"Individuals vaccinated with varicella vaccine may
potentially be capable of
transmitting the vaccine virus to close contacts (see CLINICAL PHARMACOLOGY,
Transmission.)
Therefore, vaccine recipients should avoid close association with susceptible
high risk
of individuals (e.g., newborns, pregnant women, immunocompromised persons).
The potential risk of transmission of vaccine virus should be weighed against
the risk of
transmission of natural varicella virus in such circumstances."
Mosby's GenRx®, 10th ed.
Copyright © 2000 Mosby, Inc.
Varicella Vaccine (003195)
CATEGORIES:
Indications: Immunization, varicella
Pregnancy Category C
FDA Approved 1995 Mar
FDA DRUG CLASS: Vaccines/Antisera
BRAND NAMES: Varivax (US); Varivax Vaccine (US);
DESCRIPTION:
Varivax (Varicella Vaccine) is a preparation of the Oka/Merck strain of live
attenuated
varicella virus. The virus was initially obtained from a child with natural
varicella, then
introduced into human embryonic lung cell cultures, adapted to and propagated
in
embryonic guinea pig cell cultures and finally propagated in human diploid cell
cultures
(WI-38). Further passage of the virus for varicella vaccine was performed at
Merck
Research Laboratories (MRL) in human diploid cell cultures (MRC-5) that were
free of
adventitious agents. This live, attenuated varicella vaccine is a lyophilized
preparation
containing sucrose, phosphate, glutamate, and processed gelatin as stabilizers.
Varicella vaccine, when reconstituted as directed, is a sterile preparation for
subcutaneous administration. Each 0.5 ml dose contains the following: a minimum
of
1350 PFU (plaque forming units) of Oka/Merck varicella virus when reconstituted
and
stored at room temperature for 30 minutes, approximately 25 mg of sucrose, 12.5
mg
hydrolyzed gelatin, 3.2 mg sodium chloride, 0.5 mg monosodium L-glutamate, 0.45
mg
of sodium phosphate dibasic, 0.08 mg of potassium phosphate monobasic, 0.08 mg
of
potassium chloride; residual components of MRC-5 cells including DNA and
protein;
and trace quantities of sodium phosphate monobasic, EDTA, neomycin, and fetal
bovine serum. The product contains no preservative.
To maintain potency, the lyophilized vaccine must be kept frozen at an average
temperature of -15°C (+5°F) or colder and must be used before the expiration
date
(see HOW SUPPLIED, Stability and Storage.) Storage in a frost-free freezer with
an
average temperature of -15°C (+5°F) or colder is acceptable.
CLINICAL PHARMACOLOGY:
Varicella is a highly communicable disease in children, adolescents, and adults
caused
by the varicella-zoster virus. The disease usually consists of 300 to 500
maculopapular
and/or vesicular lesions accompanied by a fever (oral temperature 100°F) in up
to
70% of individuals.1,2 Approximately 3.5 million cases of varicella occurred
annually
from 1980-1994 in the United States with the peak incidence occurring in
children five
to nine years of age.3 The incidence rate of chickenpox is 8.3-9.1% per year in
children
1-9 years of age.4 The attack rate of natural varicella following household
exposure
among healthy susceptible children was shown to be 87%.2 Although it is
generally a
benign, self-limiting disease, varicella may be associated with serious
complications
(e.g., bacterial superinfection, pneumonia, encephalitis, Reye's Syndrome),
and/or
death.
Evaluation of Clinical Efficacy Afforded by Varicella Vaccine Clinical Data in
Children: In combined clinical trials5 of varicella vaccine at doses ranging
from 1,000-17,000 PFU, the majority of subjects who received varicella vaccine
and were exposed to wild-type virus were either completely protected from
chickenpox or developed a milder form (for clinical description see below) of
the disease. The protective efficacy of varicella vaccine was evaluated in three
different ways: 1) by comparing chickenpox rates in vaccinees versus historical
controls, 2) by assessment of protection from disease following household
exposure, and 3) by a placebo- controlled, double-blind clinical trial.
