Hepatitis C
& Commercial
Sterilants and
Disinfectants
Applied and
Environmental
Microbiology,
September 1999,
p. 4255-4260,
Vol. 65, No. 9
0099-2240/99/$04.00+0
Bacterial
Spores Survive
Treatment with
Commercial
Sterilants and
Disinfectants
Jose-Luis
Sagripanti* and
Aylin Bonifacino
Molecular
Biology Branch
(HFZ-113),
Division of Life
Sciences, Office
of Science and
Technology,
Center for
Devices and
Radiological
Health, Food and
Drug
Administration,
Rockville,
Maryland
ABSTRACT
This study
compared the
activity of
commercial
liquid
sterilants and
disinfectants on
Bacillus
subtilis spores
deposited on
three types of
devices made of
noncorrodible,
corrodible, or
polymeric
material.
Products like
Renalin, Exspor,
Wavicide-01,
Cidexplus, and
cupric ascorbate
were tested
under conditions
specified for
liquid
sterilization.
These products,
at the shorter
times indicated
for
disinfection,
and popular
disinfectants,
like Clorox,
Cavicide, and
Lysol were also
studied. Data
obtained with a
sensitive and
quantitative
test suggest
that commercial
liquid
sterilants and
disinfectants
are less
effective on
contaminated
surfaces than
generally
acknowledged.
TEXT
Different
reports agree
that 5 to 10%
(1.75 to 3.5
million) of the
35 million
patients
annually
admitted to
hospitals in the
United States
acquire an
infection during
hospitalization
(5, 6, 22). More
than 850,000 of
these have been
estimated to be
implant- and
device-related
infections (2).
Abundant data
linking the
transmission of
various diseases
(including AIDS,
tuberculosis,
and
Creutzfeldt-Jakob
disease, as well
as hospital
epidemics of
infections with
Pseudomonas,
Serratia, and
Bacillus
species) to
medical devices
suggest that the
effectiveness of
disinfection and
sterilization
practices has
been
overestimated
(21).
The capacity to
kill bacterial
spores
determines how a
commercial
product will be
marketed.
Disinfectants
are not expected
to kill all
bacterial spores
and are used to
decontaminate
devices that
ordinarily do
not penetrate
tissues or that
touch only
intact skin (3,
16, 25).
Sterilants are
expected to kill
all
microorganisms,
including
bacterial
spores, and are
used to treat
devices that
penetrate tissue
or present a
high risk if
unsterile.
Viable spores
still attached
to various
materials could
remain
undetected by
current
sporicidal tests
(1), resulting
in
overestimation
of the
sporicidal
activity of
sterilizing
agents (4, 7,
11, 12, 14, 15).
The goal of this
study was to
compare the
sporicidal
activities of
commercial
liquid
sterilants under
manufacturer-specified
conditions by
using a
sensitive method
able to
quantitatively
account for the
survival of all
spores on
contaminated
carrier devices.
Selection of
carrier devices.
The device to
which spores are
attached might
alter the
sporicidal
activity of some
germicidal
agents (19).
Therefore, the
criteria used to
select the
carrier devices
that we tested
were based on
the following
practical
considerations:
(i) diverse
material
composition,
(ii) geometry
representative
of medical
devices, (iii)
similar spore
load capacities,
(iv) size
amenable to
microtesting,
and (v) cost.
Miniature
stainless steel
machine screws
(no. 0/80, pan
head, 1.5 mm in
diameter, and
12.5 mm long)
were purchased
at a local
hardware store
(Home Depot,
Rockville, Md.)
or from Thompson
& Cooke
(Bladensburg,
Md.). Dental
burs (FG 557)
made of carbon
steel were
manufactured by
Midwest Dental
Products
Corporation (Des
Plaines, Ill.).
Medical-grade
silicone rubber
tubing, 3.1-mm
outer diameter
and 1.5-mm inner
diameter (Silastic;
catalog no.
602-285), was
manufactured by
Dow Corning
Corporation
Medical Products
(Midland, Mich.)
and used in
12.5-mm-long
sections. All
devices were
cleaned prior to
use by washing
with detergent,
rinsing three
times with
distilled water,
washing once in
acetone, and
rinsing again in
distilled water
before
sterilization by
autoclaving. The
devices were
immersed 5 mm
deep in
spore-loading
suspensions.
This procedure
contaminated
areas of 20, 40,
and 78 mm2 on
dental burs,
screws, and
tubing,
respectively.
Likely due to
differences in
geometry and
materials, the
test described
below loaded
similar numbers
of spores onto
the three
devices in spite
of the different
immersed areas.
The miniature
stainless steel
screws and small
sections of
medical-grade
silicone rubber
tubing were
small enough to
fit our
microtest format
and inexpensive
(costing 6 and 3
cents each,
respectively).
Easy
availability of
tubing, burs,
and screws made
custom
manufacturing of
carriers
unnecessary.
