Rivaroxaban concentrations in acute stroke patients with different dosage forms

• Published in: PloS one Vol. 14; no. 3; p. e0214132
• Main Authors: Wada, Shinichi, Inoue, Manabu, Matsuki, Takayuki, Okata, Takuya, Kumamoto, Masaya, Tagawa, Naoki, Okamoto, Akira, Miyata, Toshiyuki, Ihara, Masafumi, Koga, Masatoshi, Toyoda, Kazunori
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.03.2019; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Analysis; Anticoagulants; Biology and Life Sciences; Cardiac arrhythmia; Comparative analysis; Crushing; Dosage; Drug dosages; Factor Xa Inhibitors - administration & dosage; Factor Xa Inhibitors - blood; Factor Xa Inhibitors - therapeutic use; Female; Granular materials; Health aspects; Hemorrhage; Hospitals; Humans; Ischemia; Male; Medical research; Medicine; Medicine and Health Sciences; Neurology; Patients; People and Places; Prospective Studies; Rivaroxaban; Rivaroxaban - administration & dosage; Rivaroxaban - blood; Rivaroxaban - therapeutic use; Stroke; Stroke - blood; Stroke - drug therapy; Tablets; Thrombosis; Treatment Outcome; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0214132

The crushed-tablet rivaroxaban concentration has been previously reported to be lower than the non-crushed concentration. However, the rivaroxaban concentration of fine granules has not yet been investigated. The anticoagulation intensity of rivaroxaban with fine granules, tablets, and crushed tablets was compared in acute stroke patients to assess the efficacy of each form. Hospitalized patients over 75 years old with acute stroke who started taking rivaroxaban from April 2012 to September 2017 were included. Blood samples were drawn just before and 4 hours after taking rivaroxaban on a median of 5 days after treatment initiation for concentration measurements (C0h, C4h) based on an anti-factor Xa chromogenic assay. Of 114 patients (49 female, 83±5 years old), 97 had ischemic strokes, 9 had transient ischemic attacks, and 8 had intracerebral hemorrhages. Rivaroxaban was administered a median of 7 days after onset. Of these, 38 patients were given the 15 mg dose, and 76 were given the 10 mg dose. In the 15 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group, with no significant difference compared to the tablet group [C0h: 27.6±6.8 vs 4.0±4.1 (P = 0.01) vs. 33.3±25.2 ng/ml, (P = 0.51), respectively], as was C4h [223.0±66.6 vs 103.0±79.5 (P = 0.02) vs. 229.5±121.6 ng/ml (P = 0.88)]. In the 10 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group and comparable to that in the tablet group [23.2±7.9 vs 7.5±6.2 (P<0.01) vs 19.0±15.8 ng/ml, (P = 0.35)], as was C4h [150.7±85.4 vs 85.1±46.8 (P<0.01) vs 189.8±92.7 ng/ml (P = 0.18)]. The rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group.