibitors (losartan) may decrease the metabolism of CYP2C9 substrates
Non-CYP450 drug–drug interactions
Albuterol sulfate and carvedilol	Major	Avoid combination	Beta-blockers may diminish the bronchodilatory effect of beta2-agonists
Carvedilol and fluticasone and vilanterol	Major	Avoid combination	Beta-blockers may diminish the bronchodilatory effect of beta2-agonists
Allopurinol and warfarin sodium	Moderate	Consider modification	Allopurinol may enhance the anticoagulant effect of vitamin K antagonists
Atorvastatin calcium and diltiazem HCl	Major	Consider modification	Diltiazem HCl may increase the serum concentration of atorvastatin calcium. Atorvastatin calcium may increase the serum concentration of diltiazem HCl
Carvedilol and tamsulosin HCl	Moderate	Consider modification	Beta-blockers may enhance the orthostatic hypotensive effect of alpha1-blockers
Furosemide and naproxen	Moderate	Consider modification	Nonsteroidal anti-inflammatory agents may diminish the diuretic effect of loop diuretics
Naproxen and warfarin sodium	Moderate	Consider modification	Nonsteroidal anti-inflammatory drug (nonselective) may enhance the anticoagulant effect of vitamin K antagonists