Their low cost
allowed these
carriers to be
used only once
and then
discarded, thus
preventing spore
carryover and
the need to wash
and sterilize
the carriers
between tests.
Direct
measurement of
spores loaded
onto carriers.
Spores of
Bacillus
subtilis subsp.
globigii (Spordex)
were purchased
from AMSCO
American
Sterilizer Co.
(Erie, Pa.) with
a reported D
value for
dry-heat killing
at 160°C of 2.2
min and a D
value for
ethylene oxide
killing (600
mg/liter at
54°C) of 3.5
min,
respectively.
The number of
spores loaded
onto carriers
was determined
by using
radioactively
labeled spores.
A method that
produces
dry-heat-resistant
spores in
synthetic medium
(8, 13, 23) was
modified in our
laboratory so
that it would
result in
maximum
incorporation of
radiolabeled
precursor as
previously
described (19).
A rapidly
growing culture
(106 bacteria in
5 ml) was
inoculated into
300 ml of
synthetic
sporulating
medium in which
methionine was
replaced with
radioactive
L-[methyl-14C]methionine
(0.33 Ci/ml;
NEC165H; 50 mCi/mmol;
New England
Nuclear, Boston,
Mass.). After 5
days of
incubation at
32°C in a shaker
operating at 140
rpm, cultures
were chilled in
ice and spores
were pelleted by
centrifugation
for 30 min at
900 × g in a
Beckman TJ-R
refrigerated
centrifuge.
After five
cycles of
centrifugation
and resuspension
in new
Luria-Bertani
(LB) broth, the
radioactivity in
the supernatant
was reduced to
less than 2% of
the
radioactivity in
the pellet
containing the
spores. Samples
from each batch
of spores
radioactively
labeled and
concentrated in
our laboratory
or
nonradiolabeled
spores obtained
commercially (Spordex)
were
microscopically
examined and
exposed to acid
for confirmation
of spore
morphology and
chemical
resistance as
previously
described (18).
No vegetative
cells (rods)
were observed
during the
counting of
1,000
radioactively
labeled or
nonlabeled
spores. Spores
were exposed for
various time
periods to
either deionized,
glass-distilled,
autoclave-sterile
water (controls)
or hydrochloric
acid (2.5 N).
After exposure
they were
neutralized with
ice-cold LB
broth (Advanced
Biotechnology
IC, Columbia,
Md.) and
titrated onto
broth-agar (LB
broth [Miller-Difco,
Detroit, Mich.],
1.5% Agar Select
[Gibco-BRL,
Paisley,
Scotland])
plates 100 mm in
diameter.
Typical spore
survival in
hydrochloric
acid for 5 and
10 min was 100
and 88%,
respectively.
Spores labeled
with
[14C]methionine
were diluted in
LB broth, and
identical
aliquots were
either titrated
for viability or
counted for
radioactivity.
The specific
activity of each
spore
preparation was
obtained from
the slope of the
regression line
of spore number
(as determined
by titration)
versus
incorporated 14C
label (measured
by scintillation
counting). We
transferred
various devices
to Eppendorf
polypropylene
tubes (1.5 ml)
containing 50 µl
of 14C-labeled
spores at
different
concentrations.
Each device was
immersed in a
separate
spore-loading
suspension for
30 min. The
devices were
then removed
from the loading
suspension with
forceps and
dried for 10 min
under vacuum
(Speed Vac;
Savant,
Farmingdale,
N.Y.). Each
50-µl suspension
was used once
and then
discharged.
The spore load
on each device
was estimated by
immersing the
loaded devices
in scintillation
liquid,
measuring
radioactivity,
and multiplying
this value by
the specific
activity of the
preparation. One
large batch with
a specific
activity of 1.7
× 103 ± 0.3 ×
103 spores per
cpm was used for
final
calibration of
all devices. The
number of spores
attached to no.
0/80 stainless
steel screws
(ranging from
6.0 × 106 to 6.5
× 106) was
comparable to
that loaded into
medical-grade
silicone rubber
tubing (3.8 ×
106) immersed in
a spore
suspension with
a similar spore
concentration
(1.7 × 109/ml).
The increase in
the number of
spores loaded
onto the
stainless steel
screws or
silicone rubber
tubing was
approximately
linear with
increasing
concentrations
of the loading
suspension in
the range of 107
to 1010
spores/ml. This
contaminating
procedure
loaded, on
average, 3
spores per 1,000
spores/ml of the
loading
suspension.
Sterilants and
disinfectants.
Cidexplus (3.4%
glutaraldehyde,
pH 8.0; Johnson
and Johnson
Medical Inc.,
Arlington, Tex.)
was activated as
specified and
used full
strength at 21°C
over a period of
either 10 h, for
sterilization,
or 20 min, as
indicated for
high-level
disinfection.
