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I wish to congratulate the authors on a thorough and useful study.(1)
The authors are correct in that the 36-42-hour half-life of racemic warfarin(2) largely explains why the time of day at which the daily dose warfarin is taken does not have much influence on the INR.
I want add my anecdotal experience of being involved in the INR clinic of an academic hospital over the last 30 years. If patients were struggling to stabilise their INR, I first tried to exclude common issues like compliance, drug interactions and a highly variable diet. Then I suggested that they drink their warfarin on an empty stomach when they wake up in the morning. I suggested that they follow their daily routine of taking their other medication a bit later, and that they need not change their breakfast routine.
My rationale was firstly that the warfarin might be at least partially absorbed before the other drugs are taken. Secondly, it appears to me that most people’s breakfasts tend not to vary as much as their evening meals do. Therefore, the interaction between diet and warfarin would probably be more predictable than if it were taken at night. The authors also mention that foods that are rich in vitamin K are usually not eaten in the morning. Unfortunately I do not have experimental evidence to support my suggestions. To my knowledge patients have never complained that the suggestion worsened their INR control, but a number have thanked me profusely. I would appreciate feedback.
1. Garrison SR, Green L, Kolber MR, et al. The Effect of Warfarin Administration Time on Anticoagulation Stability (INRange): A Pragmatic Randomized Controlled Trial. The Annals of Family Medicine 2020;18:42-9. doi:10.1370/afm.2488.
2. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and Management of the Vitamin K Antagonists. Chest 2008;133:160S-98S. doi:10.1378/chest.08-0670.