(HR=1.27; 95% CI 0.90-1.80;
p=0.167). (See TABLE 1 on page
44 for additional analyses.)
Conversely, children were
at a greater risk of developing
myeloid leukemia if mothers re-
ported recent use – particularly
use during pregnancy:
• recent use: HR=2.17 (95%
CI 1.22-3.87; p=0.008)
• use during pregnancy:
HR=3.87 (95% CI 1.48-
10.15; p=0.006)
In analyses of exposure
windows, the risk of developing
any type of leukemia appeared
to increase with more recent
exposure to hormonal
contraception, compared
with women who never used
—MARIE HARGREAVE, PhD
Jivi is not indicated for use in previously untreated patients.
Jivi is not indicated for use in children below 12 years of age [see
Clinical Studies (14)].
In completed clinical studies with 73 pediatric previously treated
patients (PTPs) < 12 years of age (44 PTPs < 6 years, 29 PTPs
6 to < 12 years), adverse reactions due to immune response to
PEG were observed in children less than 6 years of age. In 23% of
subjects in the age group < 6 years of age, loss of drug effect due
to neutralizing anti-PEG IgM antibodies during the first 4 exposure
days (EDs) was observed. In 7% of the subjects < 6 years of age,
loss of drug effect was combined with hypersensitivity reactions
[see Warnings and Precautions (5.3)].
8.5 Geriatric Use
Clinical studies of Jivi did not include sufficient numbers of
subjects aged 65 and over to determine whether they respond
differently from younger subjects. Other reported clinical
experience has not identified differences in responses between
the elderly and younger patients. In general, dose selection for an
elderly patient should be cautious, usually starting at the low end
of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease and
other drug therapy.
8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no data with Jivi use in pregnant women to inform on
drug-associated risk. Animal developmental and reproductive
toxicity studies have not been conducted with Jivi. It is not known
whether Jivi can cause fetal harm when administered to a pregnant
woman or can affect reproduction capacity.
In the U.S. general population, the estimated background risk
of major birth defects and miscarriage in clinically recognized
Resources at Bayer available to the patient:
pregnancies is 2–4% and 15–20%, respectively.
For Adverse Reaction Reporting, contact Bayer Medical
8.2 Lactation
Communications 1-888-84-BAYER (1-888-842-2937)
Risk Summary
There is no information regarding the presence of Jivi in human To receive more product information, contact Jivi Customer
milk, the effects on the breastfed infant, or the effects on milk Service 1-888-606-3780
production. The developmental and health benefits of breastfeeding Bayer Reimbursement HELPline 1-800-288-8374
should be considered along with the mother’s clinical need for Jivi For more information, visit http://www.Jivi.com
and any potential adverse effects on the breastfed infant from Jivi
Bayer HealthCare LLC
or from the underlying maternal condition.
Whippany, NJ 07981 USA
8.4 Pediatric Use
U.S. License No. 0008
The safety and effectiveness in patients below the age of 12 have
not been established.
6710900BS
17
PATIENT COUNSELING INFORMATION
• Advise the patient to read the FDA-approved patient labeling
(Patient Information and Instructions for Use).
• Hypersensitivity reactions are possible with Jivi [see Warnings
and Precautions (5.1)]. Warn patients of the early signs of
hypersensitivity reactions (including tightness of the chest
or throat, dizziness, mild hypotension and nausea during
infusion) which can progress to anaphylaxis. Advise patients
to discontinue use of the product if these symptoms occur
and seek immediate emergency treatment with resuscitative
measures such as the administration of epinephrine and
oxygen.
• Inhibitor formation may occur at any time in the treatment of a
patient with hemophilia A [see Warnings and Precautions (5.2)].
Advise patients to contact their physician or treatment center
for further treatment and/or assessment, if they experience a
lack of clinical response to Factor VIII replacement therapy, as
this may be a manifestation of an inhibitor.
• Allergic reactions to polyethylene glycol (PEG), a component of
Jivi, are possible. Advise patients to contact their physician or
treatment center if they experience a lack of clinical response
from their usual dose. [see Warnings and Precautions (5.3) and
Adverse Reactions (6.1)]
• Advise patients to discard all equipment, including any unused
product, in an appropriate container.
• Advise patients to consult with their healthcare provider prior to
travel. Advise patients to bring an adequate supply of Jivi while
traveling based on their current regimen of treatment.
5”
Table 3: Adverse Reactions reported for Jivi (cont’d)
MedDRA Standard
All
Subjects ≥12
System Organ Class
Subjects years of age
Preferred term
n (%)
n (%)
n=221
n=148
Vascular Disorders
Flushing
1 (1%)
1 (1%)
a
Includes Injection site pruritus and Injection site rash
b
Includes Erythema and Erythema multiforme
c
Includes Rash and Rash papular
Immunogenicity
Immunogenicity was evaluated during clinical trials with Jivi in
158 (including surgery subjects) previously treated adult and
adolescent (≥ 12 years of age) severe hemophilia A (Factor VIII
activity < 1%) subjects with previous exposure to Factor VIII
concentrates ≥ 150 EDs. There were 73 previously treated pediatric
subjects < 12 years of age [see Use in Specific Populations (8.4)].
Factor VIII Inhibitors
A Factor VIII inhibitor (1.7 BU/mL) was reported in one previously
treated adult subject. Repeat testing did not confirm the presence
of a Factor VIII inhibitor.
Anti-PEG Antibodies
Immunogenicity against PEG was evaluated by anti-PEG screening
and specific IgM anti-PEG ELISA assays. One subject (19 years
of age) with asthma, presented at 4 exposure days (EDs) with a
clinical hypersensitivity reaction after infusion of Jivi. The subject
reported headache, abdominal pain, shortness of breath, and
flushing, all of which resolved following his standard asthma
treatment. No further medical intervention was required. The
event was associated with a transient increase of IgM anti-PEG
antibody titer, which was negative upon retest during follow-up
within 30 days.
The detection of antibody formation depends 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. For these reasons, it may be
misleading to compare the incidence of antibodies to Jivi with the
incidence of antibodies to other products.
“The strength of the associations and the
biologic plausibility of hormones causing
cancer in children show that these results
are strong enough to cause concern.”