In this episode, I’ll discuss whether apixaban’s loading dose duration should ever be shortened.
A common clinical scenario in hospitals is the following: You have a patient with DVT or PE that has been on a therapeutic heparin infusion for several days, the physician wants to switch the patient to apixaban and asks you if the 7 day period of 10 mg po bid should be reduced by the duration the patient was on the heparin infusion.
Shout out to “Pulmonology Tony” and Hospital Pharmacy Academy members “Pharmacy David” and “Pharmacy Sally” for inspiring this episode.
When this question has come up in my practice, I’ve looked into the reason for the loading dose and the trial protocol under which apixaban was approved for DVT and PE treatment.
Venous thromboembolism has an acute phase, during which a patient is at high risk for VTE recurrence and clot extension. This period is considered by some experts to be 7 days long. The dosing protocols of all of the DOACs take this acute phase into account. Dabigatran and edoxaban require 5 full days of parenteral anticoagulation therapy first, and apixaban and rivaroxaban have a period where a loading dose is given before dropping down to a lower maintenance dose.
The trial that secured the approval of apixaban to treat VTE was published in 2013 in the New England Journal of Medicine.
99% of the patients in the apixaban group had received parenteral anticoagulants for less than 48 hours before randomization to apixaban and two-thirds of the patients for less than 24 hours.
According to the supplemental appendix for this trial, the investigators excluded patients with more than two doses of fondaparinux or a LMWH that is labeled for once-daily dosing, or more than three doses of a LMWH that is labeled for twice-daily dosing, or continuous infusion of unfractionated heparin for more than 36 hours, before the first administration of study drug.
This means that the specific scenario of a patient who has been on a therapeutic heparin infusion for several days before transitioning to apixaban has not been subject to study.
In most cases I encounter, the patient will be transitioned to the full 7 days of apixaban 10 mg po bid therapy. However, occasionally I encounter patients that might have a higher bleeding risk and in consultation with pulmonology, we consider reducing the duration of 10 mg po bid dosing by the length of time they were therapeutic on the heparin drip.
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Caveat: I say this tongue and cheek:
Love the discussion, hate the topic….This has been something that hasnt made sense to me from day one. I tried looking for anything that would convince me that the Doac PO loading dose makes sense but the best I was able to find was “because that is the way it was studied for FDA approval”…. Unfortunately, that answer historically doesn’t seem to stand up to the test of time / unbiased retrospective analysis. That said, I have a pharmacy crystal ball that just reported a glimpse into the future. These were those findings:
Things that will be shown true in the future:
1. Bridge x5 days is non inferior to current reccs (15mg PO BID for Rivarox OR 10mg PO BID for Apixaban) x 5 days in comparision to the current 7 day or 21 day regimen. All that was gained in the longer bridge doses was enhanced profit margins. Unfortunately, that data will be suppressed because this will be old news and we will have moved onto the new class of meds: Active Placebo’s for MDD demonstrating non inferiority to SSRIs with improved tolerability. Unfortunately, despite only containing 4 mg of diphenhydramine and menthol, the cost is $140/tab.
2. Enoxaparin 1mg/kg SQ q12H x 5 days in place of PO load (or therapeutic heparin gtt etc) non inferior.
3. We forget the 21 day rivarox load and burry that in the same drawer as Xigris or “Leave em Dead Norepi”. I will say “I knew it all along” only to be told ‘they why didnt you do anything about it. I will then refer them to this podcast that will by then have moved onto all facets of medicine. Pharmacy Joe, Cardiovascular Joe, Car Mechanic Joe, Chief Joe, etc etc. Pharmacy Joe has cloned himself as an early adopter of CRISPR.
4. Data comes out demonstrating a lack of CHA2DS2-VASc routinely being implemented which skewed the data so bad that it was in line with all of the other data prior to when human pharmacist were working and not their faster, smarter and overall nicer AI counterparts, now abundant in every country.
5. There are two countries: Chat GBT and Google
🙂
Enjoy,
AK