Adverse reactions occurring in ≥1% of patients undergoing hip or knee replacement surgery in
the 1 Phase II study and the 3 Phase III studies are listed in Table 4.
Table 4:
Table 7:
Bleeding Results in the AMPLIFY-EXT Study
ELIQUIS (apixaban)
2.5 mg bid
N=840
n (%)
Adverse Reactions Occurring in ≥1% of Patients in Either Group
Undergoing Hip or Knee Replacement Surgery
ELIQUIS (apixaban), Enoxaparin,
n (%)
n (%)
2.5 mg po bid
40 mg sc qd or
30 mg sc q12h
N=5924
N=5904
ELIQUIS
5 mg bid
N=811
n (%)
N=826
n (%)
Treatment of pregnant rats from implantation (gestation Day 7) to weaning (lactation Day 21)
with apixaban at a dose of 1000 mg/kg (about 5 times the human exposure based on unbound
apixaban) did not result in death of offspring or death of mother rats during labor in association
with uterine bleeding. However, increased incidence of maternal bleeding, primarily during
gestation, occurred at apixaban doses of ≥25 mg/kg, a dose corresponding to ≥1.3 times the
human exposure.
Nursing Mothers
Placebo
Major
2 (0.2)
1 (0.1)
4 (0.5)
CRNM*
25 (3.0)
34 (4.2)
19 (2.3)
Major + CRNM
27 (3.2)
35 (4.3)
22 (2.7)
Nausea
153 (2.6)
159 (2.7)
Minor
75 (8.9)
98 (12.1)
58 (7.0)
Anemia (including postoperative and hemorrhagic
anemia, and respective laboratory parameters)
153 (2.6)
178 (3.0)
All
94 (11.2)
121 (14.9)
74 (9.0)
Contusion
83 (1.4)
115 (1.9)
* CRNM = clinically relevant nonmajor bleeding.
Events associated with each endpoint were counted once per subject, but subjects may have
contributed events to multiple endpoints.
Hemorrhage (including hematoma, and vaginal
and urethral hemorrhage)
67 (1.1)
81 (1.4)
Postprocedural hemorrhage (including
postprocedural hematoma, wound hemorrhage,
vessel puncture site hematoma and catheter site
hemorrhage)
54 (0.9)
60 (1.0)
Transaminases increased (including alanine
aminotransferase increased and alanine
aminotransferase abnormal)
50 (0.8)
71 (1.2)
Aspartate aminotransferase increased
47 (0.8)
69 (1.2)
Gamma-glutamyltransferase increased
38 (0.6)
65 (1.1)
Less common adverse reactions in apixaban-treated patients undergoing hip or knee
replacement surgery occurring at a frequency of ≥0.1% to <1%:
Blood and lymphatic system disorders: thrombocytopenia (including platelet count decreases)
Vascular disorders: hypotension (including &