CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 4, July/August 2011
218
AFRICA
FDA approves rivaroxaban for prevention of deep-vein
thrombosis in surgery
Rivaroxaban has just become the first
factor Xa inhibitor and so far the only
oral anticoagulant to be approved in the
United States for orthopaedic surgery.
1,2
The press release issued by Bayer/
Johnson and Johnson notes that the FDA
approval is based entirely on rivaroxa-
ban’s performance in the three RECORD
trials: 1, 2 and 3, suggesting that no
further data were submitted to the FDA.
3
The data from the RECORD trials
showed significantly greater efficacy
of rivaroxaban, both in head-to-head
comparison with enoxaparin and when
comparing extended-duration (five
weeks) of rivaroxaban with short-dura-
tion enoxaparin (two weeks), followed by
placebo. In these trials, rivaroxaban and
enoxaparin demonstrated similar safety
profiles, including low rates of major
bleeding.
The recommended dose of rivaroxa-
ban is 10 mg taken orally once daily. The
initial dose should be taken at least six to
10 hours after hip-replacement surgery,
once homeostasis has been established.
The recommended duration of treatment
is 35 days, and for knee replacement it
is 12 days.
As in South Africa, the FDA prescrib-
ing information notes a contra-indication
on rivaroxaban in cases of active major
bleeding, and a cautionary use in patients
with severe renal impairment (creatinine
clearance
<
30 ml/min). Because of limit-
ed clinical experience on this aspect,
the FDA has requested a clinical trial to
evaluate the effect of renal impairment
(mild, moderate, severe), plus the concur-
rent use of P-glycoprotein and moderate
inhibitors of CYP3A4 on the pharmacoki-
netics, pharmacodynamics and safety of
rivaroxaban in volunteers, so that appro-
priate dosing recommendations can be
developed in these populations.
Usage of this agent should be avoid-
ed in patients with moderate or severe
impairment of liver function or in any
patients with any degree of hepatic
disease associated with coagulopathy.
Dabigatran etexilate, a direct thrombin
inhibitor is not approved in the United
States for prevention of deep-vein throm-
bosis (DVT) in knee and hip replacements.
Dr PJ Erasmus, Stellenbosch
Medi-clinic comments
My current experience with rivaroxaban
is based on experience of over 18 months.
I have routinely used rivaroxaban for all
my knee-replacement patients over this
period, during which I have done more the
500 knee replacements.
My regimen is to use a long-acting
subcutaneous heparin, nadroparin calci-
um (Fraxiparine) during the intra- and
peri-operative period. The reason being
that we have had, over a long period, very
few problems with postoperative bleeding
on this regime. We use spinal anaesthesia
and also prefer to start with anticoagulant
therapy the evening before the operation.
Rivaroxaban should not be used with
spinal anaesthesia and it should be start-
ed only after surgery. (Special instruc-
tions should be followed if the clinician
decides to use rivaroxaban with spinal
anaesthesia.)
On discharge, on the third or fourth
postoperative day, we start the patients
on rivaroxaban for 10 days. With this
regime we have had no adverse bleeding
episodes, DVTs or pulmonary embolisms
for the past 18 months.
J Aalbers, Special Assignments Editor
1.
Stiles S. FDA approves oral anticoagulant
rivaroxaban for DVT prevention at surgery.
Heartwire
, 1 July 2011.
2.
/
drugsatfda/index.cfm?fuseaction=Search.
DrugDetails
3.
Janssen Pharmaceuticals. FDA approves
Xarelto to help prevent DVT in patients
undergoing knee or hip replacement surgery.
2 July 2011.
