Sure ! The increased dosage was sustained by past studies (THRIVE II for example) which indicates that an increased dose was necessary during the initial period.

Once this initial period is done, I think that you may easily give the conventional dose

Hi Norbi,

Following 1 week of therapy with LMWH and when you want to switch the LMWH with Apixaban please do the following:

Stop the LMWH and then start Apixaban at the time when the next dose of LMWH would have been due.  Based on the previous evidence based on the clinical trials increased dosage initially followed by conventional dosing may be ideal.

Omer

In my opinion, yes, you probably can start at the lower standard therapeutic apixaban dose after 1 week of LMWH and feel it is reasonably safe for VTE treatment with a caveat.

Why? That is the approach used by two other DOACs in the approval trials for VTE (dabigatran, exdoxaban) and they were (also) non-inferior to warfarin in terms of efficacy (Blood. 2014 Aug 14;124(7):1020-8). Rivaroxaban and Apixaban choose to use a higher dose initially instead of starting with a standard parenteral anticoagulant. The logic for both of these approaches is to be more aggressive in the highest risk period (I.E. the first week(s) after the VTE) by using either the standard of care (LMWH, at the time trials) or a more aggressive DOAC doses (150-200% of the A.Fib dose for the first 1-3 weeks). 

Having said that, there are some reasons you might not always want to take this approach. When looking at the dose ranging trial for apixaban (Br J Clin Pharmacol. 2013;76(5):776-786.) it is clear the 10mg BID dose has a much higher level of anticoagulation (at day 1 & 7). There is accumulation after a week with steady state in ~3 days after starting/stopping. 

                                           Cmax       Cmin        AUC

5 mg twice daily   (Day 1)  81.9       25.3      600.6 

10 mg twice daily (Day 1) 226.2      72.7      1608.3 

5 mg twice daily   (Day 7)  128.5      49.6      1051.9 

10 mg twice daily (Day 7)  329.8    103.8      2424.9 

So if you usually have a AUC of 2400 after 7 days of 10mg BID from day 7 to 10 you are gradually being reduced to an AUC of 1000 as you reach a new (5mg BID) steady state. When you jump into 5mg BID with the LMWH first approach you are starting with an AUC of 600 and gradually moving up to and AUC of 1000  over days 7-10.  So you less protected from days 7-10. Does this matter? Hard to say. Perhaps for the massive PE patient, perhaps not for the small DVT patient. We can't say for sure with the current data.

In the end we usually feel the the patient is "protected" when LMWH or a DOAC peaks after the first dose (2-3 hrs). That plus the "parenteral-first" DOAC trials having good results gives some measure of assurance it will work for most patients. But in some cases I might suggest giving 10mg BID for 2-5 doses to give an extra measure of protection in the mentioned scenario. 

Dose ranging trial:

Frost C, Nepal S, Wang J, et al. Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. Br J Clin Pharmacol. 2013;76(5):776-786.

Apixabam is also a factor Xa inhibitor like enoxaparine. If 7 days of LMWH was administered the patient can be started on Apixabam 5mg twice daily. If patient has stage 4 CKD (creatinine clearance 15 to 29) dose may be reduced to 2.5 mg twice daily. If Apixabam is started as the primary treatment without LMWH and with normal renal function Apixabam may be given 10 mgmt twice daily for 7 days after which dose may be reduced to 5 mg twice daily.

According to guidelines...

The primary objectives for the treatment of deep venous thrombosis (DVT) are to prevent pulmonary embolism (PE), reduce morbidity, and prevent or minimize the risk of developing the postthrombotic syndrome (PTS).

Acute DVT may be treated with LMWH...

Initial treatment with LMWH, UFH, or fondaparinux should continue for at least 5 days...

But if we use Apixaban - it is no need to use Heparins/

Usual Adult Dose for Deep Vein Thrombosis

Initial dose of Apixaban: 10 mg orally 2 times a day for 7 days

Maintenance dose: 5 mg orally 2 times a day

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715858/pdf/11239_2015_Article_1317.pdf

https://www.eliquis.com/eliquis/servlet/servlet.FileDownload?file=00Pi000000pevosEAA