Calendar
2nd AMP Global 2019 Congress on
Molecular Pathology
Anaheim, CA
Oncology Nursing Society Annual Congress
May 16 – 18, 2019
Hong Kong, China
The Association for Molecular Pathology’s second
congress brings together a multidisciplinary network of
molecular and diagnostics professionals to discuss its
applications in health care.
April 11 – 14, 2019
Anaheim, CA
The 44th Annual Congress features the latest in
research, clinical practice, advanced practice, and
leadership, presented by oncology nursing professionals.
4th International Symposium on
Immunotherapy
May 24 – 25, 2019
London, UK
The Institute for Cancer Vaccines and Immunotherapy’s
symposium will feature discussions about the impact
of immunotherapies like checkpoint inhibitors and
chimeric antigen receptor T-cell therapies in a variety
of tumor types.
2019 American Society of Clinical
Oncology Annual Meeting
May 31 – June 4, 2019
Chicago, IL
The American Society of Clinical Oncology's annual
meeting brings together 32,000 oncology profession-
als from around the world to discuss state-of-the-art
treatment modalities, new therapies, and ongoing
controversies in the field.
ADVATE [Antihemophilic Factor (Recombinant)]
Rx Only
Lyophilized Powder for Reconstitution for Intravenous Injection
BRIEF SUMMARY: Consult the Full Prescribing Information for complete product information.
INDICATIONS AND USAGE ADVERSE REACTIONS
ADVATE is a recombinant antihemophilic factor indicated for use in children and
adults with hemophilia A for:
• Control and prevention of bleeding episodes.
• Perioperative management.
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
ADVATE is not indicated for the treatment of von Willebrand disease. Serious adverse reactions seen with ADVATE are hypersensitivity reactions,
including anaphylaxis, and the development of high-titer inhibitors necessitating
alternative treatments to factor VIII.
CONTRAINDICATIONS
ADVATE is contraindicated in patients who have life-threatening hypersensitivity
reactions, including anaphylaxis, to mouse or hamster protein or other constituents
of the product (mannitol, trehalose, sodium chloride, histidine, Tris, calcium
chloride, polysorbate 80, and/or glutathione).
WARNINGS and PRECAUTIONS
Hypersensitivity Reactions
Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported
with ADVATE. Symptoms include dizziness, paresthesia, rash, flushing, facial
swelling, urticaria, dyspnea, pruritus, and vomiting.
ADVATE contains trace amounts of mouse immunoglobulin G (MuIgG)
≤0.1 ng/IU ADVATE, and hamster proteins ≤1.5 ng/IU ADVATE. Patients treated with
this product may develop hypersensitivity to these non-human mammalian proteins.
Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate
emergency treatment.
Neutralizing Antibodies
Neutralizing antibodies (inhibitors) have been reported following administration
of ADVATE predominantly in previously untreated patients (PUPs) and previously
minimally treated patients (MTPs). Monitor all patients for the development of
factor VIII inhibitors by appropriate clinical observation and laboratory testing.
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.
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.
• Monitor for development of factor VIII inhibitors. Perform the Bethesda 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
ADVATE, use Bethesda Units (BU) to titer inhibitors.
– If the inhibitor titer is less than 10 BU per mL, the administration of additional
antihemophilic factor concentrate may neutralize the inhibitor and may permit
an appropriate hemostatic response.
– If the inhibitor titer is above 10 BU per mL, adequate hemostasis may not
be achieved. The inhibitor titer may rise following ADVATE infusion as a
result of an anamnestic response to factor VIII. The treatment or prevention
of bleeding in such patients requires the use of alternative therapeutic
approaches and agents.
The most common adverse reactions observed in clinical trials (frequency greater
than 5% of subjects) were pyrexia, headache, cough, nasopharyngitis, arthralgia,
vomiting, upper respiratory tract infection, limb injury, nasal congestion, and diarrhea.
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.
ADVATE has been evaluated in eleven clinical trials in previously treated patients
(PTPs) and one trial in previously untreated patients (PUPs) with severe to
moderately severe hemophilia A (factor VIII ≤2% of normal). A total of 418 subjects
have been treated with ADVATE as of January 2012. Total exposure to ADVATE
was 63,188 infusions. The median duration of participation per subject was
397 (min-max: 2−1620) days and the median number of exposure days to
ADVATE per subject was 97 (min-max: 1−709).
The summary of adverse reactions with a frequency >5% are shown in
Table 1 below.
No subject was withdrawn from a clinical trial due to an adverse reaction.
Table 1
Summary of Adverse Reactions (ARs) a with a Frequency
Greater than 5% in 418 b Subjects
MedDRA c System
Organ Class
MedDRA
Preferred Term
Number of
Adverse
Reactions Number
of
Subjects Percent
of
Subjects
General Disorders
and Administration
Site Conditions Pyrexia 110 66 16
Nervous System
Disorders Headache 114 56 13
Respiratory, Thoracic
and Mediastinal
Cough
Disorders 86 54 13
Infections and
Infestations Nasopharyngitis 72 49 12
Musculoskeletal and
Connective Tissue
Disorders Arthralgia 49 32 8
Gastrointestinal
Disorders Vomiting 41 31 7
Infections and
Infestations Upper Respiratory
Tract Infection 35 29 7
Injury, Poisoning
and Procedural
Complications Limb Injury 56 25 6
Respiratory, Thoracic
and Mediastinal
Nasal Congestion
Disorders 32 25 6
Gastrointestinal
Disorders Diarrhea 29 24 6
Injury, Poisoning
and Procedural
Complications Procedural Pain 26 22 5
Respiratory, Thoracic
Oropharyngeal
and Mediastinal
Pain
Disorders 25 22 5
Infections and
Infestations 30 21 5
Ear Infection
a
Adverse reactions are defined as all adverse events that occurred (a) within 24 hours after being
infused with investigational product, or (b) all adverse events assessed related or possibly related
to investigational product, or (c) adverse events for which the investigator’s or sponsor’s opinion of
causality was missing or indeterminate. b The ADVATE clinical program included 418 treated subjects
from 11 completed studies in PTPs and 1 completed trial in PUPs. c MedDRA version 8.1 was used.