ASH Clinical News October 2015 | Page 40
Novoeight ®, Antihemophilic Factor (Recombinant)
Rx Only
BRIEF SUMMARY: Please consult package insert for full
prescribing information
INDICATIONS AND USAGE: Novoeight ®, Antihemophilic
Factor (Recombinant), is indicated for use in adults and children
with hemophilia A (congenital factor VIII deficiency or classic
hemophilia) for: Control and prevention of bleeding episodes;
Perioperative management; Routine prophylaxis to prevent or
reduce the frequency of bleeding episodes. Novoeight ® is not
indicated for the treatment of von Willebrand disease.
CONTRAINDICATIONS: Do not use in patients who have had
life-threatening hypersensitivity reactions, including anaphylaxis,
to Novoeight ® or its components (including traces of hamster
proteins).
WARNINGS AND PRECAUTIONS: Hypersensitivity Reactions:
Hypersensitivity reactions, including anaphylaxis, are possible
with Novoeight ®. Novoeight ® contains trace amounts of hamster
proteins. Patients treated with this product may develop
hypersensitivity to these non-human mammalian proteins. Early
signs of hypersensitivity reactions that can progress to anaphylaxis
include angioedema, chest tightness, dyspnea, wheezing,
urticaria, and pruritus. Immediately discontinue administration
and initiate appropriate treatment if allergic- or anaphylactictype reactions occur. Neutralizing Antibodies: Formation of
neutralizing antibodies (inhibitors) to factor VIII can occur following
administration of Novoeight®. Monitor all patients for the development
of inhibitors by appropriate clinical observation and laboratory
testing. If the expected plasma levels of factor VIII activity are not
attained, or if bleeding is not controlled with an appropriate dose,
perform testing for factor VIII inhibitors. Monitoring Laboratory
Tests: Monitor plasma factor VIII activity levels by the one-stage
clotting assay or the chromogenic substrate assay to confirm that
adequate factor VIII levels have been achieved and maintained,
when clinically indicated. Perform assay to determine if factor VIII
inhibitor is present if expected plasma factor VIII activity levels are
not attained, or if bleeding is not controlled with the expected dose
of Novoeight ®. Determine inhibitor levels in Bethesda Units.
ADVERSE REACTIONS: The most frequently reported adverse
reactions (≥ 0.5%) were injection site reactions, increased hepatic
enzymes, and pyrexia. Clinical Trials Experience: Because
clinical trials are conducted under widely varying conditions,
adverse reaction rates observed in the clinical trials of a drug
cannot be directly compared to rates in clinical trials of another
drug and may not reflect the rates observed in clinical practice.
During the clinical development of Novoeight ®, 214 male previously
treated patients (PTPs; exposed to a factor VIII-containing
product for ≥150 days) with severe hemophilia A (factor VIII level
≤1%) received at least one dose of Novoeight ® as part of either
routine prophylaxis, on-demand treatment of bleeding episodes,
perioperative management of major and minor surgical, dental,
or other invasive procedures, or pharmacokinetic evaluation
of Novoeight®. Thirty-one subjects (14%) were <6 years of age,
32 (15%) were 6 to <12 years of age, 16 (7%) were adolescents
(12 to <16 years of age), and 135 (63%) were adults (16 years of
age and older). The subjects received a total of 33,272 injections
with a median of 127 injections of Novoeight ® (range 1-442) per
subject, and had a total of 32,929 exposure days during prevention
and treatment of bleeds. The most frequently reported adverse
reactions in previously treated patients was injection site reactions
(2.3%), increased hepatic enzymes (1.4%), and pyrexi a (0.9%).
Immunogenicity: Subjects were monitored for neutralizing
antibodies to factor VIII and binding antibodies to CHO and murine
protein. No subjects developed confirmed neutralizing antibodies
to factor VIII. One twenty-two month old child had a positive
neutralizing antibody to factor VIII of 1.3 [BU] in the Bethesda assay
after 15 exposure days that was not confirmed when checked after
20 exposure days. In vivo recovery was normal for this child and
no clinical adverse findings were observed. No patients developed
de novo anti-murine antibodies. Nineteen subjects were positive
for anti-Chinese hamster ovary (CHO) cell protein antibodies. Two
of these subjects changed from anti-CHO negative to anti-CHO
positive and 6 subjects changed from anti-CHO positive to
anti-CHO negative. The remaining 11 subjects were either positive
throughout the trials (n=6), negative at baseline and end-of trial
but with transient positive samples (n=2), or positive at baseline
and end-of trial but with negative samples in between (n=3). No
clinical adverse findings were observed in any of these subjects.
The detection of antibody formation is highly dependent on the
sensitivity and specificity of the assay. Additionally, the observed
incidence of antibody (including neutralizing antibody) positivity in
an assay may be influenced by several factors, including assay
methodology, sample handling, timing of sample collection,
concomitant medications, and underlying disease.
USE IN SPECIFIC POPULATIONS: Pregnancy: Pregnancy
Category C. Animal reproduction studies have not been conducted
with Novoeight ®. It is also not known whether Novoeight ® can cause
fetal harm when administered to a pregnant woman or can affect
reproduction capacity. Novoeight® should be given to a pregnant
woman only if clearly needed. Labor and Delivery: Novoeight®
has not been studied for use during labor and delivery. Nursing
Mothers: It is not known whether Novoeight ® is excreted in human
milk. Because many drugs are excreted in human milk, caution
should be exercised when Novoeight® is administered to a nursing
woman. Prescribe Novoeight ® only if clinically indicated. Pediatric
Use: Children have shorter half-life and lower recovery of factor VIII
than adults. Because clearance (based on per kg body weight) has
been demonstrated to be higher in the pediatric population, higher
or more frequent dosing based on body weight may be needed.
Safety and efficacy studies have been performed in 79 previously
treated pediatric patients <16 years of age. Thirty-one of these
subjects (39%) were <6 years of age, 32 (41%) were 6 to <12 years
of age, and 16 (20%) were adolescents (12 to <16 years of age).
All subjects received preventive treatment every other day or three
times weekly. A total of 244 bleeds in 54 subjects were treated
with Novoeight ®. The majority of the bleeds (91%) were of mild/
moderate severity, 41% of the bleeds were spontaneous and 58%
of the bleeds were localized in joints. Of these 244 bleeds, 210
(86%) were rated excellent or good in their response to treatment
with Novoeight ® and 3 (1.2%) were rated as having no response.
A total of 222 (91%) of the bleeds were resolved with one or two
injections of Novoeight ®. Routine prophylactic treatment has been
shown to reduce joint bleeding. Geriatric Use: Clinical studies of
Novoeight ® did not include sufficient numbers of patients aged
65 and over to determine whether they respond differently from
younger patients.
More detailed information is available upon request.
For information contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536, USA
1-844-30-EIGHT
Manufactured by:
Novo Nordisk A/S
Novo Allé, DK-2880 Bagsvaerd
Novoeight® is a registered trademark of Novo Nordisk A/S.
© 2015 Novo Nordisk
0515-00027151-1 7/2015