Rivaroxaban concentrations in acute stroke patients with different dosage forms

Abstract

BackgroundThe 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.Methods and findingsHospitalized 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)].ConclusionsThe rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group.

The Clinical Significance of Drug–Food Interactions of Direct Oral Anticoagulants

“…Drug release in the distal small intestine, or ascending colon, leads to a further reduction in its exposure [26]. For rivaroxaban, there is no contraindication to crushing tablets and mixing them with water or apple mousse to facilitate drug delivery [27]. Approximately 30% of rivaroxaban is excreted unchanged by the kidneys with P-gp and BCRP, and 6% via glomerular filtration.…”

Fixed Combination of Rivaroxaban and Aspirin: Tablet For-Mulation and Analytical Method Development

“…It has been approved in numerous countries for thromboprophylaxis after elective hip or knee arthroplasty [7,8]. Rivaroxaban is classified as a class II substance in the Biopharmaceutics Classification System (BCS), is practically insoluble in water, its absorption site is the proximal small intestine, its Tmax is 2-4 hours, its oral bioavailability is 80-100 %, and its chemical structure is shown in Figure 1 [9,10]. Aspirin, also known as acetylsalicylic acid (ASA), is a non-steroidal anti-inflammatory (NSAID).…”