Because the patient is not bleeding and is not at high risk for bleeding, interruption of warfarin therapy is appropriate. Concomitant antibiotic and warfarin use can result in INR elevation. A population-based study revealed that the over-anticoagulation risk was most strongly increased by amoxicillin, clarithromycin, norfloxacin, and trimethoprim-sulfamethoxazole. Changes in the INR were often noted in the first 3 days of antibiotic use. This patient's elevated INR is most likely related to her concomitant use of warfarin and trimethoprim-sulfamethoxazole. The appropriate treatment for patients taking warfarin whose INR is supratherapeutic depends on the absolute INR value, the absence or presence of bleeding risk factors or active bleeding, and the seriousness of bleeding, if present. Increased age, actively bleeding lesions, coagulation disorders, and use of antiplatelet drugs increase the bleeding risk while taking warfarin. If the INR is less than 5.0 and no bleeding is apparent, the next dose of warfarin is withheld and the subsequent maintenance dose is reduced. If the INR is 9.0 or less and the risk of bleeding is low, the next one or two doses of warfarin are withheld and the INR is repeated in 48 hours; in these patients who have no evidence of bleeding, the American College of Chest Physicians (ACCP) recommends against the routine use of vitamin K. If the INR is greater than 9.0, warfarin is withheld and 2.5 to 5 mg of oral vitamin K is administered.

Patients with an elevated INR and serious bleeding (or those requiring rapid anticoagulation reversal) are treated by withholding warfarin and administering 10 mg of vitamin K intravenously. For patients with critical need of anticoagulation reversal (for example, intracerebral bleeding), the ACCP recommends administration of 4-factor prothrombin complex concentrate rather than fresh frozen plasma.