Exspor (Alcide
Corp., Redmond,
Wash.),
containing 1.52%
sodium chlorite,
was activated
daily before
experiments by
mixing 1 part
base
concentrate, 4
parts water, and
1 part activator
(yielding a pH
between 2.3 and
2.7). The label
prescribes the
treatment of
medical items
with an Exspor-activated
solution for 10
h to achieve
sterilization
and for 1 to 3
min for killing
of Mycobacterium
sp. and other
bacteria,
pathogenic
fungi, and
viruses on hard
surfaces.
Renalin (Renal
Systems Division
of Minntech
Corp.,
Minneapolis,
Minn.), a
mixture of 20.0%
hydrogen
peroxide and
4.0%
peroxyacetic
acid, was used
as recommended
for
sterilization at
a dilution of
1:5 (final
dilution; pH
1.8) in sterile,
deionized, and
glass-distilled
water for an
11-h exposure.
Wavicide-01 (2%
glutaraldehyde;
Wave Energy
Systems, Wayne,
N.J.) was used
full strength
for 10 h at 21°C
as a sterilant
or at a 1:4
dilution for 10
min (at room
temperature
[21°C]), as
specified for
killing of
vegetative
bacteria and
viruses. Clorox
(5.25% sodium
hypochlorite,
manufactured by
The Clorox
Company,
Oakland, Calif.)
was used at a
1:21 dilution,
as recommended
for
disinfection.
Lysol I.C.
(7.24%
o-benzyl-p-chlorophenol
and 2.23% o-phenylphenol;
National
Laboratories,
Montvale, N.J.)
was used at the
1:128 dilution
specified for
use in
hospitals,
nursing homes,
dental offices,
and other
institutional
facilities as a
germicidal,
tuberculocidal,
pseudomonacidal,
staphylococcidal,
fungicidal, and
virucidal
compound.
Cavicide (15.30%
isopropanol and
0.25% diisobutyl
phenoxyethoxyethyl
dimethyl benzyl
ammonium
chloride; Micro
Aseptic
Products, Inc.,
Palatine, Ill.)
was used full
strength, as
specified for
disinfection of
noncritical
medical
instruments.
Cupric chloride
(CuCl2 · 2H2O;
Mallinckrodt
Specialty
Chemicals,
Paris, Ky.),
L-ascorbic acid,
and (30% wt/vol)
hydrogen
peroxide (both
from Aldrich
Chemical,
Milwaukee, Wis.)
were used in a
mixture (0.5%
cupric ions [as
cupric
chloride]-0.1%
ascorbic
acid-0.003%
hydrogen
peroxide, pH
2.9). 
Hepatitis C
Survives
Treatment with
Commercial
Sterilants and
Disinfectants
http://www.safetec.com/sanizide.php3
2001
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as,
non-corrosive.
Choosing
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helps you to
comply with the
OSHA Bloodborne
Pathogens
Standard, which
requires the use
of an
"appropriate
disinfectant"
that is
tuberculocidal
and virucidal
against HIV-1
and HBV. For use
on: glass,
porcelain,
ceramic, metal,
polyethylene,
polypropylene,
vinyl,
polyester,
rubber,
bakelite, and
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2001
Read down to the
'Warnings' it's
still not 100%
HEPATITIS B
IMMUNE GLOBULIN
(HUMAN)Rx
NABI-HB™ (Nabi)
Solvent/Detergent
Treated and
Filtered
DESCRIPTION
Hepatitis B
Immune Globulin
(Human), Nabi-HB™,
is a sterile
solution of
immunoglobulin
(5 ± 1% protein)
containing
antibodies to
hepatitis B
surface antigen
(anti-HBs). It
is prepared from
plasma donated
by individuals
with high titers
of anti-HBs. The
plasma is
processed using
a modified Cohn
6 / Oncley 9
cold-alcohol
fractionation
process 1,2 with
two added viral
reduction steps
described below.
Nabi-HB™ is
formulated in
0.075 M sodium
chloride, 0.15 M
glycine, and
0.01%
polysorbate 80,
at pH 6.2. The
product is
supplied as a
nonturbid
sterile liquid
in single dose
vials and
appears as clear
to opalescent.
It contains no
preservative and
is intended for
single use by
the
intramuscular
route only.
The
manufacturing
steps for
Nabi-HB™ are
designed to
reduce the risk
of transmission
of viral
disease. The
solvent/detergent
treatment step,
using tri- n
-butyl phosphate
and Triton®
X-100, is
effective in
inactivating
known enveloped
viruses such as
hepatitis B
virus (HBV),
hepatitis C
virus (HCV), and
human
immunodeficiency
virus (HIV) 3 .