In early clinical trials,5 a total of 4142 children received 1000-1625 PFU of
attenuated
virus per dose of varicella vaccine and have been followed for up to six years
post-single-dose vaccination. In this group there was considerable variation in
chickenpox rates among studies and study sites, and much of the reported data
were acquired by passive follow-up. It was observed that 2.1%-3.6% of vaccines
per year reported chickenpox (called breakthrough cases). This represents an
approximate 67% (57-77%) decrease from the total number of cases expected based
on attack rates in children aged over 1-9 over this same period (8.3- 9.1%).4,6
In those who developed breakthrough chickenpox postvaccination, the majority
experienced mild disease (median number of lesions <50). In one study, a
total of 47% (27/58) of breakthrough cases had <50 lesions compared with 8%
(7/92) in unvaccinated individuals, and 7% (4/58) of breakthrough cases had
>300 lesions compared with 50% (46/92) in unvaccinated individuals.7 In
studies of vaccinated children who contracted chickenpox after a household
exposure, 57% (31/54) of the cases reported <50 lesions, while 1.9% (1/54)
reported >300 lesions with an oral temperature above 100°F.
In later clinical trials5 with current vaccine, a total of 1164 children received
2900-9000 PFU of attenuated virus per dose of varicella vaccine and have been
followed for up to three years post single-dose vaccination. It was observed
that 0.2%-1.0% of vaccinees per year reported breakthrough chickenpox for up to
three years post single-dose vaccination. This represents an approximate 93%
decrease from the total number of cases expected based on attack rates in
children aged 1-9 over this same period (8.3%-9.1%).3,26 In those who developed
breakthrough chickenpox postvaccination, the majority experienced mild disease.
Among a subset of vaccinees who were actively followed, 259 were exposed to an
individual with chickenpox in a household setting. There were no reports of
breakthrough chickenpox in 80% of exposed children; 20% reported a mild form of
chickenpox.5 This represents a 77% reduction in the expected number of cases
when compared to the historical attack rate of varicella following household
exposure to chickenpox of 87% in unvaccinated individuals.2
Although no placebo-controlled trial was carried out with varicella vaccine
using the
current vaccine, a placebo-controlled trial was conducted using a formulation
containing 17,000 PFU per dose.4,8 In this trial, a single dose of varicella
vaccine protected 96-100% of children against chickenpox over a two-year
period. The study enrolled healthy individuals 1 to 14 years of age (n=491
vaccine, n=465 placebo). In the first year, 8.5% of placebo recipients
contracted chickenpox, while no vaccine recipient did, for a calculated protection
rate of 100% during the first varicella season.
In the second year, when only a subset of individuals agreed to remain in the
blinded
study (n=163 vaccine, n=161 placebo), 96% protective efficacy was calculated
for the
vaccine group compared to placebo.
There are insufficient data to assess the rate of protection against the
complications of
chickenpox (e.g., encephalitis, hepatitis, pneumonia) in children.
Clinical Data in Adolescents and Adults: Although no placebo-controlled trial
was
carried out in adolescents and adults, efficacy was determined by evaluation of
protection when vaccinees received 2 doses of varicella vaccine 4 to 8 weeks
apart
and were subsequently exposed to chickenpox in a household setting.5 In up to
two
years of active follow-up, 17 of 64 (27%) vaccinees reported breakthrough
chickenpox following household exposure; of the 17 cases, 12 (71%) reported
<50 lesions, 5 reported 50-300 lesions, and none reported >300 lesions
with an oral temperature above 100°F. In combined clinical studies of
adolescents and adults (n=1019) who received two doses of varicella vaccine and
later developed breakthrough chickenpox (42 of 1019), 25 of 42 (60%) reported
<50 lesions, 16 of 42 (38%) reported 50-300 lesions, and 1 of 42 (2%) reported
>300 lesions and an oral temperature above 100°F.5
The attack rate of unvaccinated adults exposed to a single contact in a
household has
not been previously studied. When compared to the previously reported attack
rate of
natural varicella of 87% following household exposure among unvaccinated
children, this
represents an approximate 70% reduction in the expected number of cases in the
household setting.2
There are insufficient data to assess the rate protection of varicella vaccine
against the
serious complications of chickenpox in adults (e.g., encephalitis, hepatitis,
pneumonitis)
and during pregnancy (congenital varicella syndrome).
