Latest & Greatest
Eculizumab Associated
With Increased Risk of
Meningococcal Disease
A report from the Centers for Disease
Control and Prevention (CDC) noted that
eculizumab – a drug approved by the U.S.
Food and Drug Administration (FDA) for
the treatment of paroxysmal nocturnal
hemoglobinuria and atypical hemolytic
uremic syndrome – is associated with a
1,000- to 2,000-fold risk of meningococcal
disease. The risk is also increased in those
who have received the vaccine.
In February 2017, the CDC requested
that health departments review existing
meningococcal disease case investigation
records since 2007 to identify cases. They
found that between 2008 and 2016, 16
cases of meningococcal disease occurred
in patients receiving eculizumab, and
14 of those patients had documentation
of at least one dose of meningococcal
vaccine before disease onset. All patients
(median age = 30 years; range = 16-83
years) had meningococcemia, with six
patients showing signs of meningitis. The
patients were hospitalized for a mean of
6.6 days (range = 1-14 days), and one
patient died (fatality ratio = 6%).
Source: Centers for Disease Control and Prevention press release, July 7, 2017.
FDA Committee Backs
First CAR T-Cell Therapy
The FDA’s Oncologic Drugs Advi-
sory Committee (ODAC) unanimously
recommended the approval of chimeric
antigen receptor T-cell therapy tisagen-
lecleucel (also known as CTL019) for the
treatment of pediatric and young adult
patients with relapsed/refractory B-cell
T:1
S:14
KOGENATE FS (Antihemophilic Factor [Recombinant], Formulated with Sucrose)
For Intravenous Use, Lyophilized Powder for Reconstitution with Vial Adapter
Initial U.S. Approval: 1993
BRIEF SUMMARY
CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION
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INDICATIONS AND USAGE
Kogenate ® FS is a recombinant antihemophilic factor indicated for:
• On-demand treatment and control of bleeding episodes in adults and children
with hemophilia A.
• Perioperative management of bleeding in adults and children with hemophilia A.
• Routine prophylaxis to reduce the frequency of bleeding episodes in children
with hemophilia A and to reduce the risk of joint damage in children without
pre-existing joint damage.
• Routine prophylaxis to reduce the frequency of bleeding episodes in adults
with hemophilia A.
Kogenate FS is not indicated for the treatment of von Willebrand disease.
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CONTRAINDICATIONS
Kogenate FS is contraindicated in patients who have life-threatening
hypersensitivity reactions, including anaphylaxis to mouse or hamster protein
or other constituents of the product (sucrose, glycine, histidine, sodium, calcium
chloride, polysorbate 80, imidazole, tri-n-butyl phosphate, and copper).
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WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis have been reported with
Kogenate FS. Reported symptoms included facial swelling, flushing, hives,
decrease in blood pressure, nausea, rash, restlessness, shortness of breath,
tachycardia, tightness of the chest, tingling, urticaria, and vomiting.
Kogenate FS contains trace amounts of mouse immunoglobulin G (MuIgG) and
hamster (BHK) proteins [see Description (11)]. Patients treated with this product
may develop hypersensitivity to these non-human mammalian proteins.
Discontinue Kogenate FS if symptoms occur and seek immediate emergency
treatment.
5.2 Neutralizing Antibodies
Neutralizing antibodies (inhibitors) have been reported following administration
of Kogenate FS, predominantly in previously untreated patients (PUPs) [see
Adverse Reactions (6)]. Carefully monitor patients for the development of factor
VIII inhibitors, using appropriate clinical observations and laboratory tests. 6 If
expected plasma factor VIII activity levels are not attained, or if bleeding is not
controlled with an expected dose, perform an assay that measures factor VIII
inhibitor concentration [see Warnings and Precautions (5.4)].
5.3 Cardiovascular Risk Factors
Hemophilic patients with cardiovascular risk factors or diseases may be at the
same risk to develop cardiovascular events as non-hemophilic patients when
clotting has been normalized by treatment with factor VIII.
5.4 Monitoring Laboratory Tests
• Monitor plasma factor VIII activity levels by the one-stage clotting assay to
confirm the adequate factor VIII levels have been achieved and maintained,
when clinically indicated [see Dosage and Administration (2)].
• Monitor for development of factor VIII inhibitors. Perform assay to determine
if factor VIII inhibitor is present. If expected factor VIII activity plasma levels
are not attained or if bleeding is not controlled with the expected dose of
Kogenate FS, use Bethesda Units (BU) to titer inhibitors.
If the inhibitor is less than 10 BU per mL, the administration of additional
Kogenate FS concentrate may neutralize the inhibitor and may permit an
appropriate hemostatic response.
If inhibitor titers are above 10 BU per mL, adequate hemostasis may not
be achieved. The inhibitor titer may rise following Kogenate FS infusion
as a result of an anamnestic response to factor VIII. The on-demand
treatment and control of bleeding in such patients requires the use of
alternative therapeutic approaches and agents.
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ADVERSE REACTIONS
Serious adverse reactions seen with Kogenate FS are systemic hypersensitivity
reactions, including bronchospastic reactions and/or hypotension and
anaphylaxis, and the development of high-titer inhibitors necessitating alternative
treatments to factor VIII.
The most common adverse reactions (≥ 4%) observed in clinical trials were
inhibitor formation in previously untreated patients (PUPs) and minimally treated
patients (MTPs), skin-related hypersensitivity reactions (e.g., rash, pruritus),
infusion site reactions (e.g., inflammation, pain), and central venous access
device (CVAD) associated infections.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse
reaction rates observed in th