Clinical Pharmacology and Therapeutics
Clinical Pharmacology and Therapeutics
5 years ago

Dosing considerations in the use of the direct oral anticoagulants in the antiphospholipid syndrome

Dosing considerations in the use of the direct oral anticoagulants in the antiphospholipid syndrome
K. Hassell, J. R. Schofield
Summary What is known and objectives At least four prospective trials have been initiated investigating the direct oral anticoagulants in the antiphospholipid syndrome. Preliminary reports have supported their use in patients with a history of venous thrombosis and a target INR of 2-3, but there have also been reports of failure of these agents in the antiphospholipid syndrome. The objective is to present a case report that illustrates there may be important dosing issues when considering the use of these agents in patients with the antiphospholipid syndrome. Case summary A 50-year-old woman with the antiphospholipid syndrome, manifesting clinically with recurrent pyoderma gangrenosum-like leg ulcers, was treated with apixaban, resulting in improved ulcer healing. For insurance purposes, she was switched to rivaroxaban with worsening of the ulcers which again improved when apixaban was resumed. What is new and conclusion Despite a similar half-life, pharmacokinetics and pharmacodynamics, the manufacturer-recommended maintenance dosing of apixaban is twice daily and rivaroxaban once daily. We believe this difference in recommended dose accounts for the differential clinical response noted in the present case report and that twice daily dosing and a larger daily dose of these agents may be more efficacious in potent hypercoagulable disorders, such as the antiphospholipid syndrome. Human dosing trials of the DOACs have shown that once daily dosing of these agents results in a significantly higher peak level and a significantly lower trough level. Once daily dosing may result in a greater risk of bleeding during the high early peak and inadequate anticoagulation during the prolonged trough period. Reprinted with kind permission from Wiley.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jcpt.12582

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