Question 185

Question:

Warfarin is administered to a 56-year-old man following placement of a prosthetic cardiac valve. The warfarin dosage is adjusted to maintain an INR of 2.5. Subsequently, trimethoprim-sulfamethoxazole therapy is begun for a recurring urinary tract infection. In addition to monitoring prothrombin time, which of the following actions should the physician take to maintain adequate anticoagulation?

Correct Answer: D.  Decrease the dosage of warfarin

Trimethoprim-sulfamethoxazole is a sulfa-based drug. Sulfonamides are known inhibitors of the P-450 enzymatic system, and warfarin is primarily metabolized by CYP450:2C9. Trimethoprim-sulfamethoxazole would be expected to increase the serum levels of warfarin and push the INR to super-therapeutic levels with the increased risk of bleeding. Therefore, it would be recommended to decrease the dosage of warfarin (choice D).
Begining therapy with vitamin K (choice A) is the treatment for warfarin overdose, which this patient does not have. Additionally, giving vitamin K will drop the INR to sub-therapeutic levels which will place this patient with a newly placed prosthetic valve at risk for thromboembolisms.
Increasing the dosage of warfarin (choice B) would not be recommended in this patient because trimethoprim-sulfamethoxazole will already increase the serum levels of warfarin. Further increasing the dosage of warfarin will definitely place this patient at risk for bleeding.
Making no alterations in the dosage of warfarin (choice C) is not recommended because of the risk of bleeding with a supra-therapeutic INR as a result from inhibited warfarin metabolism.
Stopping the warfarin and changing to low-dose aspirin (choice E) is not recommended because this patient with a newly placed prosthetic valve still requires anti-coagulation to prevent thromboembolisms. Additionally, aspirin has not been shown to be adequately effective in anti-coagulating patients with prosthetic valves.