title: Inadvertent exaggerated anticoagulation following use of bismuth subsalicylate in an enterally fed patient receiving warfarin therapy.
abstract: We report a case of an inadvertent increase in the international normalized ratio (INR) after the addition of bismuth subsalicylate for the treatment of diarrhea in an enterally fed patient receiving warfarin therapy. A 56-year-old Caucasian female presented to the trauma intensive care unit (ICU) with multiple lower extremity fractures. Warfarin was initiated for deep vein thrombosis prophylaxis due to the patient's inability to ambulate. The target INR was 2-3. Continuous intragastric enteral feeding was withheld 1 hour before and 1 hour after intragastric administration of warfarin. Bismuth subsalicylate 30 mL every 4 hours was prescribed for diarrhea. Within 3 days after starting bismuth subsalicylate therapy, the patient's INR increased from 2.56 to 3.54 and minor bleeding was noted from the patient's tracheostomy site. No significant change in warfarin dosage, variability in vitamin K intake, or medications that potentially alter warfarin metabolism were present during the unexpected rise in INR. When the bismuth subsalicylate was discontinued, the patient's INR stabilized into the target range on the same warfarin dose given at the time of the supratherapeutic INR. Salicylate displaces warfarin from plasma protein binding sites and may result in a significant increase in INR secondary to redistribution of warfarin to the free active form. Evaluation of this case report using the Drug Interaction Probability Scale and Naranjo Adverse Drug Reaction Probability Scale yielded scores consistent with a probable adverse drug interaction. Bismuth subsalicylate exaggerates warfarin's anticoagulant response and its concurrent use during warfarin therapy should be avoided.
authors.affiliation: Angela L. Bingham, Department of Pharmacy Practice and Pharmacy Administration, University of the Sciences, 600 S 43rd St, Philadelphia, PA 19104, USA. Email: a.bingham@usciences.edu.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Bingham
authors.forename: Rex O
authors.initials: RO
authors.lastname: Brown
authors.forename: Roland N
authors.initials: RN
authors.lastname: Dickerson
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D001729:Bismuth / Q000009:adverse effects / Q000627:therapeutic use*; D004347:Drug Interactions; D004750:Enteral Nutrition; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D012459:Salicylates / Q000009:adverse effects / Q000627:therapeutic use*; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D009942:Organometallic Compounds; D012459:Salicylates; D014859:Warfarin; C015715:bismuth subsalicylate; D001729:Bismuth
keywords: drug-nutrient interactions; enteral nutrition; food-drug interactions; international normalized ratio; warfarin