A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Benefix Warnings, Precautions, Pregnancy, Nursing, Abuse - Coagulation Factor IX (Recombinant)
Benefix Warnings, Precautions, Pregnancy, Nursing, Abuse - Coagulation Factor IX (Recombinant)
WARNINGS
Allergic type hypersensitivity reactions, including anaphylaxis, have been
reported for all factor IX products. Frequently, these events have occurred
in close temporal association with the development of factor IX inhibitors.
Patients should be informed of the early symptoms and signs of hypersensitivity
reactions including hives, generalized urticaria, angioedema, chest tightness,
dyspnea, wheezing, faintness, hypotension, tachycardia, and anaphylaxis. Patients
should be advised to discontinue use of the product and contact their physician
and/or seek immediate emergency care, depending on the type/severity of the
reaction, if any of these symptoms occur (see PRECAUTIONS
).
Nephrotic syndrome has been reported following immune tolerance induction with
factor IX products in hemophilia B patients with factor IX inhibitors and a
history of allergic reactions to factor IX. The safety and efficacy of using
BeneFIX® for immune tolerance induction has not been established.
Since the use of factor IX complex concentrates has historically been associated
with the development of thromboembolic complications, the use of factor IX-containing
products may be potentially hazardous in patients with signs of fibrinolysis
and in patients with disseminated intravascular coagulation (DIC).
PRECAUTIONS
General
Historically, the administration of factor IX complex concentrates derived
from human plasma, containing factors II, VII, IX and X, has been associated
with the development of thromboembolic complications. 1 Although
BeneFIX® contains no coagulation factor other than factor IX, the potential
risk of thrombosis and DIC observed with other products containing factor IX
should be recognized. Because of the potential risk of thromboembolic complications,
caution should be exercised when administering this product to patients with
liver disease, to patients post-operatively, to neonates, or to patients at
risk of thromboembolic phenomena or DIC. In each of these situations, the benefit
of treatment with BeneFIX® should be weighed against the risk of these complications.
Twelve days after a dose of BeneFIX® for a bleeding episode, one hepatitis
C antibody positive patient developed a renal infarct. The relationship of the
infarct to prior administration of BeneFIX® is uncertain but was judged to be
unlikely by the investigator. The patient continued to be treated with BeneFIX®.
Activity-neutralizing antibodies (inhibitors) have been detected in patients
receiving factor IX-containing products. As with all factor IX products, patients
using BeneFIX® should be monitored for the development of factor IX inhibitors
(see CLINICAL PHARMACOLOGYand WARNINGS
). Patients with factor
IX inhibitors may be at an increased risk of anaphylaxis upon subsequent challenge
with factor IX 2 . Patients experiencing allergic reactions should
be evaluated for the presence of inhibitor. Preliminary information suggests
a relationship may exist between the presence of major deletion mutations in
a patient's factor IX gene and an increased risk of inhibitor formation and
of acute hypersensitivity reactions. Patients known to have major deletion mutations
of the factor IX gene should be observed closely for signs and symptoms of acute
hypersensitivity reactions, particularly during the early phases of initial
exposure to product. In view of the potential for allergic reactions with factor
IX concentrates, the initial (approximately 10-20) administrations of factor
IX should be performed under medical supervision where proper medical care for
allergic reactions could be provided.
Dosing of BeneFIX® may differ from that of plasma-derived factor IX products
(see CLINICAL PHARMACOLOGYand DOSAGE AND ADMINISTRATION ).
Information for Patients
Patients should be informed of the early symptoms and signs of hypersensitivity
reactions including hives, generalized urticaria, angioedema, chest tightness,
dyspnea, wheezing, faintness, hypotension, tachycardia, and anaphylaxis. Patients
should be advised to discontinue use of the product and contact their physician
and/or seek immediate emergency care, depending on the type/severity of the
reaction, if any of these symptoms occur. Patients experiencing allergic reactions
should be evaluated for the presence of inhibitor.
Carcinogenesis, Mutagenesis, Impairment of Fertility
BeneFIX®, Coagulation Factor IX (Recombinant), has been shown to be nonmutagenic
in the Ames assay and nonclastogenic in a chromosomal aberrations assay. No
investigations on carcinogenesis or impairment of fertility have been conducted.
Pregnancy Category C
Animal reproduction and lactation studies have not been conducted with BeneFIX®,
Coagulation Factor IX (Recombinant). It is not known whether BeneFIX® can affect
reproductive capacity or cause fetal harm when given to pregnant women. BeneFIX®
should be administered to pregnant and lactating women only if clearly indicated.
Pediatric Use
Safety and efficacy studies are ongoing in previously treated children and
adolescents and in previously untreated children (see CLINICAL PHARMACOLOGY
, WARNINGS
and PRECAUTIONS
).
top
