XARELTO® (rivaroxaban) tablets
XARELTO® (rivaroxaban) tablets
XARELTO® (rivaroxaban) tablets
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 (%)
* Adverse reaction occurring any time following the first dose of doubleblind medication, which may have been prior to administration of
active drug, until two days after the last dose of double-blind study
medication
† Includes the placebo-controlled period of RECORD 2, enoxaparin
dosing was 40 mg once daily (RECORD 1-3)
Other clinical trial experience: In an investigational study of acute
medically ill patients being treated with XARELTO 10 mg tablets, cases of
pulmonary hemorrhage and pulmonary hemorrhage with bronchiectasis
were observed.
Postmarketing Experience: The following adverse reactions have been
identified during post-approval use of rivaroxaban. Because these
reactions are reported voluntarily from a population of uncertain size, it
is not always possible to reliably estimate their frequency or establish a
causal relationship to drug exposure.
Blood and lymphatic system disorders: agranulocytosis, thrombocytopenia
Gastrointestinal disorders: retroperitoneal hemorrhage
Hepatobiliary disorders: jaundice, cholestasis, hepatitis (including
hepatocellular injury)
Immune system disorders: hypersensitivity, anaphylactic reaction,
anaphylactic shock, angioedema
Nervous system disorders: cerebral hemorrhage, subdural hematoma,
epidural hematoma, hemiparesis
Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome
DRUG INTERACTIONS
Rivaroxaban is a substrate of CYP3A4/5, CYP2J2, and the P-gp and ATPbinding cassette G2 (ABCG2) transporters. Inhibitors and inducers of
these CYP450 enzymes or transporters (e.g., P-gp) may result in changes
in rivaroxaban exposure.
Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport
Systems: In drug interaction studies evaluating the concomitant use with
drugs that are combined P-gp and CYP3A4 inhibitors (ketoconazole,
ritonavir, clarithromycin, erythromycin and fluconazole), increases in
rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa
inhibition and PT prolongation) were observed. The increases in
exposure ranged from 30% to 160%. Significant increases in rivaroxaban
exposure may increase bleeding risk [see Clinical Pharmacology (12.3) in
full Prescribing Information].
When data suggest a change in exposure is unlikely to affect bleeding
risk (e.g., clarithromycin, e