Varicella Vaccine/Mosby's

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"

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 Persistance of antibody and efficacy in those receving

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. , 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. , 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, ls 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 .

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 .

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

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moderator

Vaccination Information & Choice Network, Nevada City CA & UK

530-478-1242 Voicemail in US

http://www.nccn.net/~wwithin/vaccine.htm

" All that is necessary for the triumph of evil is that good men ( &

women) do nothing " ...Edmund Burke

ANY INFO OBTAINED HERE NOT TO BE CONSTRUED AS MEDICAL OR LEGAL ADVICE. THE

DECISION TO VACCINATE IS YOURS AND YOURS ALONE.

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