“Meruvax II 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.1-2”
Mosby’s GenRx®, 10th ed.
Copyright © 2000 Mosby, Inc.
Rubella Virus Vaccine Live (002196)
Indications: Immunization, rubella
Pregnancy Category C
WHO Formulary
FDA Pre 1938 Drugs
FDA DRUG CLASS: Vaccines/Antisera
BRAND NAMES: Cendevax (Benin, Burkina-Faso, Ethiopia,
Gambia, Ghana, Guinea, Ivory-Coast, Kenya, Liberia, Malawi, Mali, Mauritania,
Mauritius, Morocco, Niger, Nigeria, Senegal, Seychelles, Sierra-Leone, Sudan,
Tanzania, Tunia, Uganda, Zambia, Zimbabwe); Ervevax (Australia, Austria,
Bulgaria, Czech-Republic, England, Germany, Italy, Netherlands, Switzerland, Malaysia,
Philippines, Taiwan, Thailand); Gunevax (Philippines, Thailand);
(US); Rubavax (England); Rubeaten (Austria,
Czech-Republic, Greece, Italy, Spain, Switzerland); Rubeaten Berna (Malaysia,
Philippines, Taiwan, Thailand, South-Africa);
Rudivax (Malaysia, Taiwan);
(International brand names outside U.S. in italics)
Meruvax II (Rubella Virus Vaccine Live) is a live virus
vaccine for immunization against rubella (German measles).
Meruvax II 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.1-2
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.
Meruvax II 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 Meruvax II) 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 vaccine3-9 and has been shown to induce a broader
profile of circulating antibodies including anti-theta and anti-iota
precipitating antibodies.10,11 The RA 27/3 rubella strain immunologically
simulates natural infection more closely than other rubella vaccine
viruses.11-13 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,11,13-15 and provide
greater confidence for lasting immunity.
Vaccine-induced antibody levels have been shown to persist
for at least 10 years without substantial decline.16 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.
(This section is based, in part, on the recommendation for
rubella vaccine use of the Immunitazation Practices Advisory Committee (AICP),
MMWR Report: 33 (22):
301-310, 315-318, June 8, 1984).
Children Between 12 Months of Age and Puberty: Meruvax II
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.
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).
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
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.17
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.18 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.)
Postpartum Women: It has been found convenient in many
instances to vaccinate rubella susceptible women in the immediate postpartum
period (see Nursing Mothers.)
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.19,20,21
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
Meruvax II.22
Meruvax II should not be given less than one month before
or after administration of other virus vaccines.
·
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.”17
**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.”17
Do not give Meruvax II 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;23,24 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.25
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.17
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.23,24
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 Meruvax 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 Meruvax II 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 Meruvax II.
As for any vaccine, vaccination with Meruvax II may not
result in seroconversion in 100% of susceptible persons given the vaccine.
Animal reproduction studies have not been conducted with
Meruvax II. It is also not known whether Meruvax II 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.26 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.26
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.27 In the infants with serological
evidence of rubella infection, none exhibited severe disease; however, one
exhibited mild clinical illness typical of acquired rubella.28,29 Caution
should be exercised when Meruvax II is administered to a nursing woman.
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 a thralgia and/or arthritis (usually
transient and rarely chronic). Local pain, wheal and flare, induration, and
erythema may occur at the site 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°F (38.3 - 39.4°C)) occurs
occasionally, and high fever (over 103°F (39.4°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 isolate
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%)30 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 Meruvax II.
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.
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
Meruvax II.
To insure that there is no loss of potency during
shipment, the vaccine must be maintained at a temperature of 10°C (50°F) or
less.
Before reconstitution, store Meruvax II at 2 - 8°C (36 -
46°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.
50 Dose Vial (available only to government agencies/institutions):
Withdraw the entire contents (30 ml) of diluent vial into the sterile syringe
to be used for reconstitution and introduce into the 50 dose vial of
lyophilized vaccine. Agitate to ensure thorough mixing. With full aseptic
precautions, attach the vial to the sterilized multidose jet injector apparatus.
Use 0.5 ml of the reconstituted vaccine for subcutaneous injection.
Each dose contains not less than the equivalent of 1,000
TCID50 of the U.S.
Reference
Rubella Virus.
Parenteral drug products should be inspected visually for
particulate matter and discoloration prior to administration. Meruvax II, when
reconstituted, is clear yellow.
It is recommended that the vaccine be used as soon as
possible after reconstitution.
Protect vaccine from light at all times, since such
exposure may inactivate the virus.
Store reconstituted vaccine in the vaccine vial in a dark
place at 2 - 8°C (36 - 46°F) and discard if not used within 8 hours.
1. Plotkin, S. A.;
Cornfeld, D.; Ingalls, T. H.: Studies of immunization with living rubella virus:
Trials in children with a strain cultured from an aborted fetus, Am. J. Dis. Child.
110: 381-389, 1965.
2. Plotkin, S. A.;
Farquhar, J.; Katz, M.; Ingalls, T. H.: A new attenuated rubella virus grown in
human fibroblasts: Evidence for reduced nasopharyngeal excretion, Am. J.
Epidemiol. 86: 468-477, 1967.
3. Fogel, A.;
Moshkowitz, A.; Rannon, L.; Gerichter, Ch. B.: Comparative trials of RA 27/3
and Cendehill rubella vaccines in adult and adolescent females, Am. J. Epidemiol.
93: 392-398, 1971.
4. Andzhaparidze, O.
G.; Desyatskova, R. G.; Chervonski, G. I.;
Pryanichnikova, L.
