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

Area of Science:

• Pharmacology
• Oncology
• Clinical Medicine

Background:

• Warfarin is a common anticoagulant medication.
• Vismodegib is an antineoplastic agent used for treating skin cancer.
• Drug interactions can significantly alter patient outcomes.

Observation:

• A case report details a 78-year-old male patient experiencing a sharp increase in International Normalized Ratio (INR) while on concurrent warfarin and vismodegib therapy.
• The patient's INR reached a critical level of 9.5, necessitating intervention with warfarin dose adjustments and temporary suspension.
• Despite initial stabilization, the patient was later admitted to the emergency department and subsequently died from unknown causes.

Findings:

• The concurrent administration of vismodegib and warfarin was identified as the probable cause of the acute INR elevation.
• A Drug Interaction Probability Scale assessment supported a probable interaction between these two drugs.
• Seven patient deaths have been potentially linked to vismodegib since its 2012 introduction.

Implications:

• Close monitoring of INR values is essential for patients concurrently treated with vismodegib and warfarin.
• This case highlights the potential for severe drug interactions with antineoplastic agents.
• Further research into the pharmacokinetic and pharmacodynamic interactions between vismodegib and warfarin is warranted.