title: Elevated International Normalized Ratio in a patient concurrently using warfarin and vismodegib.
abstract: OBJECTIVE
  A case report of a sharp rise in International Normalized Ratio (INR) values during a patient's concomitant use of warfarin and the antineoplastic agent vismodegib is presented.
  
  
  CONCLUSIONS
  About three weeks after he was prescribed vismodegib for skin cancer, a 78-year-old Caucasian man whose INR had been stable during nine months of warfarin use was found to have a critical INR value (9.5) during a visit to a pharmacy anticoagulation clinic. After clinic interventions including brief suspensions of warfarin therapy and an incremental 36% decrease in the weekly dose, the patient's INR returned to a high-normal value over the next few weeks, and treatment with warfarin was resumed. One week later, the man was admitted to the emergency department for altered mental status and loss of consciousness, which were thought to be unrelated to anticoagulation therapy. The patient died in the hospital shortly thereafter of unknown causes. At the time of death, laboratory values were stable, the most recent INR was 1.8, and the patient was hemodynamically stable and on a non-intensive care ward. Assessment with the Drug Interaction Probability Scale indicated a probable interaction between warfarin and vismodegib. Since its introduction in 2012, vismodegib has been implicated as a possible factor in seven reports of patient deaths.
  
  
  CONCLUSIONS
  Concurrent use of vismodegib and warfarin was deemed the probable cause of acute INR elevation in this case, suggesting the need for close monitoring of INR values in patients receiving this combination of drugs.
authors.affiliation: Shannon Lim is a Pharm.D. candidate at the University of Arizona College of Pharmacy, Tucson. Jenna Houranieh, Pharm.D., is Clinical Pharmacy Specialist in Hematology/Oncology, Lexington Veterans Affairs (VA) Medical Center, Lexington, KY; at the time of writing, she was Postgraduate Year 2 (PGY2) Oncology Pharmacy Resident; and Russell Crawford, B.S.Pharm., BCOP, is Clinical Pharmacy Specialist in Hematology/Oncology and PGY2 Oncology Pharmacy Residency Program Director, Southern Arizona VA Healthcare System, Tucson.
authors.forename: Shannon
authors.initials: S
authors.lastname: Lim
authors.forename: Jenna
authors.initials: J
authors.lastname: Houranieh
authors.forename: Russell
authors.initials: R
authors.lastname: Crawford
mesh_terms: D000368:Aged; D000813:Anilides / Q000009:adverse effects* / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000813:Anilides; D000925:Anticoagulants; D000970:Antineoplastic Agents; C538724:HhAntag691; D011725:Pyridines; D014859:Warfarin