An Open-Label Crossover Study of the Pharmacokinetics of the 60-mg Edoxaban Tablet Crushed and Administered Either by a Nasogastric Tube or in Apple Puree in Healthy Adults

Abstract

BackgroundEdoxaban is an orally active, direct factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation and for the treatment of venous thromboembolism.ObjectivesThis study assessed the pharmacokinetics, safety, and tolerability of the edoxaban 60-mg tablet crushed and administered via a nasogastric tube in a water suspension or orally mixed in apple puree.MethodsThis phase 1, open-label, crossover study randomized 30 healthy adults to receive three edoxaban treatment regimens (oral 60-mg edoxaban tablet, or 60-mg edoxaban tablet crushed and administered via a nasogastric tube or orally in apple puree) in one of six treatment sequences.ResultsTotal edoxaban exposure was similar between the intact and crushed tablet regimens (mean area under the plasma concentration–time curve from time zero to infinity: whole tablet, 2132 ng·h/mL; nasogastric tube, 2021 ng·h/mL; apple puree, 2076 ng·h/mL). Mean maximum plasma concentration, area under the plasma concentration–time curve from time zero to the time of the last measurable concentration, terminal half-life, and apparent total body clearance values were also similar. Time to maximum plasma concentration was significantly shorter for the nasogastric tube suspension and apple puree vs. the whole tablet [Hodges–Lehmann estimate of median difference (90% confidence interval): −0.75 (−1.25, −0.28); p = 0.0003 and −0.62 (−0.99, −0.26); p = 0.0024, respectively]. The maximum plasma concentation, area under the plasma concentration–time curve from time zero to infinity, and area under the plasma concentration–time curve from time zero to the time of the last measurable concentration were similar between treatment regimens; 90% confidence interval of the geometric least-squares means ratios were within the predefined 80–125% bioequivalence criterion. The safety and tolerability of edoxaban did not differ between treatment regimens.ConclusionThe results support the use of edoxaban tablets crushed and administered either via a nasogastric tube or orally mixed in apple puree in patients who are unable to swallow solid oral dose formulations.

Potential Therapeutic Roles for Direct Factor Xa Inhibitors in Coronavirus Infections

“…However, this obstacle can potentially be overcome by the use of a crushed tablet in an aqueous suspension to be administered via nasogastric tube. In fact, a recent phase I, randomized, single-dose, crossover study presented results supporting the use of 60 mg crushed edoxaban tablets for administration as an apple puree oral preparation or an aqueous suspension via a nasogastric tube [82]. One can be skeptical about the use of a nasogastric tube given the hemodynamic instability of critically ill patients.…”

Clinical controversies in the treatment of cancer-associated venous thromboembolism

“…Both apixaban and edoxaban are film-coated tablets that display comparable AUC and maximum concentration (Cmax) when crushed and administered in applesauce or via nasogastric tube. 82,83 Rivaroxaban maintains its Cmax and AUC when crushed, but should not be used in patients with jejunal access (such as a J tube), as administration distal to the stomach is not effective (56% decrease in Cmax and 29% decrease in AUC). 39 In addition, the 15 and 20 mg doses of rivaroxaban should be taken with food to maximize bioavailability.…”

Treatment of venous thromboembolism in elderly patients in the era of direct oral anticoagulants

“…16 Rivaroxaban, apixaban, and edoxaban can be administered in the crushed form if patients are unable to swallow tablets. [17][18][19] Direct oral anticoagulants have a dual mode of elimination including hepatic metabolization and renal excretion at different degrees depending on the drug used. The proportion of renal clearance to nonrenal clearance of the absorbed DOAC is 27% for apixaban, 35% for rivaroxaban, 50% for edoxaban, and 80% for dabigatran.…”