Major
Probable
Deskripsi
Methotrexate combined with warfarin increases bleeding risk and may cause enhanced anticoagulation; both drugs share protein-binding sites, amplifying free drug concentrations.
Mekanisme
Methotrexate displaces warfarin from albumin, raising free warfarin levels; warfarin may also reduce methotrexate clearance. Both drugs can impair hepatic function, affecting clotting factor synthesis.
Signifikansi Klinis
Serious bleeding events have been reported; concurrent hepatotoxicity risk adds further complexity to the interaction.
Penatalaksanaan
Closely monitor INR and signs of bleeding; consider reducing warfarin dose empirically. Monitor liver function tests regularly.