Immunogenicity of Varicella Vaccine: Clinical trials with
several formulations of the
vaccine containing attenuated virus ranging from 1000 to 17,000 PFU per dose
have
demonstrated that varicella vaccine induces detectable immune responses in a
high
proportion of individuals and is generally well tolerated in healthy
individuals ranging
from 12 months to 55 years of age.4,5,9-15
Seroconversion as defined by the acquisition of any detectable varicella
antibodies
(gpELISA >0.3, a highly sensitive assay which is not commercially available)
was
observed in 97% of vaccinees at approximately 4-6 weeks postvaccination in 6889
susceptible children 12 months to 12 years of age. Rates of breakthrough
disease were
significantly lower among children with varicella antibody titers 5 compared to
children with titers <5. Titers 5 were induced in approximately 76% of
children
vaccinated with a single dose of vaccine at 1000-17,000 PFU per dose. In a
multicenter study involving susceptible adolescents and adults 13 years of age
and older, two doses of varicella vaccine administered four to eight weeks
apart induced a seroconversion rate (gpELISA >0.3) of approximately 75% in
539 individuals four weeks after the first dose and of 99% in 479 individuals
four weeks after the second dose. The average antibody response in vaccinees
who received the second dose eight weeks after the first dose was higher than
that in those, who received the second dose four weeks after the first dose. In
another multicenter study involving adolescents and adults, two doses of
varicella vaccine administered eight weeks apart induced a seroconversion rate
(gpELISA >0.3) of 94% in 142 individuals six weeks after the first dose and
99% in 122 individuals six weeks after the second dose.5
Varicella vaccine also induces cell-mediated immune responses in
vaccinees. The
relative contributions of humoral immunity and cell-mediated immunity to
protection
from chickenpox are unknown.
Persistence of Immune Response: Studies in vaccinees examining chickenpox
breakthrough rates over 5 years showed the lowest rates (0.2- 2.9%) in the
first two
years postvaccination, with somewhat higher but stable rates in the third
through fifth
year. The severity of reported breakthrough chickenpox, as measured by number
of
lesions and maximum temperature, appeared not to increase with time since
vaccination.5
In clinical studies involving healthy children who received 1 dose of vaccine,
detectable
varicella antibodies (gpELISA >0.3) were present in 98.8% (3775/3822) at 1
year, 98.9% (1057/1069) at 2 years, 97.5% (548/562) at 3 years, and 99.5%
(220/221) at 4 years postvaccination. Antibody levels were present at least one
year in 97.2% (423/435) of healthy adolescents and adults who received two
doses of live varicella vaccine separated by 4 to 8 weeks. A boost in antibody
levels has been observed in vaccinees following exposure to natural varicella
which could account for the apparent long-term persistence of antibody levels
after vaccination in these studies. The duration of protection from varicella
obtained using varicella vaccine in the absence of wild-type boosting in
unknown. Varicella vaccine also induces cell-mediated immune responses in
vaccinees. The relative contributions of humoral immunity and cell-mediated
immunity
to protection from chickenpox are unknown.
Transmission: In the placebo-controlled trial, transmission of vaccine virus
was
assessed in household settings (during the 8-week postvaccination period in 416
susceptible placebo recipients who were household contacts of 445 vaccine
recipients.
Of the 416 placebo recipients, three developed chickenpox and seroconverted,
nine
reported a varicella-like rash and did not seroconvert, and six had no rash but
seroconverted. If vaccine virus transmission occurred, it did so at a very low
rate and
possibly without recognizable clinical disease in contacts. These cases may
represent
either natural varicella from community contacts or a low incidence of transmission of
vaccine virus from vaccinated contacts (see PRECAUTIONS.)4,16
Herpes Zoster: Overall, 9454 healthy children (12 months to 12 years of age)
and
1648 adolescents and adults (13 years of age and older) have been vaccinated
with
Oka/Merck live attenuated varicella vaccine in clinical trials. Eight cases of
herpes
zoster have been reported in children during 44,994 person years of follow-up
in clinical
trials, resulting in a calculated incidence of at least 18 cases per 100,000
person years.
The completeness of this reporting has not been determined. One case of herpes
zoster
has been reported in the adolescent and adult age group during 7826 person
years of
follow-up in clinical trials resulting in a calculated incidence of 12.8 cases
per 100,000
person years.5
All nine cases were mild and without sequelae. Two cultures (one child and one
adult)
obtained from vesicles were positive for wild-type varicella zoster virus as
confirmed by
restriction endonuclease analysis.5,17 The long-term effect of varicella
vaccine on the
incidence of herpes zoster, particularly in those vaccinees exposed to natural
varicella,
is unknown at present.
In children, the reported rate of zoster in vaccine recipients appears not to
exceed that
previously determined in a population-based study of healthy children who had
experienced natural varicella.5,18,19 The incidence of zoster in adults who
have had
natural varicella infection is higher than that in children.20
Reye's Syndrome: Reye's Syndrome has occurred in children and adolescents
following natural varicella infection, the majority of whom had received
salicylates.21 In clinical studies in healthy children and adolescents in the
United States, physicians advised varicella vaccine recipients not to use
salicylates for six weeks after vaccination. There were no reports of Reye's
Syndrome in varicella vaccine recipients during these studies.
