3.2. Remedial strategies
The remedial dose strategies for two typical patients based on edoxaban
concentration and iFXa activity are summarized in Table 3. Figure 4
showed the edoxaban concentration and iFXa profile for
patients
(aged 75 years,CrCl 80 mL/min, TBW 80kg, receiving 60 mg q24h) with full
adherent and with a proposed remedial strategies while delay 10 h. Two
typical patients had a similar optimised remedial regimen.
According
to our result, a full dose of edoxaban could be taken immediately up to
11 h after a delayed dose for both typical patients. When the delay time
was between 12 and 19 h, patients were recommended to take a half dose
and then resume the normal dosing schedule. When the delay exceeds 19 h,
a full dose followed by a half dose was preferred.
Recommendations based on PK and iFXa are similar in patients with normal
and impaired renal function.
Based on our research, the full dose needs to be taken immediately in
the first 11 h after dose delay, as recommended by the EHRA. However,
the EHRA recommends taking the full dose at a delay of 12 h and skip the
missed dose after a 12 h delay, which yields a longer total deviation
time compared to our recommendations. For example, in 80 kg patients
with normal renal function, when the dose is delayed for 14 h, the
deviation time for EHRA recommendation is 73% longer than our
recommendation (27.4 h versus 15.8 h) based on PK and 83% longer (27.2
versus 14.8 h) based on PD. A comparison between the EHRA and our
proposed remedial strategies is shown in Figure 5. The detailed
deviation time information for different strategies is listed in
Supplementary table 3.