Effect of Body Weight on Dose of Vitamin K Antagonists

Timothy H. Self, PharmD; Jessica L. Wallace, PharmD, BCPS; Sami Sakaan, PharmD, BCPS; Christopher W. Sands, MD


South Med J. 2015;108(10):637-643. 

In This Article


Dose requirements for VKA are affected by numerous factors; therefore, achieving and maintaining a therapeutic INR are often challenging and require continual consideration of these factors.[1] Perhaps the best-recognized factors by many clinicians are dietary vitamin K and major drug interactions. Although liver disease is seen as an obvious factor to affect response to VKA, other disease states such as thyroid dysfunction, decompensated heart failure, and CKD may be overlooked. In addition, the clinical relevance and cost effectiveness of pharmacogenetics in VKA dosing continue to receive much attention.[1] Overwhelmed by all of these factors to consider, it is easy for clinicians to miss the effect of body weight on VKA dose requirements.

Limitations of studies published to date include small patient populations in some investigations. In addition, several studies were retrospective. Finally, some evaluations did not include adequate specific data on body weight. Nevertheless, our review of the available literature suggests that body weight should be taken into account when dosing VKA. Most studies examining body weight and warfarin dose reveal that dose is affected by this variable.[5–10,12,14] Furthermore, studies of other VKA doses found a positive correlation as well.[11,32–35] Most pharmacogenetic studies that also examined clinical factors showed that body size or weight was a significant factor in determining the warfarin dose.[17–30,32–35] We found three studies that did not find body weight to be a significant factor in VKA dosing.[4,13,31]

As body weight increases, especially in obese and morbidly obese populations, the VKA dose requirement is found to subsequently increase. Because many clinicians overlook weight as a clinical factor to consider, obese and morbidly obese patients initially may be underdosed with VKA, and studies have shown that these patients will subsequently require a longer time to achieve therapeutic INR. One reason proposed for the higher initial dose requirements in obese and morbidly obese patients is that these patient populations have higher absolute volume of distributions warranting larger initial doses compared with normal-weight patients during the distribution phase to achieve a therapeutic INR.