Studies with Other Vaccines: In combined clinical studies involving 1080
children 12
to 36 months of age, 653 received varicella vaccine and M-M-R*II (Measles,
Mumps,
and Rubella Virus Vaccine Live) concomitantly at separate sites and 427
received the
vaccines six weeks apart. Seroconversion rates and antibody levels were
comparable
between the two groups at approximately six weeks post-vaccination to each of
the
virus vaccine components. No differences were noted in adverse reactions
reported in
those who received varicella vaccine concomitantly with M-M-R II (Measles,
Mumps,
and Rubella Virus Vaccine Live) at separate sites and those who received
varicella
vaccine and M-M-R II (Measles, Mumps, and Rubella Virus Vaccine Live) at
different times (see DRUG INTERACTIONS, Use with Other Vaccines.)5
In a clinical study involving 318 children 12 months to 42 months of age, 160
received
an investigational vaccine (a formulation combining measles, mumps, rubella,
and
varicella in one syringe) concomitantly with booster doses of DTaP (diphtheria,
tetanus,
acellular pertussis) and OPV (oral poliovirus vaccine) while 144 received M-M-R
II
(Measles, Mumps, and Rubella Virus Vaccine Live) concomitantly with booster
doses
of DTaP and OPV followed by varicella vaccine 6 weeks later. At six weeks
postvaccination, seroconversion rates for measles, mumps, rubella, and
varicella and the
percentage of vaccines whose titers were boosted for diphtheria, tetanus,
pertussis,
and polio were comparable between the two groups, but anti- varicella levels
were
decreased when the investigational vaccine containing varicella was
administered
concomitantly with DTaP. No clinically significant differences were noted in
adverse
reactions between the two groups.5
In another clinical study involving 307 children 12 to 18 months of age, 150
received an
investigational vaccine (a formulation combining measles, mumps, rubella, and
varicella
in one syringe) concomitantly with a booster dose of PedvaxHIB* [Haemophilus b
Conjugate Vaccine (Meningococcal Protein Conjugate)] while 130 received
M-M-R-II (Measles, Mumps, and Rubella Virus Vaccine Live) concomitantly with a
booster dose of PedvaxHIB followed by varicella vaccine 6 weeks later. At six
weeks postvaccination, seroconversion rates for measles, mumps, rubella, and
varicella, and geometric mean titers for PedvaxHIB were comparable between the
two groups, but anti-varicella levels were decreased when the investigational
vaccine containing varicella was administered concomitantly with PedvaxHIB. No
clinically significant differences in adverse reactions were seen between the
two groups.5
Varicella vaccine is recommended for subcutaneous administration. However,
during
clinical trials, some children received varicella vaccine intramuscularly
resulting in
seroconversion rates similar to those in children who received the vaccine by
the
subcutaneous route.22 Persistence of
antibody and efficacy in those receiving
intramuscular injections have not been defined.
INDICATIONS AND USAGE:
Varicella vaccine is indicated for vaccination against varicella in individuals
12 months
of age and older.
Revaccination: The duration of protection of varicella vaccine is unknown at
present
and the need for booster doses is not defined. However, a boost in antibody
levels has
been observed in vaccinees following exposure to natural varicella as well as
following
a booster dose of varicella vaccine administered four to six years
postvaccination.5
In a highly vaccinated population, immunity for some individuals may wane due
to lack
of exposure to natural varicella as a result of shifting epidemiology.
Post-marketing
surveillance studies are ongoing to evaluate the need and timing for booster
vaccination.
Vaccination with varicella vaccine may not result in protection of all healthy,
susceptible
children, adolescents, and adults (see CLINICAL PHARMACOLOGY.)
CONTRAINDICATIONS:
A history of hypersensitivity to any component of the vaccine, including
gelatin.
A history of anaphylactoid reaction to neomycin (each dose of reconstituted
vaccine
contains trace quantities of neomycin).
Individuals with blood dyscrasias, leukemia, lymphomas of any type, or other
malignant
neoplasms affecting the bone marrow or lymphatic systems.
Individuals receiving immunosuppressive therapy. Individuals who are on
immunosuppressant drugs are more susceptible to infections than healthy
individuals.
Vaccination with live attenuated varicella vaccine can result in a more
extensive
vaccine-associated rash or disseminated disease in individuals on
immunosuppressant
doses of corticosteroids.
