Drug products: Lixiana
ATC code: B01AF03
Substances: edoxaban, edoxaban tosilate
Similar effects in men and women treated with edoxaban have been shown in prevention of stroke in atrial fibrillation and recurrence of deep venous thrombosis. In a meta-analysis of treatment in venous thrombosis, the bleeding risk was found to be higher in women than men.
In our opinion, at present the described difference does not motivate differentiated dosing or treatment in men and women.
Analysis of pharmacokinetic studies (in total 244 men, 34 women) of edoxaban given in doses of 10-180 mg showed that clearance was 13% lower in women than men. The authors suggest that this finding is of no clinical importance . A study of single-dose edoxaban (30, 60 or 90 mg) in healthy Chinese volunteers (6 men, 6 women) observed higher plasma levels of edoxaban and the metabolite in women than in men (not corrected by weight) . A pharmacokinetic review suggest that sex do not independently affect edoxaban pharmacokinetics after accounting for body weight .
A meta-analysis has compared the effect of new oral anticoagulants (NOACs) on recurrent symptomatic venous thromboembolism (VTE) in men and women (in total 9338 men, 7034 women, on edoxaban 2360 men, 1758 women). The incidence on recurrent VTE was similar among NOACs and between men and women [4, 5].
Edoxaban has shown a dose-response relationship in reduction of VTE incidence . However, data from patients after total hip replacement (282 men, 431 women) showed that the decrease in VTE incidence with increasing edoxaban exposure was only significant in women .
The efficacy of edoxaban in atrial fibrillation compared to warfarin was evaluated in a randomized, double-blind study (13 065 men, 8040 women). Patients received either high-dose (60 mg) or low-dose (30 mg) edoxaban or dose-adjusted warfarin. All treatments prevented stroke or systemic embolism to a similar degree and no sex difference in outcome was observed .
A meta-analysis consisting of six randomized controlled trials (in total 13139 men, 9814 women, on edoxaban 2360 men, 1758 women) evaluating the risk of bleeding from NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) compared to warfarin among patients with acute VTE found a higher risk in women than men in both the warfarin and NOAC groups . Another similar meta-analysis of the same studies showed that the sex difference in incidence of bleedings was only significant for edoxaban (RR 0.52) [4, 5].
In patients with atrial fibrillation, edoxaban has been associated with lower bleeding rates and death from cardiovascular causes compared to warfarin, as shown in a randomized double-blind study (13 065 men, 8040 women). rates were similar in men and women in both the low-dose and high-dose edoxaban groups compared to warfarin .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2016-10-17
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson