Variation in Plasma Levels of Apixaban and Rivaroxaban in Clinical Routine Treatment of Venous Thromboembolism

Figures

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  Figure 1. Identification and inclusion of patient data. 1 Including dabigatran (n = 92) and edoxaban (n = 83). 2 Any dosage regimen other than apixaban 5 or 2.5 mg twice daily, and rivaroxaban 20 or 10 mg once daily. 3 Thereof 43 patients taking rivaroxaban 15 mg once daily. 4 Time post-dose >18 h for apixaban, and >36 h for rivaroxaban. DOAC—direct oral anticoagulant; VTE—venous thromboembolism.

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  Figure 2. Plasma levels of apixaban and rivaroxaban. Anti-Xa activity was measured in plasma samples obtained at the indicated intervals following intake of (A) apixaban 5 mg twice daily (bis in die, BD) (n = 360), (B) apixaban 2.5 mg BD (n = 365), (C) rivaroxaban 20 mg once daily (OD) (n = 1180), and (D) rivaroxaban 10 mg OD (n = 291). Plasma concentrations were calculated using drug-specific calibrators. Red lines indicate the percentile ranges of observed plasma levels at peak and trough post-dose intervals. Arrows indicate the expected percentile ranges, 5th–95th percentile for apixaban (summary of product characteristics, SmPC [9]), 10th–90th percentile (orange, SmPC [10]) or 5th–95th percentile (green, Mueck et al. [11,12]) for rivaroxaban.

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  Figure 3. Dependence of drug levels on age. Anti-Xa activity was measured in plasma samples obtained (A) 3–4 h after intake of apixaban 5 mg (n = 72), (B) 2–4 h after intake of rivaroxaban 20 mg (n = 476), (C) 20–28 h after intake of rivaroxaban 20 mg (n = 312), and (D) 2–4 h after intake of rivaroxaban 10 mg (n = 80). Plasma concentrations were calculated using drug-specific calibrators. BD—bis in die, twice daily; OD—once daily; r—Pearson’s correlation coefficient.

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  Figure 4. Dependence of rivaroxaban plasma levels on body weight. Anti-Xa activity was measured in plasma samples obtained 2–4 h after intake of rivaroxaban 20 mg (n = 476). Rivaroxaban plasma concentrations were calculated using drug-specific calibrators. OD—once daily; r—Pearson’s correlation coefficient.

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  Figure 5. Intra-individual agreement of drug levels. Anti-Xa activity was measured in plasma samples obtained at two different visits (I and II) from patients following intake of (A) apixaban (n = 156) and (B) rivaroxaban (n = 234) at identical dosages and a difference of 4 h or less between post-dose intervals. Plasma concentrations of apixaban and rivaroxaban were calculated using drug-specific calibrators. r—Pearson’s correlation coefficient.