Individuals with primary and acquired immunodeficiency states, including those
who are
immunosuppressed in association with AIDS or other clinical manifestations of
infection
with human immunodeficiency virus;23 cellular immune deficiencies; and
hypogammaglobulinemic and dysgammaglobulinemic states. A family history of congenital or hereditary
immunodeficiency, unless the immune competence of the potential vaccine
recipient is demonstrated.
Active untreated tuberculosis.
Any febrile respiratory illness or other active febrile infection.
Pregnancy; the possible effects of the vaccine on fetal development are unknown
at this
time. However, natural varicella is known to sometimes cause fetal harm. If
vaccination
of postpubertal females is undertaken, pregnancy should be avoided for three
months
following vaccination. (see PRECAUTIONS, Pregnancy)
WARNINGS:
Children and adolescents with acute lymphoblastic leukemia (ALL) in remission
can
receive the vaccine under an investigational protocol. More information is available
by
contacting the varicella vaccine coordinating center, Bio-Pharm Clinical
Services, Inc.,
4 Valley Square, Blue Bell, PA 19422 (215) 283-0897.
PRECAUTIONS:
General: Adequate treatment provisions, including epinephrine injection
(1:1000),
should be available for immediate use should an anaphylactoid reaction occur.
The duration of protection from varicella infection after vaccination with
varicella
vaccine is unknown.
It is not known whether varicella vaccine given immediately after exposure to
natural
varicella virus will prevent illness.
Vaccination should be deferred for at least 5 months following blood or plasma
transfusions, or administration of immune globulin or varicella immune globulin
or
varicella zoster immune globulin (VZIG).24
Following administration of varicella vaccine, any immune globulin including
VZIG
should not be given for 2 months thereafter unless its use outweighs the
benefits of
vaccination.24
Vaccine recipients should avoid use of salicylates for 6 weeks after vaccination
with
varicella vaccine as Reye's Syndrome has been reported following the use of
salicylates during natural varicella infection (see CLINICAL PHARMACOLOGY,
Reye's Syndrome.)
Individuals vaccinated with varicella vaccine may potentially be capable of
transmitting the vaccine virus to close contacts (see CLINICAL PHARMACOLOGY,
Transmission.)
Therefore, vaccine recipients should avoid close association with susceptible
high risk
of individuals (e.g., newborns, pregnant women, immunocompromised persons).
The potential risk of transmission of vaccine virus should be weighed against
the risk of
transmission of natural varicella virus in such circumstances.
the safety and efficacy of varicella vaccine have not been established in
children and
young adults who are known to be infected with human immunodeficiency viruses
with
an without evidence of immunosuppression (see also CONTRAINDICATIONS).
Care is to be taken by the health care provider for safe and effective use of
varicella
vaccine.
The health care provider should question the patient, parent, or guardian about
reactions
to a previous dose of varicella vaccine or a similar product.
The health care provider should obtain the previous immunization history of the
vaccinee.
Varicella vaccine should not be injected into a blood vessel.
Vaccination should be deferred in patients with a family history of congenital
or
hereditary immunodeficiency until the patient's own immune system has been
evaluated.
A separate sterile needle and syringe should be used for administration of each
dose of
varicella vaccine to prevent transfer of infectious diseases.
Needles should be disposed of properly and not be recapped.
Information for the Patient: The health care provider should inform the
patient,
parent or guardian of the benefits and risks of varicella vaccine.
Patients, parents, or guardians should be instructed to report any adverse
reactions to
their health care provider.
The U.S. Health Department of Health and Human Services has established a
Vaccine
Adverse Event Reporting System (VAERS) to accept all reports of suspected
adverse
events after the administration of any vaccine, including but not limited to
the reporting
of events required by the National Childhood Vaccine Injury Act of
1986.25. The
VAERS toll-free number for VAERS forms and information is 1-800-822-7967.
Pregnancy should be avoided for three months following vaccination.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: Varicella vaccine has
not been evaluated for its carcinogenic or mutagenic potential, or its
potential to impair
fertility.
Pregnancy Category C: Animal reproduction studies have not been conducted with
varicella vaccine. It is also not known whether varicella vaccine can cause
fetal harm
when administered to a pregnant woman or can affect reproduction capacity.
Therefore,
varicella vaccine should not be administered to pregnant females; furthermore,
pregnancy should be avoided for three months following vaccination (see
CONTRAINDICATIONS.)
