Evaluation of Crushed Tablet for Oral Administration and the Effect of Food on Apixaban Pharmacokinetics in Healthy Adults.
These studies evaluate the relative bioavailability of crushed apixaban tablets and the effect of food on apixaban pharmacokinetic properties.



An open-label, randomized, crossover study in 33 healthy adults compared the bioavailability of 2 × 5-mg apixaban tablets administered whole (reference), crushed and suspended in 30 mL of water, and crushed and mixed with 30 g of applesauce. A second open-label, randomized, crossover study in 22 healthy adults compared apixaban 1 × 5-mg tablet administered when fasted (reference) or immediately after consumption of a high-fat, high-calorie meal. Point estimates and 90% CIs for geometric mean ratios were generated for Cmax, AUC0-∞, and AUC0-t.



Cmax and AUC met bioequivalence criteria for crushed tablets in water. Cmax and AUC decreased by 21.1% and 16.4%, respectively, with the lower bound of the CIs falling below the bioequivalence criteria for crushed tablets with applesauce. Similarly, administration of whole tablets with a high-fat, high-calorie meal reduced apixaban Cmax and AUC by 14.9% and 20.1%, respectively. The exposure reductions in both studies were considered not clinically significant.



Apixaban tablets can be administered crushed or whole, with or without food. The results of these alternative methods of administration support their use in patients who have difficulty swallowing tablets. ClinicalTrials.gov identifiers: NCT02101112 and NCT01437839.
Bristol-Myers Squibb, Pennington, New Jersey. Electronic address: yan.song@bms.com.
Yan
Y
Song
Bristol-Myers Squibb, Pennington, New Jersey.
Ming
M
Chang
Pfizer Japan Inc, Tokyo, Japan.
Akiyuki
A
Suzuki
Bristol-Myers Squibb, Princeton, New Jersey.
Robert J A
RJ
Frost
Bristol-Myers Squibb, New Brunswick, New Jersey.
Anne
A
Kelly
Bristol-Myers Squibb, Princeton, New Jersey.
Frank
F
LaCreta
Bristol-Myers Squibb, Princeton, New Jersey.
Charles
C
Frost
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D004355:Drug Stability; D065427:Factor Xa Inhibitors / Q000493:pharmacokinetics*; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011728:Pyridones / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency
D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; D013607:Tablets; C522181:apixaban
apixaban; bioavailability; crushed tablet; food effect; formulation; stability