Virus
filtration,
using a Planova®
35 nm Virus
Filter, is
effective in
reducing some
known enveloped
and
non-enveloped
viruses 4 . The
inactivation and
reduction of
known enveloped
and
non-enveloped
model viruses
were validated
in laboratory
studies as
summarized in
the following
table:
Table 1 Log
Reduction of
Test Viruses 5
Model Virus:
Envelope/Genome:
Manufacturing
Step HIV
HIV
yes/RNA BVD
HCV
yes/RNA Test
Virus
PRV
HBV
yes/DNA EMC
Hepatitis A
no/RNA PPV
PVB19
no/DNA
Precipitation of
Cohn
Fraction III >
5.9 3.6 3.7 4.4
3.9
Cuno Filtration
NT NT NT > 6.6
5.4
Solvent/Detergent
> 4.2 > 6.9 >
6.4 NT NT
Nanofiltration >
7.4 > 6.9 > 5.7
3.0 0.7 *
Cumulative >
17.5 > 17.4 >
15.8 > 14.0 9.3
BVD = Bovine
Viral Diarrhea
Virus
EMC =
Encephalomyocarditis
Virus
HIV = Human
Immunodeficiency
Virus
PVB19 =
Parvovirus B19
PPV = Porcine
Parvovirus
PRV =
Pseudorabies
Virus
NT = not tested
* Value not
included in
cumulative
clearance
Product potency
is expressed in
international
units (IU) by
comparison to
the World Health
Organization
(WHO) standard.
Each milliliter
(mL) of product
contains greater
than 312 IU
anti-HBs. The
potency of each
milliliter of
Nabi-HB™ exceeds
the potency of
anti-HBs in a
U.S. reference
hepatitis B
immune globulin
(FDA). The U.S.
reference has
been tested by
Nabi® against
the WHO standard
and found to be
equal to 208 IU/mL.
CLINICAL
PHARMACOLOGY
Hepatitis B
Immune Globulin
(Human) products
provide passive
immunization for
individuals
exposed to the
hepatitis B
virus as
evidenced by a
reduction in the
attack rate of
hepatitis B
following use
6-9 .
Clinical studies
10,11 conducted
prior to 1983
with hepatitis B
immune globulins
similar to
Nabi-HB™
indicate the
advantage of
simultaneous
administration
of hepatitis B
vaccine and
Hepatitis B
Immune Globulin
(Human). The
Centers for
Disease Control
and Prevention
Advisory
Committee on
Immunization
Practices (ACIP)
advises that the
combination
prophylaxis be
provided in
certain
instances of
exposure based
upon the
increased
efficacy found
with that
regimen in
neonates 12 .
Cases of
hepatitis B are
rarely seen
following
exposure to HBV
in persons with
preexisting
anti-HBs.
However, no
prospective
studies have
been performed
on the efficacy
of concurrent
hepatitis B
vaccine and
Hepatitis B
Immune Globulin
(Human)
administration
following
parenteral
exposure, mucous
membrane
contact, or oral
ingestion in
adults.
Infants born to
HBsAg-positive
mothers are at
risk of being
infected with
HBV and becoming
chronic carriers
13 . The risk is
especially great
if the mother is
also HBeAg-positive
14 . Studies
conducted with
hepatitis B
immune globulins
similar to
Nabi-HB™
indicated that
for an infant
with perinatal
exposure to an
HBsAg-positive
and HBeAg-positive
mother, a
regimen
combining one
dose of
Hepatitis B
Immune Globulin
(Human) at birth
with the
hepatitis B
vaccine series
started soon
after birth is
85-98% effective
in preventing
development of
the HBV carrier
state 15-17 .
Regimens
involving either
multiple doses
of Hepatitis B
Immune Globulin
(Human) alone or
the vaccine
series alone
have a 70-90%
efficacy, while
a single dose of
Hepatitis B
Immune Globulin
(Human) alone
has 50% efficacy
18 .
Since infants
have close
contact with
primary
caregivers and
they have a
higher risk of
becoming HBV
carriers after
acute HBV
infection,
prophylaxis of
an infant less
than 12 months
of age with
Hepatitis B
Immune Globulin
(Human) and
hepatitis B
vaccine is
indicated if the
mother or
primary
caregiver has
acute HBV
infection 19 .
Sexual partners
of HBsAg-positive
persons are at
increased risk
of acquiring HBV
infection. A
single dose of
Hepatitis B
Immune Globulin
(Human) is 75%
effective if
administered
within two weeks
of the last
sexual exposure
to a person with
acute hepatitis
B 19 .
Pharmacokinetics
Pharmacokinetics
trials 20 of
Nabi-HB™,
Hepatitis B
Immune Globulin
(Human), given
intramuscularly
to 50 healthy
volunteers
demonstrated
pharmacokinetic
parameters
similar to those
reported by
Scheiermann and
Kuwert 21 . The
half-life for
Nabi-HB™ was
23.1 ± 5.5 days.
The clearance
rate was 0.35 ±
0.12 L/day and
the volume of
distribution was
11.2 ± 3.4 L.
Maximum
concentration of
Nabi-HB™ was
reached in 6.5 ±
4.3 days. The
maximum
concentration of
anti-HBs and the
area under the
time-concentration
curve achieved
by Nabi-HB™ were
bioequivalent to
that of another
licensed
Hepatitis B
Immune Globulin
(Human) when
compared in the
same
pharmacokinetics
trial.