Nursing Mothers: It is not known whether varicella vaccine virus is secreted in
human milk. Therefore, because some viruses are secreted in human milk, caution
should be exercised if varicella vaccine is administered to a nursing woman.
Pediatric Use: No clinical data are available on safety or efficacy of
varicella vaccine
in children less than one year of age and administration to infants under
twelve months of
age is not recommended.
DRUG INTERACTIONS:
See PRECAUTIONS, General, regarding the administration of immune globulins,
salicylates, and transfusions.
Use with Other Vaccines: Results from clinical studies indicate that varicella
vaccine
can be administered concomitantly with M-M- R II (Measles, Mumps, and Rubella
Virus Vaccine Live).
Limited data from an experimental product containing varicella vaccine suggest
that
varicella vaccine can be administered concomitantly with a DTaP (diphtheria,
tetanus,
acellular pertussis) and PedvaxHIB using separate sites and syringes (see
CLINICAL
PHARMACOLOGY, Studies with other Vaccines.)5 However, there are no data
relating to simultaneous administration of varicella vaccine with DTO or OPV.
ADVERSE REACTIONS:
In clinical trials,4,5,9-15 Varicella vaccine was administered to 11,102
healthy children,
adolescents, and adults. Varicella vaccine was generally well tolerated.
In a double-blind placebo controlled study among 914 healthy children and
adolescents
who were serologically confirmed to be susceptible to varicella, the only
adverse
reactions that occurred at a significantly (p<0.05) greater rate in vaccine
recipients than
in placebo recipients were pain and redness at the injection site.4
Children 1 to 12 Years of Age: In clinical trials involving healthy children
monitored
for up to 42 days after a single dose of varicella vaccine, the frequency of
fever,
injection-site complaints, or rashes were reported as follows: (TABLE 1)
TABLE 1 Fever, Local Reactions, or Rashes (%) In Children 0 to 42 Days
Postvaccination Reaction
N
Post dose
1
Peak Occurrence
In Postvaccination
Days
Fever 102°F (39°C) Oral
8827
14.7%
0-42
Injection-site complaints
(pain/soreness, swelling) and/or
erythema, rash, pruritus, hematoma,
induration, stiffness)
8916
19.3%
0-2
Varicella-like rash (injection site)
8916
3.4%
8-19
Median number of lesions
2
Varicella-like rash (generalized)
8916
3.8%
5-26
Median number of lesions
5
In addition, the most frequently (1%) reported adverse experiences, without
regard
to causality, are listed in decreasing order of frequency: upper respiratory
illness, cough,
irritability/nervousness fatigue, disturbed sleep, diarrhea, loss of appetite,
vomiting, otitis,
diaper rash/contact rash, headache, teething, malaise, abdominal pain, other
rash, nausea, eye complaints, chills, lymphadenopathy, myalgia, lower
respiratory illness, allergic reactions (including allergic rash, hives) stiff
neck, heat rash/prickly heat, arthralgia, eczema/dry skin/dermatitis, constipation,
itching.
Pneumonitis has been reported rarely (<1%) in children vaccinated with
varicella
vaccine; a casual relationship has not been established.
Febrile seizures have occurred rarely (<0.1%) in children vaccinated with
varicella
vaccine; a casual relationship has not been established.
Adolescents and Adults 13 Years of Age and Older: In clinical trials involving
healthy adolescents and adults, the majority of whom received two doses of
varicella vaccine and were monitored for up to 42 days after any dose, the
frequency of fever, injection-site complaints, or rashes were reported as
follows: (TABLES 2A and 2B)
TABLE 2A Fever, Local Reactions, or Rashes (%) in Adolescents and Adults
0-42 Days Postvaccination
Reaction
N
Post Dose 1
Peak Occurrence
in Postvaccination
Days
Fever 100°F (37.7°C) Oral
1584
10.2%
Injection-site complaints
(soreness, erythema, swelling,
rash, pruritus, pyrexia,
hematoma, induration numbness)
1606
24.4%
0-2
Varicella-like rash (injection site)
1606
3%
6-20
Median number of lesions
2
Varicella-like rash (generalized)
1606
5.5%
7-21
Median number of lesions
5
TABLE 2B Fever, Local Reactions, or Rashes (%) in Adolescents and Adults
0-42 Days Postvaccination
Reaction
N
Post Dose 2
Peak
Occurrence in
Postvaccination
Days
Fever 100°F (37.7°C) Oral
956
9.5%
0-42
Injection-site complaints
(soreness, erythema, swelling,
rash, pruritus, pyrexia, hematoma,
induration numbness)
955
32.5%
0-2
Varicella-like rash (injection site)
955
1%
0-6
Median number of lesions
2
Varicella-like rash (generalized)
955
0.9%
0-23
Median number of lesions
5.5
In addition, the most frequently (1%) reported adverse experiences, without
regard
to causality, are listed in decreasing order of frequency: upper respiratory
illness,
headache, fatigue, cough, myalgia, disturbed sleep, nausea, malaise, diarrhea,
stiff neck,
irritability/nervousness, lymphadenopathy, chills, eye complaints, abdominal
pain, loss of
appetite, arthralgia, otitis, itching, vomiting, other rashes, constipation,
lower respiratory
illness, allergic reactions (including allergic rash, hives), contact rash,
cold/canker sore.
