Warfarin Maximum Dose
There is no universally defined maximum dose of warfarin; dosing is guided by achieving the target INR (typically 2.0-3.0) rather than by an absolute dose ceiling, though interpatient variability means some patients may require doses exceeding 80 mg/week while others need only 0.5-2.0 mg/day. 1
Dose Range and Variability
Warfarin exhibits enormous interpatient dose variability, with maintenance doses ranging from as low as 0.5-2.0 mg/day in highly sensitive patients to over 80 mg/week (approximately 11-12 mg/day) in warfarin-resistant individuals 1, 2
Genetic factors account for approximately 40% of warfarin dosing variability, primarily through CYP2C9 and VKORC1 polymorphisms 1
Elderly patients typically require approximately 1 mg/day less than younger individuals to maintain comparable INR prolongation 1, 3
Initial Dosing Guidelines
Start with 5 mg daily for most patients, which produces a satisfactory anticoagulant effect within 4-6 days 3, 2
Use lower starting doses of 2-4 mg daily in elderly, debilitated, or high bleeding-risk patients 3, 2
Avoid loading doses exceeding 5 mg, as 10 mg loading doses cause excessive anticoagulation (44% with INR >2.0 at 36 hours vs. 8% with 5 mg) and precipitous protein C depletion creating a potential hypercoagulable state 4
Dose Adjustment Principles
Most dose changes should alter the total weekly dose by 5-20% rather than making large adjustments 2
Do not adjust dose for a single INR slightly out of range; wait for confirmation with repeat testing 2
The target is INR, not dose: Continue adjusting until therapeutic INR is achieved and maintained, regardless of the final dose required 1
Special Population: Pregnancy with Mechanical Valves
If warfarin dose ≤5 mg/day is required to maintain therapeutic INR, continuation throughout pregnancy is reasonable after informed consent, as embryopathy risk remains low (<3%) at this dose 1, 3
If warfarin dose >5 mg/day is required, there is a >30% risk of fetal loss or embryopathy during first trimester; switch to dose-adjusted LMWH (target anti-Xa 0.8-1.2 U/mL) during first trimester 1, 3
Warfarin Resistance
Heterozygous VKORC1 mutations causing warfarin resistance typically require doses exceeding 80 mg/week to maintain appropriate anticoagulation 1
Complete VKORC1 inactivation causes multiple coagulation factor defects responsive only to oral vitamin K, not warfarin 1
Common Pitfalls
Avoid assuming a "maximum safe dose" exists; the appropriate dose is determined by INR response, not an arbitrary ceiling 1, 2
Do not discontinue dose escalation prematurely in apparent "resistant" patients without confirming compliance, drug interactions, dietary vitamin K intake, and considering genetic testing 1
Recognize that doses >10 mg/day may be legitimately required in some patients, particularly those with VKORC1 polymorphisms conferring resistance 1
Monitor more frequently when doses exceed typical ranges (>10 mg/day) to detect unexpected INR elevation from intercurrent illness or medication changes 2