Comparability of
pharmacokinetics
between Nabi-HB™
and a
commercially
available
hepatitis B
immunoglobulin
indicate that
similar efficacy
of Nabi-HB™
should be
inferred.
INDICATIONS AND
USAGE
Nabi-HB™,
Hepatitis B
Immune Globulin
(Human), is
indicated for
treatment of
acute exposure
to blood
containing HBsAg,
perinatal
exposure of
infants born to
HBsAg-positive
mothers, sexual
exposure to
HBsAg-positive
persons and
household
exposure to
persons with
acute HBV
infection in the
following
settings:
Acute Exposure
to Blood
Containing HBsAg
Following either
parenteral
exposure (needlestick,
bite, sharps),
direct mucous
membrane contact
(accidental
splash), or oral
ingestion (pipetting
accident),
involving HBsAg-positive
materials such
as blood,
plasma, or
serum.
Perinatal
Exposure of
Infants Born to
HBsAg-positive
Mothers
Infants born to
mothers positive
for HBsAg with
or without HBeAg
12 .
Sexual Exposure
to HBsAg-positive
Persons
Sexual partners
of HBsAg-positive
persons.
Household
Exposure to
Persons with
Acute HBV
Infection
Infants less
than 12 months
old whose mother
or primary
caregiver is
positive for
HBsAg. Other
household
contacts with an
identifiable
blood exposure
to the index
patient.
Nabi-HB™ is
indicated for
intramuscular
use only.
CONTRAINDICATIONS
Individuals
known to have
had an
anaphylactic or
severe systemic
reaction to
human globulin
should not
receive Nabi-HB™,
Hepatitis B
Immune Globulin
(Human), or any
other human
immune globulin.
Nabi-HB™
contains less
than 100
micrograms per
mL IgA.
Individuals who
are deficient in
IgA may have the
potential to
develop IgA
antibodies and
have an
anaphylactoid
reaction. The
physician must
weigh the
potential
benefit of
treatment with
Nabi-HB™ against
the potential
for
hypersensitivity
reactions.
WARNINGS
In patients who
have severe
thrombocytopenia
or any
coagulation
disorder that
would
contraindicate
intramuscular
injections,
Nabi-HB™,
Hepatitis B
Immune Globulin
(Human), should
be given only if
the expected
benefits
outweigh the
potential risks.
Nabi-HB™ is made
from human
plasma. Products
made from human
plasma may
contain
infectious
agents, e.g.,
viruses, and
theoretically,
the
Creutzfeldt-Jakob
disease (CJD)
agent. The risk
that such
products can
transmit an
infectious agent
has been reduced
by screening
plasma donors
for prior
exposure to
certain viruses,
by testing for
the presence of
certain current
viral
infections, and
by inactivating
and/or reducing
certain viruses.
The Nabi-HB™
manufacturing
process includes
a
solvent/detergent
treatment step
(using tri- n
-butyl phosphate
and Triton®
X-100) that is
effective in
inactivating
known enveloped
viruses such as
HBV, HCV, and
HIV. Nabi-HB™ is
filtered using a
Planova® 35 nm
Virus Filter
that is
effective in
reducing the
levels of some
enveloped and
non-enveloped
viruses. These
two processes
are designed to
increase product
safety. Despite
these measures,
such products
can still
potentially
transmit
disease. There
is also the
possibility that
unknown
infectious
agents may be
present in such
products. ALL
infections
thought by a
physician
possibly to have
been transmitted
by this product
should be
reported by the
physician or
other health
care provider to
Nabi at
1-800-458-4244.
The physician
should discuss
the risks and
benefits of this
product with the
patient.
PRECAUTIONS
General
Nabi-HB™,
Hepatitis B
Immune Globulin
(Human), must be
administered
only
intramuscularly
for
post-exposure
prophylaxis. The
preferred sites
for
intramuscular
injections are
the
anterolateral
aspect of the
upper thigh and
the deltoid
muscle. If the
buttock is used
due to the
volume to be
injected, the
central region
should be
avoided; only
the upper, outer
quadrant should
be used, and the
needle should be
directed
anterior (i.e.,
not inferior or
perpendicular to
the skin) to
minimize the
possibility of
involvement with
the sciatic
nerve 22 .
The 50 healthy
volunteers who
received Nabi-HB
in
pharmacokinetic
studies were
followed for 84
days for
possible
development of
anti-HCV
antibodies. No
subject
seroconverted.
Drug
Interactions
Vaccination with
live virus
vaccines should
be deferred
until
approximately
three months
after
administration
of Nabi-HB™,
Hepatitis B
Immune Globulin
(Human). It may
be necessary to
revaccinate
persons who
received Nabi-HB™
shortly after
live virus
vaccination.
There are no
available data
on concomitant
use of Nabi-HB™
and other drugs;
therefore,
Nabi-HB™ should
not be mixed
with other
drugs.
Pregnancy
Category C
Animal
reproduction
studies have not
been conducted
with Nabi-HB™.
It is also not
known whether
Nabi-HB™ can
cause fetal harm
when
administered to
a pregnant woman
or can affect a
woman's ability
to conceive.