As with any vaccine, there is the possibility that broad use of the vaccine
could reveal
adverse reactions not observed in clinical trials.
DOSAGE AND ADMINISTRATION:
FOR SUBCUTANEOUS ADMINISTRATION Do not inject intravenously
Children 12 months to 12 years of age should receive a single 0.5 ml dose
administered
subcutaneously.
Adolescents and adults 13 years of age and older should receive a 0.5 ml dose
administered subcutaneously at elected date and a second 0.5 ml dose 4 to 8
weeks
later.
Varicella vaccine is for subcutaneous administration. The outer aspect of the
upper arm
(deltoid) is the preferred site of injection.
Varicella vaccine MUST BE STORED FROZEN at an average temperature of - 15°C
(+5°F) or colder is acceptable. The diluent should be stored separately at room
temperature or in the refrigerator. To reconstitute the vaccine, first withdraw
0.7 ml of
diluent into the syringe to be used for reconstitution. Inject all the diluent
in the syringe
into the vial of lyophilized vaccine and gently agitate to mix thoroughly. Withdraw the
entire contents into a syringe, change the needle, and inject the total volume
(about 0.5
ml) of reconstituted vaccine subcutaneously, preferably into the outer aspect
of the
upper arm (deltoid) or the anterolateral thigh. IT IS RECOMMENDED THAT THE
VACCINE BE ADMINISTERED IMMEDIATELY AFTER RECONSTITUTION, TO MINIMIZE LOSS OF
POTENCY. DISCARD IF RECONSTITUTED VACCINE IS NOT USED WITHIN 30 MINUTES.
Caution: A sterile syringe free of preservatives, antiseptics, and detergents
should be
used for each injection and/or reconstitution of varicella vaccine because
these
substances may inactivate the vaccine virus.
It is important to use a separate sterile syringe and needle for each patient
to prevent
transmission of infectious agents from one individual to another.
To reconstitute the vaccine, use only the diluent supplied, since it is free of
preservatives or other anti-viral substances which might inactivate the vaccine
virus.
Do not freeze reconstituted vaccine.
Do not give immune globulin including Varicella Zoster Immune Globulin
concurrently
with varicella vaccine (see also PRECAUTIONS).
Parenteral drug products should be inspected visually for particulate matter
and
discoloration prior to administration, whenever solution and container permit.
Varicella
vaccine when reconstituted is a clear, colorless to pale yellow liquid.
REFERENCES:
1. Balfour, H.H.; et al.: Acyclovir treatment of varicella in otherwise
healthy children,
Pediatr., 116: 633-639, 1990.
2. Ross, A.H.: Modification of chickenpox in family contacts by
administration of
gamma globulin, N. Engl. J. Med. 267: 369-376, 1962.
3. Preblud, S.R.: Varicella: Complications and Costs, Pediatrics, 78 (4 Pt
2): 728-735,
1986.
4. Weibel, R.E.; et al.: Live Attenuated Varicella Virus Vaccine, N. Engl.
J. Med.310
(22):1409-1415, 1984.
5. Unpublished data; files of Merck Research Laboratories.
6. Wharton, M.; et al.: Health Impact of Varicella in the 1980's. Thirtieth
Interscience
Conference on Antimicrobial Agents and Chemotherapy, (Abstract #1138), 1990.
7. Bernstein, H.H.; et al.; Clinical Survey of Natural Varicella COmpared with
Breakthrough Varicella After Immunization with Live Attenuated Oka/Merck
Varicella
Vaccine. Pediatrics 92 :833-837, 1993.
8. Kuter, B.J.; et al.: Oka/Merck Varicella Vaccine in Healthy Children:
Final Report
of a 2-Year Efficacy Study and 7-Year Follow-up Studies, Vaccine, 9 :643-647,
1991.
