Because Mr. Casagrand has a prosthetic heart valve, he must take warfarin sodium [Coumadin] 5 mg PO daily. Concomitant administration of trimethoprim-sulfamethoxazole [Bactrim] and warfarin can cause:

A. Enhanced Bactrim absorption, increasing the risk of toxicity: Trimethoprim-sulfamethoxazole does not significantly affect its own absorption when co-administered with warfarin. The interaction of concern is primarily related to warfarin metabolism and displacement rather than changes in Bactrim absorption. B. Decreased Bactrim effectiveness, requiring a dosage increase: Warfarin does not interfere with the antibacterial efficacy of trimethoprim-sulfamethoxazole. No dosage adjustment of Bactrim is usually required due to warfarin therapy, as the interaction primarily affects the anticoagulant rather than the antibiotic. C. Displaced Warfarin, increasing its effects: Trimethoprim-sulfamethoxazole can displace warfarin from plasma protein-binding sites and inhibit hepatic metabolism through CYP2C9 inhibition. This increases free warfarin levels, potentiates its anticoagulant effect, and raises the risk of bleeding complications. Careful INR monitoring and possible warfarin dose adjustment are necessary when these drugs are used concurrently. D. Increased Warfarin excretion, decreasing its effects: Co-administration of Bactrim does not enhance renal excretion of warfarin. Instead, the interaction results in increased warfarin activity, not decreased, making this inaccurate in predicting the pharmacologic effect.