Nabi-HB™ should
be given to a
pregnant woman
only if clearly
indicated.
Nursing Mothers
It is not known
whether this
drug is excreted
in human milk.
Because many
drugs are
excreted in
human milk,
caution should
be exercised
when Nabi-HB™ is
administered to
a nursing
mother.
Pediatric Use
Safety and
effectiveness in
the pediatric
population have
not been
established for
Nabi-HB™.
However, the
safety and
effectiveness of
similar
hepatitis B
immune globulins
have been
demonstrated in
infants and
children 12 .
Geriatric Use
Clinical studies
of Nabi-HB™ did
not include
sufficient
numbers of
subjects aged 65
and over to
determine
whether they
respond
differently than
younger
subjects. Other
reported
clinical
experience has
not identified
differences in
responses
between the
elderly and
younger
patients.
ADVERSE
REACTIONS
Fifty male and
female
volunteers
received Nabi-HB™,
Hepatitis B
Immune Globulin
(Human),
intramuscularly
in
pharmacokinetics
trials 20 . The
number of
patients with
reactions
related to the
administration
of Nabi-HB™
included local
reactions such
as erythema 6
(12%) and ache 2
(4%) at the
injection site,
as well as
systemic
reactions such
as headache 7
(14%), myalgia 5
(10%), malaise 3
(6%), nausea 2
(4%), and
vomiting 1 (2%).
The majority
(92%) of
reactions were
reported as
mild. The
following
adverse events
were reported in
the
pharmacokinetics
trials and were
considered
probably related
to Nabi-HB™:
elevated
alkaline
phosphatase 2
(4%), ecchymosis
1 (2%), joint
stiffness 1
(2%), elevated
AST 1 (2%),
decreased WBC 1
(2%), and
elevated
creatinine 1
(2%). All
adverse events
were mild in
intensity. There
were no serious
adverse events.
No anaphylactic
reactions with
Nabi-HB™ have
been reported.
However, these
reactions,
although rare,
have been
reported
following the
injection of
human immune
globulins 23 .
OVERDOSAGE
Although no data
are available,
clinical
experience
reported with
other human
immune globulins
suggests that
the only
manifestations
of overdose with
Nabi-HB™,
Hepatitis B
Immune Globulin
(Human), would
be pain and
tenderness at
the injection
site.
DOSAGE AND
ADMINISTRATION
This product is
for
intramuscular
use only. The
use of this
product by the
intravenous
route is not
indicated.
Parenteral drug
products should
be inspected
visually for
particulate
matter and
discoloration
prior to
administration.
It is important
to use a
separate vial,
sterile syringe,
and needle for
each individual
patient, in
order to prevent
transmission of
infectious
agents from one
person to
another. Any
vial of Nabi-HB™,
Hepatitis B
Immune Globulin
(Human) that has
been entered
should be used
promptly. Do not
reuse or save
for future use.
This product
contains no
preservative;
therefore,
partially used
vials should be
discarded
immediately.
Hepatitis B
Immune Globulin
(Human) may be
administered at
the same time
(but at a
different site),
or up to one
month preceding
hepatitis B
vaccination
without
impairing the
active immune
response to
hepatitis B
vaccine 11 .
Acute Exposure
to Blood
Containing HBsAg
Table 2
summarizes
prophylaxis for
percutaneous (needlestick,
bite, sharps),
ocular, or
mucous membrane
exposure to
blood according
to the source of
exposure and
vaccination
status of the
exposed person.
For greatest
effectiveness,
passive
prophylaxis with
Hepatitis B
Immune Globulin
(Human) should
be given as soon
as possible
after exposure,
as its value
after seven days
following
exposure is
unclear 12 . An
injection of
0.06 mL/kg of
body weight
should be
administered
intramuscularly
as soon as
possible after
exposure and
within 24 hours,
if possible.
Consult the
hepatitis B
vaccine package
insert for
dosage
information
regarding the
vaccine.
For persons who
refuse hepatitis
B vaccine or are
known
non-responders
to vaccine, a
second dose of
Hepatitis B
Immune Globulin
(Human) should
be given one
month after the
first dose 12
Table 2
Recommendations
for Hepatitis B
Prophylaxis
Following
Percutaneous or
Permucosal
Exposure 12
Exposed Person
Source
Unvaccinated
Vaccinated
HBsAg-positive
1. Hepatitis B
Immune Globulin
(Human) X 1
immediately *
2. Initiate HB
vaccine series †
1. Test exposed
person for anti-HBs
2. If inadequate
antibody ‡ ,
Hepatitis B
Immune Globulin
(Human) X 1
immediately plus
either HB
vaccine booster
dose or second
dose of
Hepatitis B
Immune Globulin
(Human) one
month later §
Known Source -
High
Risk for HBsAg-positive
1. Initiate HB
vaccine series
2. Test source
for HBsAg. If
positive,
Hepatitis B
Immune Globulin
(Human) X 1 1.
