RUBELLA VACCINE
DESCRIPTION:
R-VAC (Rubella Virus Vaccine Live) is a live virus vaccine for
immunization against rubella (German measles).
R-VAC is a sterile lyophilized preparation of the Wistar Institute RA 27/3
strain of live attenuated rubella virus. The virus was adapted to and propagated
in human diploid cell (WI-38) culture.
The reconstituted vaccine is for subcutaneous administration. When reconstituted
as directed, the dose for injection is 0.5 mL and contains not less than the
equivalent of 1,000 TCID50 (tissue culture infectious doses) of the U.S.
Reference Rubella Virus. Each dose also contains approximately 25 mcg of
neomycin. The product contains no preservative. Sorbitol and hydrolyzed gelatin
are added as stabilizers.
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ACTIONS/CLINICAL PHARMACOLOGY:
R-VAC produces a modified, non-communicable rubella infection in
susceptible persons.
Extensive clinical trials of rubella virus vaccines, prepared using RA 27/3
strain rubella virus, have been carried out in more than 28,000 human subjects
(approximately 11,000 with R-VAC) in the U.S.A. and more than 20 additional
countries. A single injection of the vaccine has been shown to induce rubella
hemagglutination- inhibiting (HI) antibodies in 97% or more of susceptible
persons. The RA 27/3 rubella strain elicits higher immediate post-vaccination
HI, complement-fixing and neutralizing antibody levels than other strains of
rubella vaccine and has been shown to induce a broader profile of circulating
antibodies including anti-theta and anti-iota precipitating antibodies. The RA
27/3 rubella strain immunologically simulates natural infection more closely
than other rubella vaccine viruses. The increased levels and broader profile of
antibodies produced by RA 27/3 strain rubella virus vaccine appear to correlate
with greater resistance to subclinical reinfection with the wild virus, and
provide greater confidence for lasting immunity.
Vaccine-induced antibody levels have been shown to persist for at least 10 years
without substantial decline. If the present pattern continues, it will provide a
basis for the expectation that immunity following vaccination will be permanent.
However, continued surveillance will be required to demonstrate this point.
INDICATIONS AND USAGE:
INDICATIONS AND USAGE*
1. Children Between 12 Months Of Age And Puberty
R-VAC is indicated for immunization against rubella (German measles) in
persons from 12 months of age to puberty. A booster is not needed. It is not
recommended for infants younger than 12 months because they may retain maternal
rubella neutralizing antibodies that may interfere with the immune response.
Children in kindergarten and the first grades of elementary school deserve
priority for vaccination because often they are epidemiologically the major
source of virus dissemination in the community. A history of rubella illness is
usually not reliable enough to exclude children from immunization.
Previously unimmunized children of susceptible pregnant women should receive
live attenuated rubella vaccine, because an immunized child will be less likely
to acquire natural rubella and introduce the virus into the household.
2. Adolescent And Adult Males
Vaccination of adolescent or adult males may be a useful procedure in preventing
or controlling outbreaks of rubella in circumscribed population groups (e.g.,
military bases and schools).
3. Non-Pregnant Adolescent And Adult Females
Immunization of susceptible non-pregnant adolescent and adult females of
childbearing age with live attenuated rubella virus vaccine is indicated if
certain precautions are observed (see below and PRECAUTIONS). Vaccinating
susceptible postpubertal females confers individual protection against
subsequently acquiring rubella infection during pregnancy, which in turn
prevents infection of the fetus and consequent congenital rubella injury.
Women of childbearing age should be advised not to become pregnant for three
months after vaccination and should be informed of the reason for this
precaution.**
It is recommended that rubella susceptibility be determined by serologic testing
prior to immunization.*/* If immune, as evidenced by a specific rubella antibody
titer of 1:8 or greater (hemagglutination-inhibition test), vaccination is
unnecessary. Congenital malformations do occur in up to seven percent of all
live births. Their chance appearance after vaccination could lead to
misinterpretation of the cause, particularly if the prior rubella-immune status
of vaccinees is unknown.
