Song Y, et al. – The effect of two 4–factor prothrombin complex concentrates (PCCs) on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects was appraised. Based on the results, apixaban's steady–state effect on several coagulation assessments was reversed by Cofact and Beriplex.

Methods

• Apixaban 10 mg twice daily for 3 days was given to subjects.
• Subjects received a 30-minute infusion of 50 IU/kg Cofact, Beriplex P/N (Beriplex), or saline, on Day 4, 3 hours after apixaban.
• The primary endpoint was change in endogenous thrombin potential (ETP), measured by a thrombin generation assay (TGA).
• Changes in other TGA parameters, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time, anti-FXa activity, apixaban pharmacokinetics, and safety, were involved in secondary endpoints.

Results

• Data demonstrated apixaban-related changes in ETP and several other pharmacodynamic measures following apixaban administration.
• In addition, both PCCs reversed apixaban's effect on ETP; difference of adjusted mean change from pre-PCC baseline to end of infusion was 425 (95% confidence interval [CI]: 219.8, 630.7) nM*min for Cofact and 91 (95% CI: -31.3, 212.4) nM*min for Beriplex.
• In comparison to 45 hours for placebo, both PCCs returned ETP to pre-apixaban baseline levels 4 hours after PCC infusion.
• Mean ETP peaked 21 hours after PCC initiation, then slowly decreased over the following 48 hours, for both PCCs.
• Apixaban's effect was reversed by both PCCs on TGA peak height, PT, and INR.
• Across treatments, apixaban pharmacokinetic and anti-FXa profiles were consistent.