PI-072

Y. Song,1 M. Chang,2 R. Frost,1 A. Kelly,3 F. LaCreta,1 C. Frost1; 1Bristol-Myers Squibb, Princeton, NJ, 2Bristol-Myers Squibb, Pennington, NJ, 3Bristol-Myers Squibb, New Brunswick, NJ

BACKGROUND: Administration of crushed tablets may benefit patients who have difficulty swallowing solid dosage forms. The relative bioavailability of apixaban administered as crushed tablets suspended in water or mixed with applesauce vs. whole tablets was evaluated.
METHODS: This was an open-label, randomized, crossover study in 33 healthy subjects. Treatments were 2 x 5 mg apixaban tablets administered whole, crushed and suspended in 30 mL water, and crushed and mixed with 30 g applesauce. Point estimates and 90% confidence intervals (CIs) for geometric mean ratios were generated for Cmax, AUC, and AUC0-T.
RESULTS: The ratio of AUC for crushed tablets in water or with applesauce vs. whole tablets was 103% and 83.6%, respectively (Table). Both AUCs and Cmax met bioequivalence criteria for crushed tablets suspended in water, but the lower bound of CIs fell below the bioequivalence criteria for crushed tablets mixed with applesauce.
CONCLUSION: Apixaban bioavailability was comparable between whole tablets and crushed tablets suspended in water. Apixaban bioavailability was slightly lower when crushed tablets were mixed with applesauce, though the decrease is not considered clinically relevant. The results from these alternative methods of administration support their use in patients who have difficulty swallowing tablets.
TreatmentCmax (ng/mL) geometric mean (%CV)AUC (ng•h/mL) geometric mean (%CV)AUC0–T (ng•h/mL) geometric mean (%CV)Tmax (h)
median (Range)
T-HALF (h)
mean (SD)
A) 2 x 5 mg apixaban tablets (n=32)233 (27)2443 (27)2406 (27) 2.00 (1.00-5.00)12.4 (5.39)
B) 2 x 5 mg apixaban tablets crushed and suspended in 30 mL water (n=33)249 (23)2528 (22)2488 (22)2.00 (0.583-4.00)12.2 (5.19)
C) 2 x 5 mg apixaban tablets crushed and mixed with 30 g applesauce (n=32)185 (23)2044 (22)2003 (23)2.00 (1.00-4.00)12.5 (5.05)
ComparisonRatio (90% CI) of adjusted geometric meanRatio (90% CI) of adjusted geometric meanRatio (90% CI) of adjusted geometric mean
B vs A1.05
(0.993, 1.12)
1.03
(0.982, 1.08)
1.03
(0.981, 1.08)
C vs A0.789
(0.742, 0.840)
0.836
(0.798, 0.875)
0.832
(0.794, 0.871)