Postpubertal females should be informed of the frequent occurrence of generally
self-limited arthralgia and/or arthritis beginning 2 to 4 weeks after
vaccination (see ADVERSE REACTIONS).
4. Postpartum Women
It has been found convenient in many instances to vaccinate rubella-susceptible
women in the immediate postpartum period (see Nursing Mothers).
5. International Travelers
Individuals planning travel outside the United States, if not immune, can
acquire measles, mumps or rubella and import these diseases to the United
States. Therefore, prior to International travel, individuals known to be
susceptible to one or more of these diseases can receive either a single antigen
vaccine (measles, mumps or rubella), or a combined antigen vaccine as
appropriate. However, M-M-R**/* II (Measles, Mumps, and Rubella Virus Vaccine
Live) is preferred for persons likely to be susceptible to mumps and rubella;
and if single-antigen measles vaccine is not readily available, travelers should
receive M-M-R II (Measles, Mumps, and Rubella Virus Vaccine Live) regardless of
their immune status to mumps or rubella.
Revaccination:
Children vaccinated when younger than 12 months of age should be revaccinated.
Based on available evidence, there is no reason to routinely revaccinate persons
who were vaccinated originally when 12 months of age or older. However, persons
should be revaccinated if there is evidence to suggest that initial immunization
was ineffective.
Use With Other Vaccines
Routine administration of DTP (diphtheria, tetanus, pertussis) and/or OPV (oral
poliovirus vaccine) concomitantly with measles, mumps and rubella vaccines is
not recommended because there are insufficient data relating to the simultaneous
administration of these antigens. However, the American Academy of Pediatrics
has noted that in some circumstances, particularly when the patient may not
return, some practitioners prefer to administer all these antigens on a single
day. If done, separate sites and syringes should be used for DTP and R-VAC.
R-VAC should not be given less than one month before or after
administration of other virus vaccines.
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* Based in part on the recommendation for rubella vaccine use of the
Immunization Practices Advisory Committee (ACIP), Morbidity and Mortality Weekly
Report: 33(22): 301-310, 315-318, June 8, 1984.
** NOTE: The Immunization Practices Advisory Committee (ACIP) has recommended
"In view of the importance of protecting this age group against rubella,
reasonable precautions in a rubella immunization program include asking females
if they are pregnant, excluding those who say they are, and explaining the
theoretical risks to the others."
*/* NOTE: The Immunization Practices Advisory Committee (ACIP) has stated "When
practical, and when reliable laboratory services are available, potential
vaccinees of childbearing age can have serologic tests to determine
susceptibility to rubella. . . . However, routinely performing serologic tests
for all females of childbearing age to determine susceptibility so that vaccine
is given only to proven susceptibles is expensive and has been ineffective in
some areas. Accordingly, the ACIP believes that rubella vaccination of a woman
who is not known to be pregnant and has no history of vaccination is justifiable
without serologic testing."
CONTRAINDICATIONS:
Do not give R-VAC to pregnant females; the possible effects of the vaccine
on fetal development are unknown at this time. If vaccination of postpubertal
females is undertaken, pregnancy should be avoided for three months following
vaccination. (See PRECAUTIONS, Pregnancy).
Anaphylactic or anaphylactoid reactions to neomycin (each dose of reconstituted
vaccine contains approximately 25 mcg of neomycin).
Any febrile respiratory illness or other active febrile infection.
Active untreated tuberculosis.
Patients receiving immunosuppressive therapy. This contraindication does not
apply to patients who are receiving corticosteroids as replacement therapy,
e.g., for Addison's disease.
Individuals with blood dyscrasias, leukemia, lymphomas of any type, or other
malignant neoplasms affecting the bone marrow or lymphatic systems.
Primary and acquired immunodeficiency states, including patients who are
immunosuppressed in association with AIDS or other clinical manifestations of
infection with human immunodeficiency viruses; cellular immune deficiencies; and
hypogammaglobulinemic and dysgammaglobulinemic states.
