Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient's risk.

The aim of the study was to summarize available literature regarding the interaction between vitamin K antagonists (VKAs) and trimethoprim-sulfamethoxazole (co-trimoxazole, TMP-SMX), and to provide recommendations for managing patient risk from this interaction. Data sources were English-language publications in the medical literature and Internet databases. Relevant publications that directly or indirectly addressed the VKA-TMP-SMX interaction were selected and reviewed. The mechanism of the VKA-TMP-SMX interaction, frequency of concurrent use, effect on international normalized ratio (INR), increased risk of bleeding, and strategies for risk reduction are summarized. The concurrent use of VKA and TMP/SMX rapidly and consistently raises INR and is associated with a two- to five-fold increase in bleeding. Concurrent use of VKA and TMP-SMX should be avoided when possible. When VKA and TMP-SMX are co-prescribed, VKA dose reduction is usually required. Patient education as well as early and frequent INR monitoring is recommended to reduce risk from this interaction.