Warfarin

Additional information

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding pharmacokinetics of warfarin have been found.

A cohort study (2 655 men, 1 961 women) found that warfarin dose was inversely related to age and was strongly associated with sex. Women required less warfarin than men, independent of age. The weekly maintenance warfarin dose for women at any given age was 4.5 mg lower than that of men. This might be explained by differences in mean body size, hepatic fat content or intrinsic differences in warfarin metabolism. However, the possible effect of weight could not be completely accounted for [1]. As dosing of warfarin is based on INR monitoring, these sex differences have little clinical impact.

Effects

A review shows that warfarin is at least equally effective in reducing the risk of thromboembolism in men and women [3]. In a large cohort study (8 850 men, 6 828 women), women with atrial fibrillation were at higher risk for incident thromboembolism than men with atrial fibrillation at both younger and older ages during off-warfarin periods. Adjusted RR for women versus men was 1.6 for those ≤ 75 years of age and 1.8 for those >75 years of age. Warfarin therapy was associated with a significant reduction in the rate of thromboembolism with an adjusted RR of 0.4 in women and 0.6 in men. In multivariable models including patients both on and off warfarin therapy, the reduction in rates of thromboembolism with warfarin was larger in women than in men [4].

Adverse effects

A cohort study (505 men, 275 women) observed that among patients with chronic warfarin treatment, women had higher risk of ischemic stroke than men. The RR of women compared to men was 2.0. The quality of the anticoagulation was similar in women and men [5].

Several studies, including a large meta-analysis, have shown that the major bleeding risk associated with warfarin is similar between men and women [3, 4, 6, 7]. However, a multicenter study (560 men, 339 women) in Canada showed that women on warfarin were 3.35 times more likely to experience a major bleed, compared to men [8].

Reproductive health issues

Warfarin may interact with oral contraceptives. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).Warfarin can cause fetal harm when administrated to a pregnant woman. Regarding teratogenic aspects, please consult Janusmed Drugs and Birt Defects (in Swedish, Janusmed fosterpåverkan).

Other information

When Vitamin K oral anticoagulants where the only available oral anticoagulants, many studies found an under treatment in women with atrial fibrillation [8,9]. However, with introduction of new oral anticoagulants (NOACs) the utilization patterns of oral anticoagulant are now more equal between men and women [10].