Individuals with a family history of congenital or hereditary immunodeficiency,
until the immune competence of the potential vaccine recipient is demonstrated.
PRECAUTIONS:
General
Adequate treatment provisions including epinephrine, should be available for
immediate use should an anaphylactic or anaphylactoid reaction occur.
Excretion of small amounts of the live attenuated rubella virus from the nose or
throat has occurred in the majority of susceptible individuals 7-28 days after
vaccination. There is no confirmed evidence to indicate that such virus is
transmitted to susceptible persons who are in contact with the vaccinated
individuals. Consequently, transmission through close personal contact, while
accepted as a theoretical possibility, is not regarded as a significant risk.
However, transmission of the vaccine virus to infants via breast milk has been
documented (see Nursing Mothers).
There is no evidence that live rubella virus vaccine given after exposure to
natural rubella virus will prevent illness. There is, however, no
contraindication to vaccinating children already exposed to natural rubella.
Children and young adults who are known to be infected with human
immunodeficiency viruses but without overt clinical manifestations of
immunosuppression may be vaccinated; however, the vaccinees should be monitored
closely for vaccine-preventable diseases because immunization may be less
effective than for uninfected persons.
Vaccination should be deferred for at least three months following blood or
plasma transfusions, or administration of human immune serum globulin. However,
susceptible postpartum patients who received blood products may receive R-VAC
II prior to discharge provided that a repeat HI titer is drawn 6-8 weeks after
vaccination to insure seroconversion. Similarly, although studies with other
live rubella virus vaccines suggest that R-VAC may be given in the
immediate postpartum period to those non-immune women who have received anti-Rho
(D) globulin (human) without interfering with vaccine effectiveness, a follow-up
post-vaccination HI titer should also be determined.
It has been reported that attenuated rubella virus vaccine, live, may result in
a temporary depression of tuberculin skin sensitivity. Therefore, if a
tuberculin test is to be done, it should be administered either before or
simultaneously with R-VAC.
As for any vaccine, vaccination with R-VAC may not result in seroconversion
in 100% of susceptible persons given the vaccine.
Pregnancy
Pregnancy Category C
Animal reproduction studies have not been conducted with R-VAC. It is also
not known whether R-VAC can cause fetal harm when administered to a
pregnant woman or can affect reproduction capacity. There is evidence suggesting
transmission of rubella vaccine viruses to products of conception. Therefore,
rubella vaccine should not be administered to pregnant females (see
CONTRAINDICATIONS).
In counseling women who are inadvertently vaccinated when pregnant or who become
pregnant within 3 months of vaccination, the physician should be aware of the
following: In a 10 year survey involving over 700 pregnant women who received
rubella vaccine within 3 months before or after conception, (of whom 189
received the Wistar RA 27/3 strain) none of the newborns had abnormalities
compatible with congenital rubella syndrome.
Nursing Mothers
Recent studies have shown that lactating postpartum women immunized with live
attenuated rubella vaccine may secrete the virus in breast milk and transmit it
to breast-fed infants. In the infants with serological evidence of rubella
infection, none exhibited severe disease; however, one exhibited mild clinical
illness typical of acquired rubella. Caution should be exercised when R-VAC
is administered to a nursing woman.
ADVERSE REACTIONS:
Burning and/or stinging of short duration at the injection site have been
reported.
Symptoms of the same kind as those seen following natural rubella may occur
after vaccination. These include mild regional lymphadenopathy, urticaria, rash,
malaise, sore throat, fever, headache, dizziness, nausea, vomiting, diarrhea,
polyneuritis, and arthralgia and/or arthritis (usually transient and rarely
chronic). Local pain, wheal and flare, induration, and erythema may occur at the
site of injection. Reactions are usually mild and transient. Erythema multiforme
has also been reported rarely.
Cough and rhinitis have also been reported.
Vasculitis has been reported rarely.
Anaphylaxis and anaphylactoid reactions have been reported.
