NovoSeven ® RT
Coagulation Factor VIIa (Recombinant)
Rx only
BRIEF SUMMARY. Please consult package insert for full prescribing
information.
WARNING: THROMBOSIS: Serious arterial and venous thrombotic events
following administration of NovoSeven ® RT have been reported. Discuss the
risks and explain the signs and symptoms of thrombotic and thromboembolic
events to patients who will receive NovoSeven ® RT. Monitor patients for signs
or symptoms of activation of the coagulation system and for thrombosis. [See
Warnings and Precautions]
INDICATIONS AND USAGE: NovoSeven® RT (Coagulation Factor VIIa
[Recombinant]) is a coagulation factor indicated for: Treatment of bleeding episodes
and peri-operative management in adults and children with hemophilia A or B with
inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia
with refractoriness to platelet transfusions, with or without antibodies to platelets;
Treatment of bleeding episodes and peri-operative management in adults with
acquired hemophilia
CONTRAINDICATIONS: None known.
WARNINGS AND PRECAUTIONS: Thrombosis: Serious arterial and
venous thrombotic events have been reported in clinical trials and postmarketing
surveillance. Patients with disseminated intravascular coagulation (DIC), advanced
atherosclerotic disease, crush injury, septicemia, or concomitant treatment with
aPCCs/PCCs (activated or nonactivated prothrombin complex concentrates)
and uncontrolled post-partum hemorrhage have an increased risk of developing
thromboembolic events due to circulating tissue factor (TF) or predisposing
coagulopathy [See Adverse Reactions and Drug Interactions]. Exercise caution when
administering NovoSeven ® RT to patients with an increased risk of thromboembolic
complications. These include, but are not limited to, patients with a history of
coronary heart disease, liver disease, disseminated intravascular coagulation, postoperative immobilization, elderly patients and neonates. In each of these situations,
the potential benefit of treatment with NovoSeven® RT should be weighed against
the risk of these complications. Monitor patients who receive NovoSeven ® RT
for development of signs or symptoms of activation of the coagulation system or
thrombosis. When there is laboratory confirmation of intravascular coagulation or
presence of clinical thrombosis, reduce the dose of NovoSeven ® RT or stop the
treatment, depending on the patient’s condition. Hypersensitivity Reactions:
Hypersensitivity reactions, including anaphylaxis have been reported with
NovoSeven® RT. Administer NovoSeven ® RT only if clearly needed in patients
with known hypersensitivity to NovoSeven ® RT or any of its components, or in
patients with known hypersensitivity to mouse, hamster, or bovine proteins. Should
symptoms occur, discontinue NovoSeven ® RT, administer appropriate treatment
and weigh the benefit/risks prior to restarting treatment with NovoSeven ® RT.
Antibody Formation in Factor VII Deficient Patients: Factor VII deficient
patients should be monitored for prothrombin time (PT) and factor VII coagulant
activity before and after administration of NovoSeven ® RT. If the factor VIIa activity
fails to reach the expected level, or prothrombin time is not corrected, or bleeding is
not controlled after treatment with the recommended doses, antibody formation may
be suspected and analysis for antibodies should be performed. Laboratory Tests:
Laboratory coagulation parameters (PT/INR, aPTT, FVII:C) have shown no direct
correlation to achieving hemostasis. Assays of prothrombin time (PT/INR), activated
partial thromboplastin time (aPTT), and plasma FVII clotting activity (FVII:C), may
give different results with different reagents. Treatment with NovoSeven ® has been
shown to produce the following characteristics: PT: As shown below, in patients
with hemophilia A/B with inhibitors, the PT shortened to about a 7-second plateau
at a FVII:C level of approximately 5 units per mL. For FVII:C levels > 5 units per
mL, there is no further change in PT. The clinical relevance of prothrombin time
shortening following NovoSeven ® RT administration is unknown.
PT (sec)
PT versus FVII:C
INR: NovoSeven® has demonstrated the ability to
14
normalize INR. However, INR
13
values have not been shown
12
to directly predict bleeding
11
outcomes, nor has it been
10
possible to demonstrate the
9
impact of NovoSeven® on
8
bleeding times/volume in
7
models of clinically-induced
6
bleeding in healthy volunteers
who had received Warfarin,
5
when laboratory parameters
4
(PT/INR, aPTT, thromboelas3
togram) have normalized.
2
aPTT: While administration of
1
NovoSeven® shortens the
0
30
40 prolonged aPTT in hemo0
10
20
philia A/B patients with
FVII:C (unit per mL)
NOSV15CDPR3303_Leadership_HCP_Journal_Ad_KING_BS_r2_FSU.indd 1
inhibitors, normalization has usually not been observed in doses shown to induce
clinical improvement. Data indicate that clinical improvement was associated with a
shortening of aPTT of 15 to 20 seconds. FVIIa:C: FVIIa:C levels