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Purpose: Some patients have difficulty swallowing whole tablets. Accordingly, this study compared the relative bioavailability of rivaroxaban administered as a whole tablet or in alternative formulations.
Methods: This was a single-center, open-label crossover study. Healthy subjects were randomized to 1 of 6 dosing sequences, with each sequence consisting of 3 treatment periods that were each separated by a 6-14 day washout. On day 1, subjects received a single 20mg oral dose of rivaroxaban as a whole tablet (Reference), a crushed tablet mixed in applesauce (Crushed-Oral) or a crushed tablet in a water-suspension administered via nasogastric tube (Crushed-NG). Dosing was followed by a 100mL standardized liquid meal. The total administered volume was identical for each group (500mL). Serial blood samples were collected predose and over 48 hours postdose. Plasma concentrations of rivaroxaban were measured and Cmax and AUC estimated. While not a formal bioequivalence study, tablet formulations were considered bioequivalent if the ratios of geometric least squares means and associated 90%CIs were within the range of 80-125%.
Results: Forty-four subjects completed the study and were included in the PK analysis set. Their mean age and BMI were approximately 38 years and 25 kg/m2, respectively. The geometric mean ratios for Cmax and AUC∞ were 90.0% and 95.4%, respectively, comparing Crushed-Oral to Reference; and 82.0% and 89.1% respectively, comparing Crushed-NG to Reference. The Cmax and AUC∞ were within the 80-125% range between the Crushed-Oral and Reference formulations. The AUC∞ but not Cmax (90% CI=78.5%-85.8%) was within the 80-125% range between the Crushed-NG and Reference formulations. The 3 tablet formulations were well tolerated.
Conclusion: Rivaroxaban tablets may be crushed and either mixed in applesauce or suspended in water and administered via an NG tube to appropriate patients who have difficulty swallowing a whole tablet.