Moderate fever (101-102.9 deg F (38.3-39.4 deg C)) occurs occasionally, and high
fever (over 103 deg F (39.4 deg C)) occurs less commonly.
Syncope, particularly at the time of mass vaccination, has been reported.
Chronic arthritis has been associated with natural rubella infection and has
been related to persistent virus and/or viral antigen isolated from body
tissues. Only rarely have vaccine recipients developed chronic joint symptoms.
Following vaccination in children, reactions in joints are uncommon and
generally of brief duration. In women, incidence rates for arthritis and
arthralgia are generally higher than those seen in children (children: 0-3%;
women: 12-20%) and the reactions tend to be more marked and of longer duration.
Symptoms may persist for a matter of months or on rare occasions for years. In
adolescent girls, the reactions appear to be intermediate in incidence between
those seen in children and in adult women. Even in older women (35-45 years),
these reactions are generally well tolerated and rarely interfere with normal
activities. Myalgia and paresthesia have been reported rarely after
administration of R-VAC.
Forms of optic neuritis, including retrobulbar neuritis and papillitis may
infrequently follow viral infections, and have been reported to occur 1 to 3
weeks following inoculation with some live virus vaccines.
Isolated reports of polyneuropathy including Guillain-Barre syndrome have been
reported after immunization with rubella-containing vaccines.
Clinical experience with live rubella vaccines thus far indicates that
encephalitis and other nervous system reactions have occurred very rarely in
subjects who were given the vaccines, but a cause and effect relationship has
not been established.
Thrombocytopenia with or without purpura has been reported.
DOSAGE AND ADMINISTRATION:
FOR SUBCUTANEOUS ADMINISTRATION
Do Not Inject Intravenously
The dosage of vaccine is the same for all persons. Inject the total volume of
the single dose vial (about 0.5 mL) or 0.5 mL of the multiple dose vial of
reconstituted vaccine subcutaneously, preferably into the outer aspect of upper
arm. Do Not Give Immune Globulin (IG) Concurrently With R-VAC.
To insure that there is no loss of potency during shipment, the vaccine must be
maintained at a temperature of 10 deg C (50 deg F) or less.
Before reconstitution, store R-VAC at 2-8 deg C (36-46 deg F). Protect From
Light.
CAUTION: A sterile syringe free of preservatives, antiseptics, and detergents
should be used for each injection and/or reconstitution of the vaccine because
these substances may inactivate the live virus vaccine. A 25 gauge, 5/8'' needle
is recommended.
To reconstitute, use only the diluent supplied, since it is free of
preservatives or other antiviral substances which might inactivate the vaccine.
Single Dose Vial--First withdraw the entire volume of diluent into the syringe
to be used for reconstitution. Inject all the diluent in the syringe into the
vial of lyophilized vaccine, and agitate to mix thoroughly. Withdraw the entire
contents into a syringe and inject the total volume of restored vaccine
subcutaneously.
It is important to use a separate sterile syringe and needle for each individual
patient to prevent transmission of hepatitis B and other infectious agents from
one person to another.
10 Dose Vial (Available Only To Government Agencies/Institutions)--Withdraw the
entire contents (7 mL) of the diluent vial into the sterile syringe to be used
for reconstitution, and introduce into the 10 dose vial of lyophilized vaccine.
Agitate to ensure thorough mixing. The outer labeling suggests "For Jet Injector
or Syringe Use". Use with separate sterile syringes is permitted for containers
of 10 doses or less. The vaccine and diluent do not contain preservatives;
therefore, the user must recognize the potential contamination hazards and
exercise special precautions to protect the sterility and potency of the
product. The use of aseptic techniques and proper storage prior to and after
restoration of the vaccine and subsequent withdrawal of the individual doses is
essential. Use 0.5 mL of the reconstituted vaccine for subcutaneous injection.
It is important to use a separate sterile syringe and needle for each individual
patient to prevent transmission of hepatitis B and other infectious agents from
one person to another.
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