UMEM Educational Pearls

Category: Pharmacology & Therapeutics

Title: DOAC "Loading Dose" = Misnomer

Keywords: DOAC, apixaban, rivaroxaban, loading dose (PubMed Search)

Posted: 9/14/2023 by Wesley Oliver (Updated: 7/14/2024)
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DOACs (dabigatran*, apixaban, rivaroxaban) each have different dosing strategies based on indication and patient characteristics. While there is no official term for the doses, the higher initial doses for apixaban (10 mg BID for 7 days) and rivaroxaban (15 mg BID for 21 days) for the treatment of venous thromboembolism (VTE) are commonly referred to as “loading doses.” However, the term “loading dose” is actually a misnomer.

Loading doses are used to reach therapeutic drug levels quicker with medications such as vancomycin and phenytoin/fosphenytoin. However, this is not the purpose of the higher initial doses of apixaban and rivaroxaban. The purpose of the higher doses is to provide increased levels of anticoagulation during the acute phase of VTE when patients are hypercoagulable. For this reason, VTE and heparin-induced thrombocytopenia are the only indications where a higher dose is used initially, all other indications start with the standard dose. The difference in duration of these higher doses between apixaban (7 days) and rivaroxaban (21 days) are due to the durations used in trials by the drug company, versus any pharmacokinetic reasons.

To apply this concept:

Apixaban/Rivaroxaban: For the treatment of VTE, a higher dose is only required for the initial 7- (apixaban) or 21-day period (rivaroxaban). After this period, if there is any interruption in therapy, the standard dose can be restarted because therapeutic levels are rapidly achieved and higher doses are not needed outside of the acute phase.

One caveat to this would be if the patient developed a new VTE while therapy is interrupted, in which case another period of the higher dosing could be considered.

 

*Remember: Dabigatran cannot be used for initial treatment of VTE and must be started only after at least 5 days of a parenteral anticoagulant. (Dabigatran and the parenteral anticoagulant should not be overlapped).

References

References

Eliquis (apixaban) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; April 2021.

Pradaxa (dabigatran) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; June 2021.

Xarelto (rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; February 2023.