Test source for
HBsAg only if
exposed is
vaccine
nonresponder; if
source is HBsAg-positive,
give Hepatitis B
Immune Globulin
(Human) X 1
immediately plus
either HB
vaccine booster
dose or second
dose of
Hepatitis B
Immune Globulin
(Human) one
month later §
Known Source -
Low
Risk for HBsAg-positive
Initiate HB
vaccine series
Nothing required
Unknown Source
Initiate HB
vaccine series
Nothing required
* Hepatitis B
Immune Globulin
(Human) dose of
0.06 mL/kg IM.
† See
manufacturers'
recommendation
for appropriate
dose.
‡ Less than 10
mIU/mL anti-HBs
by
radioimmunoassay,
negative by
enzyme
immunoassay.
§Two doses of
Hepatitis B
Immune Globulin
(Human) is
preferred if no
response after
at least four
doses of
vaccine.
Prophylaxis of
Infants Born to
Mothers who are
Positive for
HBsAg with or
without HBeAg
Table 3 contains
the recommended
schedule of
hepatitis B
prophylaxis for
infants born to
mothers that are
either known to
be positive for
HBsAg or have
not been
screened.
Infants born to
mothers known to
be HBsAg-positive
should receive
0.5 mL Hepatitis
B Immune
Globulin (Human)
after
physiologic
stabilization of
the infant and
preferably
within 12 hours
of birth. The
hepatitis B
vaccine series
should be
initiated
simultaneously,
if not
contraindicated,
with the first
dose of the
vaccine given
concurrently
with the
Hepatitis B
Immune Globulin
(Human), but at
a different
site. Subsequent
doses of the
vaccine should
be administered
in accordance
with the
recommendations
of the
manufacturer.
Women admitted
for delivery,
who were not
screened for
HBsAg during the
prenatal period,
should be
tested. While
test results are
pending, the
newborn infant
should receive
hepatitis B
vaccine within
12 hours of
birth (see
manufacturers'
recommendations
for dose). If
the mother is
later found to
be HBsAg-positive,
the infant
should receive
0.5 mL Hepatitis
B Immune
Globulin (Human)
as soon as
possible and
within seven
days of birth;
however, the
efficacy of
Hepatitis B
Immune Globulin
(Human)
administered
after 48 hours
of age is not
known 10,19 .
Testing for
HBsAg and anti-HBs
is recommended
at 12-15 months
of age. If HBsAg
is not
detectable and
anti-HBs is
present, the
child has been
protected 12 .
Table 3
Recommended
Schedule of
Hepatitis B
Immunoprophylaxis
to Prevent
Perinatal
Transmission of
Hepatitis B
Virus Infection
19 Age of Infant
Administer
Infant Born to
mother known
to be HBsAg-positive
Infant born to
mother not
screened for
HBsAg
First
Vaccination *
Birth (within 12
hours) Birth
(within 12
hours)
Hepatitis B
Immune
Globulin (Human)
† Birth (within
12 hours) If
mother is found
to be HBsAg-
positive,
administer dose
to infant as
soon as
possible, not
later than 1
week after birth
Second
Vaccination * 1
month 1-2 months
Third
Vaccination * 6
months ‡ 6
months ‡
* See
manufacturers'
recommendations
for appropriate
dose.
† 0.5 mL
administered IM
at a site
different from
that used for
the vaccine.
‡ See ACIP
recommendation.
Sexual Exposure
to HBsAg-positive
Persons
All susceptible
persons whose
sexual partners
have acute
hepatitis B
infection should
receive a single
dose of
Hepatitis B
Immune Globulin
(Human) (0.06 mL/kg)
and should begin
the hepatitis B
vaccine series,
if not
contraindicated,
within 14 days
of the last
sexual contact
or if sexual
contact with the
infected person
will continue.
Administering
the vaccine with
Hepatitis B
Immune Globulin
(Human) may
improve the
efficacy of post
exposure
treatment. The
vaccine has the
added advantage
of conferring
long-lasting
protection 19 .
Household
Exposure to
Persons with
Acute HBV
Infection
Prophylaxis of
an infant less
than 12 months
of age with 0.5
mL Hepatitis B
Immune Globulin
(Human) and
hepatitis B
vaccine is
indicated if the
mother or
primary
caregiver has
acute HBV
infection.
Prophylaxis of
other household
contacts of
persons with
acute HBV
infection is not
indicated unless
they had an
identifiable
blood exposure
to the index
patient, such as
by sharing
toothbrushes or
razors. Such
exposures should
be treated like
sexual
exposures. If
the index
patient becomes
an HBV carrier,
all household
contacts should
receive
hepatitis B
vaccine 19 .
HOW SUPPLIED
Nabi-HB™,
Hepatitis B
Immune Globulin
(Human), is
supplied as:
NDC Number
Contents
59730-4202-1 a
carton
containing a 1
mL dose in a
single-use vial
(>312 IU) and
package insert
59730-4203-1 a
carton
containing a 5
mL dose in a
single-use vial
(>1560 IU) and
package insert
STORAGE
Refrigerate
between 2 to 8
°C (36 to 46
°F). Do not
freeze. Do not
use after
expiration date.