V.: Immunogenicity and reactogenicity of live
attenuated rubella virus vaccines, Am. J.
Epidemiol. 91: 527-530, 1970.
5. Freestone, D. S.;
Reynolds, G. M.; McKinnon, J. A.; Prydie, J.:
Vaccination of schoolgirls against rubella. Assessment
of serological status and a comparative trial of Wistar RA 27/3 and Cendehill
strain live attenuated rubella vaccines in 13-year-old schoolgirls in Dudley,
Br. J. Prev. Soc. Med. 29: 258-261, 1975.
6. Grillner, L.;
Hedstrom, C. E.; Bergstrom, H.; Forssman, L.; Rigner,A.;
Lycke, E.:
Vaccination against rubella of newly delivered women,
Scand.J. Infect. Dis. 5:
237-241, 1973.
7. Grillner, L.:
Neutralizing antibodies after rubella vaccination of newly delivered women: a
comparison between three vaccines, Scand. J. Infect. Dis. 7: 169-172, 1975.
8. Wallace, R. B.;
Isacson, P.: Comparative trial of HPV-77, DE-5 and RA 27/3 live-attenuated
rubella vaccines, Am. J. Dis. Child. 124: 536-538, 1972.
9. Lalla, M.; Vesikari,
T.; Virolainen, M.: Lymphoblast proliferation and humoral antibody response
after rubella vaccination, Clin. Exp. Immunol.15:
193-202, 1973.
10. LeBouvier, G. L.;
Plotkin, S. A.: Precipitin responses to rubella vaccine RA 27/3, J. Infect.
Dis. 123: 220-223, 1971.
11. Horstmann, D. M.:
Rubella: the challenge of its control, J. Infect.
Dis. 123:
640-654, 1971.
12. Ogra, P. L.;
Kerr-Grant, D.; Umana, G.; Dzierba, J.; Weintraub, D.:
Antibody response in serum and nasopharynx after
naturally acquired and vaccine-induced infection with rubella virus, N. Engl.
J. Med.285: 1333-1339, 1971.
13. Plotkin, S. A.;
Farquhar, J. D.; Ogra, P. L.: Immunologic properties of
RA 27/3 rubella virus vaccine, J. Am. Med. Assoc. 225:
585-590, 1973.
14. Liebhaber, H.;
Ingalls, T. H.; LeBouvier, G. L.; Horstmann, D. M.:
Vaccination with RA 27/3 rubella vaccine. Persistence
of immunity and resistance to challenge after two years, Am. J. Dis. Child.
123: 133-136, 1972.
15. Farquhar, J. D.:
Follow-up on rubella vaccinations and experience with subclinical reinfection,
J. Pediatr. 81: 460-465, 1972.
16. Hillary, I. B.;
Griffith, A. H.: Persistence of antibody 10 years after vaccination with Wistar
RA 27/3 strain live attenuated rubella vaccine. Br. Med. J. 280 (6231):
1580-1581, 1980.
17. Recommendation of the
Immunization Practices Advisory Committee (ACIP), Morbidity and Mortality
Weekly Report 33 (22): 301-310, 315-318, June 8, 1984.
18. Mclntosh, R.;
Merritt, K. K.; Richards, M. R.; Samuels, M. H.; Bellows, M. T.:
The incidence of congenital malformations: A study of
5,964 pregnancies, Pediatrics 14:
505-521, 1954.
19. Recommendations of
the Immunization Practices Advisory Committee (ACIP), Measles Prevention, MMWR
36 (26): 409-425, July 10, 1987.
20. Jong, E. C., The
Travel and Tropical Medicine Manual, W. B. Saunders Company, p. 12-16, 1987.
21. Committee on Immunization
Council of Medical Societies, American
College of
Physicians, Phila., PA, Guide for Adult Immunization,
First Edition, 1985.
22. American Academy of
Pediatrics: Report of the Committee on Infectious Disease, Evanston, III.,
1982, p. 17.
23. Center for Disease
Control: Immunization of Children Infected with Human T-Lymphotropic Virus Type
III/Lymphadenopathy-Associated Virus, Annals of Internal Medicine, 106: 75-78,
1987.
24. Krasinski, K.;
Borkowsky, W.; Krugman, S.: Antibody following measles immunization in children
infected with human T-cell lymphotropic virus-type III/lymphadenopathy
associated virus (HTLV-III/LAV) (Abstract). In: Program and abstracts of the
International Conference on Acquired Immunodeficiency Syndrome, Paris, France,
June 23-25, 1986.
25. Recommendation of the
Immunization Practices Advisory Committee (ACIP), General Recommendations on
Immunization, Morbidity and Mortality Weekly Report 32 (1): 13, January 14,
1983.
26. Rubella vaccination
during pregnancy—United States, 1971-1981,
Morbidity and
Mortality Weekly Report 31 (35): 477-481, September
10, 1982.
27. Losonsky, G. A.;
Fishaut, J. M.; Strussenberg, J.; Ogra, P. L.: Effect of immunization against
rubella on lactation products. II. Maternal-neonatal interactions, J.
Infect. Dis. 145: 661-666, 1982.
28. Landes, R. D.; Bass,
J. W.; Millunchick, E. W.; Oetgen, W. J.: Neonatal rubella following postpartum
maternal immunization, J. Pediatr.97: 465-467, 1980. (Letter)
29. Lerman, S. J.:
Neonatal rubella following postpartum maternal immunization, J. Pediatr. 98: 668, 1981. (Letter)
30. Unpublished data from
the files of Merck Sharp & Dohme Research Laboratories.
MD Consult L.L.C.
http://www.mdconsult.com
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INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR
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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.