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

J Clin Pharm Ther. 2018 Feb;43(1):104-106. doi: 10.1111/jcpt.12582. Epub 2017 Jun 27.

Abstract

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.

Keywords: anticoagulation; clinical pharmacokinetics.

Publication types

  • Case Reports

MeSH terms

  • Anticoagulants / administration & dosage*
  • Anticoagulants / therapeutic use*
  • Antiphospholipid Syndrome / drug therapy*
  • Female
  • Humans
  • Middle Aged
  • Prospective Studies
  • Pyrazoles / administration & dosage
  • Pyrazoles / therapeutic use
  • Pyridones / administration & dosage
  • Pyridones / therapeutic use
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / therapeutic use

Substances

  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban