Written in Blood
predominant HL classification based on clinical
data that indicate potential progression to Tcell histiocyte-rich large B-cell lymphoma and
a more aggressive clinical course, therefore
requiring different management.
Other research has indicated that irrespective of myeloid or mesenchymal origin, some
of these neoplasms are associated with or
preceded by FL, CLL, B- or T-lymphocytic
neoplasms, or PTCL.
Histiocytic and Dendritic Cell Neoplasms
REFERENCE
Much of the 2008 classification is still
accepted for histiocytic and dendritic cell
neoplasms (HDCN), though Erheim-Chester
disease (ECD) has been added as an entity.
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health
Organization (WHO) classification of lymphoid neoplasms. Blood. 2016 March
15. [Epub ahead of print]
EDITOR’S NOTE: The World Health Organiza-
tion also revised its classification of myeloid
neoplasms and acute leukemia, published in
the April 11, 2016, edition of Blood. Look for
our coverage of the revisions in “What To Call
What We Treat, Part II: WHO Releases Updated
Classification of Myeloid Neoplasms and Acute
Leukemia” in our June issue.
T:8.25”
S:7”
KOVALTRY [Antihemophilic Factor (Recombinant)]
Lyophilized Powder for Solution f or Intravenous Injection –
Reconstitution with Vial Adapter
Initial U.S. Approval: 2016
BRIEF SUMMARY
CONSULT PACKAGE INSERT FOR
FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
KOVALTRY, Antihemophilic Factor (Recombinant), is a
recombinant, human DNA sequence derived, full length Factor
VIII concentrate indicated for use in adults and children with
hemophilia A (congenital Factor VIII deficiency) for:
• On-demand treatment and control of bleeding episodes
• Perioperative management of bleeding
• Routine prophylaxis to reduce the frequency of bleeding
episodes
KOVALTRY is not indicated for the treatment of von Willebrand
disease.
4
CONTRAINDICATIONS
KOVALTRY is contraindicated in patients who have a history
of hypersensitivity reactions to the active substance, to any
of the excipients, or to mouse or hamster proteins [see
Description (11)].
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, are possible
with KOVALTRY. Early signs of hypersensitivity reactions,
which can progress to anaphylaxis, may include chest or throat
tightness, dizziness, mild hypotension and nausea. Discontinue
KOVALTRY if symptoms occur and seek immediate emergency
treatment.
KOVALTRY may contain trace amounts of mouse and hamster
proteins [see Description (11)]. Patients treated with this
product may develop hypersensitivity to these non-human
mammalian proteins.
5.2 Neutralizing Antibodies
Neutralizing antibody (inhibitor) formation can occur following
administration of KOVALTRY. Previously untreated patients
(PUPs) are at greatest risk for inhibitor development with all
Factor VIII products [see Adverse Reactions (6.1)]. Carefully
monitor patients for the development of Factor VIII inhibitors,
using appropriate clinical observations and laboratory tests.
If expected plasma Factor VIII activity levels are not attained or
if bleeding is not controlled as expected with administered dose,
suspect the presence of an inhibitor (neutralizing antibody)
[see Warnings and Precautions (5.5)].
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 Catheter-related Infections
Catheter-related infections may be observed when KOVALTRY is
administered via central venous access devices (CVADs). These
infections have not been associated with the product itself.
5.5 Monitoring Laboratory Tests
• Monitor plasma Factor VIII activity levels using a
validated test to confirm that adequate Factor VIII levels
have been achieved and maintained [see Dosage and
Administration (2.1)].
• M
onitor for development of Factor VIII inhibitors. Perform
a Bethesda inhibitor assay if expected Factor VIII plasma
levels are not attained or if bleeding is not controlled with
the expected dose of KOVALTRY. Use Bethesda Units (BU)
to report inhibitor titers.
6
ADVERSE REACTIONS
The most frequently reported adverse reactions in clinical trials
(≥3%) were headache, pyrexia, and pruritus (see Table 3).
6.1 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.
The safety profile of KOVALTRY was evaluated in 193 previously
treated patients (PTPs) (inclusive of 51 pediatric patients
<12 years of age) with at least three months of exposure to
KOVALTRY. The safety analysis was done using a pooled
database from three multi-center, prospective, open-label
clinical studies. The median time on study for patients ≥12
years of age was 372 days with a median of 159 exposure days
(EDs). The median time on study for patients <12 years of age
was 182 days with a median of 73 EDs. Subjects who received
KOVALTRY for perioperative management (n=5) with treatment
period of 2 to 3 weeks and those who received single doses
of KOVALTRY for PK studies (n=6) were excluded from safety
analysis. Table 3 lists the adverse reactions reported during
clinical studies. The frequency, type, and severity of adverse
reactions in children are similar to those in adults.
Table 3: Adverse Reactions in PTPs (N=193)
MedDRA Primary System Organ Class
Preferred term
Frequency
N (%)
Blood and the Lymphatic System Disorders
Lymphadenopathy
2 (1.0%)
Cardiac Disorders
2 (1.0%)
Palpitation
Sinus tachycardia
2 (1.0%)
Gastrointestinal Disorders
Abdominal pain
4 (2.1%)
Abdominal discomfort
3 (1.6%)
Dyspepsia
4 (2.1%)
General Disorders and
Administration Site Conditions
8 (4.1%)
Pyrexia
2 (1.0%)
Chest discomfort
5 (2.6%)
Injection site reactionsa
Immune System Disorders
Hypersensitivity
1 (0.5%)
Nervous System Disorders
Dizziness
2 (1.0%)
Dysgeusia
1 (0.5%)
Headache
14 (7.3%)
Psychiatric Disorders
Insomnia
5 (2.6%)
Skin and Subcutaneous Tissue Disorders
Dermatitis allergic
2 (1.0%)
Pruritus
6 (3.1%)
Rashb
5 (2.6%)
Urticaria
1 (0.5%)
Vascular disorders
Flushing
1 (0.5%)
a
Includes injection site extravasation and hematoma, infusion
site pain, pruritus, and swelling
b
Includes rash, rash erythematous, and rash pruritic