9. Arbeter, A.M.; et al.: Varicella Vaccine Trials in Healthy Children, A
Summary of
Comparative and Follow-up Studies, AJDC 138: 434-438, 1984.
10. Weibel, R.E.; et al.: Live Oka/Merck Varicella Vaccine in Healthy
Children,
JAMA 254 (17):2435-2439, 1985.
11. Chartrand, D.M.; et al.: New Varicella Vaccine Production Lots in Healthy
Children and Adolescents, Abstracts of the 1988 Interscience Conference
Antimicrobial
Agents and Chemotherapy: 237 (Abstract #731).
12. Johnson, C.E.; et al.: Live Attenuated Vaccine in Healthy 12 to 24
month old
Children, Pediatrics 81: 512-518, 1988.
13. Gershon, A.A.; et al.: Immunization of Healthy Adults with Live Attenuated
Varicella Vaccine, Journal of Infectious Diseases,158 (1): 132-137, 1988.
14. Gershon, A.A.; et al.: Live Attenuated Varicella Vaccine: Protection in
Healthy
Adults Compared with Leukemic Children, Journal of Infectious Diseases, 161
:661-666, 1990.
15. White, C.J.; et al.; Varicella Vaccine (Varivax) in Healthy Children and
Adolescents: Results From Clinical Trials, 1987 to 1989, Pediatrics, 875
(5):604-610,
1991.
16. Asano, Y.; et al.: Contact Infection from Live Varicella Vaccine
Recipients,
Lancet1 (7966):965, 1976.
17. Hammerschlag, M.R.; et al.: Herpes Zoster in an Adult Recipient of Live
Attenuated
Varicella Vaccine, J Infect Dis 160 (3);535-537, 1989.
18. White, C.J.: Letters to the Editor, Pediatrics 318 :354, 1992.
19. Guess H.A.; et al.: Epidemiology of Herpes Zoster in Children and
Adolescents: A
Population Based Study, Pediatrics 76 (4):512-517, 1985.
20. Ragozzino, M.; et al.: Population-Based Study of Herpes Zoster and Its
Sequelae,
Medicine 61 (5):310-316, 1982.
21. Morbidity and Mortality Weekly Report 34 (1): 13-16, Jan. 11, 1985.
22. Dennehy, P.H.; et al.: Immunogenicity of Subcutaneous Versus Intramuscular
Oka/Merck Varicella Vaccination in Healthy Children, Pediatrics 88
(3):604-607,
1991.
23. Center for Disease Control: Immunization of Children Infected with Human
T-Lymphotropic Virus Type III/Lymohadenopathy - Associated Virus, Annals of
Internal Medicine, 106 :75-78, 1987.
24. Recommendations of the Advisory Committee on Immunization Practices
(ACIP);
General Recommendations on Immunization, MMWR43 (No.RR- 1):15-18, January
28, 1994.
25. Vaccine Adverse Event Reporting System - United States, MMWR 39
(41):730-733, 1990.
HOW SUPPLIED:
Varivax is supplied as follows: (1) a single-dose vial of lyophilized
vaccine, (package
A); and (2) a box of 10 vials of diluent (package B).
Varivax is supplied as follows: (1) a box of 10 single-dose vials of
lyophilized vaccine
(package A), and (2) a box of 10 vials of diluent (package B).
Stability and Storage: Varivax retains a potency level of 1500 PFU or
higher per
dose for at least 18 months in a frost-free freezer with an average
temperature of -15°C
(+5°F) or colder.
Varivax has a minimum potency level approximately 1350 PFU 30 minutes after
reconstitution at room temperature (20-25°C, 68- 77°F).
For information regarding stability at temperatures other than those
recommended for
storage call 1-800-9-Varivax.
During shipment, to ensure that there is no loss of potency, the vaccine
must be
maintained at a temperature of -20°C (-4°F) or colder.
Before reconstitution, store the lyophilized vaccine in a freezer at an
average
temperature of -15°C (+5°F) or colder. Storage in a frost-free freezer with an
average temperature of -15°C (+5°F) or colder is acceptable.
Before reconstitution, protect from light.
The diluent should be stores separately at room temperature, or in the
refrigerator.
MD Consult L.L.C. http://www.mdconsult.com
Bookmark URL: /das/drug/view/1/3195/top
ALL INFORMATION, DATA,
AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION
PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR
OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING
MEDICAL OR LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN
IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN
CONSULTATION WITH YOUR HEALTH CARE PROVIDER.