Use within 6
hours after the
vial has been
entered.
REFERENCES
Cohn E.J.,
Strong W.L.,
Mulford D.J.,
Ashworth J.N.,
Melin M., Taylor
H.L. Preparation
and Properties
of Serum and
Plasma Proteins
IV. A system for
the separation
into fractions
of the protein
and lipoprotein
components of
biological
tissues and
fluids. J Am
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68: 459-475.
Oncley J.L,
Melin M, Richert
D.A, Cameron J.
W, Gross P.M.
The separation
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issogglutinins,
prothrombin,
plasminogen and
b1-lipoproteins
into
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Am Chem Soc
1949,
71:541-550.
Horowitz B:
Investigations
into the
application of
tri( n -butyl)phosphate/detergent
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Morgenthaler J
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Inactivation in
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Curr Stud
Hematol Blood
Transfus 1989;
56:83-96.
Burnouf T: Value
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method for
improving the
safety of plasma
products. Vox
Sang 1996;
70:235-236.
Unpublished data
on file, Viral
Validation Study
Reports, Nabi.
Grady GF, and
Lee VA:
Hepatitis B
immune globulin
- prevention of
hepatitis from
accidental
exposure among
medical
personnel. N
Engl J Med 1975;
293:1067-1070.
Seeff LB, et al.
: Type B
hepatitis after
needle-stick
exposure:
Prevention with
hepatitis B
immune globulin.
Ann Int Med
1978;
88:285-293.
Krugman S, and
Giles JP: Viral
hepatitis, type
B (MS-2-strain).
Further
observations on
natural history
and prevention.
N Engl J Med
1973;
288:755-760.
Hoofnagle JH, et
al. : Passive -
active immunity
from hepatitis B
immune globulin.
Ann Int Med
1979;
91:813-818.
Beasley RP, et
al. : Efficacy
of hepatitis B
immune globulin
for prevention
of perinatal
transmission of
the hepatitis B
virus carrier
state: Final
report of a
randomized
double-blind,
placebo -
controlled
trial.
Hepatology 1983;
3:135-141.
Szmuness W, et
al. : Passive
active
immunisation
against
hepatitis B:
Immunogenicity
studies in adult
Americans.
Lancet 1981;
1:575-577.
Centers for
Disease Control:
Recommendations
for protection
against viral
hepatitis.
Recommendations
of the
Immunization
Practices
Advisory
Committee (ACIP).
MMWR 1985;
34(22):313-335.
Shiraki Y, et
al. : Hepatitis
B surface
antigen and
chronic
hepatitis in
infants born to
asymptomatic
carrier mothers.
Am J Dis Child
1977;
131:644-647.
Beasley RP, et
al. : The e
antigen and
vertical
transmission of
hepatitis B
surface antigen.
Am J Epidemiol
1977; 105:94-98.
Wong VCW, et al.
: Prevention of
the HBsAg
carrier state in
newborn infants
of mothers who
are chronic
carriers of
HBsAg and HBeAg
by
administration
of hepatitis B
vaccine and
hepatitis B
immunoglobulin:
Double-blind
randomized
placebo-controlled
study. Lancet
1984; 1:921-926.
Poovorawan Y, et
al. : Long term
hepatitis B
vaccine in
infants born to
hepatitis B e
antigen positive
mothers.
Archives of
Diseases in
Childhood 1997;
77:F47-F51.
Stevens CE, et
al. : Perinatal
Hepatitis B
virus
transmission in
the United
States:
Prevention by
passive-active
immunization.
JAMA 1985;
253:1740-1745.
Jhaveri R, et
al. : High titer
multiple dose
therapy with
HBIG in newborn
infants of HBsAg
positive
mothers. J
Pediatr 1980;
97:305-308.
Centers for
Disease Control:
Hepatitis B
virus: A
comprehensive
strategy for
eliminating
transmission in
the United
States through
universal
childhood
vaccination.
Recommendations
of the
Immunization
Practices
Advisory
Committee (ACIP).
MMWR 1991;
40(13):1-25.
Data on file,
Nabi®
Scheiermann N,
Kuwert EK:
Uptake and
elimination of
hepatitis B
immunoglobulins
after
intramuscular
application in
man. Develop
Biol Standard
1983; 54:347.
Centers for
Disease Control:
General
recommendations
on immunization.
Recommendations
of the Advisory
Committee on
Immunization
Practices (ACIP).
MMWR 1994;
43:1-38.
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CS: Adverse
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following
administration
of human gamma
globulin. J
Allerg 1969;
43:45-54.
Manufactured by:
Nabi®
Boca Raton, FL
33487
U.S. License No.
1022
November 2001
3-440-1118
July 29, 2004
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All Press
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July 29, 2004
|
