Despite its effectiveness, treatment with warfarin has several shortcomings. Many commonly used medications interact with warfarin, as do some foods (particularly fresh plant-based foods containing vitamin K) and its activity has to be monitored by blood testing for the international normalized ratio (INR) to ensure an adequate yet safe dose is taken.^[2] A high INR predisposes to a high risk of bleeding, while an INR below the therapeutic target indicates that the dose of warfarin is insufficient to protect against thromboembolic events.

Warfarin and related 4-hydroxycoumarin-containing molecules decrease blood coagulation by inhibiting vitamin K epoxide reductase, an enzyme that recycles oxidized vitamin K to its reduced form after it has participated in the carboxylation of several blood coagulation proteins, mainly prothrombin and factor VII. For this reason, drugs in this class are also referred to as vitamin K antagonists.^[2] When administered, these drugs do not anticoagulate blood immediately. Instead, onset of their effect requires about a day before clotting factors being normally made by the liver have time to naturally disappear in metabolism, and the duration of action of a single dose of warfarin is 2 to 5 days. Under normal pharmacological therapy the drugs are administered to decrease the action of the clotting factors they affect by 30 to 50%.^[3]