Elevated International Normalized Ratio in a patient concurrently using warfarin and vismodegib

Abstract

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. 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. 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.