Rivaroxaban crushed tablet suspension characteristics and relative bioavailability in healthy adults when administered orally or via nasogastric tube

Clin Pharmacol Drug Dev. 2014 Jul;3(4):321-7. doi: 10.1002/cpdd.123. Epub 2014 May 16.

Abstract

Purpose: Because some patients have difficulty swallowing a whole tablet, we investigated the relative bioavailability of a crushed 20 mg rivaroxaban tablet and of 2 alternative crushed tablet dosing strategies.

Methods: Stability and nasogastric (NG) tube adsorption characteristics of a crushed rivaroxaban tablet were assessed. Then, in 55 healthy adults, relative bioavailability of rivaroxaban administered orally as a whole tablet (Reference [Whole-Oral]), crushed tablet in applesauce suspension (Crushed-Oral), or crushed tablet in water suspension via NG tube (Crushed-NG) were determined.

Results: There were no significant changes in mean percent of non-degraded rivaroxaban recovered over 4 hours from crushed tablet suspensions (>98.4% recovery across all suspensions and time points) or after NG tube exposure (recovery: 99.1% for silicone and 98.9% for polyvinyl chloride NG tubes). Relative bioavailability was similar between Crushed-Oral and Reference dosing (Cmax and AUC∞ were within the 80-125% bioequivalence limits). Relative bioavailability was also similar between the Crushed-NG and Reference dosing (AUC∞ was within bioequivalence limits; Cmax [90% CI range: 78.5-85.8%] was only slightly below the 80% lower bioequivalence limit).

Conclusions: A crushed rivaroxaban tablet was stable and when administered orally or via NG tube, displayed similar relative bioavailability compared to a whole tablet administered orally.

Keywords: bioavailability; factor Xa inhibitor; nasogastric tube; pharmacokinetics; rivaroxaban.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Area Under Curve
  • Biological Availability
  • Drug Compounding
  • Drug Monitoring
  • Drug Stability
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / chemistry
  • Factor Xa Inhibitors / pharmacokinetics*
  • Female
  • Half-Life
  • Healthy Volunteers
  • Humans
  • Intubation, Gastrointestinal
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / adverse effects
  • Rivaroxaban / chemistry
  • Rivaroxaban / pharmacokinetics*
  • Tablets
  • Young Adult

Substances

  • Factor Xa Inhibitors
  • Tablets
  • Rivaroxaban