XARELTO® (rivaroxaban) tablets
Table 3: Bleeding Events* in EINSTEIN Extension Study
XARELTO†
20 mg
N = 598
n (%)
Placebo†
4 (0.7)
0
Decrease in Hb ≥2 g/dL
4 (0.7)
0
Transfusion of ≥2 units of whole blood
or packed red blood cells
2 (0.3)
0
Gastrointestinal
3 (0.5)
0
Menorrhagia
1 (0.2)
0
Parameter
Major bleeding event‡
Clinically relevant non-major bleeding
Any bleeding
N = 590
n (%)
32 (5.4)
7 (1.2)
104 (17.4)
63 (10.7)
* Bleeding event occurred after the first dose and up to 2 days after the
last dose of study drug. Although a patient may have had 2 or more
events, the patient is counted only once in a category.
† Treatment schedule: XARELTO 20 mg once daily; matched placebo once
daily
‡ There were no fatal or critical organ bleeding events.
Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement
Surgery: In the RECORD clinical trials, the overall incidence rate of
adverse reactions leading to permanent treatment discontinuation was
3.7% with XARELTO.
The rates of major bleeding events and any bleeding events observed in
patients in the RECORD clinical trials are shown in Table 4.
Table 4: Bleeding Events* in Patients Undergoing Hip or Knee
Replacement Surgeries (RECORD 1-3)
XARELTO 10 mg Enoxaparin†
Total treated patients
N = 4487
N = 4524
n (%)
n (%)
Major bleeding event
Fatal bleeding
Bleeding into a critical organ
Bleeding that required re-operation
Extra-surgical site bleeding
requiring transfusion of >2 units of
whole blood or packed cells
Any bleeding event‡
Hip Surgery Studies
Major bleeding event
Fatal bleeding
Bleeding into a critical organ
Bleeding that required re-operation
Extra-surgical site bleeding requiring transfusion of >2 units of whole
blood or packed cells
Any bleeding event‡
Knee Surgery Study
14 (0.3)
1 (<0.1)
2 (<0.1)
7 (0.2)
4 (0.1)
9 (0.2)
0
3 (0.1)
5 (0.1)
1 (<0.1)
261 (5.8)
N = 3281
n (%)
7 (0.2)
1 (<0.1)
1 (<0.1)
2 (0.1)
3 (0.1)
251 (5.6)
N = 3298
n (%)
3 (0.1)
0
1 (<0.1)
1 (<0.1)
1 (<0.1)
201 (6.1)
N = 1206
n (%)
7 (0.6)
0
1 (0.1)
5 (0.4)
1 (0.1)
191 (5.8)
N = 1226
n (%)
6 (0.5)
0
2 (0.2)
4 (0.3)
0
Major bleeding event
Fatal bleeding
Bleeding into a critical organ
Bleeding that required re-operation
Extra-surgical site bleeding
requiring transfusion of >2 units of
whole blood or packed cells
60 (5.0)
60 (4.9)
Any bleeding event‡
* Bleeding events occurring any time following the first dose of doubleblind study medication (which may have been prior to administration of
active drug) until two days after the last dose of double-blind study
medication. Patients may have more than one event.
† Includes the placebo-controlled period for RECORD 2, enoxaparin dosing was 40 mg once daily (RECORD 1-3)
‡ Includes major bleeding events
Following XARELTO treatment, the majority of major bleeding complications (≥60%) occurred during the first week after surgery.
Other Adverse Reactions: Non-hemorrhagic adverse reactions reported
in ≥1% of XARELTO-treated patients in the EINSTEIN Extension study are
shown in Table 5.
Table 5: Other Adverse Reactions* Reported by ≥1% of XARELTOTreated Patients in EINSTEIN Extension Study
System Organ Class
Preferred Term
Gastrointestinal disorders
Abdominal pain upper
Dyspepsia
Toothache
General disorders and administration site
conditions
Fatigue
Infections and infestations
Sinusitis
Urinary tract infection
Musculoskeletal and connective tissue
disorders
Back pain
Osteoarthritis
Respiratory, thoracic and mediastinal
disorders
Oropharyngeal pain
XARELTO
N = 598
n (%)
Placebo
N = 590
n (%)
10 (1.7)
8 (1.3)
6 (1.0)
1 (0.2)
4 (0.7)
0
6 (1.0)
3 (0.5)
7 (1.2)
7 (1.2)
3 (0.5)
3 (0.5)
22 (3.7)
10 (1.7)
7 (1.2)
5 (0.8)
6 (1.0)
2 (0.3)
* Adverse reaction (with Relative Risk >1.5 for XARELTO versus placebo)
occurred after the first dose and up to 2 days after the last dose of
study drug. Incidences are based on the number of patients, not the
number of events. Although a patient may have had 2 or more clinical
adverse reactions, the patient is counted only once in a category. The
same patient may appear in different categories.
XARELTO® (rivaroxaban) tablets
XARELTO® (rivaroxaban) tablets
Non-hemorrhagic adverse reactions reported in ≥1% of XARELTO-treated
patients in RECORD 1-3 studies are shown in Table 6.
USE IN SPECIFIC POPULATIONS
Pregnancy: Pregnancy Category C: There are no adequate or wellcontrolled studies of XARELTO in pregnant women, and dosing for
pregnant women has not been established. Use XARELTO with caution in
pregnant patients because of the potential for pregnancy related
hemorrhage and/or emergent delivery with an anticoagulant that is not
readily reversible. The anticoagulant effect of XARELTO cannot be
reliably monitored with standard laboratory testing. Animal reproduction
studies showed no increased risk of structural malformations, but
increased post-implantation pregnancy loss occurred in rabbits.
XARELTO should be used during pregnancy only if the potential
benefit justifies the potential risk to mother and fetus [see Warnings
and Precautions].
Rivaroxaban crosses the placenta in animals. Animal reproduction
studies have shown pronounced maternal hemorrhagic complications in
rats and an increased incidence of post-implantation pregnancy loss in
rabbits. R